Models of inflammation: Carrageenan- or complete Freund's Adjuvant (CFA)-induced edema and hypersensitivity in the rat.
Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. This unit details methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections of either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) and by the trigeminal ganglion neurons (vibrissal pad).


Age-related changes in tooth enamel as measured by electron microscopy: implications for porcelain laminate veneers.
Available information on the dimensions of the enamel and pulp tissues of tooth structure, as well as their correlation with chronologic age, is limited. However, this information is a significant determinate in planning the tooth reduction for a porcelain laminate veneer (PLV) restoration. This study examined variations in tooth enamel thickness and its correlation with chronologic age as it relates to available tooth substrate for PLV restorations. Forty human maxillary central incisors extracted from patients within the age range of 30 to 69 years were used to evaluate the thickness of tooth layers. Measurements were made for the following tooth areas using scanning electron microscopy (SEM): facial enamel thickness at 1, 3, and 5 mm above the cemento-enamel junction (CEJ), palatal enamel thickness at 5 mm above the CEJ, facial and palatal enamel thickness at the incisal edge, maximum facial-palatal (MFP) width at incisal edge, physiologic secondary dentin (PSD) height, facial-cervical enamel-pulp (FCEP) distance, and the incisal edge enamel-pulp (IEP) distance. The relationship between thickness and age was evaluated with a regression analysis (alpha=.05). Significant differences (P<.001) were observed in all of the relationships between tooth thicknesses and chronological age. Outcome variables of enamel thickness related to age showed a steady decrease, beginning at approximately age 50. Mean values of facial enamel thickness at 1, 3, and 5 mm above the CEJ were 0.31 +/- 0.01, 0.54 +/- 0.01, and 0.75 +/- 0.02 mm, respectively, for the age range of 30 to 69 years. The thickness of maximum incisal width (R(2) = 0.95), PSD height (R(2) = 0.76), and IEP distance (R(2) = 0.99) indicated that all are subject to an increase in relation to age. Facial enamel thickness above the CEJ decreases, while MFP increases in relation to age. The PSD height and IEP distance also increased with age.


A spinal cord injured animal model of lower urinary tract function: observations using direct bladder and pelvic plexus stimulation with model microstimulators.
Microstimulators are new devices that should be considered for management of lower urinary tract problems following spinal cord injury (SCI) such as urinary retention. These devices are small (less than 25 mm by 5 mm) with the electrodes located on the ends of the stimulator. However, it is not known whether the small electrodes on these devices would be effective in stimulating the plexus of nerves that innervate the bladder. The aim of the present study was to provide preliminary observations with model microstimulators (M-Micro) for inducing bladder contractions in an SCI animal model. Bladder wall and pelvic plexus stimulation sites were compared. Additional investigations evaluated parameters such as stimulation polarity, frequency, and period as well as bladder filling volume. In an initial survival surgery, bilateral M-Micros were implanted on the bladder wall and the pelvic plexus along the urethra in 3 female cats. A second survival surgery was conducted 3 to 5 weeks later to produce a T1 0 SCI. Studies are reported following the second survival surgery. These studies included the effects of stimulation and bladder filling. The postmortem location of the implanted pelvic plexus M-Micro was previously described as near the bladder neck. Therefore, the pelvic plexus location is described in this report as "pelvic plexus (bladder neck)" stimulation. The observations showed effective stimulation with pelvic plexus (bladder neck) stimulation and voiding in some cases. Stimulation was limited by side effects of increased abdominal pressure and leg movement. Other factors also affected the response to stimulation, including the initial bladder volume and stimulating parameters. Fluoroscopy showed that when stimulation did not induce voiding the striated urethral sphincter was closed. This case series of 3 SCI animals showed that the small electrodes on the M-Micro could be used to stimulate the bladder with contractions and voiding in some cases. The pelvic plexus (bladder neck) location for the M-Micro may be a better location than higher on the bladder wall. Limiting side effects of stimulation included leg movement and increased abdominal pressure. Additional important factors included the stimulation parameters, initial bladder volume, and the function of the skeletal urethral sphincter.


The structure and stability of temperament from infancy to toddlerhood: a one-year prospective study.
This study investigated the factor structure and longitudinal stability of temperament in a multi-informant (i.e., as reported by mothers and fathers), one-year prospective study from infancy (8-13 months) to toddlerhood (20-25 months). Confirmatory factor analyses (CFAs) replicate and extend earlier studies; in that evidence was found for a three-factor structure for both infant and toddler temperament, consisting of Surgency/Extraversion, Negative Affectivity and Effortful Control. There were, especially in toddlerhood, few differences between mother and father reports in average scores on the three temperament factors, which were in part related to differences in parental involvement between mothers and fathers. In addition, there were few differences between average scores for boys and girls on these temperament factors, with the exception that both mothers and fathers rated girls higher on Effortful Control, and fathers rated boys higher on Extraversion/Surgency, especially in toddlerhood. Finally, results showed that the three factors showed high relative, absolute, and structural stability over a one-year period. The implications of these findings for contemporary temperament research are discussed.


Arginine 45 is a major part of the antigenic determinant of human beta 2-microglobulin recognized by mouse monoclonal antibody BBM.1.
Monoclonal antibody BBM.1 (Brodsky, F.M., Bodmer, W. F., and Parham, P. (1979) Eur. J. Immunol. 9, 536-545) identifies an antigenic determinant of human beta 2-microglobulin (beta 2-M). The antibody binds free and HLA-A,B-associated beta 2-M with similar affinity, showing that the BBM.1 antigenic determinant does not involve residues of beta 2-M that interact with HLA-A,B heavy chains. Peptides (SWH.1-5) synthesized from residues 35-50 of the beta 2-M sequence specifically inhibit the binding of BBM.1 to cell surfaces. Their inhibitory activity is destroyed by trypsin treatment. The observations (i) that BBM.1 does not bind to beta 2-M of species other than man, gorilla, and chimpanzee and (ii) that arginine 45 is the only human-specific residue between positions 35 and 50 suggested that this residue might be part of the BBM.1 antigenic determinant. This hypothesis was confirmed by reversible modification of arginine residues with cyclohexanedione. Modification of arginines in native beta 2-M and of the single arginine, corresponding to position 45, in the peptide SWH.5 resulted in up to 95% loss of BBM.1 inhibitory activity. Reversal of the modification by treatment with hydroxylamine resulted in complete recovery of activity. Rabbit antibodies elicited by immunization of SWH.5 conjugated to bovine serum albumin showed no detectable reaction with native beta 2-M but did specifically react with human beta 2-M after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoresis onto nitrocellulose. These results thus identify a region around residue 45 of the beta 2-M polypeptide which is exposed to the environment and not involved in binding HLA-A,B heavy chain. Analysis of the beta 2-M sequence by calculating local hydrophilicity indices (Hopp, T. P., and Woods, K. R. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 3824-3828) agree with this region being a major antigenic determinant. Models of beta 2-M structure as an immunoglobulin domain show this region of polypeptide to be part of a loop between the two layers of beta-pleated sheet, also consistent with it being a major antigenic determinant. The position of the loop favors a model in which beta 2-M interacts with HLA across the four-stranded beta-pleated sheet like an immunoglobulin constant region domain.


A BrdU-requiring fragile site on chromosome 12.
A BrdU-requiring fragile site, fra(12)(q24.2), on human chromosome 12 of some individuals is reported. This fragile site is inherited in a Mendelian codominant fashion and does not seem to be associated with any physical or mental abnormality in carriers. It was mostly observed as a chromatid gap: no acentric fragments, triradials or deleted chromosomes were found. The fra(12)(q24.2) was expressed in 34%-48% of metaphases in lymphocyte cultures from carriers when BrdU and FdU were added 6.5 h before harvest, while the expression ranged between 5% and 20% when the cultures were treated with BrdU alone. The fra(12)(q24.2) represents the second BrdU-requiring rare fragile site described on human chromosomes.


An Unusual Intraoral Lipoma: A Case Report and Literature Review.
BACKGROUND Lipoma is a painless tumor derived from mesenchymal connective tissue. It manifests itself on soft tissue and is characterized by a slow and circumscribed growth. Its incidence in the oral cavity is relatively low (1-4%). Despite the fact that it poses very little threat, as it is a benign form, as opposed to liposarcomas, its position in the oral cavity can create the prerequisite conditions for the buccal mucosa to be continuously traumatised by chewing and thus be altered. Given the fact that it is a painless lesion, patients can undergo years with an intraoral lipoma without ever recognizing it. There, we report a case of an unusual, large, intraoral lipoma that caused speech problems. CASE REPORT A 46-year-old man presented a large, soft mass in the buccal mucosa. No pain was described by the patient, but there was a slight impediment in chewing and talking. The patient underwent surgical excision of the lesion, which was then sent for histological examination. Results confirmed the initial hypothesis that the lesion was a lipoma. CONCLUSIONS Lipomas can be subtle lesions that may go unnoticed for several years until their size causes difficulties with normal masticatory movement and aesthetic problems. However, given the benignity of the mass, it rarely poses a serious threat to health. They are relatively sporadic lesions and, after being removed, relapse is rare.


