Innovative Fixation Technique for Avulsion Fractures of the Calcaneal Tuberosity.
Avulsion fractures of the calcaneal tuberosity, although relatively uncommon, occur more frequently in patients with osteoporosis and in the elderly. The results of closed manipulation are poor in these fractures, usually requiring open reduction and internal fixation. However, it is difficult to fix the bone fragment rigidly, because the avulsed bone fragment is small and thin, and the bone quality of the calcaneal body in the elderly is poor. Hence, it is necessary to limit prolonged weight-bearing after the operation. We performed an innovative surgical procedure of suture fixation to the anchor screw in four cases, following which earlier postoperative rehabilitation with full weight-bearing walking and range of motion exercises was possible, and bony union was achieved without repeated displacement of the fragment in all patients. We believe this technique would prove useful in surgical management of calcaneal tuberosity avulsion fractures.


A new parameter predicting chronic total occlusion of coronary arteries: platelet distribution width.
Platelet distribution width (PDW) measures the variability in platelet size and is a marker of platelet activation. We investigated whether PDW is associated with the extent of coronary artery disease (CAD) and coronary total occlusions (CTOs). We studied 162 patients: 108 had a coronary lesion with a diameter stenosis of ≥50%, the CAD(+) group, and 54 patients had normal coronary anatomy, the CAD(-) group. The CAD(+) group was subdivided into CAD(+) CTO(+) and CAD(+) CTO(-) groups. Among patients with CAD, the CTO(+) group had a significantly greater PDW (%) than the CTO(-) group (16.9 ± 2.8, 15.4 ± 3.0, and 15.4 ± 1.9, respectively; P = .008). In a receiver-operating characteristic analysis, a PDW cut point of 15.7% was identified in patients with CTO(+) (area under curve = 0.64, 95% confidence interval 0.54-0.75). A PDW value of more than 15.7% demonstrated a sensitivity of 64% and a specificity of 66%. The PDW is a simple platelet index that may predict the presence of CTO.


SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.
SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories.


Ultrasensitive Detection of Bacillus anthracis by Real-Time PCR Targeting a Polymorphism in Multi-Copy 16S rRNA Genes and Their Transcripts.
The anthrax pathogen Bacillus anthracis poses a significant threat to human health. Identification of B. anthracis is challenging because of the bacterium's close genetic relationship to other Bacillus cereus group species. Thus, molecular detection is founded on species-specific PCR targeting single-copy genes. Here, we validated a previously recognized multi-copy target, a species-specific single nucleotide polymorphism (SNP) present in 2-5 copies in every B. anthracis genome analyzed. For this, a hydrolysis probe-based real-time PCR assay was developed and rigorously tested. The assay was specific as only B. anthracis DNA yielded positive results, was linear over 9 log10 units, and was sensitive with a limit of detection (LoD) of 2.9 copies/reaction. Though not exhibiting a lower LoD than established single-copy PCR targets (dhp61 or PL3), the higher copy number of the B. anthracis-specific 16S rRNA gene alleles afforded ≤2 unit lower threshold (Ct) values. To push the detection limit even further, the assay was adapted for reverse transcription PCR on 16S rRNA transcripts. This RT-PCR assay was also linear over 9 log10 units and was sensitive with an LoD of 6.3 copies/reaction. In a dilution series of experiments, the 16S RT-PCR assay achieved a thousand-fold higher sensitivity than the DNA-targeting assays. For molecular diagnostics, we recommend a real-time RT-PCR assay variant in which both DNA and RNA serve as templates (thus, no requirement for DNase treatment). This can at least provide results equaling the DNA-based implementation if no RNA is present but is superior even at the lowest residual rRNA concentrations.


A modified Susceptible-Infected-Recovered model for observed under-reported incidence data.
Fitting Susceptible-Infected-Recovered (SIR) models to incidence data is problematic when not all infected individuals are reported. Assuming an underlying SIR model with general but known distribution for the time to recovery, this paper derives the implied differential-integral equations for observed incidence data when a fixed fraction of newly infected individuals are not observed. The parameters of the resulting system of differential equations are identifiable. Using these differential equations, we develop a stochastic model for the conditional distribution of current disease incidence given the entire past history of reported cases. We estimate the model parameters using Bayesian Markov Chain Monte-Carlo sampling of the posterior distribution. We use our model to estimate the transmission rate and fraction of asymptomatic individuals for the current Coronavirus 2019 outbreak in eight American Countries: the United States of America, Brazil, Mexico, Argentina, Chile, Colombia, Peru, and Panama, from January 2020 to May 2021. Our analysis reveals that the fraction of reported cases varies across all countries. For example, the reported incidence fraction for the United States of America varies from 0.3 to 0.6, while for Brazil it varies from 0.2 to 0.4.


Human monocytes in a long-term culture with interleukin-2 show high tumoricidal activity against various tumor cells.
We compared the tumoricidal activity of human monocytes cultured with interleukin-2 (IL-2) or human recombinant interferon-gamma (IFN-gamma) alone, or IFN-gamma in combination with a small amount of lipopolysaccharides (LPS). Human monocytes cultured with IL-2 for 7 days or longer, termed lymphokine-activated macrophages (LAMs), showed higher tumoricidal activity than those cultured for 1 day. In contrast, monocytes cultured with IFN-gamma alone or in combination with LPS for 7 days or longer showed lower tumoricidal activity. LAMs were identified as macrophages by nonspecific esterase staining and immunofluorescence staining with anti-CD14 antibody. LAMs were not induced in fetal calf serum-containing medium, but they were induced when colony-stimulating factor-1 was added to the medium. LAMs showed high tumoricidal activity against all human and murine tumor cell lines tested, although they showed no cytotoxic activity against human normal cells. During incubation with IL-2, tumoricidal activity of LAMs was maximal at days 8-16 and was sustained until day 28. The difference in tumoricidal mechanism between LAMs and lymphokine-activated killer (LAK) cells was also shown by using two kinds of cytotoxic assay systems. LAMs require a long incubation time to kill tumor cells, but LAK cells can kill them immediately. Furthermore, LAMs kill tumor cells with complete DNA degradation, whereas LAK cells can induce significant but not complete DNA degradation. These results indicate that LAMs and LAK cells have different tumoricidal mechanisms for killing target cells, although they were induced by incubation with the same lymphokine, IL-2.


Peritoneal dialysis travel "tool box".
Patients on peritoneal dialysis (PD) face many challenges when traveling, but these challenges can be minimized by pre-travel education, organization, and planning. PD nurses play an important role in helping patients on peritoneal dialysis understand that travel can continue to be a part of their lives and in helping them prepare for, plan, and organize their travel experiences.


Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.
Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease.


[Mental health and public health: an essential bond].
The Mental Health domain is larger than psychiatry because it implies the establishment of strategies aiming at the promotion of the well-being of the population, the prevention of mental disorders and their treatment and care. Politicians, planners, users and families and society at large have a great expectations and this require health professionals to be able to provide public mental health knowledge. It is necessary to identify those specific public mental health actions to which general practitioners and specialist could contribute. To do so more knowledge in public mental health is needed and more training is necessary.


Surgical treatment of metabolic syndrome.
This article explores the surprising finding that bariatric surgery can produce full and durable remission of the metabolic syndrome as well as other comorbidities of obesity including type II diabetes, hypertension, polycystic ovary syndrome, gastroesophageal reflux disease, nonalcoholic steatotic hepatitis, adult asthma and improvement in weight-bearing arthropathy. Such an outcome was previously deemed impossible. One effect of the surgery is the correction of hyperinsulinemia, a common denominator in the various expressions of the metabolic syndrome. Basal insulin levels return to normal levels within a matter of days following surgery, allowing a return of the first phase of insulin secretion. This effect is 'dose related' to the extent of the reduction of contact between food and the gut. The resolution of the spectrum of diseases that comprise the metabolic syndrome following bariatric surgery suggests that hyperinsulinemia may be the common cause that is corrected by lowering contact between food and the gut. If this concept is true, then the cause of the syndrome, including diabetes, could be a diabetogenic signal from the gut that forces the islets to produce excessive and harmful levels of insulin, or the cause could be the removal of a signal that blocks excessive insulin secretion. If either of these mechanisms is proven correct, the current treatment of diabetes with long-term insulin administration deserves review.


Factors Associated With Failure to Achieve the Intensive Blood Pressure Target in the Systolic Blood Pressure Intervention Trial (SPRINT).
SPRINT (Systolic Blood Pressure Intervention Trial) found that randomization of nondiabetic participants at high cardiovascular risk to an intensive (systolic blood pressure [SBP] <120 mm Hg) versus standard (SBP <140 mm Hg) target resulted in 25% risk reduction in the first cardiovascular composite event (ie, cardiovascular death or nonfatal myocardial infarction, stroke, or hospitalization for heart failure) and a 27% risk reduction in all-cause mortality. In this post hoc analysis, we sought to determine the factors associated with failure to achieve the SBP target in 4678 SPRINT participants randomized to the intensive treatment group. Using a generalized estimating equation model, we assessed variables associated with failure to achieve the intensive SBP target as a repeated outcome collected during serial follow-up visits, including the occurrence of serious adverse events. In the multivariable model adjusted for baseline demographic, clinical, and laboratory variables, older age, higher SBP, underlying chronic kidney disease, higher number of antihypertensives, and moderate cognitive impairment at screening were associated with failure to achieve the intensive SBP target. Occurrence of a serious adverse event during the trial was associated with 20% higher odds of failure to achieve the SBP target. Participants of Hispanic ethnicity had 47% lower odds of failure to achieve the intensive SBP target relative to non-Hispanic Whites. Understanding barriers to achieving intensive SBP targets should allow clinicians to optimize management of hypertension in patients at high risk for cardiovascular disease.


