Beliefs, Attitudes, and Practices of Latinas Related to Gestational Weight Gain: A Qualitative Meta-Synthesis.
Excessive and inadequate gestational weight gain (GWG) are associated with a number of negative health outcomes for mother and infant. Approximately two-thirds or more of Latinas gain outside of GWG guidelines. Acculturation plays a role in GWG-related factors, however the views of Latinas are often aggregated in overall study samples, thus trivializing the specific needs of this demographic group. The purpose of the present meta-ethnography was to better understand GWG beliefs, attitudes, and practice among Latinas by synthesizing extant qualitative findings on this topic. Qualitative studies offer an important window into Latinas' views and practices related to GWG. A qualitative meta-ethnography (a form of meta-synthesis) was implemented to synthesize qualitative studies about Latinas' views of GWG-related factors. An initial sample of articles was distilled based on meta-ethnography guidelines from Noblit and Hare (1988) to a final sample of six qualitative articles that included perspectives from Latinas. Six concepts emerged across the studies, they included: shifts in feeling control, inconsistent/lacking information, self vs. other, applied wisdom, isolation vs. support, and everyday practicality. Studies met most quality assessment criteria (Atkins et al., BMC Medical Research Methodology 8:21, 2008). The views of Latinas about GWG-related factors are often buried in with perspectives of other women, which hides important details that are valuable for health program interventions designed to support these women. Future research should further explore the cultural differences in experience among Latinas to produce information and resources that are culturally relevant and relatable.


Vancomycin for multi-drug resistant Enterococcus faecium cholangiohepatitis in a cat.
A 12-year-old, neutered male domestic shorthair cat was evaluated with a life-long history of intermittent, predominantly small bowel diarrhea and a 3 day history of hematochezia. At presentation, the cat had increased liver enzyme activities and an inflammatory leukogram. Histopathology demonstrated inflammatory bowel disease (IBD), cholangiohepatitis and pancreatitis. The cholangiohepatitis was associated with a multi-drug resistant Enterococcus faecium. Gallbladder agenesis was also documented. Treatment with vancomycin was safely instituted for 10 days. Clinical signs resolved, however, cure of the bacterial cholangiohepatitis was not achieved. The risk of vancomycin resistant enterococci (VRE) in human and veterinary medicine is discussed.


Exhaled nitric oxide in preterm infants.
Nitric oxide (NO) is detectable in the exhaled gas of adults during spontaneous respiration and, according to current knowledge, mainly originates from the paranasal sinuses. We studied total NO excretion rates by chemiluminescence in preterm infants whose paranasal sinuses are known to be only partially pneumatized. NO excretion was 7.15 +/- 1.13 nl/min (mean +/- SD, range 6.33-9.36 nl/min) measured from spontaneously exhaled nasal gas (n = 6) and 0.3 +/- 0.05 nl/min (range 0.26-0.36 nl/min) measured from the lower airways in intubated individuals (n = 3). These values are considerably lower than those reported for older children and adults. Body weight-related amounts of NO excretion, however, seem comparable between infants and adults.


Impact of insulin resistance on the developmental potential of immature oocytes retrieved from human chorionic gonadotropin-primed women with polycystic ovary syndrome undergoing in vitro maturation.
In a homeostasis model assessment-insulin resistance (HOMA-IR)-positive group of women with polycystic ovary syndrome undergoing in vitro maturation (IVM), the maturation rate of immature oocytes was significantly lower compared with a HOMA-IR negative group of women (47% vs. 59%). The results of our study showed that IR and hyperinsulinemia have an adverse effect on the developmental potential of immature oocytes retrieved in the IVM procedure.


Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens.
The HIV-1 Tat protein is able to raise a humoral immune response in the absence of adjuvant. Here, we investigated whether this property can be transferred to unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell-dependent phenomenon in which a Th2 profile predominates. Then, we showed that the determinant governing the property is located in the region 1-57 of Tat and that fragment Tat1-57 can make two unrelated model antigens immunogenic in the absence of adjuvant. We found a Th2 pattern of immune response for both antigens, suggesting that Tat1-57 mediates this response. Next, we showed that, although less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the adjuvant property to other antigens. We also observed that preservation of cysteine 37 is absolutely required for the transfer, suggesting the role of disulphide-mediated dimerization in the transfer of the adjuvant property. Our observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby opening up new perspectives in vaccination.


Automatic mode of acquisition of spatial sequences in a serial reaction time paradigm.
In this study, the acquisition of spatial sequences was investigated. It was found that the acquisition of spatial sequence order could be acquired under strictly automatic conditions, namely, when not being part of the task requirement nor when being beneficial to purposive behavior. The results are discussed from the perspective of the difference between spatial versus non-spatial sequence learning.


First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study.
Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy. We reviewed 144 patients with NSCLC with major EGFR mutations, but not T790M, who received first- or second-generation EGFR tyrosine kinase inhibitors (TKIs), registered in the prospective, umbrella-type lung cancer patient registry (CS-Lung-003). Overall, 63 patients (44%) underwent the first rebiopsy. In the first rebiopsy, 51 (81%) and 12 (19%) of 63 underwent histological/cytological rebiopsy and liquid biopsy with the blood sampling, respectively. In the repeat rebiopsy, 23 (85%) and 4 (15%) of 27 underwent histological/cytological rebiopsy and liquid biopsy, respectively. The most frequently rebiopsied site was a pulmonary lesion (n = 24, 38.7%). Overall, 29 (46.0%) of 63 patients harbored the T790M mutation. Interestingly, a high detection rate of cancer cells did not necessarily indicate a high detection rate of the T790M mutation (p < 0.01). Among 34 patients with T790M-negative tumors confirmed on the first rebiopsy, 20 (58.8%) underwent repeat rebiopsies following interval therapy, revealing that seven (36.8%) had T790M-positive tumors. Osimertinib yielded median progression-free survival of 11.8 and 16.2 months in patients with the 790M mutation detected by the first rebiopsy and repeat rebiopsy, respectively. In our prospective cohort, the T790M mutation was detected in 46% of patients who underwent the first rebiopsy. Repeat rebiopsy may increase the ability to detect the T790M mutation positivity rate.


Evaluation of PCR Approaches for Detection of Bartonella bacilliformis in Blood Samples.
The lack of an effective diagnostic tool for Carrion's disease leads to misdiagnosis, wrong treatments and perpetuation of asymptomatic carriers living in endemic areas. Conventional PCR approaches have been reported as a diagnostic technique. However, the detection limit of these techniques is not clear as well as if its usefulness in low bacteriemia cases. The aim of this study was to evaluate the detection limit of 3 PCR approaches. We determined the detection limit of 3 different PCR approaches: Bartonella-specific 16S rRNA, fla and its genes. We also evaluated the viability of dry blood spots to be used as a sample transport system. Our results show that 16S rRNA PCR is the approach with a lowest detection limit, 5 CFU/μL, and thus, the best diagnostic PCR tool studied. Dry blood spots diminish the sensitivity of the assay. From the tested PCRs, the 16S rRNA PCR-approach is the best to be used in the direct blood detection of acute cases of Carrion's disease. However its use in samples from dry blood spots results in easier management of transport samples in rural areas, a slight decrease in the sensitivity was observed. The usefulness to detect by PCR the presence of low-bacteriemic or asymptomatic carriers is doubtful, showing the need to search for new more sensible techniques.


Stimulation and inhibition of mitogen-induced lymphoproliferation by serum fractions.
Normal guinea pig serum was fractionated by filtration through a Sephacryl S200 column. The various fractions were assayed on concanavalin A and phytohemagglutinin-induced mitogenesis as measured by 3H-thymidine uptake in newly formed DNA. Alpha-Globulin, gamma-globulins and albumin were shown to modulate lymphoproliferation. The enhancing or depressing effects of these various fractions depended upon the nature and dose of the mitogen used, the concentration of the fraction added, and the time interval between the addition of fractions and the addition of mitogens. The results suggest that serum fractions can at least modulate the immune response through their activity on the proliferation of lympohocytes.


Basal cell carcinoma of the scrotum. Report of three cases and review of the literature.
Although basal cell carcinoma (BCC) is the most common human malignancy, only 21 cases involving the scrotum have been previously reported. Our purpose is to describe three additional cases of scrotal BCC and review the literature summarizing the clinical features and identifying any predisposing factors. We retrospectively reviewed 21 cases of scrotal BCC and described three new cases. Polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV) DNA in our biopsy specimens. Scrotal BCCs present as persistent ulcerations or plaques without identifiable predisposing factors. Lymphatic, pulmonary, or skin metastases were present in 3 of 24 cases (13%) resulting in death in one case. PCR did not detect HPV DNA in our three cases. Scrotal BCC rarely occurs and should be considered in the diagnosis of a persistent scrotal ulcer or plaque. Metastatic disease may be more common than with other BCCs and wide local excision or Mohs micrographic surgery may be the most appropriate initial therapeutic approach.


The effects of continuous naltrexone infusions on diet preferences are modulated by adaptation to the diets.
Two groups of male rats were placed on a feeding regimen in which a fat/protein diet and a carbohydrate/protein diet were available ad lib. Naltrexone was infused via osmotic minipumps either at the time the diets were introduced or after one week of adaptation to the diets. In rats adapted to the diets, naltrexone caused a decrease in the intakes of fat/protein and carbohydrate/protein diets. Relative preferences for the two diets were generally unchanged. In contrast, when naltrexone was infused at the time of introduction of the diets, a polarization phenomenon was observed: rats tended to consume nearly all of their daily calories from either one diet or the other. Six rats (out of 10) showed a stronger preference for the carbohydrate/protein diet than did any of the saline-treated rats, while 3 showed a stronger preference for the fat/protein diet than did any of the saline-treated rats. Thus, the effect was not diet- or macronutrient-specific. These preferences became significantly less extreme after termination of naltrexone infusions. Conditioned aversions and naltrexone-induced reductions in exploratory behavior are discussed as potential explanations for this polarization effect. These results indicate that naltrexone has differential effects on the development versus the maintenance of diet preferences. Further, they emphasize the importance of examining individual differences as well as baseline preferences in studies on the control of intake and diet selection.