A safe and feasible "clock-face" duct-to-mucosa pancreaticojejunostomy with a very low incidence of anastomotic failure: A single center experience of 248 patients.
Postoperative pancreatic fistula (POPF) is one of the most frequent and serious postoperative complications of pancreatoduodenectomy (PD). We sought to assess the impact of a novel pancreaticojejunostomy (PJ) on the rates of POPF and overall postoperative complications. Between 01/2010 and 12/2013, a total of 248 consecutive patients who underwent PD with a modified PJ were identified from our database and retrospectively analyzed. POPF cases were divided into three categories (ISGPF-international study group-guidelines): biochemical fistula without clinical sequelae (grade A), fistula requiring any therapeutic intervention (grade B), and fistula with severe clinical sequelae (grade C). Perioperative outcomes were recorded and analyzed. The overwhelming majority of patients had no evidence of fistula. Grade A POPF was observed in 9 (3.62%), grade B in 1 (0.40%), and grade C in 0 patients. There were no postoperative deaths. Overall complications occurred in 61 patients (24.59%) of patients after PD. This modified pancreaticojejunostomy is widely applicable and is associated with very low rates of POPF, low postoperative morbidity and mortality. Overall, it is a feasible and safe novel approach with excellent short-term outcomes.


Escherichia coli RNA polymerase mutations located near the upstream edge of an RNA:DNA hybrid and the beginning of the RNA-exit channel are defective for transcription antitermination by the N protein from lambdoid phage H-19B.
Transcription antitermination is an important mechanism that can control regulation of gene expression. The N protein of lambdoid phages modifies the transcription elongation complex (EC) and helps it to overcome downstream terminators. In this modified EC, the C-terminal domain of N makes specific interactions with RNA polymerase (RNAP). The interacting surface of RNAP for N is unknown. Here, we report five mutations in the beta (G1045D) and beta' (P251S, P254L, R270C and G336S) subunits of RNAP that are specifically defective for antitermination by N protein of the lambdoid phage, H-19B. A mutation in the C-terminal domain of N, L108F, suppresses the defect of beta'-P254L. Purified mutant holoenzymes exhibit less processive antitermination. The amino acid substitutions in the mutant RNAPs cluster very close to the RNA:DNA hybrid at the beginning of the RNA-exit channel of the EC. We suggest that the action of H-19B N is exerted through the region defined by these amino acids. Wild-type N stabilizes the EC at terminator sites and in this modified EC a part of the terminator hairpin may form but appears to be unstable. We propose that the action of N close to the active center alters the RNAP-nucleic acid interactions around the RNA:DNA hybrid, which impairs proper folding of the terminator hairpin or stabilizes the weak RNA:DNA hybrid, or both.


Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer.
Recent clinical trials for the biological therapy of solid tumours have used recombinant human cytokines in combination with conventional chemotherapy. In patients with progressive metastatic renal cell carcinoma, we established a three-drug combination comprising interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy. Treatment consisted of 8 weeks each of IFN-alpha [6-9 MU/m2 once to three times weekly subcutaneously (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (i.v.) weekly for 4 weeks]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13 partial responders (37.1%), with an overall objective response rate of 48.6% (95% confidence interval 32-66%). Regressions occurred in local relapse, in lung, lymph node, bone, pleural, renal and thyroid metastases. Median response duration was calculated at 7+ months. An additional 13 patients (37.1%) were stable throughout therapy and thereafter (median of 6+ months). Response rate of this three-drug combination regimen compared favourably with single agent IFN-alpha (objective response rate approximately 16%) and against the sc IFN-alpha/IL-2 combination (objective response rate approximately 28%). Systemic toxicity was mild to moderate with no severe 5-FU-related mucositis and no dose-limiting adverse effects of sc IL-2. While the exact mechanisms of the potentially additive or synergistic effects of 5-FU and IFN-alpha/IL-2 remain to be established in more detail, it appears that the sequential use of IFN-alpha/IL-2 and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic index of IFN-alpha/IL-2-based biological therapy. Based on the present data, combined biochemotherapy may be a promising new approach to the therapy of advanced renal cancer.


[Tracheo-bronchial toilet using the technic of blind nasal intubation in conscious patients (author's transl)].
A temporary naso-tracheal intubation with a small tube is well tolerated by conscious patients. It is an appropriate alternative treatment intending a tracheobronchial toilet in case of retained mucus. The method and the experiences are described.


Implementation of safeguards to improve patient safety in chemotherapy.
To evaluate the effectiveness of safeguards introduced in the process of using cytostatic agents for increasing the safety of oncology patients. Prospective hospital study conducted in two stages, before and after the implementation of safeguards: staff training, standardized procedures, computerized prescription, pharmaceutical validation, implementation of bar codes, and a new manual on drug interactions. Medication errors (MEs) were actively recorded during the process of administering chemotherapy in the Medical Oncology Department. The study classified MEs by the stage of the medication process in which they occurred and assessed their severity. 500 patients, 250 before implementing safeguards and 250 afterward, were included in this study . Out of all patients included before, 43.1% had at least 1 error, compared to 27% of those included later. The number of MEs detected before and after was 144 vs. 95: 125 vs. 55 prescription errors, 2 vs. 5 validation errors, 14 vs. 4 preparation errors, 3 vs. 1 dispensation errors and 0 vs. 30 administration errors. The number of MEs that reached the patient before and after safeguard implementation was 16.7% vs. 6.3%. After the safeguards were introduced, all MEs that could have caused harm or required monitoring of some kind were prevented. Implementing safeguards in the hospital's cytostatic treatment cycle is useful for preventing MEs. Computerized prescription, pharmaceutical validation, and the creation/dissemination of proper work procedures are effective barriers that keep MEs from reaching the patient. Administering chemotherapy with a bar-code system facilitates detection error detection at this stage of the cycle and prevents them from reaching the patient.


Plasma thrombin-activatable fibrinolysis inhibitor as an indicator of inflammation and disease severity in acute pancreatitis.
In addition to suppressing fibrinolysis, thrombin activatable fibrinolysis inhibitor (TAFI) was suggested to be involved in inflammation. To date, no study has been published that reports the role of TAFI in acute pancreatitis (AP). Therefore, the objective of the present study was to investigate the role of plasma TAFI as an indicator of inflammation in AP, and its association with disease severity. Plasma TAFI antigen levels quantitatively determined by using ELISA kits in 21 AP patients at onset and remission and 17 healthy controls. Associations of TAFI with inflammatory markers to determine AP and disease severity were assessed. To predict the severity of AP, modified Glasgow prognostic score (mGPS) and computerized tomography severity index (CTSI) were used for each subject. Plasma TAFI levels was higher in AP patients at onset of the disease compared with healthy controls. The disease severity according to mGPS was significantly correlated with TAFI levels. Overall, accuracy of TAFI in determining AP was 83.3% with a sensitivity, specificity, NPV and PPV of 80.9%, 85.7%, 81.8%, and 85% respectively (AUC: 0.915). The present study for the first time demonstrated that TAFI is elevated in AP. The appraisal of TAFI levels in patients with AP in conjunction with other markers of inflammation may provide additional information in estimating AP severity.


Richard Dickerson, Molecular Clocks, and Rates of Protein Evolution.
Proteins approximately behave as molecular clocks, accumulating amino acid replacements at a more or less constant rate. Nonetheless, each protein displays a characteristic rate of evolution: whereas some proteins remain largely unaltered over large periods of time, others can rapidly accumulate amino acid replacements. An article by Richard Dickerson, published in the first issue of the Journal of Molecular Evolution (J Mol Evol 1:26-45, 1971), described the first analysis in which the rates of evolution of many proteins were compared, and the differences were interpreted in the light of their function. When comparing the sequences of fibrinopeptides, hemoglobin, and cytochrome c of different species, he observed a linear relationship between the number of amino acid replacements and divergence time. Remarkably, fibrinopeptides had evolved fast, cytochrome c had evolved slowly, and hemoglobin exhibited an intermediate rate of evolution. As the Journal of Molecular Evolution celebrates its 50th anniversary, I highlight this landmark article and reflect on its impact on the field of Molecular Evolution.


Binding of [125I]Bolton Hunter conjugated eledoisin to rat brain cortex membranes--evidence for two classes of tachykinin receptors in the mammalian central nervous system.
[125I]Bolton Hunter conjugated eledoisin was prepared and purified by ion-paired reverse phase chromatography. The ligand binds to rat brain cortex membranes, and the binding is inhibited over 95% by unlabeled eledoisin (6.6 microM). The binding site appears to be distinct from the [125I]Bolton Hunter conjugated substance P receptor based on the relative potencies of substance P, eledoisin, kassinin, physalaemin and [pGlu]substance P (6-11) hexapeptide to displace the binding of these two ligands.