Doppler effects in the propagation of a few-cycle pulse through a dense medium.
This numerical study demonstrates that Doppler redshift exists in the reflected spectrum of a few-cycle pulse, propagating through a dense medium. It manifests itself in two different forms, a sharp low-frequency spike (LFS) located at the red edge of the reflected spectrum and a relatively broader redshift near the carrier frequency. With the variation of the laser and medium parameters, the dominant reflection mechanism changes between bulk generation of backwards propagation waves and nonlinear reflection near the front face. This leads to the manifestation of Doppler effect changing accordingly between the two different forms. This study unifies the physical mechanism behind the LFS and dynamic nonlinear optical skin effect, which enriches the theoretical explanation of the spectral redshift of few-cycle pulse propagation beyond the intrapulse four-wave mixing.


Toxicity studies of o-chloropyridine administered dermally and in drinking water to F344/N rats and B6C3F1/N mice.
o-Chloropyridine is used as an intermediate in synthetic organic, pharmaceutical, and agricultural chemical (fungicides, herbicides) manufacture. It is also used as a catalyst for phase transfer and is a key intermediate in the manufacture of pyrithione-based biocides for use in cosmetics and various pharmaceutical products. o-Chloropyridine is available in purified (99%), technical (95%), or crude (80%) grades. o-Chloropyridine was nominated for testing by the NTP based on increasing production and use as a site-limited pharmaceutical and agrochemical intermediate, the potential for occupational and environmental exposures during its manufacture, its persistence in the environment (lasting longer than 6 months), evidence of mutagenicity based on results of several short-term test systems, and suspicion of carcinogenicity based on effects associated with structurally related chemicals. Male and female F344/N rats and B6C3F1/N mice received o-chloropyridine (99% pure) dermally for 2 weeks or in drinking water for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).


Functional organization of mammalian hexokinases: both N- and C-terminal halves of the rat type II isozyme possess catalytic sites.
Previous work has shown that catalytic function is associated exclusively with the C-terminal half of the Type I isozyme of mammalian hexokinase. In contrast, we now demonstrate that both halves of the Type II isozyme possess comparable catalytic activities. Mutation of a catalytically important Ser residue to Ala at analogous positions in either the N- or the C-terminal halves (S155A or S603A, respectively) of the rat Type II isozyme resulted in approximately 60% reduction in specific activity of the enzyme, with more than 90% reduction in the doubly mutated enzyme (S155A/S603A). Catalytic activity was retained in a chimeric hexokinase comprising the N-terminal half of Type II hexokinase and catalytically inactive (by site-directed mutation) C-terminal half of the Type I isozyme. The N- and C-terminal catalytic sites of Type II hexokinase are similar in V(max) and K(m) (approximately equal to 130 microM) for glucose; however, the N-terminal site has a lower (0.45 vs 1.1 mM) K(m) for ATP, is slightly more sensitive to inhibition by the product analog 1,5-anhydroglucitol-6-P, and is much more sensitive to inhibition by P(i). It is suggested that the Type II isozyme most closely resembles the 100-kDa hexokinase which resulted from duplication and fusion of a gene encoding an ancestral 50-kDa hexokinase and which was the precursor for the contemporary Type I, Type II, and Type III mammalian isozymes. Subsequent evolutionary changes could then have led to functional differentiation of the N- and C-terminal halves, as seen with the Type I (and possibly the Type III) isozyme.


Differences in gene expression in Atlantic salmon parr and smolt after challenge with Piscine orthoreovirus (PRV).
Heart and skeletal muscle inflammation (HSMI) are a disease of farmed Atlantic salmon (Salmo salar) associated with Piscine orthoreovirus (PRV). The disease appears mainly during the marine production phase. This study examined if smoltification and transfer to seawater could compromise immune responses to PRV. Parr and smolts of the same origin were challenged by cohabitation with intraperitoneally injected salmon. Peak levels of PRV in spleen of cohabitants were reached after 8 weeks, but at a lower level in parr compared to smolts. Thereafter the virus levels declined, but remained significantly lower in parr than in smolts. Both groups developed typical HSMI histopathological heart lesions, which were most prominent after 10 weeks. Microarray and qPCR analyses revealed slightly lower expression of immune genes in spleen and head kidney of smolts before challenge. Infected parr showed earlier induction of genes involved in innate antiviral immunity, as well as for genes related to B and T cell responses. Gene expression profiles also indicated stimulation of heme and iron metabolism and erythropoiesis in smolts, which may indicate replacement of PRV-infected erythrocytes.


Prognostic factors for survival of non-Hodgkin's lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation.
Prognostic factors to identify patients with high-risk non-Hodgkin's lymphoma (NHL) have recently been developed. We retrospectively investigated the relation between prognostic factors and treatment outcome after autologous bone marrow transplantation (ABMT). From 1984 to 1994, 80 consecutive patients with NHL responding slowly to or relapsing after front-line therapy were treated with high-dose chemotherapy and ABMT. Prognostic factors at the time of diagnosis and of ABMT were related to clinical outcome after ABMT. The cumulative 5-year overall survival (OS) was 51%, progression-free survival (PFS) 41%, and relapse-free survival (RFS) 53%. Absence of B symptoms and intermediate-grade malignancy at first presentation of disease were independently related to prolonged OS (P = 0.02 and P < 0.01, respectively) and prolonged PFS (P = 0.005 and P = 0.01, respectively). At the time of ABMT, first PR or CR, normal LDH levels and tumour stage I + II were associated with prolonged OS (P = 0.0005, P = 0.03 and P = 0.004, respectively). A Coiffier index of 0 or 1, first PR or CR and no extranodal disease involvement were related to prolonged PFS (P = 0.0002, P = 0.005 and P = 0.07, respectively). Treatment-related deaths occurred in 10% of patients. Assessment of disease status, LDH level, tumour stage, extranodal disease involvement and Coiffier index at the time of ABMT is respectively efficient in predicting treatment outcome after ABMT.


cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue.
Prolyl endopeptidase is a cytoplasmic serine protease. The enzyme was purified from porcine kidney, and oligonucleotides based on peptide sequences from this protein were used to isolate a cDNA clone from a porcine brain library. This clone contained the complete coding sequence of prolyl endopeptidase and encoded a polypeptide with a molecular mass of 80,751 Da. The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases. [3H]Diisopropyl fluorophosphate was used to identify the active-site serine of prolyl endopeptidase. One labeled peptide was isolated and sequenced. The sequence surrounding the active-site serine was Asn-Gly-Gly-Ser-Asn-Gly-Gly. This sequence is different from the active-site sequences of other known serine proteases. This difference and the lack of overall homology with the known families of serine proteases suggest that prolyl endopeptidase represents a new type of serine protease.


Non-IPR C60 solids.
Films comprising predominantly novel isomers of C(60) [=C(60)(nIPR)] have been generated by low energy ion beam deposition of vibronically excited C(60)(+) onto graphite followed by selective sublimation of C(60)(I(h)) from the deposited isomer mixture. The incident ions were generated by electron impact ionization/fragmentation of sublimed C(70). Images of the C(60)(nIPR) films obtained by applying atomic force microscopy show aggregates, which we attribute to covalently interlinked C(60)(nIPR) units. The covalent bonds are inferred from the significantly higher thermal stability of the C(60)(nIPR) films compared to the C(60)(I(h)) van der Waals solid-as measured by thermal desorption with mass spectrometric detection of the C(60) mass channel (the only desorbable species). In contrast to the characteristic doublet structure of the occupied valence band in the ultraviolet photoelectron spectrum of pure C(60)(I(h)), the valence band of C(60)(nIPR) films exhibits a triplet feature with the additional peak occurring at a binding energy of approximately 2.6 eV. This is an indicator of the electronic modifications induced by intermolecular bonding. C(60)(nIPR) films exhibit a narrower band gap than found for C(60)(I(h)). They also have significantly different chemical reactivity toward incorporation of thermal energy deuterium atoms. In order to model the experimental photoelectron spectra, various covalently linked oligomers of (#1809)C(60)(C(2v)), the second most stable conventional 60-atom fullerene cage, were calculated by means of the density functional theory. These spectral predictions together with analogous previous observations on related fullerene solids such as C(58) lead us to infer that C(60)(nIPR) films consist of fullerene cage isomers containing one or more adjacent pentagon pairs, which mediate covalent cage-cage interconnection.


[Typing, resistance behavior and occurrence of methicillin-resistant Staphylococcus aureus strains in a surgical intensive care unit].
Over a period of three years, the frequency of the appearance of methicillin-resistant S. aureus strains (MRSA) was observed on a surgical intensive care unit. During this above-mentioned period of investigation it came to a heaped occurrence of nosocomial infections on this ICU with altogether 332 S. aureus-stems being isolated from different patient specimen. 204 (61.5%) of these were resistant against methicillin and could be divided into 48 first- and 156 follow-up-isolates. The thereupon accomplished differentiation of the 48 MRSA-first isolates by means of lysotyping and the pioneered GenePath Strain Typing System for a standardized pulsed-field-gel-electrophoresis (PFGE) gave the proof of 7 different MRSA-types. Around 7 different, in part parallel chains of infection on this ICU were observed, which could be led back to different strains. In reference to all analyzed S. aureus, an especially high rate (90%) of MRSA on this ICU could be isolated in taken wound-swabs, followed by 83.3% MRSA at catheter tips and 71,9% in tracheal and bronchial secretion. A consideration of the antibiotic susceptibility yielded, that also gentamicin and the quinolones showed an in-vitro resistance against MRSA, while fosfomycin, fusidic acid, chloramphenicol and trimethoprim/sulfamethoxazole reached positive responding rates between 80 and 100%. On the other hand, presently still 100% of the explored MRSA-strains are susceptible for glycopeptides such as vancomycin and teicoplanin. Because of intensive hospital hygienic measures the number of newly isolated MRSA could be reduced clearly on this ward.