Multiple 5-HT receptors in the guinea-pig superior cervical ganglion.
1. We have studied the pharmacology of the depolarization by 5-hydroxytryptamine (5-HT) of the guinea-pig isolated superior cervical ganglion (SCG) using the grease-gap technique. We studied the effects of selective and non-selective antagonists on the responses to 5-HT and other 5-HT receptor agonists. 2. We have extended the pharmacology of the 5-HT3 receptor in this preparation by studying the effects of granisetron, BRL 46470 and mianserin on the concentration-response curve (CRC) to 2-methyl-5-HT. As with other 5-HT3 receptor antagonists, these compounds exhibited a lower affinity for guinea-pig 5-HT3 receptors than for rat 5-HT3 receptors. 3. We have confirmed that low concentrations of 5-HT (< or = 1 microM) mediate ketanserin-sensitive responses and higher concentrations of 5-HT also recruit 5-HT3 receptors. The responses to low concentrations of 5-HT were antagonized by low concentrations of ketanserin, spiperone, mianserin, DOI and LSD indicating probably mediation by 5-HT2A receptors. At high concentrations, the hallucinogen, DOI, but not LSD, evoked a ketanserin-sensitive depolarization. 4. Although mianserin could bind to the 5-HT2A receptors in this preparation, we could not demonstrate a down-regulation of depolarizations evoked by these receptors after a 10 day oral treatment with mianserin (10 mg kg-1, daily). 5. 5-Carboxamidotryptamine (5-CT) evoked a prolonged depolarization. Although high concentrations of 5-CT (> or = microM) appeared to activate 5-HT2A receptors, lower concentrations of 5-CT evoked a response with a distinct pharmacology. After studying the action of 20 selective and non-selective 5-HT receptor ligands we believe that this response may be mediated by a novel receptor; but its pharmacology is closest to that of receptors in the 5-HT2 receptor family. Like 5-CT, 5-HT (3-300 microM) could evoke an LSD-sensitive response in the presence of the 5-HT2 receptor antagonist, ketanserin and the 5-HT3 receptor antagonist, tropisetron (all 1 microM). 6. We conclude that 5-HT activates three pharmacologically distinct receptors to depolarize the guinea-pig SCG. Low concentrations of 5-HT appear to activate 5-HT2A receptors. Higher concentrations of 5-HT also activate 5-HT3 receptors and a possible novel 5-HT receptor. The novel receptor could be a species homologue of a 5-HT2 receptor or an, as yet, unclassified 5-HT receptor.


Trading off safety against food: state dependent habitat choice and foraging in crucian carp.
The influence of hunger level and predation risk on habitat choice and foraging in crucian carp, Carassius carassius, were studied in a laboratory experiment. Experiments were carried out in aquaria with or without a predator (pike, Esox lucius). Habitat use and foraging activity of three-fish foraging groups of either fed or hungry crucian carp were studied. Fish were allowed to choose between an open (risky) habitat with Tubifex worms and a habitat with dense vegetation (safe) without food. Habitat use was significantly affected by both risk of predation and hunger level. Crucian carp spent less time in the open habitat when there was a predator present and they also spent less time there when fed than when hungry. Furthermore, there was a significant interaction between risk of predation and hunger level, indicating a state-dependent trade-off between food acquisition and predator avoidance.


The expression of p53 and bcl-2 in superficial bladder transitional cell carcinoma and its role in the outcome of postoperative intravesical chemotherapy.
We evaluated whether p53 and bcl-2 expression has any predictive value on the outcome of postoperative adjuvant intravesical chemotherapy for superficial bladder transitional cell carcinoma (TCC). Immunostaining for p53 and bcl-2 was performed on paraffin-embedded tumor tissues obtained from 100 patients with superficial bladder TCC. 56 had solitary and 44 had multiple tumors; 36 were grade I, 53 grade II and 11 grade III; 50 were stage pTa and 50 stage pT1. They all received transurethral resection (TUR) and weekly intravesical instillation chemotherapy with either Thiotepa (70 patients) or Epirubicin (30 patients) for consecutive 8 doses postoperatively. Overall, 7 (7%) tumors were p53+ and 12 (12%) tumors were bcl-2+. Of these, only one tumor was combined p53+ and bcl-2+. The status of tumor p53 and bcl-2 positivity was found to be not significantly correlated with either tumor grade or stage. After adjuvant intravesical chemotherapy, tumor recurrence is significantly correlated with tumor multifocality (p = 0.0002) but not with tumor grade and stage. Compared with p53- or bcl-2- tumors, patients with p53+ or bcl-2+ tumors do not show a higher tumor recurrence rate. The number of recurrence-free patients was also not significantly different in p53+ versus p53- tumors, bcl-2+ versus bcl-2- tumors. Six (6%) patients eventually developed disease progression, and none stained positively for either p53 or bcl-2. We conclude that in superficial bladder TCC the status of tumor p53 and bcl-2 expression is not correlated with stage and grade. Their expression, either alone or combined, has no predictive role on the outcome of post-TUR intravesical chemotherapy on tumor recurrence.


Spinal mechanisms of pudendal nerve stimulation-induced inhibition of bladder hypersensitivity in rats.
Bilateral electrical pudendal nerve stimulation (bPNS) reduces bladder hypersensitivity in rat models of bladder pain and anecdotally reduces pain in humans with pelvic pain of urologic origin. The spinal neurochemical mechanisms of this antinociception are unknown. In the present study, bladder hypersensitivity was produced by neonatal bladder inflammation in rat pups coupled with a second inflammatory insult as an adult. Visceromotor responses (VMRs; abdominal muscle contractions) to urinary bladder distension (UBD) were used as a nociceptive endpoint under urethane-isoflurane anesthesia. bPNS consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory component of the pudendal nerves. Following determination of the inhibitory effect of bPNS on VMRs, pharmacological antagonists were administered via an intrathecal catheter onto the lumbosacral spinal cord and bPNS effects on VMRs redetermined. bPNS resulted in statistically significant inhibition of VMRs to UBD in hypersensitive rats that was statistically reduced by the intrathecal administration of methysergide, WAY100636, CGP35348 and strychnine but was unaffected by naloxone, bicuculline, phentolamine, ondansetron and normal saline. This study suggests that inhibitory effects of bPNS may include serotonergic, GABA-B-ergic and glycinergic mechanisms suggesting the potential for interaction of the neuromodulatory effect with concommitant drug therapies.


The use of diagnostic ratios, biomarkers and 3-way Kohonen neural networks to monitor the temporal evolution of oil spills.
Oil spill identification relies usually on a wealth of chromatographic data which requires advanced data treatment (chemometrics). A simple approach based on Kohonen neural networks to handle three-dimensional arrays is presented. A suite of 28 diagnostic ratios was considered to monitor six oils along four months. It was found that some traditional diagnostic ratios were not stable enough. In particular, alkylated PAHs (e.g. 1-methyldibenzothiophene, 4-methylpyrene, 27bbSTER and the TA21 and TA26 triaromatic steroids) seemed less resistant to medium-weathering than biomarkers. One (or two) ratios were found to differentiate each product: 30O, 28ab (and 25nor30ab), C3-dbt/C3-phe, 27Ts, TA26 and 29Ts characterized Ashtart, Brent, Maya, Sahara, IFO and Prestige oils, respectively.


The relationship between frontal sinus drainage and osteomeatal complex disease: a CT study in 217 patients.
Over a period of 2 years we reviewed the CT scans of 217 patients with recurrent sinusitis. Our findings revealed a number of cases of osteomeatal complex disease with no frontal sinus involvement. This result is difficult to reconcile with the concept of a common drainage in the middle meatus shared by the frontal and anterior ethmoid sinuses. We conclude that the frontal sinus drains separately from the other paranasal sinuses in a large percentage of cases, and that the frontal sinus is frequently spared when there is ethmoid or maxillary sinusitis.


A polyether sponge constituent which is antioxidant, anti-inflammatory and increases prostaglandin concentrations at the inflamed site.
Granuloma formation was studied in rats following s.c. implantation of polyether sponges soaked in carrageenin. Sponges, which had been boiled in ethanol, produced larger granulomata and more exudate than unboiled sponges, but prostaglandin (PG) concentrations were lower in exudates from boiled sponges. Sub-cutaneous injection of the ethanolic sponge extract inhibited the delayed phase of carrageenin-induced rat hind paw oedema. A counter irritant action was ruled out by the demonstration that local administration of the extract also inhibited hind paw oedema. Ultra-violet spectrophotometry of the anti-inflammatory extract indicated that the main constituent was probably a phenolic material, commonly used as an antioxidant in the manufacture of polymers. The antioxidant nature of the extract was confirmed by its inhibition of the autoxidation of adrenaline. The results are discussed in the light of recent reports on the anti-inflammatory properties of phenolic antioxidants and their effects on the PG biosynthetic pathway.