Primary central nervous system malignant melanoma with leptomeningeal melanomatosis: a case report and review of the literature.
Leptomeningeal melanomatosis is an extremely rare variant of primary central nervous system (CNS) melanoma and has a poor prognosis and no standard treatment. Primary CNS melanoma is derived from the melanocytes of the leptomeninges. Here, we describe a case of a 37-year-old male who visited our hospital due to worsening headaches. Characteristic imaging findings of this tumor type include hyper-dense lesions that are enhanced by contrast medium on computed tomography and hyper-intensity on T1-weighted magnetic resonance images and iso- to hypo-intensity on T2-weighted magnetic resonance images. Imaging of the CNS in our patient showed several lesions of this type. Pathological diagnosis and exclusion of systemic melanoma are required to confirm primary CNS malignant melanoma. Partial resection of the mass in the left temporal lobe of this patient was performed, and histological analysis showed pigmentation, melanin black-45 positivity, and BRAF mutation. Because no lesions were found outside the CNS following a thorough whole-body search, he was diagnosed with primary CNS malignant melanoma with leptomeningeal melanomatosis. He was treated with whole-brain radiation and the BRAF kinase inhibitor vemurafenib. His condition worsened, and he was given the anti-programmed cell death-1 antibody nivolumab as second-line therapy. This was also unsuccessful, and he died 5 months after treatment initiation. Further studies are needed to improve treatment and prognosis of this rare but serious disease.


Prognostic modeling of cutaneous melanoma stage I patients using cancer registry data identifies subsets with very-low melanoma mortality.
Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize subsets of melanoma patients with very-low risk of death that may be contributing to overdiagnosis. Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database were selected. Classification and regression tree and logistic regression models were developed and validated to identify patients with very-low risk of death from melanoma within 7 years. Logistic models were also used to identify patients at higher risk of death among this group of stage I patients. Compared to an overall 7-year mortality from melanoma of 2.5% in these patients, a subset comprising 25% had a risk below 1%. Younger age at diagnosis and Clark level II were associated with low risk of death in all models. Breslow thickness below 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex were also associated with lower mortality. A small subset of high-risk patients with >20% risk of death was also identified. Patients with very-low risk of dying from melanoma within 7 years of diagnosis were identified. Such cases warrant further study and consensus discussion to develop classification criteria, with the potential to be categorized using an alternative term such as "melanocytic neoplasms of low malignant potential." Although melanoma is the most serious skin cancer, most melanoma patients have high chances of survival. There is evidence that some lesions diagnosed as melanoma would never have caused symptoms or death, a phenomenon known as overdiagnosis. In this study, we used cancer registry data to identify a subset of early-stage melanoma patients with almost no melanoma deaths. Using two statistical approaches, we identified patients with <1% risk of dying from melanoma in 7 years. Such patients tended to be younger with minimal invasion into the skin. We also identified a very small patient subset with higher mortality risk.


Feasibility of therapeutic music listening in fibromyalgia: a randomised controlled pilot study.
Fibromyalgia patients can benefit from music approaches as complementary treatments. In the literature, it was shown that these interventions managed pain conditions as well as reduced complaints, increased relaxation, and improved moods. This study aimed at evaluating music therapy, in the form of therapeutic music listening, specifically for patients with fibromyalgia, to treat chronic pain by reducing pain perception, increasing well-being, and improving quality of life. Twenty-four patients with fibromyalgia were recruited to take part in this feasibility pilot study that adopted a between-subject and within-subject design. Participants were randomised into three groups: (1) standard care, (2) standard care plus preferred music listening, (3) standard care plus Melomics-Health music listening, composed by an algorithm. Participants in experimental groups listened to 30 min of music at home, twice a day for a month. Patients' perceptions of changes following the listening, the intensity of pain and its interference in their lives, physical and mental well-being, and reported attitudes towards listening to music were evaluated respectively through the patients' global impression of change, the brief pain inventory, the Short Form Healthy Survey-12, and the cognitive behavioural assessment-outcome evaluation. The study showed that music listening can significantly affect mental well-being compared to no music. Moreover, the effects in the Melomics-Health group are maintained at follow-up. No significant effect on pain perception was noted. The study provides information supporting a possible role of music listening in improving well-being of patients with fibromyalgia.


Increased intracerebral cerebrospinal fluid spaces predict unemployment and negative symptoms in psychotic illness. A prospective study.
It has been suggested that the dimensions of cerebral ventricles are a risk factor for poor outcome in psychotic illness. A cohort of 140 patients with functional psychoses of recent onset who had undergone CT scanning, were followed up for an average of 46 months and assessed on six dimensions of course and outcome of illness. Left and right sylvian fissure volumes and, to a lesser extent, third ventricular volume predicted negative symptoms and unemployment over the course of follow-up, the latter association being mediated by poor cognitive functioning. There was significant linear trend in risk over the distribution of sylvian fissure volumes in the cohort, and associations were especially evident in schizophrenic patients. No associations were found with global severity of illness, duration of hospital stay, homelessness, or affective symptoms. These findings support the notion that dimensions of the cerebral ventricles are a continuous risk factor for some measures of outcome in the functional psychoses.


The flexible and iterative steps within the NHEJ pathway.
Cellular and biochemical studies of nonhomologous DNA end joining (NHEJ) have long established that nuclease and polymerase action are necessary for the repair of a very large fraction of naturally-arising double-strand breaks (DSBs). This conclusion is derived from NHEJ studies ranging from yeast to humans and all genetically-tractable model organisms. Biochemical models derived from recent real-time and structural studies have yet to incorporate physical space or timing for DNA end processing. In real-time single molecule FRET (smFRET) studies, we analyzed NHEJ synapsis of DNA ends in a defined biochemical system. We described a Flexible Synapsis (FS) state in which the DNA ends were in proximity via only Ku and XRCC4:DNA ligase 4 (X4L4), and in an orientation that would not yet permit ligation until base pairing between one or more nucleotides of microhomology (MH) occurred, thereby allowing an in-line Close Synapsis (CS) state. If no MH was achievable, then XLF was critical for ligation. Neither FS or CS required DNA-PKcs, unless Artemis activation was necessary to permit local resection and subsequent base pairing between the two DNA ends being joined. Here we conjecture on possible 3D configurations for this FS state, which would spatially accommodate the nuclease and polymerase processing steps in an iterative manner. The FS model permits repeated attempts at ligation of at least one strand at the DSB after each round of nuclease or polymerase action. In addition to activation of Artemis, other possible roles for DNA-PKcs are discussed.


Visceral adipose tissue area predicts intensive care unit admission in COVID-19 patients.
We retrospectively investigated, in 62 consecutive hospitalised COVID-19 patients (aged 70 ± 14 years, 40 males), the prognostic value of CT-derived subcutaneous adipose tissue and visceral adipose tissue (VAT) metrics, testing them in four predictive models for admission to intensive care unit (ICU), with and without pre-existing comorbidities. Multivariate logistic regression identified VAT score as the best ICU admission predictor (odds ratios 4.307-12.842). A non-relevant contribution of comorbidities at receiver operating characteristic analysis (area under the curve 0.821 for the CT-based model, 0.834 for the one including comorbidities) highlights the potential one-stop-shop prognostic role of CT-derived lung and adipose tissue metrics.


Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis.
Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of ROS production and the attenuation of adult hippocampal neurogenesis in a hypomagnetic field. The results of our calculations favor a singlet-born radical pair over a triplet-born radical pair. Our model predicts hypomagnetic field effects on the triplet/singlet yield of comparable strength as the effects observed in experimental studies on adult hippocampal neurogenesis. Our predictions are in qualitative agreement with experimental results on superoxide concentration and other observed ROS effects. We also predict the effects of applied magnetic fields and oxygen isotopic substitution on adult hippocampal neurogenesis.


Nursing students and geriatric care: the influence of specific knowledge on evolving values, attitudes, and actions.
This descriptive study explored the influence of specific geriatric knowledge on second and third year nursing students in their provision of care to older adults. Nineteen student participants provided qualitative data on their values and beliefs about nursing older adults prior to their attendance at a 1-h session teaching about two assessment tools: SPICES (Sleep disorders, Problems with feeding, Incontinence, Confusion, Evidence of falls, Skin breakdown) and BPI-SF (Brief Pain Inventory-Short Form). Data were again collected following a 6-week practice experience in which the same students had the opportunity to implement the tools. Four emerging themes, beliefs, knowledge, attitudes, and application, suggested how the students' geriatric knowledge and attitudes evolved and took on personal meaning in their intermediate practice experiences. Their realization of the hegemony associated with devaluing of the care of older adults warrants further examination into how geriatric knowledge is conveyed and assimilated.


Computed tomography and magnetic resonance imaging of a superior gluteal artery pseudoaneurysm.
The magnetic resonance and computed tomography appearances of a superior gluteal artery pseudoaneurysm are described, with emphasis on the relative advantages and disadvantages of these two imaging procedures.


Innate immunity in pluripotent human cells: attenuated response to interferon-β.
Type I interferon (IFN-α/β) binds to cell surface receptors IFNAR1 and IFNAR2 and triggers a signaling cascade that leads to the transcription of hundreds of IFN-stimulated genes. This response is a crucial component in innate immunity in that it establishes an "antiviral state" in cells and protects them against further damage. Previous work demonstrated that, compared with their differentiated counterparts, pluripotent human cells have a much weaker response to cytoplasmic double-stranded RNA (dsRNA) and are only able to produce a minimal amount of IFN-β. We show here that human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) also exhibit an attenuated response to IFN-β. Even though all known type I IFN signaling components are expressed in these cells, STAT1 phosphorylation is greatly diminished upon IFN-β treatment. This attenuated response correlates with a high expression of suppressor of cytokine signaling 1 (SOCS1). Upon differentiation of hESCs into trophoblasts, cells acquire the ability to respond to IFN-β, and this is accompanied by a significant induction of STAT1 phosphorylation as well as a decrease in SOCS1 expression. Furthermore, SOCS1 knockdown in hiPSCs enhances their ability to respond to IFN-β. Taken together, our results suggest that an attenuated cellular response to type I IFNs may be a general feature of pluripotent human cells and that this is associated with high expression of SOCS1.