Antibacterial activity of Mn(I) and Re(I) tricarbonyl complexes conjugated to a bile acid carrier molecule.
A bifunctional cholic acid-bis(2-pyridylmethyl)amine (bpa) ligand featuring an amide linker was coordinated to a manganese(i) or rhenium(i) tricarbonyl moiety to give [M(bpacholamide)(CO)3] with M = Mn, Re in good yield and very high purity. Strong antibacterial activity was observed against four strains of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, with minimum inhibitory concentrations (MICs) in the range of 2-3.5 μM. No difference in response was observed for the MSSA vs. MRSA strains. Activity was also independent of the nature of the metal center, as the Mn and Re complexes showed essentially identical MIC values. In contrast to some other metal carbonyl complexes, the activity seems to be unrelated to the release of carbon monoxide, as photoactivation of the Mn complex reduced the potency by a factor of 2-8. Both metal complexes were non-toxic in Galleria mellonella larvae at concentrations of up to 100× the MIC value. In vivo testing in Galleria larvae infected with MRSA/MSSA demonstrated a significant increase in overall survival rates from 46% in the control to 88% in the group treated with the metal complexes. ICP-MS analysis showed that the Mn and Re cholamide complexes are efficiently internalized by E. coli cells and do not interfere with membrane integrity, as evident from a lack of release of intracellular ATP. An increased sensitivity was observed in acrB, acrD, and mdt mutants that are defective in multidrug exporters, indicating that the compounds have an intracellular mechanism of action. Furthermore, E. coli mntP mutants defective in the gene encoding an Mn exporter were more sensitive than the wildtype, while inactivation of the regulator that controls expression of the Mn uptake proteins MntP and MntH slightly increased sensitivity to the compound. Single knockout mutants defective in genes linked to bile salt and oxidative stress response (dinF, yiaH, sodA, katE, and soxS) did not show increased sensitivity relative to the wild type. Overall, neither the cholic acid moiety nor the metal-carbonyl fragment alone appear to be responsible for the biological activity observed and thus the search for the primary intracellular target continues.


[Use of videolaparoscopy in treatment of peritonitis of appendicular origin].
Videolaparoscopic appendectomy was carried out in 108 patients with acute destructive appendicitis complicated by peritonitis. Local peritonitis was noted in 65 patients, diffuse peritonitis in 33 patients, periappendicular abscess in 10 patients. Postoperative complications were observed in 6 (5.6%) patients. Nobody died. A comparison of results of treatment with a group of 143 patients who underwent appendectomy by laparotomic approach has shown that after endovideosurgical treatment there was no such a serious complication as early adhesive intestinal obstruction. The number of wound complications statistically reliably decreased as well as the time of stay at hospital. The authors consider that videolaparoscopic appendectomy should be used in treatment of peritonitis of appendicular origin much wider.


Intradermal positivity after negative prick testing for inhalants.
Examine the incidence of positive intradermal tests after a negative skin prick test for 24 inhalant antigens. Retrospective study. Charts from patients who underwent modified quantitative testing (MQT) over a 3-year period were reviewed. Patients were initially tested with Multi-Test II. Subjects with negative wheals to a specific allergen were then tested with a 1:500 weight:volume intradermal injection of that allergen. One hundred thirty-three patients underwent MQT for 24 antigens. Allergens with the highest incidence of positive intradermal wheals after negative prick testing were Dermatophagoides pteronyssinus and Dermatophagoides farinae at 26.67%. Allergens with elevated incidence of positive intradermals included fusarium, cockroach, cocklebur, rough marsh elder, and ragweed, all with incidences of 16% to 19%. Positive intradermal responses after negative prick testing occur commonly. Future study is needed to determine the generalizability and clinical significance of these findings. C-4.


Harnessing DNA Replication Stress for Novel Cancer Therapy.
DNA replication is the fundamental process for accurate duplication and transfer of genetic information. Its fidelity is under constant stress from endogenous and exogenous factors which can cause perturbations that lead to DNA damage and defective replication. This can compromise genomic stability and integrity. Genomic instability is considered as one of the hallmarks of cancer. In normal cells, various checkpoints could either activate DNA repair or induce cell death/senescence. Cancer cells on the other hand potentiate DNA replicative stress, due to defective DNA damage repair mechanism and unchecked growth signaling. Though replicative stress can lead to mutagenesis and tumorigenesis, it can be harnessed paradoxically for cancer treatment. Herein, we review the mechanism and rationale to exploit replication stress for cancer therapy. We discuss both established and new approaches targeting DNA replication stress including chemotherapy, radiation, and small molecule inhibitors targeting pathways including ATR, Chk1, PARP, WEE1, MELK, NAE, TLK etc. Finally, we review combination treatments, biomarkers, and we suggest potential novel methods to target DNA replication stress to treat cancer.


Chemical Composition and Bioactivity of Essential Oil of Ten Labiatae Species.
Using antibiotics as feed additives have been successively banned worldwide from 1986; therefore, it is an urgent task to finding safe and effective alternatives. As natural products of plant origin, essential oils (EOs) are an outstanding option due to their reported bioactivity. In this research, ten EOs of Labiatae species were extracted by steam distillation and its chemical constituents were identified by gas chromatography-mass spectrometry (GC-MS). A total of 123 chemical compounds, including alkenes, phenols, aldehydes and ketones, were identified. The results of antioxidant activity carried out through DPPH free radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP), showing that EOs of Ocimum basilicum Linn. (ObEO), Thymus mongolicus Ronn. (TmEO), Origanum vulgare Linn. (OvEO) and Mosla chinensis Maxim. (McEO) have strong antioxidant activities. Their 50%-inhibitory concentration (IC50) value was <1.00, 1.42, 1.47 and 1.92 μg/mL, respectively; and their FRAP value was 1536.67 ± 24.22, 271.84 ± 4.93, 633.71 ± 13.14 and 480.66 ± 29.90, respectively. The results of filter paper diffusion showing that McEO, OvEO and TmEO inhibition zone diameter (IZD) are all over 30 mm. The results of two-fold dilution method showed that McEO, OvEO and TmEO have strong antibacterial activities against Staphylococcus aureus (S. aureus) and their minimal inhibitory concentrations (MIC) value was 1 μL/mL, 2 μL/mL, and 2 μL/mL, respectively. In conclusion, the results in this work demonstrate the possibility for development and application of EOs as potential feed additives.


Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation.
The role of ribosomal protein S6 (rpS6) phosphorylation in mRNA translation remains poorly understood. Here, we reveal a potential role in modulating the translation rate of chemokine (C-X-C motif) ligand 8 (CXCL8 or Interleukin 8, IL8). We observed that more CXCL8 protein was being secreted from less CXCL8 mRNA in primary macrophages and macrophage-like HL-60 cells relative to other cell types. This correlated with an increase in CXCL8 polyribosome association, suggesting an increase in the rate of CXCL8 translation in macrophages. The cell type-specific expression levels were replicated by a CXCL8- UTR-reporter (Nanoluc reporter flanked by the 5' and 3' UTR of CXCL8). Mutations of the CXCL8-UTR-reporter revealed that cell type-specific expression required: 1) a 3' UTR of at least three hundred bases; and 2) an AU base content that exceeds fifty percent in the first hundred bases of the 3' UTR immediately after the stop codon, which we dub AU-rich proximal UTR sequences (APS). The 5' UTR of CXCL8 enhanced expression at the protein level and conferred cell type-specific expression when paired with a 3' UTR. A search for other APS-positive mRNAs uncovered TNF alpha induced protein 6 (TNFAIP6), another mRNA that was translationally upregulated in macrophages. The elevated translation of APS-positive mRNAs in macrophages coincided with elevated rpS6 S235/236 phosphorylation. Both were attenuated by the ERK1/2 signaling inhibitors, U0126 and AZD6244. In A549 cells, rpS6 S235/236 phosphorylation was induced by TAK1, Akt or PKA signaling. This enhanced the translation of the CXCL8-UTR-reporters. Thus, we propose that the induction of rpS6 S235/236 phosphorylation enhances the translation of mRNAs that contain APS motifs, such as CXCL8 and TNFAIP6. This may contribute to the role of macrophages as the primary producer of CXCL8, a cytokine that is essential for immune cell recruitment and activation.


Deep learning opens new horizons in personalized medicine.
Although the idea of the personalization of patient care dates back to the time of Hippocrates, recent advances in diagnostic medical imaging and molecular medicine are gradually transforming healthcare services, by offering information and diagnostic tools enabling individualized patient management. Facilitating personalized / precision medicine requires taking into account multiple heterogenous parameters, such as sociodemographics, gene variability, environmental and lifestyle factors. Therefore, one of the most critical challenges in personalized medicine is the need to transform large, multi-modal data into decision support tools, capable of bridging the translational gap to the clinical setting. Towards these challenges, deep learning (DL) provides a novel approach, which enables obtaining or developing high-accuracy, multi-modal predictive models, that allow the implementation of the personalized medicine vision in the near future. DL is a highly effective strategy in addressing these challenges, with DL-based models leading to unprecedented results, matching or even improving state-of-the-art prediction/detection rates based on both intuitive and non-intuitive disease descriptors. These results hold promise for significant socio-economic benefits from the application of DL personalized medicine.


Immunotherapy combinations and chemotherapy sparing schemes in first line non-small cell lung cancer.
In recent years, studies have explored different combinations of immunotherapy and chemotherapy. The rationale behind these is the improved survival outcomes of new immunologic therapies used in first-line-treatment of advanced non-small cell lung cancer. Moreover, for the most-studied combinations of anti-programed death-1 (PD-1)/programed death ligand-1 (PD-L1) with the addition of platinum- based chemotherapy, recent research is investigating whether combining different immunologic antitumoral mechanisms of action, such as anti-PD-1/PD-L1 and anti-CTLA-4, or anti-PD-L1 and anti-TIGIT, with or without chemotherapy, can improve efficacy outcomes compared with more classical combinations, or compared with standard chemotherapy alone. Here, we present the data of the main randomized studies that have evaluated these combinations, focusing on the basic rationale behind the different combinations, and the efficacy and tolerability data available to date.