A kinetic study of the mechanism of conversion of alpha-hydroxyheme to verdoheme while bound to heme oxygenase.
O2-dependent reactions of the ferric and ferrous forms of alpha-hydroxyheme complexed with water-soluble rat heme oxygenase-1 were examined by rapid-scan stopped-flow measurements. Ferric alpha-hydroxyheme reacted with O2 to form ferric verdoheme with an O2-dependent rate constant of 4x10(5) M(-1) s(-1) at pH 7.4 and 9.0. A decrease of the rate constant to 2.8x10(5) M(-1) s(-1) at pH 6.5 indicates that the reaction proceeds by direct attack of O2 on the pi-neutral radical form of alpha-hydroxyheme, which is generated by deprotonation of the alpha-hydroxy group. The reaction of ferrous alpha-hydroxyheme with O2 yielded ferrous verdoheme in a biphasic fashion involving a new intermediate having absorption maxima at 415 and 815 nm. The rate constants for this two-step reaction were 68 and 145 s(-1). These results show that conversion of alpha-hydroxyheme to verdoheme is much faster than the reduction of coordinated iron (<1 s(-1)) under physiological conditions [Y. Liu, P.R. Ortiz de Montellano, Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1, J. Biol. Chem. 275 (2000) 5297-5307], suggesting that, in vivo, the conversion of ferric alpha-hydroxyheme to ferric verdoheme precedes the reduction of ferric alpha-hydroxyheme.


Two superoxide dismutases from TnOtchr are involved in detoxification of reactive oxygen species induced by chromate.
Superoxide dismutases (SOD) have been reported as the most relevant bacterial enzymes involved in cells protection from reactive oxygen species (ROS). These toxic species are often the product of heavy metal stress. Two genes, chrC and chrF, from TnOtchr genetic determinant of strain Ochrobactrum tritici 5bvl1 were cloned in Escherichia coli in order to overexpress the respective proteins. Both proteins were purified and characterized as superoxide dismutases. ChrC was confirmed as being a Fe-SOD, and the enzymatic activity of the ChrF, not inhibited by hydrogen peroxide or potassium cyanide, suggested its inclusion in the Mn-SOD family. This identification was supported by chemical quantification of total metal content in purified enzyme. Both enzymes showed a maximum activity between pH 7.2-7.5. ChrF retained nearly full activity over a broader range of pH and was slightly more thermostable than ChrC. The genes encoding these enzymes in strain O. tritici 5bvl1 were inactivated, developing single and double mutants, to understand the contribution of these enzymes in detoxification mechanism of reactive oxygen species induced by chromate. During chromate stress, assays using fluorescent dyes indicated an increase of these toxic compounds in chrC, chrF and chrC/chrF mutant cells. In spite of the multiple genes coding for putative superoxide dismutase enzymes detected in the genome of O. tritici 5bvl1, the ChrC and ChrF might help the strain to decrease the levels of reactive oxygen species in cells.


Insights into DNA polymerase δ's mechanism for accurate DNA replication.
Our study examines the mechanisms by which DNA polymerase (pol) δ faithfully replicates DNA. To better understand this process, we have performed all-atom molecular dynamics simulations of several DNA pol δ systems to identify conformational changes occurring prior to chemistry and investigate mechanisms by which mutations in the fingers domain (R696W and A699Q) lower fidelity. Our results indicate that, without the incoming nucleotide, a distinct open conformation occurs defined by a rotation in the fingers. The closed form, adopted when the correct nucleotide is bound, appears best organized for chemistry when three magnesium ions coordinate protein and DNA residues in the active site. Removing an unusual third metal ion from the polymerase active site causes shifting in the fingers and thumb as well as stimulating specific exonuclease β-hairpin-DNA interactions that fray the primer terminus base pair. These changes suggest that dissociation of the third divalent ion (metal ion 'C') signals a transfer of the DNA primer from the polymerase to the exonuclease active site and implies a role for the β-hairpin in DNA switching. Analysis of β-hairpin movement in several systems reveals a dependence on active-site changes and suggests how Lys444 and Tyr446 present in the β-hairpin can affect proofreading. Analysis of A699Q and R696W pol δ mutant systems reveal marked differences in the open-to-closed transition as well as β-hairpin repositioning that explain reduced nucleotide selectivity and higher error rates.


Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V deficiency due to a novel mutation in the APOA5 gene.
APOA5 encodes a novel apolipoprotein (apo A-V) which appears to be a modulator of plasma triglyceride (TG). In apoA5 knock out mice plasma TG level increases almost fourfold, whereas in human APOA5 transgenic mice it decreases by 70%. Some SNPs in the APOA5 gene have been associated with variations in plasma TG in humans. In addition, hypertriglyceridaemic (HTG) patients have been identified who carried rare nonsense mutations in the APOA5 gene (Q139X and Q148X), predicted to result in apo A-V deficiency. In this study we report a 17-year-old male with high TG and low high density lipoprotein cholesterol (HDL-C), who at the age of two had been found to have severe HTG and eruptive xanthomas suggesting a chylomicronaemia syndrome. Plasma postheparin LPL activity, however, was normal and no mutations were found in LPL and APOC2 genes. The sequence of APOA5 gene revealed that the patient was homozygous for a point mutation (c.289 C>T) in exon 4, converting glutamine codon at position 97 into a termination codon (Q97X). Apo A-V was not detected in patient's plasma, indicating that he had complete apo A-V deficiency. The administration of a low-fat and low-oligosaccharide diet, either alone or supplemented with omega-3 fatty acids, started early in life, reduced plasma TG to a great extent but had a negligible effect on plasma HDL-C. Loss of function mutations of APOA5 gene may be the cause of severe HTG in patients without mutations in LPL and APOC2 genes.


Bovine skin lesions of possible filarial origin associated with heavy hornfly infestations (Haematobia meridiana).
Circumscribed, ulcerative skin lesions, usually situated caudal to the scapula, affected cattle in the Republic of Venda during the summer of 1981-82. The occurrence of the lesions was associated with heavy infestations of the hornfly. Haematobia meridiana. Microscopically the lesions were characterized by intense eosinophilic dermatitis. Microfilariae were seen in histological sections of one lesion, but a species identification could not be made. The possible cause of the lesions is discussed.


Mitochondrial DNA damage and repair in neurodegenerative disorders.
By producing ATP and regulating intracellular calcium levels, mitochondria are vital for the function and survival of neurons. Oxidative stress and damage to mitochondrial DNA during the aging process can impair mitochondrial energy metabolism and ion homeostasis in neurons, thereby rendering them vulnerable to degeneration. Mitochondrial abnormalities have been documented in all of the major neurodegenerative disorders-Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Mitochondrial DNA damage and dysfunction may be downstream of primary disease processes such as accumulation of pathogenic proteins. However, recent experimental evidence demonstrates that mitochondrial DNA damage responses play important roles in aging and in the pathogenesis of neurodegenerative diseases. Therapeutic interventions that target mitochondrial regulatory systems have been shown effective in cell culture and animal models, but their efficacy in humans remains to be established.


Extending the search pattern in computed tomography.
Computed tomography has made new demands upon the traditional search patterns used by radiologists. These demands reflect not only the novel orientation of the images, being a series of axial slices, but also increased detail shown on the films. The scope for macropathological correlation with the image has also increased. Review areas are suggested which are pertinent to interpretation of the scans.


Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese.
Lung cancer is a complex disease influenced by a variety of genetic and environmental factors. The cytokine interleukin 1 encoded by IL1B is an important mediator of the inflammatory response, and is involved in a variety of cellular activities. The effect of single nucleotide polymorphisms (SNP) at IL1B has been investigated in relation to cancer with inconsistent results. This Northeastern-Chinese case-control study involving 627 cases and 633 controls evaluated the role of three haplotype-tagging single nucleotide polymorphisms (htSNP) (rs1143633, rs3136558 and rs1143630) representing 95% of the common haplotype diversity across the IL1B gene and assessed interactions with IL1B, PPP1R13L, POLR1G and smoking duration in relation to lung cancer risk. The analyses of five genetic models showed associations with lung cancer risk for rs1143633 in the dominant model [adjusted-OR (95% CI) = 0.67 (0.52-0.85), P = 0.0012] and rs3136558 in the recessive model [adjusted-OR (95% CI) = 1.44 (1.05-1.98), P = 0.025]. Haplotype4 was associated with increased lung cancer risk [adjusted-OR (95% CI) = 1.55 (1.07-2.24), P = 0.021]. The variant G-allele of rs1143633 was protective in smoking sub-group of > 20 years. Using multifactor dimensionality reduction (MDR) analyses, we identified the three best candidate models of interactions and smoking-duration or IL1B rs1143633 as main effect. In conclusion, our findings suggest that IL1B SNP rs1143633 may associate with lower risk of lung cancer, confirming previously identified marker; IL1B SNP rs3136558 and haplotype4 consisting of IL1B htSNPs may associate with increasing risk of lung cancer; interactions of IL1B with POLR1G or PPP1R13L or smoking-duration, which is independent or combined, may involve in risk of lung cancer and lung squamous cell carcinoma.


Valve-sparing aortic root replacement and aortic valve repair for a 2-year-old girl with Loeys-Dietz syndrome.
We report the case of a 2-year-old girl with Loeys-Dietz syndrome complicated by aortic root dilatation and aortic regurgitation. We performed valve-sparing aortic root replacement with reimplantation technique and aortic valve repair using central plication and free-margin reinforcement simultaneously. The postoperative course was uneventful and the latest echocardiography, 5 years after procedure, revealed trivial aortic insufficiency.