Phenol degradation by halophilic fungal isolate JS4 and evaluation of its tolerance of heavy metals.
Phenol is one of the most common pollutants in many kinds of industrial wastewater, some of which are in high salinity, resulting in more difficulties of biodegradation. In this work, a halophilic strain capable of utilizing phenol as sole source of carbon and energy in both hypersaline and no-salt media was isolated and identified as genus Debaryomyces. The optimization of environmental parameters including phenol concentration, pH, dissolved oxygen as well as salinity was carried out and tolerance of heavy metals by the strain was evaluated. The strain Debaryomyces sp. was able to grow in culture when initial phenol concentration, pH, agitation and salinity were at wide ranges (0-1200 mg L(-1), 4.0-10.0, 50-200 rpm, 0 %-15 %, respectively). High removal efficiency was hardly affected in the presence of 5 mM of Zn (II) and Mn (II). Under optimal conditions (pH 6.0, 200 rpm, 1 % of salinity without heavy metals), 500 mg L(-1) of phenol could be completely degraded within 32 h. The high removal efficiency of phenol by the strain with significant variations of process parameters might contribute to the bioremediation of phenol-polluted environments under hypersaline or no-salt conditions.


M-DNA: A novel metal ion complex of DNA studied by fluorescence techniques.
M-DNA, a complex formed in solution between divalent metal ions (M) and duplex DNA, has been studied extensively using fluorescence quenching. This review examines the methods used to examine the formation of M-DNA, and its ability to serve as a pathway for electron transfer between donor and acceptor chromaphores. A mass action model for M-DNA formation is presented based upon the results of fluorescence quenching studies using fluorescein/QSY-7 labeled duplexes. From the mass action analysis, it was determined that approximately 1.4 protons are released per base pair, with k(eq) on the order of 10(-8), indicative of a strong interaction. As resonance energy transfer is shown to be unlikely over the distances involved in this work, the observed quenching in M-DNA is discussed in terms of an electron hopping mechanism for electron transfer, with k(hop)=2.5 x 10(11)s(-1).


Fluoride ion release from two methacrylate polymer systems.
The release of fluoride ions from two room-temperature polymerising systems containing sodium and potassium fluoride, respectively, has been studied. The polymer systems comprised poly(ethyl methacrylate) powder (PEM), with tetrahydrofurfuryl methacrylate (THFM), and n-butyl methacrylate (nBM), respectively. The water uptake of these systems was drastically increased by the presence of fluorides, the increase being much higher with the PEM/THFM system. In both cases, uptake was a monotonic function of the molarity of the fluoride added. The uptake process was in general non-Fickian. However, for all systems, the fluoride release process was Fickian, and diffusion coefficients could be calculated. The amount of fluoride released, and the diffusion coefficients obtained, appeared unrelated to the extent of water uptake of the parent polymers.


Twenty years of trials, tribulations, and research progress in bioethanol technology: selected key events along the way.
The projected cost of ethanol production from cellulosic biomass has been reduced by almost a factor of four over the last 20 yr. Thus, it is now competitive for blending with gasoline, and several companies are working to build the first plants. However, technology development faced challenges at all levels. Because the benefits of bioethanol were not well understood, it was imperative to clarify and differentiate its attributes. Process engineering was invaluable in focusing on promising opportunities for improvements, particularly in light of budget reductions, and in tracking progress toward a competitive goal. Now it is vital for one or more commercial projects to be successful, and improving our understanding of process fundamentals will reduce the time and costs for commercialization. Additionally, the cost of bioethanol must be cut further to be competitive as a pure fuel in the open market, and aggressive technology advances are required to meet this target.


Muscle fat content in the intact infraspinatus muscle correlates with age and BMI, but not critical shoulder angle.
Muscle fat content of the rotator cuff increases after a tear. In the healthy rotator cuff, the influence of age, body mass index (BMI) and critical shoulder angle (CSA) on muscle fat content is unknown. The primary aim was to correlate muscle fat content with age, BMI and CSA. The secondary aims were (1) to correlate muscle fat content in the entire muscle and slice Y (most lateral sagittal slice with scapular spine) and (2) assessed the reliability for CSA measurement in MRI. In 26 healthy shoulders (17 subjects), aged 40-65 years, BMI 20-35 kg/m2, Goutallier grade 0, Dixon MRI was applied. The CSA was > 35° in 14 shoulders and < 30° in 12 shoulders. Muscle fat content was calculated from Dixon MRI. Infraspinatus muscle fat content correlates moderately with age (r = 0.553; p = 0.003) and BMI (r = 0.517; p = 0.007). Supraspinatus muscle fat content does not correlate with age (r = 0.363, p = 0.069) and BMI (r = 0.342, p = 0.087). No correlation between CSA and muscle fat content was found. Muscle fat content measurement in the entire muscle correlates strongly with measurement in slice Y (intraclass correlation coefficient supraspinatus muscle: 0.757; infraspinatus muscle: 0.794). CSA intermethod analysis between radiography and MR images shows very high reliability (intraclass correlation coefficient > 0.9) and no systematical deviation in Bland-Altman analysis. Muscle fat content in the healthy infraspinatus muscle does correlate with age and BMI, but not with the CSA. Muscle fat content measurement in the rotator cuff using Dixon MRI showed a high reliability between slice Y and the entire muscle. III.


Abcd1 deficiency accelerates cuprizone-induced oligodendrocyte loss and axonopathy in a demyelinating mouse model of X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD), the most frequent, inherited peroxisomal disease, is caused by mutations in the ABCD1 gene encoding a peroxisomal lipid transporter importing very long-chain fatty acids (VLCFAs) from the cytosol into peroxisomes for degradation via β-oxidation. ABCD1 deficiency results in accumulation of VLCFAs in tissues and body fluids of X-ALD patients with a wide range of phenotypic manifestations. The most severe variant, cerebral X-ALD (CALD) is characterized by progressive inflammation, loss of the myelin-producing oligodendrocytes and demyelination of the cerebral white matter. Whether the oligodendrocyte loss and demyelination in CALD are caused by a primary cell autonomous defect or injury to oligodendrocytes or by a secondary effect of the inflammatory reaction remains unresolved. To address the role of X-ALD oligodendrocytes in demyelinating pathophysiology, we combined the Abcd1 deficient X-ALD mouse model, in which VLCFAs accumulate without spontaneous demyelination, with the cuprizone model of toxic demyelination. In mice, the copper chelator cuprizone induces reproducible demyelination in the corpus callosum, followed by remyelination upon cuprizone removal. By immunohistochemical analyses of oligodendrocytes, myelin, axonal damage and microglia activation during de-and remyelination, we found that the mature oligodendrocytes of Abcd1 KO mice are more susceptible to cuprizone-induced cell death compared to WT mice in the early demyelinating phase. Furthermore, this effect was mirrored by a greater extent of acute axonal damage during demyelination in the KO mice. Abcd1 deficiency did not affect the function of microglia in either phase of the treatment. Also, the proliferation and differentiation of oligodendrocyte precursor cells and remyelination progressed at similar rates in both genotypes. Taken together, our findings point to an effect of Abcd1 deficiency on mature oligodendrocytes and the oligodendrocyte-axon unit, leading to increased vulnerability in the context of a demyelinating insult.


The effects of adenotonsillar hypertrophy corrective surgery on left ventricular functions and pulmonary artery pressure in children.
Comparison of left ventricular functions in preoperative and postoperative periods of children with adenotonsillar hypertrophy (ATH) who have findings of upper airway obstruction (UAO), using echocardiographic parameters. Thirty children who were diagnosed with UAO due to ATH, and who have undergone adenoidectomy/adenotonsillectomy and 30 healthy children, between 2 and 11 years of age, were included in the study. Patient group was evaluated by the pulsed wave tissue Doppler echocardiography, as well as with conventional echocardiography, before and 6 months after the operation. Of 30 children in study group, 18 (60%) had adenotonsillectomy and 12 (40%) had adenoidectomy. The differences between groups regarding myocardial performance index (MPI) was not statistically significant (p = 0.847). There was not any statistically significant difference between groups in terms of mitral isovolemic acceleration (MIVA) (2.28 ± 0.67, 2.24 ± 0.55, 2.23 ± 0.49; p = 0.943, respectively). Interventricular septum diameter (IVSD) was significantly higher in preoperative group than postoperative and control groups (3.68 ± 0.52, 3.50 ± 0.40, 3.38 ± 0.60; p = 0.028, respectively). Pulmonary acceleration time (PAcT) was found to be significantly lower in preoperative group compared to postoperative and control groups (107.64 ± 16.60, 119.52 ± 15.95, 120.47 ± 16.19; p = 0.004, respectively). Mean pulmonary arterial pressure (mPAP) was significantly higher in preoperative group than postoperative and control groups (30.58 ± 8.11, 25.23 ± 9.07, 25.00 ± 6.52; p = 0.002, respectively). In postoperative group mPAP was found to be similar to the control group. Clinical or subclinical left ventricle (LV) dysfunction in children with ATH who have findings of UAO was not determined while mean pulmonary arterial pressure was significantly higher compared with the control cases. Besides early adenotonsillectomy is a beneficial treatment option for these patients.