Abnormal membrane fluidity and acetylcholinesterase activity in erythrocytes from insulin-dependent diabetic patients.
An alteration in the enzymatic properties of the erythrocyte membrane acetylcholinesterase (AchE) and Na+,K+-ATPase has been described in experimental diabetes mellitus. We studied erythrocyte membrane fluidity and AchE and Na+,K+-ATPase activities in 15 insulin-dependent diabetic patients and 11 normal subjects. Fluidity was assessed by fluorescence polarization, using 1,6-diphenyl-1,3,5-hexatriene as a probe, and AchE and Na+,K+-ATPase activities were measured enzymatically. We found a significant increase in the enzymatic activity of AchE and a change in its enzymatic properties in diabetic patients compared with those in normal subjects. AchE activity correlated inversely with membrane fluorescence polarization, which was decreased in the diabetic patients, indicating an increase in membrane fluidity. Na+,K+-ATPase activity was reduced in the diabetic patients and correlated positively with the fluorescence polarization values. We hypothesize that the abnormal dynamic properties of the erythrocyte membrane may play a major role in determining the described change in enzymatic activity.


In vitro resistance selection studies of RLP068/Cl, a new Zn(II) phthalocyanine suitable for antimicrobial photodynamic therapy.
Resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The development of alternative therapies against nosocomial infections caused by clinically relevant pathogens represents a major public health concern. RLP068/Cl is a novel Zn(II) phthalocyanine proposed as a photosensitizer suitable for antimicrobial photodynamic therapy (APDT) for localized infections. Its ability, following activation by light, to induce resistance in three major human pathogens after 20 daily passages was studied. Simultaneously for the same strains, the ability of daily sequential subcultures in subinhibitory concentrations of RLP068/Cl to develop resistant mutants without illumination was evaluated. We demonstrate that 20 consecutive APDT treatments with RLP068/Cl did not result in any resistant mutants and that, in dark conditions, only Staphylococcus aureus strains had increased MICs of RLP068/Cl. However, even in this case, the susceptibility of the mutated bacteria to APDT was not affected by their MIC increase.


Relationship between temporomandibular joint pain and magnetic resonance imaging findings of internal derangement.
In terms of clinical decision-making in instances of temporomandibular disorders (TMD) and orofacial pain, there is controversy in the literature over the diagnostic significance of the temporomandibular joint (TMJ)-related variable disk-condyle relationship (DCR). The purpose of this study was to investigate whether in patients with TMJ-related pain, the variable of TMJ pain may be linked to magnetic resonance (MR) imaging findings of internal derangement (ID). The study comprised 163 consecutive TMJ pain patients. Criteria for including a patient were report of orofacial pain referred to the TMJ, and the presence of uni- or bilateral TMJ pain during palpation, during function, and/or during unassisted or assisted mandibular opening. Bilateral sagittal and coronal MR images were obtained to establish the prevalence of TMJ ID types. Analysis of the data revealed the presence of TMJ pain to be associated with significantly more MR imaging diagnoses of ID than an absence of ID (P<0.001), and disk displacement without reduction than disk displacement with reduction (P<0.001). Using chi-square analysis, the results showed a significant relationship between the presence of TMJ-related pain and the MR imaging diagnosis of TMJ ID (P=0.001), and TMJ ID type (P=0.000). Use of the Kappa statistical test indicated poor diagnostic agreement between the presence of TMJ pain and the MR imaging diagnosis of ID (K=0.16). The results suggest that the clinical variable of TMJ pain may have a significant effect on the prevalences of MR imaging diagnoses of TMJ ID. The data confirm the biological concept of DCR as a diagnostic approach in patients with signs and symptoms of TMJ-related pain.


Photocontrol of the germination of onoclea spores: v. Analysis of germination processes by means of temperature.
The physiological nature of photoinduced germination of Onoclea sensibilis L. spores was investigated by temporarily applying a range of temperatures, particularly 40 C, before and after short light treatment. Controls were germinated at 25 C.The preinduction phase, during which photosensitivity is maximally developed in the dark, is sensitive to temperature. Treatment at 40 C for 8 or more hours reduces the developed photosensitivity to a minimal level, but the inhibition by 40 C treatment is reversed slowly after subsequent incubation at 25 C in the dark. The postinduction phase, in which dark processes lead to stain uptake and eventually to visible protrusion, is also sensitive to temperature. Inhibition by 40 C occurs shortly after photoinduction, but disappears 6 or more hours after irradiation. Postinduction spores whose germination is inhibited by 40 C treatment recover the ability to germinate after subsequent incubation at 25 C plus a second light treatment. The inhibition and recovery take place faster in postinduction spores than in preinduction spores. In addition, escape from 40 C inhibition is found in the postinduction phase but not in the preinduction phase. Temperatures lower than 25 C exert slow inhibition of both pre- and postinduction processes, and 30 to 35 C act to stimulate germination.In comparison with our earlier work with anaerobiosis and cycloheximide, the postinduction step inhibited by 40 C can be located shortly after the step inhibited by anaerobiosis but before the cycloheximide sensitive step.


Differential scanning calorimetric study of the effect of cholesterol on the thermotropic phase behavior of a homologous series of linear saturated phosphatidylcholines.
We have studied the effects of cholesterol on the thermotropic phase behavior of aqueous dispersions of a homologous series of linear saturated phosphatidylcholines, using high-sensitivity differential scanning calorimetry and an experimental protocol which ensures that broad, low-enthalpy phase transitions are accurately monitored. We find that the incorporation of small amounts of cholesterol progressively decreases the temperature and the enthalpy, but not the cooperativity, of the pretransition of all phosphatidylcholines exhibiting such a pretransition and that the pretransition is completely abolished at cholesterol concentrations above 5 mol % in all cases. The incorporation of increasing quantities of cholesterol also alters the main or chain-melting phase transition of these phospholipid bilayers in both hydrocarbon chain length-dependent and hydrocarbon chain length-independent ways. At cholesterol concentrations of from 1 to 20-25 mol %, the DSC endotherms of all phosphatidylcholines studied consist of a superimposed sharp and broad component, the former ascribed to the melting of cholesterol-poor and the latter to the melting of the cholesterol-rich phosphatidylcholine domains. The temperature and cooperativity of the sharp component are reduced only slightly and in a chain length-independent manner with increasing cholesterol concentration, an effect we ascribe to the colligative effect of the presence of small quantities of cholesterol at the domain boundaries. Moreover, the enthalpy of the sharp component decreases and becomes zero at 20-25 mol % cholesterol for all of the phosphatidylcholines examined.(ABSTRACT TRUNCATED AT 250 WORDS)


The dehydrogenation mechanism during the incubation period in nanocrystalline MgH2.
The dehydrogenation mechanism during the incubation period in nanocrystalline MgH2 (low α: converted metal fraction and dα/dt) and the reasons for the occurrence of the incubation period at 320, 350, and 400 °C were investigated. Pre-existing Mg crystallites can enhance Mg nucleation during the incubation period, as suggested by the estimated activation energy for nucleation (12 ± 2 kJ per mol H). The released H-atoms enter MgH2 as interstitials, as indicated by the MgH2 unit-cell contraction, resulting in increased equatorial Mg-H bond length, decreased charge-density distribution in the interstitial region, as observed from the charge-density maps, and decreased H-H distance in the {001} plane up to the midway of the incubation period. Eventually, hydrogen vacancies are created, as indicated by the red shift in the Eg and A1g peaks of Raman spectra. The high estimated activation energy for the growth of Mg (209 ± 8 kJ per mol H) renders it difficult and explains the reason for the presence of an incubation period.


Perinatal outcomes of fetal abdominal cysts and comparison of prenatal and postnatal diagnoses.
The differential diagnosis of an abdominal cyst can be challenging, and an accurate diagnosis is crucial for optimal antenatal management. The aim of this study was to compare the ante- and postnatal diagnoses of cases with abdominal cyst and to determine the diagnostic accuracy of ultrasonography. A database review was performed regarding the diagnosis of fetal abdominal cyst covering the period 2002-2009. Structural characteristics and localizations of the cysts in the abdomen were recorded. Ante- and postnatal diagnoses were classified into systems according to the origin of the cyst and were compared. Perinatal outcomes were obtained for all cases. 71 cases with an abdominal cyst were identified. The mean gestational age at the time of diagnosis was 25 ± 5.1 weeks. In 9 cases, there were extra-fetal structural abnormalities, and in 5 cases a chromosomal abnormality was determined. Seven pregnancies were terminated. Overall spontaneous mortality was 11/64 (17%). In 12/64 cases (18%), the cyst resolved at birth. After birth, nearly half of the cases required surgical correction and of these, 20% died. Sensitivity, specificity and positive predictive value of ultrasonography in identifying the system of origin were 88.1, 95.7 and 92.0%, respectively, with a 4.1% false-positive rate. Incorporation of different disciplines in the counseling, management and postpartum follow-up is crucial. Postnatal physical examination of fetuses with an abdominal cyst will help to prevent unnecessary surgery.


A single-dose PLGA encapsulated protective antigen domain 4 nanoformulation protects mice against Bacillus anthracis spore challenge.
Bacillus anthracis, the etiological agent of anthrax, is a major bioterror agent. Vaccination is the most effective prophylactic measure available against anthrax. Currently available anthrax vaccines have issues of the multiple booster dose requirement, adjuvant-associated side effects and stability. Use of biocompatible and biodegradable nanoparticles to deliver the antigens to immune cells could solve the issues associated with anthrax vaccines. We hypothesized that the delivery of a stable immunogenic domain 4 of protective antigen (PAD4) of Bacillus anthracis encapsulated in a poly (lactide-co-glycolide) (PLGA)--an FDA approved biocompatible and biodegradable material, may alleviate the problems of booster dose, adjuvant toxicity and stability associated with anthrax vaccines. We made a PLGA based protective antigen domain 4 nanoparticle (PAD4-NP) formulation using water/oil/water solvent evaporation method. Nanoparticles were characterized for antigen content, morphology, size, polydispersity and zeta potential. The immune correlates and protective efficacy of the nanoparticle formulation was evaluated in Swiss Webster outbred mice. Mice were immunized with single dose of PAD4-NP or recombinant PAD4. The PAD4-NP elicited a robust IgG response with mixed IgG1 and IgG2a subtypes, whereas the control PAD4 immunized mice elicited low IgG response with predominant IgG1 subtype. The PAD4-NP generated mixed Th1/Th2 response, whereas PAD4 elicited predominantly Th2 response. When we compared the efficacy of this single-dose vaccine nanoformulation PAD4-NP with that of the recombinant PAD4 in providing protective immunity against a lethal challenge with Bacillus anthracis spores, the median survival of PAD4-NP immunized mice was 6 days as compared to 1 day for PAD4 immunized mice (p<0.001). Thus, we demonstrate, for the first time, the possibility of the development of a single-dose and adjuvant-free protective antigen based anthrax vaccine in the form of PAD4-NP. Further work in this direction may produce a better and safer candidate anthrax vaccine.