The influence of gestational age and preeclampsia on the presence and magnitude of serum endogenous digoxin-like immunoreactive substance(s).
Digoxin-like immunoreactive substance(s) has been measured in serum during pregnancy. Because of its presence in pregnancy, investigators have suggested that digoxin-like immunoreactive substance may play an etiologic role in the development of preeclampsia. The objectives of this study were to evaluate the relationship between maternal digoxin-like immunoreactive substance and gestational age and compare digoxin-like immunoreactive substance concentrations in patients with and without preeclampsia who were in the third trimester. Two hundred twenty patients were studied during either the first (n = 53), second (n = 56), or third (n = 111) trimester of pregnancy. Digoxin-like immunoreactive substance was undetectable in the serum of patients during the first trimester; however, 11% of second-trimester and 96% of third-trimester patients had measurable levels of serum digoxin-like immunoreactive substance (p less than 0.05). The mean +/- SEM concentration of digoxin-like immunoreactive substance in serum in third-trimester patients was 0.29 +/- 0.01 ng/ml (range 0 to 0.58 ng/ml). Gestational age at delivery was significantly lower in patients with preeclampsia than in those without preeclampsia (36.3 +/- 0.6 versus 38.8 +/- 0.4 weeks; p less than 0.001). In addition, there was no statistical difference in mean +/- SEM concentration of digoxin-like immunoreactive substance between 27 patients without preeclampsia (0.32 +/- 0.02 ng/ml) and 27 patients with preeclampsia (0.30 +/- 0.02 ng/ml; p = 0.47) matched for gestational age. We conclude that (1) digoxin-like immunoreactive substance appearance and increasing serum concentration during pregnancy are correlated with increasing gestational age and (2) there is no difference in digoxin-like immunoreactive substance values between patients with and without preeclampsia, which may exclude digoxin-like immunoreactive substance as a predictor of preeclampsia.


Standardized Feeding Approach Mitigates Weight Loss in Infants with Congenital Heart Disease.
To evaluate the effect of a standardized feeding approach using a clinical nutrition pathway on weight-for-age Z score (WAZ) over hospital length of stay (HLOS) for infants with congenital heart disease (CHD). A 10-year retrospective cohort study examined eligible infants who underwent neonatal cardiac surgery between July 2009 and December 2018 (n = 987). Eligibility criteria included infants born at least 37 weeks of gestation and a minimum birth weight of 2 kg who underwent cardiac surgery for CHD within the first 30 days of life. Using the best linear unbiased predictions from a linear mixed effects model, WAZ change over HLOS was estimated before and after January 2013, when the standardized feeding approach was initiated. The best linear unbiased predictions model included adjustment for patient characteristics including sex, race, HLOS, and class of cardiac defect. The change in WAZ over HLOS was significantly higher from 2013 to 2018 than from 2009 to 2012 (β = 0.16; SE = 0.02; P < .001), after controlling for sex, race, HLOS, and CHD category, indicating that infants experienced a decreased WAZ loss over HLOS after the standardized feeding approach was initiated. Additionally, differences were found in WAZ loss over HLOS between infants with single ventricle CHD (β = 0.26; SE = 0.04; P < .001) and 2 ventricle CHD (β = 0.04; SE = 0.02; P = .04). These data suggest that an organized, focused approach for nutrition therapy using a standardized pathway improves weight change outcomes before hospital discharge for infants with single and 2 ventricle CHD who require neonatal cardiac surgery.


Charge transfer through DNA/DNA duplexes and DNA/RNA hybrids: complex theoretical and experimental studies.
Oligonucleotides conduct electric charge via various mechanisms and their characterization and understanding is a very important and complicated task. In this work, experimental (temperature dependent steady state fluorescence spectroscopy, time-resolved fluorescence spectroscopy) and theoretical (Density Functional Theory) approaches were combined to study charge transfer processes in short DNA/DNA and RNA/DNA duplexes with virtually equivalent sequences. The experimental results were consistent with the theoretical model - the delocalized nature of HOMO orbitals and holes, base stacking, electronic coupling and conformational flexibility formed the conditions for more effective short distance charge transfer processes in RNA/DNA hybrids. RNA/DNA and DNA/DNA charge transfer properties were strongly connected with temperature affected structural changes of molecular systems - charge transfer could be used as a probe of even tiny changes of molecular structures and settings.


Advances in the analysis of iminocyclitols: Methods, sources and bioavailability.
Iminocyclitols are chemically and metabolically stable, naturally occurring sugar mimetics. Their biological activities make them interesting and extremely promising as both drug leads and functional food ingredients. The first iminocyclitols were discovered using preparative isolation and purification methods followed by chemical characterization using nuclear magnetic resonance spectroscopy. In addition to this classical approach, gas and liquid chromatography coupled to mass spectrometry are increasingly used; they are highly sensitive techniques capable of detecting minute amounts of analytes in a broad spectrum of sources after only minimal sample preparation. These techniques have been applied to identify new iminocyclitols in plants, microorganisms and synthetic mixtures. The separation of iminocyclitol mixtures by chromatography is particularly difficult however, as the most commonly used matrices have very low selectivity for these highly hydrophilic structurally similar molecules. This review critically summarizes recent advances in the analysis of iminocyclitols from plant sources and findings regarding their quantification in dietary supplements and foodstuffs, as well as in biological fluids and organs, from bioavailability studies.


Postmortem Ultrastructural Analysis of the Retina from COVID-19 Deceased Patients.
COVID-19 (coronavirus disease 2019) is an infectious disease caused by SARS-CoV-2, first reported in 2019 in Wuhan, China. Among the common complications is a pro-inflammatory and hypercoagulative response that compromises the vasculature among various organs. In this report, we present the postmortem retinal findings of five patients observed by means of optical microscopy and transmission and scanning electron microscopy techniques. Clinical manifestations such as retinal hemorrhages and exacerbated inflammatory infiltrate, altered ultra structure with swollen mitochondria and pyknotic cells in both layers of the retina were observed in all analyzed eyes. Our data point to the fragility of this tissue in cases of severe COVID-19.


Revertants of v-fos-transformed fibroblasts have mutations in cellular genes essential for transformation by other oncogenes.
Morphologic revertants of FBJ murine sarcoma virus (v-fos)-transformed rat-1 fibroblasts were isolated using a novel selection procedure based on prolonged retention of rhodamine 123 within mitochondria of v-fos-transformed versus normal fibroblasts. Two classes of revertants were isolated: class I revertants have sustained mutations in cellular genes, and a class II revertant has a nonfunctional v-fos provirus. Somatic-cell hybridization studies suggested that the revertant phenotype was recessive to the transformed phenotype. Class I revertants were also resistant to retransformation by v-gag-fos-fox, v-Ha-ras, v-abl, and v-mos, but could be retransformed by the trk oncogene and polyoma virus middle T antigen. These results suggest that the class I revertants sustained mutations in one or more cellular genes essential for transformation by some, but not all, oncogenes. Our data suggest the existence of common biochemical pathways for transformation.


On the Reproduction Number of a Gut Microbiota Model.
A spatially structured linear model of the growth of intestinal bacteria is analysed from two generational viewpoints. Firstly, the basic reproduction number associated with the bacterial population, i.e. the expected number of daughter cells per bacterium, is given explicitly in terms of biological parameters. Secondly, an alternative quantity is introduced based on the number of bacteria produced within the intestine by one bacterium originally in the external media. The latter depends on the parameters in a simpler way and provides more biological insight than the standard reproduction number, allowing the design of experimental procedures. Both quantities coincide and are equal to one at the extinction threshold, below which the bacterial population becomes extinct. Optimal values of both reproduction numbers are derived assuming parameter trade-offs.


[Morphometric analysis of the ultrastructure of tumor cells with a varying protein synthesis specificity].
The author has studied morphometrically the cell ultrastructure of fibroblastic and smooth muscle human tumors. There were found some differences in the quantitative features of the energetic (mitochondria) and protein-synthesizing (ergastoplasm and polyribosomes) cellular apparatus of these neoplasms. The specific criteria of the malignancy grade were identified for both groups of tumors.


Membrane-associated adenosine triphosphatase in normal and injured hypoglossal nuclei.
The hypoglossal nuclei of adult male albino rats, either normal, or from 1 to 70 days after left hypoglossal nerve transection, were studied cytochemically with a lead method for sodium- and potassium-activated membrane ATP-ase, using light and electron microscopy. Reaction product was measured at the light microscopical level by microdensitometry, and significance determined statistically. Light microscopy revealed a brown reaction product in the neuropil, but none in cell bodies. Blood vessel walls were more strongly coloured. Reaction product was undiminished by ouabain pre-incubation, or by incubation without sodium or potassium, or by incubation with calcium instead of magnesium. Reaction product was diminished by absence of magnesium if calcium was also absent, and abolished if sections were boiled before incubation, or if substrate was absent. Axotomy caused a statistically significant increase in neuropil reaction product in injured nuclei, maximal at 35 days postoperatively, and subsequently decreasing to normal at 70 days. Electron microscopy showed a predominantly surface membrane reaction product, with occasional positive intracellular cisternae. Basal lamina and intra-endothelial vacuoles were also positive. Axotomy resulted in the arrival and disappearance of microglis (2 to 35 days), followed by astrocyte hypertrophy (35 days), and increase in thickness and homogeneity of surface membrane reaction product. The results suggest the presence of one or more calcium- or magnesium-dependent membrane ATP-ases. The peak of the increase after axotomy is probably partly attributable to hypertrophic astrocytes, and partly to the surfaces of neuronal processes. Increase of membrane movements might explain such enzyme activity.


Designing of sampling programmes for industrial effluent monitoring.
Monitoring of effluent discharges from industrial establishments discharging directly into municipality sewers is one of the major water pollution control activities conducted by municipalities. For largely industrialised municipalities, the task can be quite expensive and not effective if sampling programmes are not properly designed. In most cases, samples are randomly collected without proper knowledge of the discharge patterns of various industries. As a result, the information obtained does not give a good reflection of the quality of effluent being discharged. These problems can be resolved by adapting a statistical approach to the design of sampling programmes. This approach is useful in determining the frequency of sampling, the number of samples needed to estimate the average concentration of target pollution indicator parameters and the magnitude of the uncertainty involved. The benefits and applications of this approach are demonstrated by a case study presented in this paper. It was found that the number of samples and cost of sample analysis can be greatly reduced by the use of systematic instead of random sampling. The statistical approach greatly improves the estimate of monthly means of pollution indicator parameters and is an effective approach for pollution control when coupled with the "polluter pays principle".