Apico-aortic conduits in children with severe left ventricular outflow tract obstruction.
Infrequently, congenital heart defects are complicated by left ventricular outflow tract obstruction (LVOTO) not amenable to conventional reconstruction. Apico-aortic conduits provide a means of palliating such patients until definitive repair is possible. The purpose of this study was to review a single institution's current experience with apico-aortic conduits. The medical records of pediatric patients receiving apico-aortic conduits were reviewed. Demographics, operative techniques, preoperative and postoperative physiologic variables, morbidity, mortality, and functional class were recorded. Off-pump and on-pump procedures were categorized for comparison. Ten cases of apico-aortic conduits for left ventricular outflow tract obstruction were identified. Indications included congenital aortic stenosis, aortic atresia, and subaortic stenosis. Six procedures were performed off-pump and four required median sternotomy with cardiopulmonary bypass as necessitated by concomitant procedures. There was one operative death. The remaining patients demonstrated hemodynamic improvements and are all alive to date. One patient required conduit valve replacement. All patients are in New York Heart Association classification I or II at the time of last follow-up. Apico-aortic conduits provide a safe and effective treatment alternative for select cases of left ventricular outflow tract obstruction. Off-pump techniques are feasible in the majority of cases. This valuable adjunct should be considered whenever conventional repair of left ventricular outflow tract obstruction is considered prohibitive.


Even "Bigger Gods" developed amongst the pastoralist followers of Moses and Mohammed: Consistent with uncertainty and disadvantage, but not prosocality.
The gods of monotheistic religions, which began amongst pastoralists and defeated exiles, are closer to Big Gods than those associated with ancient city-based polities. The development of Big Gods is contingent upon a need to reduce uncertainty and negative feelings in combination with a relatively high level of prosociality, rather than a need to induce or assess prosociality.


A thiocholine ester of cinnamic acid inhibits crosslinking of fibrin without specific binding to donor lysines.
In the presence of activated factor XIII, 2-diethylbenzyl-aminoethylthiol-14C-transcinnamate bromide completely inhibited the crosslinking of fibrin. However, all three fibrin chains bound the cinnamic acid, and, in the alpha- and gamma-chains, the binding of label was not restricted to the crosslinking donor sites as might be expected. Furthermore, even in the absence of activated factor XIII, fibrinogen and fibrin incorporated cinnamic acid. Thus, as well as reacting with the functional thiol group of factor XIII, the thiocholine ester of cinnamic acid is incorporated non-specifically throughout the fibrinogen and fibrin subunit chains. The thiocholine ester used differs in this respect from dansyl cadaverine which is incorporated enzymatically and exclusively to the (acceptor) sites involved in crosslinking. Thiocholine ester of cinnamic acid cannot be used as a label for localization of specific crosslinking donor sites.


Knockdown of the long noncoding RNA HOTTIP inhibits cell proliferation and enhances cell sensitivity to cisplatin by suppressing the Wnt/β-catenin pathway in prostate cancer.
Prostate cancer (PCa) is a prevalent and deadly cancer worldwide. Considering the malignant progression and therapeutic resistance of PCa, further dissection of the underlying mechanisms and exploration of novel therapeutic targets for PCa are urgently needed. The long noncoding RNA HOTTIP has recently been revealed as an oncogenic regulator in different cancers; however, whether HOTTIP is involved in PCa remains poorly understood. Here, we examined the crucial roles of HOTTIP in the proliferation and chemoresistance of PCa. Quantitative real-time PCR (qRT-PCR) was performed to detect the HOTTIP messenger RNA (mRNA) levels in PCa samples from patients and PCa cells. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell cycle and flow cytometry assays were performed to investigate the proliferation and cisplatin-resistance of PCa cells with silenced HOTTIP compared with a negative control. We applied Western blotting, qRT-PCR and a TOP/FOP assay to explore the relevant mechanisms. In this study, we found that the HOTTIP mRNA levels were increased in the PCa patient samples and PCa cell lines compared with the controls. The knockdown of HOTTIP not only inhibited the proliferation of PCa cells but also facilitated cell cycle arrest and chemosensitivity to cisplatin. Furthermore, the qRT-PCR, Western blotting, TOP/FOP assays, MTT assay, and flow cytometry revealed that Wnt/β-catenin signaling was related to the regulation of HOTTIP in cell proliferation, cell cycle arrest, and chemoresistance to cisplatin in PCa. Taken together, our findings suggest that HOTTIP may be a potent therapeutic target for PCa, and HOTTIP inhibitors might be regarded as effective strategies for PCa therapy.


4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives as novel non-nucleoside agonists for the adenosine A1 receptor.
Three 4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives (4-6) were investigated as potential non-nucleoside agonists at human adenosine receptors (ARs). When tested in competition binding experiments, these compounds exhibited low micromolar affinity (Ki values comprised between 1.2 and 1.9 μm) for the A1 AR and no appreciable affinity for the A2A and A3 ARs. Evaluation of their efficacy profiles by measurement of intracellular cAMP levels revealed that 4 and 5 behave as non-nucleoside agonists of the A1 AR with EC50 values of 0.47 and 0.87 μm, respectively. No clear concentration-response curves could be instead obtained for 6, probably because this compound modulates one or more additional targets, thus masking the putative effects exerted by its activation of A1 AR. The three compounds were not able to modulate A2B AR-mediated cAMP accumulation induced by the non-selective AR agonist NECA, thus demonstrating no affinity toward this receptor.


Heart and kidney transplantation in the rat using a mixed cuff-stent microsurgical technique.
A method has been described for heart and kidney transplantation in rats using a mixed cuff-stent microsurgical technique. The advantages of the method include reduction of total ischemia time to an average of 11 minutes for heart grafting and 6 minutes for kidney grafting, provided donor and recipient operations are performed simultaneously; ease of performance and short training period, which allows the method to be employed by transplantation novices and to be extended to laboratories that lack experienced microsurgeons; and the possibility of applying the method to transplantation of other vascularized organs in the rat.


Columnaris disease in fish: a review with emphasis on bacterium-host interactions.
Flavobacterium columnare (F. columnare) is the causative agent of columnaris disease. This bacterium affects both cultured and wild freshwater fish including many susceptible commercially important fish species. F. columnare infections may result in skin lesions, fin erosion and gill necrosis, with a high degree of mortality, leading to severe economic losses. Especially in the last decade, various research groups have performed studies aimed at elucidating the pathogenesis of columnaris disease, leading to significant progress in defining the complex interactions between the organism and its host. Despite these efforts, the pathogenesis of columnaris disease hitherto largely remains unclear, compromising the further development of efficient curative and preventive measures to combat this disease. Besides elaborating on the agent and the disease it causes, this review aims to summarize these pathogenesis data emphasizing the areas meriting further investigation.


Transdiagnostic time-varying dysconnectivity across major psychiatric disorders.
Dynamic functional connectivity (DFC) analysis can capture time-varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting-state functional magnetic resonance imaging and a sliding-window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k-means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4-group differences (SZ, BD, MDD, and HC groups; q < .05, false-discovery rate [FDR]-corrected) in DFC were nearly only in State 1. Post hoc analyses (q < .05, FDR-corrected) in State 1 showed that transdiagnostic dysconnectivity patterns among SZ, BD and MDD featured consistently decreased connectivity within most networks (the visual, somatomotor, salience and frontoparietal networks), which was most obvious in both range and extent for SZ. Our findings suggest that there is more common dysconnectivity across SZ, BD and MDD than we previously expected and that such dysconnectivity is state-dependent, which provides new insights into the pathophysiological mechanism of major psychiatric disorders.


P-th moment and almost sure stability of stochastic switched nonlinear systems.
This paper mainly tends to utilize [Formula: see text]-type function to investigate p-th moment and almost sure stability for a class of stochastic switched nonlinear systems. Based on the multiple Lyapunov functions approach, some sufficient conditions are derived to check the stability criteria of stochastic switched nonlinear systems. One numerical example is provided to demonstrate the effectiveness of the proposed results.


Comparison of three antigen detection methods for diagnosis and therapeutic monitoring of malaria: a field study from southern Vietnam.
To compare the sensitivity, specificity and post-treatment persistence of three commonly used rapid antigen detection methods. We studied 252 Vietnamese patients aged from 4 to 60 years, 157 with falciparum and 95 with vivax malaria and 160 healthy volunteers. An initial blood sample was taken for microscopy, and OptiMAL, immunochromatographic test (ICT) malaria P.f./P.v. and Paracheck-Pf tests. Patients with falciparum malaria were treated with an artesunate-based combination regimen and those with vivax malaria received chloroquine. Eighty-seven patients with falciparum malaria who were initially positive for one of the antigen tests and who remained blood smear-negative underwent follow-up testing over 28 days. Paracheck-Pf was the most sensitive test for Plasmodium falciparum (95.8% vs. 82.6% for ICT malaria P.f./P.v. and 49.7% for OptiMAL). Specificities were all 100%. For vivax malaria, OptiMAL performed better than ICT malaria P.f./P.v. (sensitivities 73.7% and 20.0%, respectively), with 100% specificity in both cases. All tests had low sensitivities (< or = 75.0%) at parasitaemias < 1000/microl regardless of malaria species. During follow-up, Paracheck-Pf remained positive in the greatest proportion of patients, especially at higher parasitaemias (> 10,000/microl). Residual OptiMAL positivity occurred only in a relatively small proportion of patients (< 10%) with parasitaemias > 10,000/microl during the first 2 weeks after treatment. Although microscopy remains the gold standard for malaria diagnosis, Paracheck-Pf may prove a useful adjunctive test in uncomplicated falciparum malaria in southern Vietnam. OptiMAL had the lowest sensitivity for P. falciparum but it might have a use in the diagnosis of vivax malaria and perhaps to monitor efficacy of treatment for falciparum malaria where microscopy is unavailable.