Comparative wear and wear debris under three different counterface conditions of crosslinked and non-crosslinked ultra high molecular weight polyethylene.
The wear debris generated from ultra high molecular weight polyethylene (UHMWPE) have been recognised as one of the major causes of failure in total hip replacements (THR). It is essential to reduce the wear debris generated from UHMWPE acetabular cups in order to minimise this problem. Debris in the submicron size range is believed to have greater osteolytic potential. It is now known that crosslinked UHMWPE acetabular cups have reduced volumetric wear rates but little is known about the influence of crosslinking on the size and morphology of the wear debris. In this study, the wear of grade GUR 1020 crosslinked (vacuum gamma irradiated), GUR 1120 crosslinked (acetylene enhanced irradiated) and non cross linked (ethylene oxide sterilised) GUR 1020 UHMWPE was compared in multidirectional pin-on-plate wear tests under three different counterface conditions (smooth, isotropically rough and scratched counterfaces). Multidirectional motion was chosen because this motion was closer to the relative motion in the natural hip. From this study, better wear resistance of crosslinked UHMWPE compared with non-crosslinked UHMWPE was demonstrated for the smooth counterface conditions. However, in the rough and scratched counterface conditions, the vacuum gamma irradiated crosslinked material produced significantly higher wear rates than the non-crosslinked material. The analysis of the wear debris showed that the majority of the volume of the acetylene enhanced crosslinked UHMWPE wear debris was in the most biologically active size range (0.1 to 0.5 microm). In contrast, the non-crosslinked material and the vacuum gamma irradiated crosslinked material had a greater proportion of the volume of the debris in the larger size ranges which are less biologically active. This has important implications for its osteolytic potential.


A microfluidic flow meter with micromachined thermal sensing elements.
The design, fabrication, operation, calibration, and performance of a microfluidic flow meter utilizing a micromachined (MEMS) thermal time-of-flight sensing chip are presented. The MEMS sensing chip integrates multiple sensing elements (thermistors) on a silicon substrate. This sensing chip works on the principle of thermal excitation with a modulated power source from the microheater while the responses of the sensing elements at both upstream and downstream of the modulated thermal source are processed for both the time differences and the amplitudes of the heat transfer in the microfluidic flow. Unlike most of the current flow meter products based on the thermal sensing principle that only offer the calorimetric mass flow rates, this flow meter can measure not only the mass flow rate but also the flow media properties. Experimental results for water and isopropyl alcohol are discussed, which demonstrate the capability and performance of the novel microfluidic flow meter.


Studying histone modifications and their genomic functions by employing chromatin immunoprecipitation and immunoblotting.
Histones are one of the most abundant and highly conserved proteins in eukaryotes. Apart from serving as structural entities for orderly compaction of genomes, they play an instrumental role in the regulation of many important biological processes involving DNA such as transcription, DNA repair, and the cell cycle. Histone modifications have been implicated in maintaining the transcriptionally poised state of important genesin embryonic stem cells. Histone modifications are believed to be responsible for compartmentalization of chromatin into active and inactive domains. Hence, the tools and techniques required for studying these proteins are of utmost importance to biologists. This chapter provides a brief review of the posttranslational modifications of the N-terminal tails of histones and their biological roles, followed by step-by-step protocols for the most common techniques employed to study them. Here, we describe chromatin immunoprecipitation (ChIP) for studying the genomic functions of the most widely studied histone modifications, namely, histone H3 lysine 9 acetylation and histone H3 lysine 9 trimethylation that are typically associated with transcriptional activation and repression, respectively. Special emphasis has been given on the method of preparation of sonicated chromatin prior to immunoprecipitation since this single step affects the success of ChIP greatly and is often poorly described in published protocols. Protocol for histone isolation by acid-extraction and detection by Coomassie staining has also been described. We also describe the protocol for immunoblot analysis of histones using antibodies against key histone modifications. This chapter will serve as a useful resource in the study of histones and their posttranslational modifications.


Large-scale assessment of organic contaminant emissions from chemical and pharmaceutical manufacturing into Swiss surface waters.
This study presents a nation-wide assessment of the influence of chemical and pharmaceutical manufacturing (CPM) wastewaters on synthetic organic contaminant (SOC) emissions to Swiss surface waters. Geographic Information System (GIS) based analysis of the presence of CPM in wastewater treatment plant (WWTP) catchments revealed wide distribution of this industrial sector across Switzerland, suggesting that one-third of the 718 Swiss WWTPs may be influenced by CPM wastewaters. To reflect the diversity of this type of wastewaters, we investigated the effluents of 11 WWTPs of diverse sizes and technologies, which treated 0-100% wastewater from a variety of CPM activities. In an extensive sampling campaign, we collected temporally high resolved (i.e., daily) samples for 2-3 months to capture the dynamics of CPM discharges. The > 850 samples were then measured with liquid chromatography high-resolution mass spectrometry (LC-HRMS). Non-target characterization of the LC-HRMS time series datasets revealed that CPM wastewaters left a highly variable and site-specific signature in the effluents of the WWTPs. Particularly, compared to WWTPs with purely domestic input, a larger variety of substances (up to 15 times more compounds) with higher maximum concentrations (1-2 orders of magnitude) and more uncommon substances were found in CPM-influenced effluents. Moreover, in the latter, highly fluctuating discharges often contributed to a substantial fraction of the overall emissions. The largely varying characteristics of CPM discharges between different facilities were primarily related to the type of activities at the industries (i.e., production versus processing of chemicals) as well as to the pre-treatment and storage of CPM wastewaters. Eventually, for one WWTP, LC-HRMS time series were correlated with ecotoxicity time series obtained from bioassays and major toxic components could be identified. Overall, in view of their potential relevance to water quality, a strong focus on SOC discharges from CPM is essential, including the design of situation-specific monitoring, as well as risk assessment and mitigation strategies that consider the variability of industrial emissions.


[A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].
A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.


Imaging tumor oxyhemoglobin and deoxyhemoglobin concentrations with ultrasound-guided diffuse optical tomography.
We present an ultrasound (US)-guided diffuse optical tomography for mapping tumor deoxyhemoglobin (deoxyHb) and oxyhemoglobin (oxyHb) concentrations in blood phantoms and in in-vivo patients. Because oxyHb and deoxyHb respond differently at different wavelengths, four laser diodes of wavelengths 740 nm, 780 nm, 808 nm and 830 nm were used in the study. Tumor model experiments were performed using phantoms of different hemoglobin oxygen saturations (14%-89%) representing hemoglobin oxygenation in tissue. Targets of different sizes and located at different depths were used to validate the accuracy of oxygen saturation estimation. The absolute deviations between the estimated hemoglobin oxygen saturations obtained from reconstructed absorption maps and oxygen measurements obtained using a pO2 electrode were less than 8% over the measured range of oxygen saturation. An inhomogeneous concentric blood phantom of deoxygenated center core and oxygenated outer shell was imaged and deoxyHb and oxyHb maps revealed corresponding distributions which correlated well with inhomogeneous deoxy- and oxy- distributions frequently seen in breast cancers. Clinical examples are given to demonstrate the utility of US-guided optical tomography in mapping heterogeneous deoxyHb and oxyHb distributions in breast cancers.


The relation of echo-derived lateral MAPSE to left heart functions and biochemical markers in patients with preserved ejection fraction: Short-term prognostic implications.
Mitral annular plane systolic excursion (MAPSE) is a simple way to evaluate-left ventricle (LV) function. Our aim was to explain the relationship of MAPSE with LV function and biochemical markers in patients with preserved ejection fraction (EF), and to determine whether it has an effect on prognosis in echocardiography (echo) practice. Consecutive patients referred to the echo laboratory between November 2020 and March 2021 were included in the study. In addition to conventional parameters, MAPSE of the lateral mitral annulus was measured in all patients. Patients were divided into three groups according to lateral MAPSE: low (<12 mm), relatively preserved (12-15 mm), and high (≥15 mm). A total of 512 patients with preserved EF were included in the study. MAPSE was low in 44 patients (9%), relatively preserved in 231 patients (45%), and high in 237 patients (46%). The mean age was higher in the low group compared to the other two groups (p < 0.001) and the body mass index was increased in the low group compared to the high group (p = 0.010). Atrial fibrillation and hypertension were more common in patients with low MAPSE. The rate of diastolic dysfunction (DD) and all-cause hospitalization were higher in the low and relatively preserved groups than in the high group (p < 0.001, p = 0.002; respectively). The pro-BNP level and mortality rate were higher in the low group compared to the relatively preserved and high groups (p = 0.007, p = 0.005; respectively). MAPSE was identified as independent predictor of hospitalization (OR: 0.284, 95% CI: 0.093-0.862, p = 0.026) via multivariate analysis and independent predictor of in-hospital mortality (HR: 0.002, 95% CI: 0-0.207, p = 0.008). Analysis of LV longitudinal function by echo-derived lateral MAPSE when LV ejection fraction is normal provides important information about DD and related heart failure and may predict prognosis in echo practice.