Assessment of requests for medication-related follow-up after hospital discharge, and the relation to unplanned hospital revisits, in older patients: a multicentre retrospective chart review.
The discharge of older hospitalised patients is critical in terms of patient safety. Inadequate transfer of information about medications to the next healthcare provider is a known problem, but there is a lack of understanding of this problem in settings where shared electronic health records are used. The aims of this study were to evaluate the prevalence of patients for whom hospitals sent adequate requests for medication-related follow-up at discharge, the proportion of patients with unplanned hospital revisits because of inadequate follow-up requests, and the association between medication reviews performed during hospitalisation and adequate or inadequate follow-up requests. We conducted a retrospective chart review. The study population was randomly selected from a cluster-randomised crossover trial which included patients 65 years or older who had been admitted to three hospitals in Sweden with shared electronic health records between hospital and primary care. Each patient was assessed with respect to the adequacy of the request for follow-up. For patients where the hospitals sent inadequate requests, data about any unplanned hospital revisits were collected, and we assessed whether the inadequate requests had contributed to the revisits. The association between medication reviews and adequate or inadequate requests was analysed with a Chi-square test. A total of 699 patients were included. The patients' mean age was 80 years; an average of 10 medications each were prescribed on hospital admission. The hospitals sent an adequate request for 418 (60%) patients. Thirty-eight patients (14%) had a hospital revisit within six months of discharge which was related to an inadequate request. The proportion of adequate or inadequate requests did not differ between patients who had received a medication review during hospitalisation and those who had not (p = 0.83). The prevalence of patients for whom the hospitals sent adequate follow-up requests on discharge was low. More than one in every ten who had an inadequate request revisited hospital within six months of discharge for reasons related to the request. Medication reviews conducted during hospitalisation did not affect the proportion of adequate or inadequate requests sent. A communication gap still exists despite the usage of a shared electronic health record between primary and secondary care levels.


The Interplay of ABC Transporters in Aβ Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer's Disease.
The occurrence of Alzheimer's disease (AD) worldwide has been progressively accelerating at an alarming rate, without any successful therapeutic strategy for the disease mitigation. The complexity of AD pathogenesis needs to be targeted with an alternative approach, as provided by the superfamily of ATP-binding cassette (ABC) transporters, which constitutes an extensive range of proteins, capable of transporting molecular entities across biological membranes. These protein moieties have been implicated in AD, based upon their potential in lipid transportation, resulting in maintenance of cholesterol homeostasis. These transporters have been reported to target the primary hallmark of AD pathogenesis, namely, beta-amyloid hypothesis, which is associated with accumulation of beta-amyloid (Aβ) plaques in AD patients. The ABC transporters have been observed to be localized to the capillary endothelial cells of the blood-brain barrier and neural parenchymal cells, where they exhibit different roles, consequently influencing the neuronal expression of Aβ peptides. The review highlights different families of ABC transporters, ABCB1 (P-glycoprotein), ABCA (ABCA1, ABCA2, and ABCA7), ABCG2 (BCRP; breast cancer resistance protein), ABCG1 and ABCG4, as well as ABCC1 (MRP; multidrug resistance protein) in the CNS, and their interplay in regulating cholesterol metabolism and Aβ peptide load in the brain, simultaneously exerting protective effects against neurotoxic substrates and xenobiotics. The authors aim to establish the significance of this alternative approach as a novel therapeutic target in AD, to provide the researchers an opportunity to evaluate the potential aspects of ABC transporters in AD treatment.


Improving Asthma Management in the Elementary School Setting: An Education and Self-management Pilot Project.
To increase daily asthma symptom self-assessments of elementary school students using Green Means Go, an asthma education and self-assessment program, via a partnership between an elementary school and a school of nursing. Over four months, accelerated MSN nursing students provided small group education sessions to teach students and teachers to identify asthma symptoms by Asthma Action Plan (AAP) zones and actions for each zone. To promote continuity of care between school and home, a teacher-parent communication log during yellow zone days was encouraged. Students with asthma (n = 90), teachers (n = 12) and parents (n = 1) participated. Previously no students performed daily self-assessments and at program end, all students accurately identified symptoms, AAP zones, and action steps. A total of 789 symptom self-assessments were recorded. Teachers reported increased asthma knowledge. One parent attended an education session and one home visit was completed. No communication logs were returned. Partnerships between elementary and nursing schools may be an effective strategy for delivery of health programs to high-risk children with chronic diseases. Self-assessment of symptoms and taking appropriate actions at school are critical components of early asthma intervention, particularly when a school nurse is not always available. Training teachers to follow a child's AAP within school policies is a critical second step. Home visits showed potential as a strategy for engaging parents. In the current climate of school nurse shortages, management of asthma-related episodes in school can be improved with similar partnerships and programs that promote health education and self-management.


Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure.
Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the V̇E /V̇CO2 slope in HFrEF vs. HFpEF. Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2 slope via linear regression, and VD /VT = 1 - [(863 × V̇CO2 )/(V̇E × PaCO2 )]. Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2 = 0.30 and R2 = 0.50, respectively) and PaCO2 (R2 = 0.64 and R2 = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Relationships between the V̇E /V̇CO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.


Muscular degeneration in Duchenne's dystrophy may be caused by a mitochondrial defect.
Duchenne's dystrophy (DMD), a recessive chromosome X-related disease, is the most common and severe form of myopathy. The different theories (vascular, neurogenic, membraneous, calcic and auto-immune) formulated to account for this disease have not been swept away by the discovery of the DMD gene and the deficient protein, dystrophin, since the exact cellular role played by the latter is still unknown. Our work on skeletal muscle has demonstrated a mitochondrial deficiency of the calcium-specific protein, calmitine, in degenerating muscle of myopathic persons and animals. Considering its great affinity for calcium, this protein specific to skeletal muscle could be essential to mitochondrial calcium regulation and thus to the functioning of the entire muscle cell. Its deficiency in Duchenne's and Becker type muscular dystrophy could be due to a mitochondrial genome alteration solely accountable for muscular degeneration. This hypothesis challenges the supposedly essential but still undefined role that researchers have attributed to dystrophin.


Pregnancy among three national samples of runaway and homeless youth.
To compare estimates of the prevalence of pregnancy among runaway and homeless youth between the ages of 14 and 17 years in various settings with each other and with youth in the general population. Comparisons used three surveys of youth: (a) the first nationally representative survey of runaway and homeless youth residing in federally and nonfederally funded shelters, (b) a multicity survey of street youth, and (c) a nationally representative household survey of youth with and without recent runaway and homeless experiences. Youth living on the streets had the highest lifetime rates of pregnancy (48%), followed by youth residing in shelters (33%) and household youth (<10%). Shelter and street youth were at much greater risk of having ever been pregnant than were youth in households, regardless of whether they had recent runaway or homeless experiences. Such youth need comprehensive services, including pregnancy prevention, family planning, and prenatal and parenting services.


Visualization of the Brassica self-incompatibility S-locus on identified oilseed rape chromosomes.
Seventy years after Karpechenko [15] first reported the accurate chromosome number of oilseed rape (Brassica napus L., 2n=38), we have developed a quantitative chromosome map of rape using computer imaging technology. The capacity to identify individual rape chromosomes will facilitate a wide range of genetic studies. Here we demonstrate the use of imaging methods in combination with fluorescence in situ hybridization to localize, on identified chromosomes, the single copy S-locus glycoprotein and S-locus-related genes involved in the self-incompatibility system of Brassica. These techniques have a broader application in plant genome research involving the mapping of single-copy genes and markers, irrespective of the plant species.


Visualization of proteinaceous granules in the clear synaptic vesicles.
A method for demonstration of electron-dense particles within clear synaptic vesicles from various areas of the CNS as well as from neuromuscular junctions of rat is described. Electron-dense granules of 70-250 A were visible in the center of the synaptic vesicles, or in some cases excentrically situated and bound to the vesicular membrane. Digestion with proteolytic enzymes lead to a negative reaction, whereas treatment with hyaluronidase and neuraminidase, as well as the lipid extraction had no effect. Based on the obtained data, it may be assumed that this method manifests the proteinaceous structures.


Pituitary adenoma and visual function. The prognostic value of clinical, ophthalmological and neuroradiologic findings in 51 patients subjected to operation.
The series studied included 51 patients subjected to operation for pituitary adenoma. The visual status was analysed both pre- and postoperatively. The pre- and postoperative parameters were compared with clinical information, ophthalmological and neuroradiological findings with a view to an evaluation of their prognostic value. In 36 patients with chromophobe adenoma, visual field defects were present in 92% before the operation; visual function improved in 62% and returned to normal in 24%. Among 15 patients with eosinophil or mixed adenoma, only two (13%) had visual field defects pre-operatively. In those patients where operation was followed by a distinct visual improvement, the pre-operative ophthalmological findings were as follows: visual acuity greater than 6/24, normal optic discs, visual field defects up to two quadrants, and pneumoencephalographic findings suggestive of only a small suprasellar tumour.


Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes.
The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic insulin resistance. Twenty obese patients with type 2 diabetes were randomized to etanercept treatment (25 mg subcutaneously twice weekly for 4 weeks) or used as controls in an open parallel study. Forearm blood flow and glucose uptake were measured during intra-arterial infusions of serotonin, sodium nitroprusside and insulin co-infused with serotonin. Beta-cell function was assessed with oral and intra-venous glucose tolerance tests and whole-body insulin sensitivity by hyperinsulinemic euglycemic clamps. Plasma levels of C-reactive protein and interleukin-6 decreased significantly with etanercept (C-reactive protein from 9.9 +/- 3.1 to 4.8 +/- 1.4 mg l(-1), p = 0.04; interleukin-6 from 3.1 +/- 0.4 to 1.9 +/- 0.2 ng l(-1), p = 0.03). Vasodilatory responses to serotonin and sodium nitroprusside infusions remained unchanged. Insulin effect on vasodilatation and on whole-body and forearm glucose uptake remained unchanged as well. Beta-cell function tended to improve. Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed.