Mossy fiber synapses on glutamate decarboxylase-immunoreactive neurons: evidence for feed-forward inhibition in the CA3 region of the hippocampus.
Mossy fibers are known to form excitatory synapses on pyramidal neurons in regio inferior of the hippocampus. This study demonstrates that the mossy fibers also establish synaptic contacts with glutamate decarboxylase-immunoreactive, supposedly GABAergic inhibitory neurons in the CA3 region. The observed connection provides a morphological basis for feed-forward inhibition of the pyramidal cells.


Bone marrow-derived cells migrate to line the vessels of the CNS: opportunities for gene delivery to CNS vasculature.
Using bone marrow (BM)-directed gene transfer and permanent transduction via recombinant SV40-derived vectors, we previously reported that BM-derived cells may be progenitors of CNS cells, such as neurons in normal adult animals. In this study, we asked whether the same was true for the CNS blood vessels, that is, whether marrow-resident precursors can migrate to the vasculature of the CNS. SV40-derived gene delivery vectors, carrying marker epitopes (FLAG or AU1), appended to carrier proteins, were injected directly into the femoral BM of rats or rabbits. Controls received intramarrow SV(BUGT), a control vector. Transgene expression was then examined in the vasculature. Endothelial cells expressing the transgenes were observed in the vessels of the striatum, principally localized in laminin- or CD31-positive structures (markers of brain blood vessels). Results in both animal models and with both transgenes were similar. Thus, under physiologic conditions and in the absence of CNS or vascular injury, BM-derived cells can migrate to, and form an endothelial lining for, brain blood vessels. Intramarrow gene delivery may provide an avenue to deliver genes to the vascular endothelium of the CNS.


Surgical Outcomes of LigaSure Hemorrhoidectomy in the Elderly Population: A retrospective cohort study.
This study aims to assess the association between age and outcomes in patients undergoing hemorrhoidectomy. This is a population-based cohort study. A retrospectively collected database with consecutive patients whose symptomatic prolapsed hemorrhoids managed by the LigaSure hemorrhoidectomy between Jan. 2015 and May 2017 was reviewed. Among 1238 patients, 1075 were under 65 years old (group 1), and 163 were 65 years old or older (group 2). Both groups were compared regarding baseline characteristics and surgical outcomes. All patients tolerated the whole course of the operation in the prone jackknife position without anesthetic-associated complications. There was no significant difference between these two groups regarding sex, hemorrhoids grade, operation time, duration of hospital stays, postoperative pain score, analgesic consumption, total postoperative complications, re-admission rate, reoperation rate and follow-up times. The multivariate logistic regression analysis that may contribute to postoperative complications revealed no significant difference for all complications between both groups. The LigaSure hemorrhoidectomy for elderly patients is safe and effective without significant difference in short-term operative outcomes and all complication rates, compared with younger patients.


Equity of Cancer and Diabetes Co-Occurrence: A National Study With 44 Million Person-Years of Follow-Up.
The co-occurrence of diabetes and cancer is becoming increasingly common, and this is likely to compound existing inequities in outcomes from both conditions within populations. In this study, we investigate the co-occurrence of cancer and diabetes by ethnic groups in New Zealand. National-level diabetes and cancer data on nearly five million individuals over 44 million person-years were used to describe the rate of cancer in a national prevalent cohort of peoples with diabetes versus those without diabetes, by ethnic group (Māori, Pacific, South Asian, Other Asian, and European peoples). The rate of cancer was greater for those with diabetes regardless of ethnic group (age-adjusted rate ratios, Māori, 1.37; 95% CI, 1.33 to 1.42; Pacific, 1.35; 95% CI, 1.28 to 1.43; South Asian, 1.23; 95% CI, 1.12 to 1.36; Other Asian, 1.31; 95% CI, 1.21 to 1.43; European, 1.29; 95% CI, 1.27 to 1.31). Māori had the highest rate of diabetes and cancer co-occurrence. Rates of GI, endocrine, and obesity-related cancers comprised a bulk of the excess cancers occurring among Māori and Pacific peoples with diabetes. Our observations reinforce the need for the primordial prevention of risk factors that are shared between diabetes and cancer. Also, the commonality of diabetes and cancer co-occurrence, particularly for Māori, reinforces the need for a multidisciplinary, joined-up approach to the detection and care of both conditions. Given the disproportionate burden of diabetes and those cancers that share risk factors with diabetes, action in these areas is likely to reduce ethnic inequities in outcomes from both conditions.


Generation of a fast and homogeneous temperature step.
A method is described for the fast and homogeneous increase of the temperature of a biological specimen with a volume of 1 mm3 or less. Heating is obtained by joule dissipation from a 30 MHz alternating current. The step quality is determined by measuring the temporal and spatial behaviour of the temperature after a power pulse in and around the biological preparation. With the described equipment a temperature step of 3 degrees C can be obtained in 8 ms. The temperature step inhomogeneity is less than 15%. The compatibility of the method with electrophysiological and mechanical measurement and instrumentation is demonstrated by the detection of transients in transmembrane potential and force of a papillary muscle from the rabbit heart.


Possible dementia risk of proton pump inhibitors and H2 receptor blockers use in the treatment of Helicobacter pylori: A meta-analysis study.
The risk of dementia when using proton-pump-inhibitors (PPIs) and H2-receptor-blockers as a treatment of Helicobacter-pylori have a lot of controversial-research with different results; however, no final recommendation was deduced from all these researches. A meta-analysis study was performed to evaluate the relationship between PPIs and H2-receptor-blockers use and dementia. Through a systematic literature search up to December-2019, 10-studies with 371951-subjects of them 71021Helicobacter-pylori-positive subjects using either PPIs or H2-receptor-blockers or both were identified reporting-relationships between PPIs and H2-receptor-blockers uses and dementia (10-studies contained PPIS, 4-contained H2-receptor-blockers). Odd-ratio (OR) with 95% confidence-intervals (CIs) was calculated comparing PPIs and H2-receptor-blockers users and to non-user subjects on the bases of dementia using the dichotomous-method with a random-effect-model. No significant difference was found between PPIs-users or non-user (OR, 0.87; 95% CI, 0.62-1.22) or between H2-receptor blockers-users and non-users (OR, 1.21; 95% CI, 0.91-1.59) as a risk of dementia. The extent of increases in dementia with H2-receptor-blockers was higher than that with PPIs. The impact of PPIs and H2-receptor-blockers was similar in all populations. Based on this meta-analysis, the contentious use of PPIs or H2-receptor-blockers may not have an independent-relationship to dementia. This suggests that using PPIs or H2-receptor-blockers is not related to dementia. However, we still have to recommend careful use of PPIs and H2-receptor-blockers when treating Helicobacter-pylori and sticking to the dose and length of treatment and not to extend it to avoid any possible risk.


Influence of recasting on the quality of dental alloys: A systematic review.
Dental alloy manufacturers advise against the reuse of previously melted alloy. However, for economic reasons, dental laboratories often reuse the casting surplus (sprue and metal remaining in the crucible former). Such reuse remains a controversial topic in dental practice. The purpose of this systematic review was to assess the effects of remelting dental alloys by evaluating the following parameters: reasons for recasting and associated processes, feasible number of recastings, treatment of alloys before recasting and its effects on cytotoxicity, color of opaque porcelain, castability of alloys, marginal accuracy, mechanical properties, porcelain-metal interfaces, and corrosion. The systematic review included all studies on dental alloy recasting. MEDLINE, Dentistry and Oral Science Source, Science Direct, and ISI Web of Science were searched (up to July 2014). Data were extracted and the quality of studies was assessed. Thirty-four studies published between 1983 and 2014 were included. The number of recastings ranged from 1 to 10. The percentage of new alloy ranged from 0 to 100 wt%, although the mean value was 50 wt%. Evidence for the feasibility of adding 50% new metal at each recasting is limited. The number of recastings should be limited to a maximum of 4. No general test protocol can be deduced from these studies, which limits the comparison and exploitation of data. Furthermore, no consensus protocol exists for the evaluation of recasting. Future studies should work toward establishing a standard protocol.