Forensic aspects of mild brain injury.
Many cases of mild brain injury ate not identified even in litigated cases. Failure to recognize mild brain injury may be due to insensitivity of neuroradiologic procedures, coding limitations, patient denial, lack of obvious head trauma, or focus of attention toward more obvious physical injuries. Neurocognitive and neurobehavioral sequelae of mild brain injury are often attributed to psychogenic etiology resulting in lost opportunities for timely and appropriate interventions.


3-Tesla Kinematic MRI of the Cervical Spine for Evaluation of Adjacent Level Disease After Monosegmental Anterior Cervical Discectomy and Arthroplasty: Results of 2-Year Follow-Up.
We prospectively evaluated adjacent disc levels after anterior cervical discectomy and arthroplasty (ACDA) using kinematic magnetic resonance imaging (MRI) and plain functional radiographs. ACDA is an established treatment for degenerative cervical disc disease. The objective of this study was to evaluate the use of kinematic MRI for assessing the range of motion (ROM) before and after ACDA compared with plain functional radiographs and to evaluate adjacent degenerative disc disease (aDDD) at mid-term follow-up. Twenty patients (12 females, 8 males; median age 45.6 ± 6.9 yrs) treated by ACDA (BryanDisc; Medtronic, MN) underwent plain functional radiography and kinematic MRI of the cervical spine at 3 T before and 6 and 24 months after surgery. A sagittal T2-weighted (T2w) 2D turbo spin echo (TSE) sequence and a 3D T2w dataset with secondary axial reconstruction were acquired. Signal intensity of all nonoperated discs was measured in regions of interest (ROI). Disc heights adjacent to the operated segment were measured. ROM was evaluated and compared with plain functional radiographs. Clinical outcome was evaluated using the visual analog scale (VAS) for head, neck and radicular pain, and the neck disability index (NDI). Mean ROM of the cervical spine on functional plain radiographs was 21.25 ± 8.19°, 22.29 ± 4.82°, and 26.0 ± 6.9° preoperatively and at 6-month and 24-month follow-up, respectively. Mean ROM at MRI was 27.1 ± 6.78°, 29.45 ± 9.51°, and 31.95 ± 9.58°, respectively. There was a good correlation between both techniques. Follow-up examinations demonstrated no signs of progressive degenerative disc disease of adjacent levels. All patients had clinical improvement up to 24 months after surgery. After ACDA, kinematic MRI allows evaluation of the ROM with excellent correlation to plain functional radiographs. Mid-term follow-up after ACDA is without evidence of progressive DDD of adjacent segments. 3.


Characterization of a complete genome of a circular single-stranded DNA virus from porcine stools in Korea.
Porcine circular single-stranded DNA viruses have been just identified from swine feces in Korea. This virus was mentioned as bovine stool-associated circular DNA virus (BoSCV)-like virus discovered from porcine stools. However, the thorough characteristics of the virus were not identified. Therefore, this research focuses on finding a full genome sequence and analyzing the genetic features of the virus. The virus, now called porcine stool-associated circular DNA virus in Korea (PoSCV Kor), consists of 2,589 bases forming circular structure. It has two major ORFs inversely encoding replicase and capsid protein, with each stem-loop structure between 5' ends and 3' ends of the two putative ORFs. This characteristics is the same as PoSCV in New Zealand, but different from chimpanzee stool-associated circular virus (ChiSCVs) and BoSCV, which have one stem-loop structure. Therefore, it would be sure that PoSCV Kor is very similar to PoSCV in respect to the genetic aspect; the same number of nucleotide bases and the amino acid identity of replicase and capsid protein (96 and 93 %, respectively). This fact could be certified through the finding that PoSCV Kor and PoSCV are in the same cluster by phylogenetic analysis based on the comparison with full-sequences of other circular ssDNA viruses.


Acenocoumarol and phenytoin toxicity in the presence of CYP2C9 mutation.
This case report describes a rare interaction between therapeutic doses of phenytoin and acenocoumarol resulting in both acute phenytoin toxicity and increased international normalized ratio (INR). Interactions between these drugs are due to the pharmacokinetics and the common metabolising pathway by hepatic cytochrome P450 isoenzyme-CYP2C9. Our patient was detected to be homozygous for CYP2C9*3 by PCR-RFLP analysis resulting in markedly decreased metabolism of both the drugs. Given that these two drugs are often given concomitantly in the medical out patient department, and that CYP2C9 polymorphisms are not uncommon, clinicians should be aware of this interaction and suspect this in patients with toxicity to these drugs.


Ibuprofen protects alpha-crystallin against posttranslational modification by preventing protein cross-linking.
Posttranslational modification of bovine alpha-crystallin by D-erythrose-4-phosphate, fructose-6-phosphate, D-ribose-5-phosphate and carbamylation using potassium cyanate induced the loss of chaperone-like activity, as assessed by gamma-crystallin aggregation. The presence of high-molecular-weight aggregates indicated that erythrosylated, fructosylated and carbamylated alpha-crystallins were modified by non-reducible cross-linking. In contrast, ribosylation of alpha-crystallin induced the formation of reducible cross-links. Analysis of ribosylated, erythrosylated and carbamylated alpha-crystallin using non-denaturing acrylamide gels showed that the cross-linking did not sterically inhibit the normal aggregate formation or alter the oligomerisation of the aggregate. Co-incubation of ibuprofen in the presence of alpha-crystallin and the modifying agents protected the chaperone-like activity of alpha-crystallin, enabling the inhibition of gamma-crystallin aggregation. In addition, ibuprofen inhibited the formation of both reducible and non-reducible cross-linked high-molecular-weight alpha-crystallin aggregates. We show in this paper that ibuprofen can inhibit in vitro cross-linking events responsible for the loss of chaperone-like activity of alpha-crystallin and suggest that the protective effect of ibuprofen may be exerted by the binding of ibuprofen breakdown products to alpha-crystallin lysine groups, preventing posttranslational modification responsible for the loss of chaperone-like activity.


Highly purified collagen coating enhances tissue adherence and integration properties of monofilament polypropylene meshes.
Complications related to tissue integration of polypropylene implants used in the treatment of pelvic organ prolapse are relatively prevalent. Collagen, a biocompatible, less immunogenic material with modulating properties on the inflammatory process, may improve polypropylene integration. The objective was to study biomechanical and histological effects of monofilament polypropylene mesh coated with purified collagen gel. Forty rats were implanted with two fragments of polypropylene mesh in their abdominal walls (one on each side of the linea alba). One of the fragments had a collagen gel coating (group I) while the other one did not (group II). The animals were euthanized at 7, 14, 90, and 180 days after implantation and their abdominal walls were excised for analysis. The biomechanical study showed that mesh adherence to neighboring tissue increased significantly in group II (p < 0.05). Acute (p < 0.001) and chronic (p = 0.004) inflammatory responses as well as granulation tissue formation (p = 0.001) were less intense in group II at 7 and 14 days. Granulomatous inflammation and foreign body reaction was less significant at 7 days in group II (p = 0.029 and p < 0.001). The birefringence analysis showed higher mean brightness density in the late phase of implantation in group II meshes (p = 0.000). Polypropylene mesh coated with purified collagen gel increases adherence to tissue, promotes a less intense and lasting inflammatory response and triggers a greater organization and packing arrangement of collagen fibers in the late phase of implantation.


[Studies on the suppressor cells acting on the mitogen-induced blastogenesis in tumor-bearing hosts. I. Suppressor cells in the spleens and peripheral blood of tumor-bearing rats (author's transl)].
When Walker carcinosarcoma 256 cells were transplanted to the inbred Fischer male rats, the responses of spleen cells to Concanavalin A (Con A) or Phytohemagglutinin (PHA) stimulation were gradually reduced as tumor grew up. However, these responses were significantly restored in most cases when the phagocytic or adherent cells were removed from spleen cell suspensions by treating them with a carbonyl iron-magnetic procedure or the passing through a Sephadex G-10 column. Similarly, the decreased responses of peripheral blood mononuclear cells from tumor-bearing rats to Con A stimulation were also restored by removal of the adherent cells with a Sephadex G-10 column. These results strongly suggest a possibility that the suppressor cells, probably the monocyte-macrophage series, were contained in both spleen cells and peripheral blood mononuclear cells and these cells exert their suppressive effect on the mitogen-induced lymphocyte transformation.


Prescriptive contraceptive use among isotretinoin users in the Netherlands in comparison with non-users: a drug utilisation study.
To assess the compliance with the isotretinoin Pregnancy Prevention Programme (PPP) by evaluating the use of prescribed contraceptives among isotretinoin users. The PPP contains a requirement for the use of contraceptive methods for women of childbearing potential. A drug utilisation study was performed using data from a drug prescription database (containing Dutch community pharmacy data) covering a population of 500 000 patients. Contraceptive use in female isotretinoin users and in a reference group of female non-isotretinoin users (aged 15-49 years) was compared using data from 1999 until 2006 in 2-year periods. Descriptive statistics were used. Of the female isotretinoin users (n = 651), 52%-54% filled prescriptions on contraceptives in strict accordance to the PPP, used before, during, and after discontinuation of isotretinoin, compared with 39%-46% in the reference group. A more liberal approach of a minimum of one prescription for a contraceptive method showed 61%-64% use of contraceptives among isotretinoin users. Similar patterns were seen when data were broken down in age groups. Furthermore, a higher proportion of female patients using isotretinoin prescribed by general practitioners used prescribed contraceptives compared with those receiving isotretinoin by specialists. Compliance with the contraceptive use according to a PPP for a teratogenic drug such as isotretinoin is 52%-64%, which is lower than anticipated. Reasons for the low compliance will need to be clarified before further measures can be taken.