C-reactive protein may be a prognostic factor in hepatocellular carcinoma with malignant portal vein invasion.
Hepatocellular carcinoma (HCC) has a high predilection for portal vein invasion, and the prognosis of HCC with malignant portal vein invasion is extremely poor. The objective of this study was to investigate the outcomes and the prognostic factor of recurrence in HCC patients with malignant portal vein invasion. We retrospectively reviewed the clinicopathologic data and outcomes of 83 HCC patients with malignant portal vein invasion and 1,056 patients without portal vein invasion who underwent liver resection. Increased serum alkaline phosphatase (ALP) levels, increased maximum tumor size, and intrahepatic metastasis were predisposing factors for malignant portal vein invasion by multivariate analysis. The median disease-free survival and overall survival of HCC patients with malignant portal vein invasion was 4.5 months and 25 months, respectively. The 1-year, 2-year, and 3-year disease-free survival rates were 30.6%, 26.1%, and 21.2%, respectively, and the overall survival rates for HCC patients with malignant portal vein invasion were 68.6%, 54.2%, and 41.6%, respectively. The initial detection site was the lung in HCC patients with portal vein invasion and the liver in HCC patients without portal vein invasion. C-reactive protein (CRP) was a significant independent predictor of tumor recurrence in HCC with malignant portal vein invasion after surgery. Increased ALP levels, increased maximum tumor size, and intrahepatic metastasis were independent predictors of malignant portal vein invasion in HCC. CRP level was closely associated with the predisposing factor of tumor recurrence in HCC patients with malignant portal vein invasion after a surgical resection, and lung metastasis was common.


Lymph node-targeted immune-activation mediated by imiquimod-loaded mesoporous polydopamine based-nanocarriers.
Toll-like receptor (TLR) agonists are the potent stimulants of innate immune system and hold promises as an adjuvant for anticancer immunotherapy. Unfortunately, most of them are limited by a prompt dissemination, and thus caused "wasted inflammation". Hence, how to restrict their action radius into lymphoid tissues is of great relevance to enhance their efficacy and concomitantly alleviates the side effects. Here, imiquimod (R837), a TLR 7 agonist, was loaded into mesoporous polydopamine (MPDA) nanocarriers with high efficiency. Moreover, its surface was modified by polyvinyl pyrrolidone (PVP) to enhance their lymphatic drainage ability. These nano-adjuvants have obvious advantages in promoting dendritic cell (DC) maturation in comparison to free R837. Moreover, their transportation and retention ability in proximal lymph nodes (LNs) were also confirmed, by which lymphatic drug exposure can be maximized to a great extent. Consequently, effective DC activation and CD8+ T cell responses were observed as expected by R837 released in draining LNs. This effect was further enhanced by the presence of endogenous tumor antigens from apoptosis debris induced by MPDA-based photothermal effect, and thus led to the growth inhibition of subcutaneous B16 melanomas. The results demonstrated the great potency against melanoma of the designed PVP-MPDA@R837 nano-adjuvants by combining photothermal conversion property of MPDA with lymphatic-focused immune-activation.


Substrate stiffness regulates the differentiation profile and functions of osteoclasts via cytoskeletal arrangement.
Aging and common diseases alter the stiffness of bone tissue, causing changes to the microenvironment of the mechanosensitive bone cells. Osteoclasts, the sole bone-resorbing cells, play a vital role in bone remodeling. This study was performed to elucidate the mechanism through which osteoclasts sense and react to substrate stiffness signals. We fabricated polydimethylsiloxane (PDMS) substrates of different stiffness degrees for osteoclast formation progressed from osteoclast precursors including bone marrow-derived macrophages (BMMs) and RAW264.7 monocytes. Osteoclast differentiation in response to the stiffness signals was determined by examining the cell morphology, fusion/fission activities, transcriptional profile, and resorption function. Cytoskeletal changes and mechanosensitive adhesion molecules were also assessed. Stiffer PDMS substrates accelerated osteoclast differentiation, firstly observed by variations in their morphology and fusion/fission activities. Upregulation of canonical osteoclast markers (Nfatc1, Acp5, Ctsk, Camk2a, Mmp9, Rela, and Traf6) and the fusion master regulator DC-stamp were detected on stiffer substrates, with similar increases in their bone resorption functions. Additionally, the activation of cytoskeleton-associated adhesion molecules, including fibronectin and integrin αvβ3, followed by biochemical signaling cascades of paxillin, FAK, PKC, and RhoA, was detected on the stiffer substrates. This is the first study to provide evidence proving that extracellular substrate stiffness is a strong determinant of osteoclast differentiation and functions. Higher stiffness upregulated the differentiation profile and activity of osteoclasts, revealing the mechanical regulation of osteoclast activity in bone homeostasis and diseases.


Culturable heterotrophic bacterial diversity study from an Indian lignite mine habitat.
Diversity lifts the productivity of any ecosystem as all the species have a vital role to play that is present within the ecosystem. The characterization is essential to delve into the ecological functions of microbial communities and discover the type of microorganisms present within the ecosystem. As microbial diversity in ecosystems responds to environmental disturbances, it functions as a marker to indicate the change in such ecosystems. Mine ecology differs significantly from other habitats due to the presence of acidic runoff. This paper provides insight into the diversity of cultivable bacteria isolated from lignite mines located in south Gujarat. A total of 67 heterotrophic isolates were successfully cultivated from the collected solid and water samples of the Rajpardi and Tadkeshwar Lignite mine sites. The isolates were characterized morphologically and biochemically, and intra- and extracellular enzyme synthesis were studied. Moreover, the relative density and frequency of cultivated isolates from the samples were calculated. The similarity and evenness of the heterotrophic isolated were studied by calculating diversity indices such as Shannon and Simpson. Alpha diversity was calculated in PAST software to analyse the similarity between the selected two mine sites. This research also explored the relationship between the variance in heterotrophic microbial diversity and substrate utilization richness of the studied lignite mines of Gujarat.


Surgical treatment and prognosis of adult patients with brainstem gliomas.
The paper presents 47 adult patients who were surgically treated due to brainstem gliomas. Thirteen patients presented with contrast-enhancing Grades III and IV gliomas, according to the WHO classification, 13 patients with contrast-enhancing tumours originating from the glial cells (Grade I; WHO classification), 9 patients with diffuse gliomas, 5 patients with tectal brainstem gliomas and 7 patients with exophytic brainstem gliomas. During the surgical procedure, neuronavigation and the diffusion tensor tractography (DTI) of the corticospinal tract were used with the examination of motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs) with direct stimulation of the fundus of the fourth brain ventricle in order to define the localization of the nuclei of nerves VII, IX, X and XII. Cerebellar dysfunction, damage to cranial nerves and dysphagia were the most frequent postoperative sequelae which were also the most difficult to resolve. The Karnofsky score established preoperatively and the extent of tumour resection were the factors affecting the prognosis. The mean time of progression-free survival (14 months) and the mean survival time after surgery (20 months) were the shortest for malignant brainstem gliomas. In the group with tectal brainstem gliomas, no cases of progression were found and none of the patients died during the follow-up. Some patients were professionally active. Partial resection of diffuse brainstem gliomas did not prolong the mean survival above 5 years. However, some patients survived over 5 years in good condition.


Digestive cancers in Morocco: Fez-Boulemane region.
To describe the epidemiological and pathological aspects of gastrointestinal cancers in Fez-Boulemane. This was a retrospective descriptive study of 1120 gastrointestinal cancers diagnosed between 2004 and 2010 in the department of Pathology of Hassan II University Hospital in Fez Morocco. The average age of our patients was 53 years with a male predominance in 52% of cases. Digestive cancers in this study are distinguished by the predominance of colorectal and stomach location. Gastrointestinal cancers are the most frequent cancer in our region. An epidemiological monitoring program is needed.


[Histochemical investigations on the fish kidney (Gasterosteus aculeatus L.) (author's transl)].
The kidney of the stickleback has a double function in the spawn period, the excretion and secretion. This functions limited a different enzyme pattern (phosphatases and oxidoreductases) in the different parts of the kidney.


Does fascia hold memories?
The idea that tissues may possess some sort of memory is a controversial topic in manual medicine, calling for research and clinical exploration. Many bodyworkers, at some point in their practice, have experienced phenomena that may be interpreted as representing a release of memory traces when working on dysfunctional tissues. This feeling may have been accompanied by some type of sensory experience, for the therapist and/or the patient. In some cases, early traumatic experiences may be recalled. When this happens, the potency of the memory may be erased or eased, along with restoration of tissue function. Hence the questions: can memories be held in the fascia? And: are these memories accessible during manual fascial work? Modern research has proposed a variety of different interpretations as to how memory might be stored in soft tissues, possibly involving other forms of information storage not exclusively processed neurologically (Box 1).


Addicted to Acidic Microenvironment.
Acidic pH levels are often observed in growing tumors, with profound effects on cancer cells and surrounding microenvironment. In this issue of Developmental Cell, Funato et al. (2020) show that expression of oncogenic phosphatase of regenerating liver 3 (PRL3) shifts cellular preference for environmental pH, leading to acid addiction.