Serum bicarbonate levels and gait abnormalities in older adults: a cross-sectional study.
Metabolic acidosis is associated with impaired physical function in patients with chronic kidney disease (CKD) and older adults. However, whether acidosis is associated with gait abnormalities has received little attention. In a cohort of 323 community-dwelling adults ≥ 65 years old who underwent quantitative gait analysis, we examined associations of serum bicarbonate with eight individual gait variables. After multivariable adjustment, participants in the lowest bicarbonate tertile (< 25 mEq/L) had 8.6 cm/s slower speed (95% confidence interval [CI] 3.2-13.9), 7.9 cm shorter stride length (95% CI 3.5-12.2), and 0.03 s longer double support time (95% CI 0.002-0.1) compared with those in the middle tertile (25-27 mEq/L). Furthermore, lower bicarbonate levels were associated with more severe gait abnormalities in a graded manner. After further adjustment for possible mediating factors, associations were attenuated but remained significant. Among participants with CKD, associations were of similar or greater magnitude compared with those without CKD. Factor analysis was performed to synthesize the individual gait variables into unifying domains: among the pace, rhythm, and variability domains, lower serum bicarbonate was associated with worse performance in pace. In sum, lower serum bicarbonate was independently associated with worse performance on several quantitative measures of gait among older adults.


Item Understanding of Common Quality of Life Measures for use with Autistic Adults.
Quality of life (QOL) and life satisfaction are important research priorities for autistic adults. As such, we saw a need to evaluate individual items of commonly used subjective QOL scales to understand how they are interpreted and perceived by autistic adults. This study used cognitive interviews and repeated sampling to evaluate the accessibility, test-retest reliability and internal consistency of several common QOL measures in a sample of young autistic adults (n = 20; aged 19-32). Cognitive interviews suggested that the Satisfaction with Life Scale was well understood and demonstrated excellent internal consistency and test-retest reliability. While the WHOQoL-BREF and WHOQoL Disability Modules had adequate reliability, cognitive interviews suggested that additional instructions and examples would further enhance their accessibility for use with autistic adults.


Psychological impact and perceptions of orthodontic treatment of adult patients with different motivations.
Motivations, perceptions, and psychosocial states of adult patients with orthodontic disorders in China have not been widely studied. The study assessed the psychosocial states and perceptions of adult patients undergoing orthodontic treatments with different motivations. Two hundred forty-three adult patients (mean age, 30.2 ± 7.4 years; women, 79.0%) undergoing orthodontic treatment were recruited from a tertiary stomatology hospital. The patients answered a patient-centered questionnaire regarding motivations and perceptions of orthodontic treatment and the Psychosocial Impact of Dental Aesthetics Questionnaire. Data were analyzed using the chi-square test on the basis of multiple responses. Multiple linear regression analyses were performed to determine the association between motivation factors and the Psychosocial Impact of Dental Aesthetics Questionnaire subscale scores (P <0.05). Patients with various motivations were as follows: occlusal function reason (70.4%), dental esthetic reason (54.7%), facial esthetic reason (24.3%), and following others' suggestions (18.5%). Patients with esthetic or occlusal motivations exhibited significantly greater need and interest for orthodontic treatment (P <0.001). Multiple linear regression analyses revealed that the scores of social impact, psychological impact, and esthetic concern subscales were significantly associated with both dental and facial esthetic motivations (P <0.001). The primary motivations of Chinese patients were observed to be improved esthetics and occlusal function. Patients with esthetic or occlusal motivations exhibited significantly greater need and interest in treatment. Patients with facial or dental esthetic motivations experienced greater impacts of psychosocial states. Therefore, the patient motivations and impacts of esthetic-related psychosocial states on them should be considered during treatment.


Afriflu2--second international workshop on influenza vaccination in the African continent--8 November 2012, Cape Town (South Africa).
The second meeting of the Afriflu conferences took place in Cape Town, South Africa, with over 60 participants from 15 countries in Africa and also outside the continent. Significant progress in surveillance has been made in better understanding the illness burden of influenza on the continent, which limited evidence suggests is greater than that in the developed world. In southern Africa HIV and TB coinfections play a major role in increasing hospitalisation and mortality, while elsewhere in Africa other cofactors still need to be determined. There is currently no indigenous vaccine production in sub-Saharan Africa and only one facility, based in South Africa, capable of filling imported bulk. Innovative vaccine strategies will need to be explored, such as maternal immunisation, and also the possibility of other influenza vaccine options, such as live attenuated influenza vaccine for young children. Sustained indigenous vaccine production is essential for the continent to have vaccine security in the event of a pandemic even though establishing local production faces considerable challenges especially ensuring adequate markets on the continent. There is an urgent need to develop effective communication messages for decision makers as well as healthcare workers addressing the importance of influenza even in the face of the major competing health burdens of the continent.


Political change and course of schizophrenia in East Germany, 1984-1994.
We tested the hypothesis that the political change occurring in East Germany after the fall of the Berlin Wall in November 1989 affected patients with long-term schizophrenia, resulting in more and longer hospitalisations. In two samples in East Germany (120 patients in East Berlin, 70 patients in Chemnitz) and in a control group from West Berlin (40 patients), hospitalisations for each month between November 1984 and October 1994 were assessed. Each sample included all schizophrenia patients who were in continuous treatment in the given community mental health centre throughout the full observation period. Hospitalisation indices were not higher after November 1989 than before in any of the groups. There is no evidence that political change in East Germany negatively affected the course of longterm schizophrenia as assessed by hospitalisations. If consistent medical care is provided, characteristics of the political system may have less impact on the course of schizophrenia than is sometimes assumed.


Epistaxis duration predicts bleeding in immune thrombocytopenia: a cohort study.
To test for an association between duration of epistaxis and clinically relevant bleeding in the following 12 months in children with immune thrombocytopenia (ITP). Prospective cohort study. The national UK Paediatric ITP registry, a multicentre prospective clinical registry of new cases of ITP between 2006 and February 2020. All children aged between 2 months and 16 years in participating UK centres. Epistaxis at presentation defined as none, <10 min, 10-30 min and >30 min. Incident severe bleeds, combined moderate and severe bleeds and drop in haemoglobin (Hb) by ≥20 g/L. The sample included 1793 patients, of which 334 had epistaxis <10 min, 88 lasting 10-30 min and 97 >30 min. In the 12 months following presentation, 19 had a severe bleed, 140 had a moderate bleed and 54 had a drop in Hb ≥2 g/dL. Epistaxis >30 min duration was associated with increased odds of severe bleeds (OR 1.43-15.67), moderate or severe bleeding (OR 1.33-4.2) and drop in Hb (OR 1.23-6.91). Shorter duration epistaxis was not associated with increased odds of any outcome. A trend for increased odds with longer duration epistaxis was significant for all outcomes. The longer the duration of epistaxis at presentation with ITP, the higher the risk of a clinically significant bleeding event in the 12 months following. This should inform clinical severity ratings and treatment decisions.


Binary Horse herd optimization algorithm with crossover operators for feature selection.
This paper proposes a binary version of Horse herd Optimization Algorithm (HOA) to tackle Feature Selection (FS) problems. This algorithm mimics the conduct of a pack of horses when they are trying to survive. To build a Binary version of HOA, or referred to as BHOA, twofold of adjustments were made: i) Three transfer functions, namely S-shape, V-shape and U-shape, are utilized to transform the continues domain into a binary one. Four configurations of each transfer function are also well studied to yield four alternatives. ii) Three crossover operators: one-point, two-point and uniform are also suggested to ensure the efficiency of the proposed method for FS domain. The performance of the proposed fifteen BHOA versions is examined using 24 real-world FS datasets. A set of six metric measures was used to evaluate the outcome of the optimization methods: accuracy, number of features selected, fitness values, sensitivity, specificity and computational time. The best-formed version of the proposed versions is BHOA with S-shape and one-point crossover. The comparative evaluation was also accomplished against 21 state-of-the-art methods. The proposed method is able to find very competitive results where some of them are the best-recorded. Due to the viability of the proposed method, it can be further considered in other areas of machine learning.


On the origin of cardiac mucosa: a histological and immunohistochemical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach.
To examine the fetal and neonatal esophagogastric junction region (EGJ) histologically for the presence of an equivalent to adult cardiac mucosa (CM); to study the expression patterns of all cytokeratins (CK) relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin (H and E) to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age (GA). The proximal part of this segment consisted of mucus-producing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the co-ordinate CK7+/20+ and the CK7-/20- immunophenotypes between different locations. The prevalence of the CK7+/20- immunophenotype decreased, and that of the CK7-/20+ immunophenotype increased significantly from the distal esophagus to the distal stomach. Fetal columnar-lined lower esophagus (fetal CLE) may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells (ESN) may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression patterns support the conclusion that adult CM has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.


Critical asthma syndrome in trauma patients - A case report and literature review.
Critical asthma syndrome (CAS) is an umbrella term for many acute, life-threatening, and treatment resistant variants of asthma exacerbation, including refractory asthma, near fatal asthma, and status asthmaticus. The asthma mortality rate has steadily increased through the last decade and disproportionately affects women, African-Americans, patients of low socioeconomic status, and adults over the age of 55. Increased awareness of the diagnosis and therapies for CAS can help establish a therapeutic strategy for asthma beyond corticosteroids, bronchodilators, and other conventional treatments. A 37 year-old African American woman presented to our Level 1 Trauma Center after a high-speed motor vehicle crash and was intubated on arrival for airway protection. The patient developed diffuse wheezing and persistent tachycardia, with elevated peak airway pressures and air trapping on mechanical ventilation. Her symptoms were refractory to inhaled steroids, systemic steroids, intravenous magnesium, continuous albuterol administration and ventilator optimization. Heliox, an admixture of 80:20 percent helium to oxygen, was initiated to assist with laminar flow. Throughout the next 24 h, the patient's air trapping improved, subsequently decreasing intrathoracic pressure, improving venous return and resolving her tachycardia. The patient's multiple orthopedic injuries were treated and she was eventually weaned off of Heliox, steroids, and continuous albuterol. She was extubated and endorsed a history of poorly controlled asthma requiring hospitalizations and multiple intubations. Recognition of CAS can be challenging in the trauma patient with distracting injuries. This case illustrates the utility of a stepwise approach to a trauma patient suffering from CAS, and should encourage further research into novel therapies when conventional treatment fails. Given that the populations most affected by CAS are often also subject to a disproportionate burden of trauma, trauma surgeons should maintain both a vigilance for the syndrome as well as a working knowledge of the treatment modalities available.