Observing treatment outcomes in other patients can elicit augmented placebo effects on pain treatment: a double-blinded randomized clinical trial with patients with chronic low back pain.
Clinical research on social observational learning (SoL) as an underlying mechanism for inducing expectancy and eliciting analgesic placebo effects is lacking. This double-blinded randomized controlled clinical trial investigated the influence of SoL on medication-augmenting placebo effects in 44 patients with chronic low back pain. Our hypothesis was that observing positive drug effects on pain and mobility in another patient could increase pain reduction and functional capacity. To test this, we compared the effects of observing positive treatment outcomes in a sham patient (the social learning group [SoLG]) vs hearing the same sham patient report neutral effects (the control group). In the SoLG, the sham patient told peers about pain reduction due to amitriptyline and demonstrated his improved mobility by bending forwards and sideways while he told the control group only that he was taking amitriptyline. The primary outcome was a reduction in clinical low back pain self-ratings. The secondary outcome was perceptions of pain-related disability. The exploratory outcome was mood and coping statements. Data collection occurred before and after the intervention and 2 weeks later. After the intervention, pain decreased in both groups (F [1, 41] = 7.16, P < 0.05, d = 0.83), with no difference between groups. However, the SoLG showed a significantly larger decrease in perceived disability (F [1, 41] = 5, P < 0.05, d = 0.63). The direct observation of patient with chronic low back pain of positive treatment outcomes in the sham patient seems to have enhanced the treatment effects while indirect verbal reports of reduced pain did not.


Optical Photoacoustic Detection of Circulating Melanoma Cells In Vitro.
The purpose of this research was to investigate the sensitivity of a system for the detection of circulating melanoma cells based on the thermoelastic properties of melanoma. The method employs photoacoustic (PA) excitation coupled with an optical transducer capable of determining the presence of cells within the circulating system in vitro. The transducer is based on stress wave-induced changes of the optical reflectance of a glass-water interface, probed with a continuous laser beam that is incident at an angle close to the critical angle of total internal reflection. A frequency tripled Nd:YAG laser pumping an optical parametric oscillator was employed to provide 532 nm and 620 nm laser light with a pulse duration of 10 ns. A custom-made flow chamber was used as an excitation and acoustic wave collection device. The targets were a human melanoma cell line HS 936 with an average diameter of about 15 μm. Melanoma cells were suspended in 10 mL of two types of media. The first one was Tyrode's buffer in concentrations ranging from 10 to 50 cells per μL, and the second one included 10(6) healthy white blood cells per mL of Tyrode's buffer. PA pressure waves were detected by an optical stress transducer. Detection trials resulted in a detection threshold of the order of one individual cell, indicating the effectiveness of the proposed mechanism. Results imply the potential to assay simple blood samples, from healthy and metastatic patients, to test the presence of cancerous melanoma providing an unprecedented method for screening metastatic disease.


Anterior drawer sign.
The traditional method for testing for anterior stability of the knee has often lead to inaccurate assessment of ligament stability because of the jerky nature of the test and the small amount of force applied. A method of testing the anterior drawer of a knee by flexing the hip and knee to 90 degrees and applying a steady upward force using the body weight as counterpull provides a more reliable test for assessing ligament stability. This method can be used to overcome hamstring spasm and causes less pain in the acutely injured knee.


Chemical Composition, Antioxidant and Antihyperglycemic Activities of the Wild Lactarius deliciosus from China.
The wild mushroom Lactarius deliciosus from China was studied for the first time to obtain information about its chemical composition, antioxidant, and antihyperglycemic activities. Nutritional value, dietary fiber, fatty acids, metal elements, free sugars, free amino acids, organic acids, flavor 5'-nucleotides, and volatile aroma compounds were determined. Potential antioxidant and antihyperglycemic activities were also tested by investigating 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals scavenging activities, ferric ion reducing activity, as well as α-amylase and α-glucosidase inhibitory activities using ethanol and aqueous extracts. The results showed that L. deliciosus was a good wild mushroom with high protein, carbohydrate, and dietary fiber contents, while low in fat and calorie, extensive unsaturated fatty acids contents, with negligible health risks about harmful metal elements. Twenty kinds of free amino acids were detected with a total content 3389.45 mg per 100 g dw. Flavor 5'-nucleotides including 5'-CMP, 5'-UMP, 5'-IMP, and 5'-AMP were 929.85, 45.21, 311.75, and 14.49 mg per 100 g dw, respectively. Mannitol (7825.00 mg per 100 g dw) was the main free sugar, and quininic acid (729.84 mg per 100 g dw) was the main organic acid. Twenty-five kinds of volatile aroma compounds were identified, acids (84.23%) were the most abundant compounds based on content, while aldehydes (15 of 25) were the most abundant compounds based on variety. In addition, both ethanol and aqueous extracts from L. deliciosus exhibited excellent antioxidant activity. While in antihyperglycemic activity tests, only ethanol extracts showed inhibitory effects on α-amylase and α-glucosidase.


Validity of family history data on severe headache and migraine.
This study evaluated the validity of family history data on severe headache and migraine obtained from adult probands with epilepsy in a family study of seizure disorders. We compared the probands' reports of severe headaches and migraines in their parents and full siblings with symptom-based diagnoses based on self-reports. Overall sensitivity was 48% for severe headache and 44% for migraine. When we used reports of severe headaches to screen for migraine headaches in the relatives, sensitivity was 56%. These results indicate that severe headache and migraine are underreported in family history interviews with first-degree relatives. To obtain accurate information on headaches in families for clinical practice and genetic research, direct interviews with each relative may be required.


Activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB in tumour necrosis factor-induced eotaxin release of human eosinophils.
The CC chemokine eotaxin is a potent eosinophil-specific chemoattractant that is crucial for allergic inflammation. Allergen-induced tumour necrosis factor (TNF) has been shown to induce eotaxin synthesis in eosinophils. Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK) have been found to play an essential role for the eotaxin-mediated eosinophilia. We investigated the modulation of NF-kappaB and MAPK activation in TNF-induced eotaxin release of human eosinophils. Human blood eosinophils were purified from fresh buffy coat using magnetic cell sorting. NF-kappaB pathway-related genes were evaluated by cDNA expression array system. Degradation of IkappaBalpha and phosphorylation of MAPK were detected by Western blot. Activation of NF-kappaB was determined by electrophoretic mobility shift assay. Eotaxin released into the eosinophil culture medium was measured by ELISA. TNF was found to up-regulate the gene expression of NF-kappaB and IkappaBalpha in eosinophils. TNF-induced IkappaBalpha degradation was inhibited by the proteasome inhibitor N-cbz-Leu-Leu-leucinal (MG-132) and a non-steroidal anti-inflammatory drug sodium salicylate (NaSal). Using EMSA, both MG-132 and NaSal were found to suppress the TNF-induced NF-kappaB activation in eosinophils. Furthermore, TNF was shown to induce phosphorylation of p38 MAPK time-dependently but not extracellular signal-regulated kinases (ERK). Inhibition of NF-kappaB activation and p38 MAPK activity decreased the TNF-induced release of eotaxin from eosinophils. These results indicate that NF-kappaB and p38 MAPK play an important role in TNF-activated signalling pathway regulating eotaxin release by eosinophils. They have also provided a biochemical basis for the potential of using specific inhibitors of NF-kappaB and p38 MAPK for treating allergic inflammation.


Restriction enzyme analysis of tomato chloroplast and chromoplast DNA.
Plastid DNA was isolated from the chloroplasts of tomato (Lycopersicon esculentum var Traveler 76) leaves and the chromoplasts of ripe tomato fruit. Comparisons of the two DNAs were made by restriction endonuclease analysis using PvuII, HpaI, and Bg1I. No differences in the electrophoretic banding patterns of the restricted plastid DNAs were detected, indicating that no major rearrangements, losses, or gains of plastid DNA accompany the transition from chloroplast to chromoplast.


Biological effects of inorganic arsenic on primary cultures of rat astrocytes.
It is well established that inorganic arsenic induces neurotoxic effects and neurological defects in humans and laboratory animals. The cellular and molecular mechanisms of its actions, however, remain elusive. Herein we report the effects of arsenite (NaAsO2) on primary cultures of rat astrocytes. Cells underwent induction of heat shock protein 70 only at the highest doses of inorganic arsenic (30 and 60 microM), suggesting a high threshold to respond to stress. We also investigated arsenic genotoxicity with the comet assay. Interestingly, although cells treated with 10 microM arsenite for 24 h maintained >70% viability, with respect to untreated cells, high DNA damage was already observed. Since arsenic is not known to be a direct-acting genotoxic agent, we investigated the possibility that its effects are due, in astrocytes as well, to ROS formation, as already described for other cell types. However, FACS analysis after CM-H2DCFDA staining did not evidence any significant increase of ROS production while, on the contrary, at the highest arsenite concentrations used, ROS production decreased. Concordantly, we found that, if most cells in the culture are still alive (i.e. up to 10 microM arsenite), they show a treatment-dependent increase in the concentration of SOD1. On the other hand, SOD2 concentration did not change. Finally, we found that astrocytes also synthesize PIPPin, an RNA-binding protein, the concentration of which was recently reported to change in response to stress induced by cadmium. Here we also report that, in cells exposed to high doses of arsenite, an anti-PIPPin antibody-positive faster migrating protein appears.


PFPP re-introduces DMPA.
The Philippine Family Planning Program formally re-introduced depomedroxyprogesterone acetate (DMPA) or DepoProvera as a program method last March 22, 1994. DMPA will be added to the choices available to couples who desire to practice responsible parenthood. DMPA is an injectable contraceptive containing synthetic progestin which resembles progesterone. It is a scientifically effective, medically safe and legal contraceptive which is injected every three months. Its effectivity reaches up to 99.7% in the first year of use. A WHO [World Health Organization] study had shown that its effectiveness is comparable to bilateral tubal ligation. DMPA's mechanism of action is the inhibition of ovulation and the thinning of the endometrium. It is a safe contraceptive which the US Drug and Food Authority (USDFA) and our own Bureau of Food and Drug Authority had approved for contraceptive use. WHO studies had shown that DMPA does not lead to increased cancer risk, congenital malformation and infertility. DMPA was initially developed in the 1960s as a treatment for endometrial and renal cancer. Its contraceptive effects then led to its use as a family planning method. Over 9 million women had used DMPA. It is a very safe, reversible and effective family planning method with manageable side effects. These include: menstrual irregularities, amenorrhea, weight gain, nausea and vomiting. These effects can be adequately managed by a trained service provider. DMPA will be initially introduced by the Department of Health in 10 pilot areas. IMCH will soon introduce the method in our clinics once the supplies are available and the clinic staff are prepared in the service provision of DMPA.