Catchment properties and the photosynthetic trait composition of freshwater plant communities.
Unlike in land plants, photosynthesis in many aquatic plants relies on bicarbonate in addition to carbon dioxide (CO2) to compensate for the low diffusivity and potential depletion of CO2 in water. Concentrations of bicarbonate and CO2 vary greatly with catchment geology. In this study, we investigate whether there is a link between these concentrations and the frequency of freshwater plants possessing the bicarbonate use trait. We show, globally, that the frequency of plant species with this trait increases with bicarbonate concentration. Regionally, however, the frequency of bicarbonate use is reduced at sites where the CO2 concentration is substantially above the air equilibrium, consistent with this trait being an adaptation to carbon limitation. Future anthropogenic changes of bicarbonate and CO2 concentrations may alter the species compositions of freshwater plant communities.


Four new species of the genus Diduga Moore, [1887] (Lepidoptera, Erebidae, Arctiinae) from China and Malaysia.
In this paper, four species of the genus Diduga Moore, [1887] from China (Chongqing and Guangdong) and Malaysia (Borneo, Sabah) are described as new to science, namely D. simianshana sp. nov., D. chebalinga sp. nov., D. chewi sp. nov., and D. hollowayi sp. nov. Adults of these species are illustrated in color, and images of the male and female genitalia are provided. A distribution map of the new species is provided, together with an updated checklist of all species of Diduga.


Prognostic Value of Lymph Node Density in Node-Positive Oral Squamous Cell Carcinoma.
Lymph node status is an important prognostic factor in head and neck cancer. The purpose of this study is to investigate the prognostic value of lymph node density (LND) in node-positive oral cavity cancer patients who received surgery plus adjuvant radiotherapy. From January 2008 to December 2013, a total of 61 oral cavity squamous cell cancer patients who had positive lymph node and received surgery and adjuvant radiotherapy were analysed. LND was calculated for each patient. The endpoints were 5-year overall survival (OS) and 5-year disease-free survival. All patients were followed for a period of 5 years. Mean 5-year overall survival for cases with LND of ≤ 0.05 was 56.1 ± 11.6 months, whereas mean 5-year overall survival for cases with LND > 0.05 was 40.0 ± 21.6 months. Log rank is 0.04 95% CI = 53.4-65. Mean 5-year disease-free survival for cases with LND of ≤ 0.05 was 50.5 ± 15.8 months, whereas mean disease-free survival for cases with LND > 0.05 was 15.8 ± 22.9 months. Log rank 0.03 95% CI = 43.3-57.6. Nodal status, disease stage and lymph node density were found to be significant predictors of prognosis in univariate analysis. In multivariate analysis, only lymph node density is found to be the predictor of prognosis. LND is an important prognosis factor for 5-year OS and 5-year DFS in oral cavity squamous cell carcinoma.


An unusual cause of intra-abdominal calcification: A lithopedion.
We report a case of a 77-year-old female who was admitted to the emergency department complaining of diffuse abdominal pain for five days, associated with nausea, vomiting and constipation. Physical examination disclosed a large incarcerated umbilical hernia, which was readily apparent on supine abdominal plain films. These also showed a calcified heterogeneous mass in the mid-abdominal region, which was further characterized by CT as a lithopedion (calcified ectopic pregnancy). This is one of the few cases studied on a MDCT equipment, and it clearly enhances the post-processing abilities of this imaging method which allows diagnostic high-quality MIP images. Lithopedion is a rare entity, with less than 300 cases previously described in the medical literature. However, many reported cases corresponded to cases of skeletonization or collections of fetal bone fragments discovered encysted in the pelvic region at surgery or autopsy. It is thus estimated that true lithopedion is a much rarer entity. The diagnosis may be reached by a suggestive clinical history and a palpable mass on physical examination, while the value of modern cross-sectional techniques is still virtually unknown. Ultrasonography may depict an empty uterine cavity and a calcified abdominal mass of non-specific characteristics, and computed tomography or magnetic resonance imaging are able to reach a conclusive diagnosis and may additionally define the involvement of adjacent structures. The differential diagnosis includes other calcified pathologic situations, including ovarian tumors, uterine fibroids, urinary tract neoplasms, inflammatory masses or epiploic calcifications.


Calcitonin gene-related peptide release from intact isolated dorsal root and trigeminal ganglia.
Neuropeptides like calcitonin gene-related peptide (CGRP) and substance P are found in significant proportions of primary afferent neurons. Release of these neuropeptides as well as prostaglandin E(2) is an approved index for the activation of these primary afferents. Previous studies have used cultures of enzyme-treated and mechanically dissociated primary afferent neurons, fresh tissue slices or cubes. In the present study we demonstrate CGRP and prostaglandin E(2) release from intact isolated dorsal root and trigeminal ganglia. Stimulation with noxious heat, low pH, inflammatory mediators and high potassium concentration increased CGRP release. In conclusion, neuropeptide release from intact isolated ganglia is a reliable method to study the responsiveness of sensory neurons in situ in comparison with neuronal cell cultures.


Cryo-EM structure of SMG1-SMG8-SMG9 complex.
Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity.


Mechanical and functional validation of a perfused, robot-assisted partial nephrectomy simulation platform using a combination of 3D printing and hydrogel casting.
There is a scarcity of high-fidelity, life-like, standardized and anatomically correct polymer-based kidney models for robot-assisted partial nephrectomy (RAPN) simulation training. The purpose of this technical report is to present mechanical and functional testing data as evidence for utilizing a perfused hydrogel kidney model created utilizing 3D printed injection casts for RAPN simulation and training. Anatomically correct, tumor-laden kidney models were created from 3D-printed casts designed from a patient's CT scan and injected with poly-vinyl alcohol (PVA). A variety of testing methods quantified Young's modulus in addition to comparing the functional effects of bleeding and suturing among fresh porcine kidneys and various formulations of PVA kidneys. 7% PVA at three freeze-thaw cycles (7%-3FT) was found to be the formula that best replicates the mechanical properties of fresh porcine kidney tissue, where mean(± SD) values of Young's modulus of porcine tissue vs 7%-3FT samples were calculated to be 85.97(± 35) kPa vs 80.97(± 9.05) kPa, 15.7(± 1.6) kPa vs 74.56(± 10) kPa and 87.46(± 2.97) kPa vs 83.4(± 0.7) kPa for unconfined compression, indentation and elastography testing, respectively. No significant difference was seen in mean suture tension during renorrhaphy necessary to achieve observable hemostasis and capsular violation during a simulated perfusion at 120 mmHg. This is the first study to utilize extensive material testing analyses to determine the mechanical and functional properties of a perfused, inanimate simulation platform for RAPN, fabricated using a combination of image segmentation, 3D printing and PVA casting.


Plasmonic CROWs for Tunable Dispersion and High Quality Cavity Modes.
Coupled resonator optical waveguides (CROWs) have the potential to revolutionise integrated optics, to slow-light and enhance linear and non-linear optical phenomena. Here we exploit the broad resonances and subwavelength nature of localized surface plasmons in a compact CROW design where plasmonic nanoparticles are side coupled to a dielectric waveguide. The plasmonic CROW features a low loss central mode with a highly tunable dispersion, that avoids coupling to the plasmonic nanoparticles close to the band-edge. We show that this low loss character is preserved in finite plasmonic CROWs giving rise to Fabry-Perot type resonances that have high quality factors of many thousands, limited only by the CROW length. Furthermore we demonstrate that the proposed CROW design is surprisingly robust to disorder. By varying the geometric parameters one can not only reduce the losses into dissipative or radiative channels but also control the outcoupling of energy to the waveguide. The ability to minimise loss in plasmonic CROWs while maintaining dispersion provides an effective cavity design for chip-integrated laser devices and applications in linear and non-linear nano-photonics.


Pyridyl aminothiazoles as potent Chk1 inhibitors: optimization of cellular activity.
Translation of significant biochemical activity of pyridyl aminothiazole class of Chk1 inhibitors into functional CEA potency required analysis and adjustment of both physical properties and kinase selectivity profile of the series. The steps toward optimization of cellular potency included elimination of CDK7 activity, reduction of molecular weight and polar surface area and increase in lipophilicity of the molecules in the series.


Impact of enteral nutrition on intestinal bacterial translocation and mortality in burned mice.
The aim of these experiments was to study the effect of early enteral nutrition with either standard or enriched (arginine, n-3 fatty acids, RNA) enteral formulas on translocation of bacteria from the gut and acute mortality rate following thermal injury. In the first experiment 60 Balb c mice were gavaged with 10(10)Escherichia coli and received a 20% burn injury. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after injury and stopped 36 h later. In the control group (n = 20) aliquotes of Ringer's solution was administered intragastrically. Mortality rate was observed for 10 days post-injury. In the second experiment 60 Balb c mice were gavaged with 10(10)E. coli labelled with biotin(111) Indium and then burned. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after burn. The control group (n = 20) received aliquotes of Ringer's solution. 4 h after injury all animals were sacrificed and liver, lungs, kidneys, spleen and systemic blood were harvested, and radionuclide counts were measured. No animal died after day 3 post-burn. The mortality rate was significantly lower at day 1 in the groups infused with both enteral solutions (15%) compared to controls (30%; p = 0.05). At day 3 the animals fed with the enriched diets showed a lower mortality (5%) versus the standard and control groups (10%). Bacterial translocation to the liver and lungs was significantly higher in Ringer's group than in both enterally fed groups. Early post-burn enteral nutrition reduces both translocation and acute mortality. Supplementation of the diets with specific nutrients appears to exert additional advantages on outcome.


A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block.
C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB). This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop. There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 ± 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 ± 0.71, P = 0.042) and beside the table (5.69 ± 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 ± 19.0, 0.97 ± 0.92, and 9.53 ± 8.16), resepectively. Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.