Serum Level of Transferrin Unique Peptide Is Decreased in Patients With Acute Ischemic Stroke.
Objectives: Free irons are transported into brain tissues by transferrin and play an important role in neuronal/glial cell damage. Lower serum levels of transferrin have been found in patients with ischemic stroke, compared with healthy subjects. In present study, we investigated whether transferrin unique peptide (TF-UP) could be employed as a serum biomarker for brain tissue damage in acute ischemic stroke. Methods: The venous blood samples of 94 ischemic stroke patients and 35 brain tumor-stroke mimics (BT-SM) patients were collected within the first 72 h (Median time 23.25, Interquartile range 60.75) of acute onset in the emergency room. Total TF-UP and total albumin unique peptide (Alb-UP) were identified with liquid chromatography/mass spectrometry (LC-MS/MS) and quantified by multiple reaction monitoring (MRM) method using labeled reference peptide (LRP) for further analysis. Results: Median ratio of total TF-UP/LRP was 0.85 (Interquartile range, 0.21) in the brain tumor-stroke mimics (BT-SM) group, and 0.45 (0.14) in the ischemic stroke group; median Alb-UP/LRP ratio was 0.66 (0.16) in the BT-SM group, and 0.55 (0.20) in the ischemic stroke group. The overall trend from low to high levels was statistically significant for TF-UP/LRP (P < 0.0001), but not for Alb-UP/LRP (P = 0.1667). According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9565 and the optimal cutoff value of serum TF-UP was 0.6317, which yielded a sensitivity of 91.49% and a specificity of 88.57%. The odds ratio (95% confidence intervals) of serum TF-UP/LRP was 83.31 (23.43, 296.22, P < 0.0001). Conclusions: Serum TF-UP/LRP level is decreased in patients with acute ischemic stroke in comparison with brain tumor, and it may serve as a serum biomarker for the neuronal/glial cell damage in cerebral infarction.


Big data and the industrialization of neuroscience: A safe roadmap for understanding the brain?
New technologies in neuroscience generate reams of data at an exponentially increasing rate, spurring the design of very-large-scale data-mining initiatives. Several supranational ventures are contemplating the possibility of achieving, within the next decade(s), full simulation of the human brain.


Advanced neuroimaging techniques: their role in the development of future fetal and neonatal neuroprotection.
Injury to the developing brain is associated with significant risk for potential lifelong, and wide-ranging neurodevelopmental consequences. Despite major advances in neonatal intensive care in recent decades, truly informed brain-oriented care of the critically ill neonate remains lacking. Consequently, this has hindered the development of preventive neuroprotective interventions, which is in large part due to the inherent difficulties in diagnosis, timing, and the severity of insults. Recent advances in understanding the cellular mechanisms of neonatal brain injury, together with the successful application of cutting-edge neuroimaging techniques, have markedly improved our understanding of the timing and evolution of structural injury to the immature brain, and its functional consequences. Triggered by these important advances, there is intense and renewed interest in the development of brain-oriented therapies, including neuroprotective strategies aimed at circumventing the injurious effects of neonatal brain insults. This article will provide an overview of normal and abnormal brain development, and explore the role of advanced neuroimaging techniques in neuroprotective therapies in the neonatal intensive care unit.


The Role of Extracellular Matrix Proteins in Breast Cancer.
The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell-cell and cell-matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors' action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.


Family Caregiver Comfort with Telehealth Technologies: Differences by Race and Ethnicity in a Cross-Sectional Survey.
Background: Telehealth has seen widespread use since the onset of the COVID-19 pandemic, and 82% patients required assistance in accessing their telehealth appointments. This assistance commonly comes from a family caregiver who may or may not be comfortable using the technologies associated with telehealth. The objective of our study was to analyze a demographically representative survey of U.S. family caregivers to understand the level of comfort using telehealth technologies among family caregivers. Methods: A secondary analysis of survey data collected during the COVID-19 pandemic in 2020. Level of caregiver comfort using computers, smartphones, and tablets was determined through three Likert-style questions. Proportional odds logistic regression was used to understand the associations between demographic variables and level of caregiver comfort using each technology, when adjusting for covariates. Results: A total of 340 caregivers were included in the analysis. Compared with non-Hispanic white caregivers, Asian caregivers had higher odds (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.36, 8.02; p = 0.01) of expressing comfort using computers; black caregivers (OR 0.46; 95% CI 0.21, 0.98; p = 0.04) and Hispanic caregivers (OR 0.36; 95% CI 0.17, 0.79; p = 0.01) expressed lower odds of comfort using smartphones; and Asian caregivers had higher odds (OR 4.64; 95% CI 2.05, 11.69; p = 0.001) of expressing comfort using tablets. Conclusion and Implications: There are identified disparities in the level of technological comfort using computers, smartphones, and tablets by different racial and ethnic groups. Health systems should consider early stakeholder involvement in the design of telehealth technologies, culturally responsive training materials on telehealth technology use to reduce disparities in comfort using telehealth technologies.


Unveiling Monoterpene Biosynthesis in Taiwania cryptomerioides via Functional Characterization.
Taiwania cryptomerioides is a monotypic species, and its terpenoid-rich property has been reported in recent years. To uncover monoterpene biosynthesis in T. cryptomerioides, this study used transcriptome mining to identify candidates with tentative monoterpene synthase activity. Along with the phylogenetic analysis and in vitro assay, two geraniol synthases (TcTPS13 and TcTPS14), a linalool synthase (TcTPS15), and a β-pinene synthase (TcTPS16), were functionally characterized. Via the comparison of catalytic residues, the Cys/Ser at region 1 might be crucial in determining the formation of α-pinene or β-pinene. In addition, the Cupressaceae monoterpene synthases were phylogenetically clustered together; they are unique and different from those of published conifer species. In summary, this study aimed to uncover the ambiguous monoterpenoid network in T. cryptomerioide, which would expand the landscape of monoterpene biosynthesis in Cupressaceae species.


Minimally invasive spine stabilisation with long implants.
Originally aimed at treating degenerative syndromes of the lumbar spine, percutaneous minimally invasive posterior fixation is nowadays even more frequently used to treat some thoracolumbar fractures. According to the modern principles of saving segment of motion, a short implant (one level above and one level below the injured vertebra) is generally used to stabilise the injured spine. Although the authors generally use a short percutaneous fixation in treating thoracolumbar fractures with good results, they observed some cases in which the high fragmentation of the vertebral body and the presence of other associated diseases (co-morbidities) did not recommend the use of a short construct. The authors identified nine cases, in which a long implant (two levels above and two levels below the injured vertebra) was performed by a percutaneous minimally invasive approach. Seven patients (five males/two females) were affected by thoracolumbar fractures. T12 vertebra was involved in three cases, L1 in two cases, T10 and L2 in one case, respectively. Two fractures were classified as type A 3.1, two as A 3.2, two as A 3.3 and one as B 2.3, according to Magerl. In the present series, there were also two patients affected by a severe osteolysis of the spine (T9 and T12) due to tumoral localisation. All patients operated on with long instrumentation had a good outcome with prompt and uneventful clinical recovery. At the 1-year follow-up, all patients except one, who died 11 months after the operation, did not show any radiologic signs of mobilisation or failure of the implant. Based on the results of the present series, the long percutaneous fixation seems to represent an effective and safe system to treat particular cases of vertebral lesions. In conclusion, the authors believe that a long implant might be an alternative surgical method compared to more aggressive or demanding procedures, which in a few patients could represent an overtreatment.


The mortality experience of early old-age and disability pensioners from unskilled- and semiskilled labour groups in Fredericia.
Survival of early old-age and disability pensioners from unskilled and semiskilled labourers was compared with the employed workers from the same local trade union. All members receiving early old-age or disability pensions during the period October 1, 1969 to September 30, 1973 were assigned to the index group provided they were still alive September 30, 1973. 2 active workers were selected as controls for each pensioner according to the closest age match. The pensioners had about 7 times higher mortality risk than their active fellow workers in the follow-up period from September 30, 1973 to January 1, 1979. It is emphasized that proper comparison is needed if excess mortality associated with early retirement is to be estimated.


Repeated echocardiography after first ever ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention--is it necessary?
Changes in left ventricular (LV) function using echocardiography and cardiac magnetic resonance (CMR) imaging were assessed in a contemporary ST-segment elevation myocardial infarction (STEMI) population to assess whether repeated imaging is necessary. In a prospective study patients with first STEMI were treated with primary percutaneous coronary intervention (PCI) and examined with 2D-echocardiography and CMR at baseline (<72 h) and at a three-month follow-up. A total of 138 patients were included (60±11 years). Using 2D-echocardiography at baseline preserved left ventricular ejection fraction (LVEF) (>50%) was found in 48 patients (35%), mild/moderate systolic dysfunction (35-50%) in 76 patients (55%) and severe dysfunction (<35%) in 14 patients (10%). Improvement in systolic function group was seen in 58 patients (64%) and 11 patients (79%) with severe systolic dysfunction at baseline were re-classified as having preserved or mild/moderate systolic dysfunction at follow-up. Irrespective of baseline LVEF, deterioration in systolic function group was noted in 14 patients (11%), but no patients declined from preserved to severe systolic dysfunction. The recovered myocardium measured with the myocardial salvage index by CMR was significantly lower with declining LVEF at baseline. The majority of patients with severely depressed LVEF immediately after STEMI significantly improved systolic function after three months. This study emphasises the importance of a repeated LV function assessment at follow-up in patients with mild/moderate or severe systolic dysfunction after STEMI, but re-assessment may not be needed in patients with preserved LVEF at baseline.