The changes in complete blood count in thyroid cancer patients treated with radioactive iodine ablation therapy.
The aim of this study was to evaluate the effect of radioactive iodine (RAI) ablation therapy on the complete blood count (CBC) in thyroid cancer patients. One hundred sixty four patients undergoing RAI ablation therapy after total thyroidectomy were included. CBC results were available from the patients' medical records at the time of ablation and at the 1st, 6th, and 12th months after RAI therapy. Hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) values were significantly lower than baseline at 1 month after treatment (p <0.0001). Hb and WBC values were increased at the 6th month and at the 1st year. Plt values increased at the 6th month but had decreased again at the 1st year. The values were usually in normal ranges except in the patients with low pretreatment Hb and WBC values. RAI ablation therapy in thyroid cancer patients is a safe treatment modality without any serious or persistent hematological side effects.


Longitudinal assessment of 1H-MRS (GABA and Glx) and TMS measures of cortical inhibition and facilitation in the sensorimotor cortex.
The purpose of the present study was to investigate the long-term stability of water-referenced GABA and Glx neurometabolite concentrations in the sensorimotor cortex using MRS and to assess the long-term stability of GABA- and glutamate-related intracortical excitability using transcranial magnetic stimulation (TMS). Healthy individuals underwent two sessions of MRS and TMS at a 3-month interval. A MEGA-PRESS sequence was used at 3 T to acquire MRS signals in the sensorimotor cortex. Metabolites were quantified by basis spectra fitting and metabolite concentrations were derived using unsuppressed water reference scans accounting for relaxation and partial volume effects. TMS was performed using published standards. After performing stability and reliability analyses for MRS and TMS, reliable change indexes were computed for all measures with a statistically significant test-retest correlation. No significant effect of time was found for GABA, Glx and TMS measures. There was an excellent ICC and a strong correlation across time for GABA and Glx. Analysis of TMS measure stability revealed an excellent ICC for rMT CSP and %MSO and a fair ICC for 2 ms SICI. There was no significant correlation between MRS and TMS measures at any time point. This study shows that MRS-GABA and MRS-Glx of the sensorimotor cortex have good stability over a 3-month period, with variability across time comparable to that reported in other brain areas. While resting motor threshold, %MSO and CSP were found to be stable and reliable, other TMS measures had greater variability and lesser reliability.


SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents.
Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.


Current use of biologic therapies for musculoskeletal disease: A survey of board-certified equine specialists.
To evaluate the use of mesenchymal stem cells (MSCs), autologous conditioned serum (ACS), platelet-rich plasma (PRP), and autologous protein solution (APS) for the treatment of equine musculoskeletal disease by diplomates of the American College of Veterinary Surgery (ACVS), and American College of Veterinary Sports Medicine and Rehabilitation (ACVSMR). Cross-sectional study. Diplomates (n = 423). An email link was sent to ACVS and ACVMR diplomates. A survey contained 59 questions regarding demographics, as well as indications, frequency, adverse effects, and limitations of use. Responses were analyzed using Fisher's exact test. One hundred and fifty four surveys were analyzed. Years in practice and type of practice were not associated with biologic therapy use. PRP was the most used therapy (120/137; 87.5%). PRP and MSCs were most often administered intralesionally while ACS and APS were most often administered intra-articularly. ACS (50/104; 48.1%) treatment was repeated commonly within 2 weeks of initial injection. MSCs (39/90; 43.3%) and PRP (38/100; 38%) were commonly repeated 1-2 months after initial injection and APS was typically repeated >4 months after initial injection (21/53; 39.6%). Local inflammation and expense were the most common adverse effect and limitation of use. Diplomates most commonly utilized PRP and MSC intralesionally for soft-tissue injuries, and ACS and ACP intra-articularly for joint injury. Protocols for repeated administration varied widely. Local inflammation was a clinical concern with the use of biologics. Biologic therapies are used commonly by ACVS and ACVSMR diplomates for soft tissue and joint disease.


Matrix completion under complex survey sampling.
Multivariate nonresponse is often encountered in complex survey sampling, and simply ignoring it leads to erroneous inference. In this paper, we propose a new matrix completion method for complex survey sampling. Different from existing works either conducting row-wise or column-wise imputation, the data matrix is treated as a whole which allows for exploiting both row and column patterns simultaneously. A column-space-decomposition model is adopted incorporating a low-rank structured matrix for the finite population with easy-to-obtain demographic information as covariates. Besides, we propose a computationally efficient projection strategy to identify the model parameters under complex survey sampling. Then, an augmented inverse probability weighting estimator is used to estimate the parameter of interest, and the corresponding asymptotic upper bound of the estimation error is derived. Simulation studies show that the proposed estimator has a smaller mean squared error than other competitors, and the corresponding variance estimator performs well. The proposed method is applied to assess the health status of the U.S. population.


Purification of tryptase from a human mast cell line.
The neutral protease tryptase has been isolated from a human mast cell line, HMC-1. The HMC-1 line was established from the peripheral blood of a patient with mast cell leukemia and maintained as continuously proliferating clones in vitro and as solid mast cell tumors in nude mice. HMC-1-derived tryptase was purified by sequential chromatography on Dowex 1, DEAE 5 PW, and heparin-agarose. Purified tryptase has an apparent molecular weight of 150,000, as determined by molecular sieve HPLC, but migrates as a doublet of bands of 32/35,000 on SDS-PAGE gels. Maximal enzymatic activity was observed at pH 8.5. Cleavage of tosyl-L-arginine methyl ester by purified tryptase was inhibited by dansyl-L-glutamyl-glycyl-L-arginine chloromethyl ketone 2 HCl, HgCl2, tosyl-L-lysine chloromethyl ketone, leupeptin, and PMSF but not by benzamidine, aprotinin, tosyl-L-phenyl-alanine chloromethyl ketone, soybean trypsin inhibitor, human plasma, ovomucoid inhibitor, or lima bean trypsin inhibitor. Microsequencing of purified tryptase yielded an amino terminal sequence that was identical to that previously reported for human pituitary-derived tryptase.


Carbon nanotubes enhance intercalated disc assembly in cardiac myocytes via the β1-integrin-mediated signaling pathway.
Carbon nanotubes (CNTs) offer a new paradigm for constructing functional cardiac patches and repairing myocardial infarction (MI). However, little is known about how CNTs enhance the mechanical integrity and electrophysiological function of cardiac myocytes. To address this issue, we investigated the regularity and precise mechanism of the influence of CNTs on the assembly of intercalated disc (IDs). Here, single walled CNTs incorporated into collagen substrates were utilized as growth supports for neonatal cardiomyocytes, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, western blotting, transmission electron microscopy, and intracellular calcium transient measurement, we discovered that the addition of CNTs remarkably increased ID-related protein expression and enhanced ID assembly and functionality. On that basis, we further explored the underlying mechanism for how CNTs enhanced ID assembly through the use of immunohistochemical staining and western blotting. We found that the β1-integrin-mediated signaling pathway mediated CNT-induced upregulation of electrical and mechanical junction proteins. Notably, CNTs remarkably accelerated gap junction formation via activation of the β1-integrin-mediated FAK/ERK/GATA4 pathway. These findings provide valuable insight into the mechanistic effects that CNTs have on neonatal cardiomyocyte performance and will have a significant impact on the future of nanomedical research.


Visible to infrared low temperature photoluminescence of rare earth doped bismuth germanate crystals.
In this paper, the influence of a series of rare earth (Eu, Tm, Nd) and Cr ion doping on the optical properties of BGO was investigated by means of photoluminescence (PL) from visible to IR region in the 10-300K temperature range using different types of detectors, namely, photomultiplier tube (PMT), InGaAs (IGA), and Si. Several samples were investigated having dopants concentrations of 0.3wt%Nd, 0.4wt%Tm, 0.06wt% Cr and 3ppm Eu. The PL spectra of the samples showed different luminescence behaviour which is assigned to the 4f intra shell transition from rare earth ions. The temperature dependence of the PL from rare earth doped BGO crystals is also examined.


Patients with Mild COVID-19 Symptoms and Coincident Pulmonary Embolism: A Case Series.
Frequent thrombotic complications have been reported in patients with severe coronavirus disease 2019 (COVID-19) infection. The risk in patients with mild disease is unknown. We report a case series of three individuals recently diagnosed with COVID-19, who presented to the emergency department with chest pain and were found to have pulmonary emboli. The patients had mild symptoms, no vital sign abnormalities, and were negative according to the pulmonary embolism rule-out criteria. This suggests that patients with active or suspected COVID-19 should be considered at elevated risk for pulmonary embolism when presenting with chest pain, even without common risk factors for pulmonary embolism.


[Interagency collaboration in Spanish scientific production in nursing: social network analysis].
The objectives of this paper are to analyze the Spanish scientific production in nursing, define its temporal evolution, its geographical and institutional distribution, and observe the interinstitutional collaboration. We analyze a comprehensive sample of Spanish scientific production in the nursing area extracted from the multidisciplinary database SciVerse Scopus. The nursing scientific production grows along time. The collaboration rate is 3.7 authors per paper and 61% of the authors only publish one paper. Barcelona and Madrid are the provinces with highest number of authors. Most belong to the hospitalary environment, followed closely by authors belonging to the university. The most institutions that collaborate, sharing authorship of articles are: University of Barcelona, Autonomous University of Barcelona and Clinic Hospital of Barcelona. The nursing scientific production has been increasing since her incorporation at the university. The collaboration rate found is higher than found for other papers. It shows a low decrease of occasional authors. It discusses the outlook of scientific collaboration in nursing in Spain, at the level of institutions by co-authorship of papers, through a network graph. It observes their distribution, importance and interactions or lack thereof. There is a strong need to use international databases for research, care and teaching, in addition to the national specialized information resources. Professionals are encouraged to normalization of the paper's signature, both, surnames and institutions to which they belong. It confirms the limited cooperation with foreign institutions, although there is an increasing trend of collaboration between Spanish authors in this discipline. It is observed, clearly defined three interinstitutional collaboration patterns.