Can biliary carcinoembryonic antigen identify colorectal cancer patients with occult hepatic metastases?
Twenty-five percent of radically treated colorectal cancer patients already have occult hepatic metastases (OHM) that will later be observed during postoperative follow-up. Instrumental examinations, i.e., intraoperative ultrasound or Doppler perfusion index, have not improved diagnosis. As carcinoembyonic antigen (CEA) levels are useful to reveal hepatic metastases from colorectal cancer, determination of CEA in the bile rather than the blood may allow preclinical diagnosis of OHM thanks to the reduced volume of bile. One hundred radically treated colorectal cancer patients were enrolled in the study. Bile was withdrawn from the gallbladder intraoperatively and biliary CEA levels determined using an immuno-enzymatic method (normal value 0-5 ng/ml). Eighty-nine fully evaluable patients were followed up for three years postoperatively to monitor hepatic metastases. Preoperative blood CEA, lymph node metastases and biliary CEA were compared in order to assess which procedure was more efficient in identifying patients who would develop hepatic metastases. Eleven of the 89 evaluable patients developed hepatic metastases: 9/11 presented elevated biliary CEA levels (mean: 12.73; range: 5.1-26.2); 8/11 had high preoperative blood CEA values; and 9/11 were at anatomopathological stage N+. In the 78 patients who did not develop hepatic metastases, biliary CEA was within normal limits in 73/78, preoperative blood CEA was normal in 60/78, and 58/78 patients were at anatomopathological stage N-. Hence, the sensitivity of biliary CEA was 81.8%, specificity was 93.6%, and diagnostic accuracy was 92.1%. Determination of biliary CEA seems to be more efficient in identifying patients presenting OHM who require frequent clinical examinations or adjuvant cancer treatment.


Molecular cloning and characterization of WD40-repeat protein from Clonorchis sinensis.
WD40-repeat proteins have four to eight repeating units flanked by Gly-His (GH) and Trp-Asp (WD) at both termini and folds into a beta-propeller. A polypeptide deduced from a Clonorchis sinensis cDNA clone analyzed to have seven WD40-repeats and predicted to form a beta-propeller (CsWD1). The CsWD1 protein was expressed stage-specifically in the metacercariae and localized in the tegumental syncytium. The CsWD1 protein is suggested to serve as a platform for interacting partner proteins in the tegumental syncytium of C. sinensis metacercariae.


Bain circuit occluded by foreign body.
The purpose of this report is to describe a potentially hypoxic event which occurred during mask induction with the Bain circuit in a healthy. ASA I boy. Failure of induction occurred because a pop-off weight from a bubble bottle was lodged in the elbow connecting the Bain circuit to the mask and prevented gas flow. Pethick and Foëx-Crampton Smith tests of the Bain circuit could also have missed this condition. Such an anaesthetic mishap could occur with any breathing circuit which is re-used. Although there was no serious misadventure, the potential for an hypoxic complication with either intra-venous induction of anaesthesia, or dislodging of the weight into the airway was significant. We conclude that the standard tests of system patency do not ensure safety.


Growth of human-human hybridomas in serum-free media enhances antibody secretion.
Human-human hybridomas derived from fusing lymph node lymphocytes with UC 729-6 were adapted to grow in commercially available serum-free medium and were compared with serum-supplemented [10% fetal bovine serum (FBS)] cultures. Over a 6-d period, no significant changes occurred in the growth of the cells in 10% FBS or serum-free medium. In cultures supplemented with 10% FBS more total proteins were secreted than in serum-free cultures. However, there was an enhanced secretion of three- to four-fold of both immunoreactive human IgG and IgM under serum-free conditions compared to serum-supplemented conditions. Serum-free conditions may provide the appropriate milieu for the increased level of Ig secretion from human hybridomas derived from UC 729-6 in that there are no inhibitors that may be present in serum.


Vasopressin gene transcripts in the bovine corpus luteum are defective.
cDNA clones corresponding to vasopressin gene transcripts were isolated from a lambda gt11 library made using mRNA extracted from a bovine corpus luteum of the early non-pregnant cycle. None of the characterized clones included the vasopressin-encoding exon A sequence, instead two of these clones included sequence from the first intron. Together these data and controls indicate that vasopressin gene transcription in this tissue does not yield translatable mRNA and that positive RNA-DNA hybridization signals are not necessarily evidence for local biosynthesis of the neuropeptide.


Novel preparation protocol for the expression and purification of recombinant staphylokinase.
Staphylokinase (Sak), produced by lysogenic strains of Staphylococcus aureus, can convert plasminogen into its proteolytic form, plasmin, and thus is widely used to dissolve pathological clots in clinical applications. In the present paper, we report a novel approach to produce r-Sak (recombinant Sak) using an engineered Escherichia coli expression system. The expression plasmid was constructed by placing the Sak gene into the expression vector pET32(a), resulting in the expression of 35% fusion protein. Subsequently, a rapid and simple chromatographic procedure was developed for the large-scale purification of therapeutic-grade r-Sak from E. coli, which includes Ni(2+)-affinity chromatography, ultrafiltration and Q-Sepharose Fast Flow chromatography. This method led to the production of highly pure r-Sak (>99%), according to SDS/PAGE and HPLC analysis.


Multifocal and diffusely infiltrating breast cancers are highly fatal subgroups needing further improvement in diagnostic and therapeutic strategies.
Physicians treating breast cancer patients often wonder why this dreaded disease is still fatal in some women despite our best diagnostic and therapeutic efforts. Our own studies on prospectively documented cases spanning several decades have given us new insights for approaching this problem. By using imaging biomarkers to classify breast cancer subtypes according to their apparent site of origin, we found that a majority of breast cancer deaths (71%) occur in a minority of breast cancers (45%). Breast cancer deaths are significantly more likely to occur in women with multifocal acinar adenocarcinoma of the breast, AAB (13.1%), diffusely invasive breast cancers of ductal origin, DAB (24 %) and breast malignancies of mesenchymal hybrid cell origin, BCMO (33.7%) compared with women having unifocal invasive breast cancers (6.1%). Preventing more of these fatal events will require a re-evaluation of the current imperfect histopathologic terminology of breast cancer with special attention to the diffuse breast cancer subtypes, intensification of multimodality imaging and multidisciplinary management, as well as application of image guided large format histopathology.


Renal tolerance of rubidium chloride: short-term clinical evaluation.
The rubidium and lithium ions are known to have opposite effects on a wide range of biochemical and behavioral parameters in experimental animals. Based on the proven effectiveness of lithium as an antimanic agent, several trials have been conducted with rubidium in the acute treatment of the depressive phase of bipolar illness. The results to date are promising. However, the 30- to 60-day biologic half-life of rubidium has mandated careful studies of potential toxicity before engaging in long-term administration of this ion to depressive subjects. One area of potential concern is the possibility of renal toxicity, which could be expressed as unexpectedly increased retention of rubidium. The data in this paper show that after 15 days of rubidium administration, there are no changes beyond the normal range in a variety of kidney function tests, including in four enzymes which are specific markers of tubule cell function.


Gaps and Resemblances in Current Heart Failure Guidelines: A Clinical Perspective.
The newly available clinical guidelines in heart failure (HF) from Europe (2012), the United States (2010 and 2013), and Canada (2015) were compared, focusing on the systems for grading the evidence and classifying the recommendations, HF definitions, pharmacologic treatment, and devices used in HF. Some gaps were evident in the methodology for assessing evidence or in HF definitions. Pharmacologic treatments and recommendations for cardiac resynchronization therapy and implantable cardioverter-defibrillators are similar but some differences need to be considered by the practicing clinician. Guideline recommendations regarding new emergent treatments are becoming available.


Draft Genome Sequence of Ligilactobacillus salivarius FFIG58, Isolated from the Intestinal Tract of Wakame-Fed Pig.
Ligilactobacillus salivarius FFIG58 was isolated from the intestine of a wakame-fed pig and sequenced with an Illumina HiSeq system. FFIG58 genome sequencing revealed a genome size of 1,984,180 bp, with 1,994 protein-coding genes and a GC content of 32.9%. This draft genome sequence will contribute to a better understanding of the porcine gut microbiome.


Common and plantar warts with trichilemmal keratinization-like keratinizing process: a possible existence of pseudo-trichilemmal keratinization.
Thirty-one common and five plantar warts were investigated histopathologically and electron microscopically in order to reveal whether or not these warts keratinize in a fashion similar or identical to trichilemmal keratinization (TK). Histopathologically, parts of 12 of 31 common, and 3 of 5 plantar warts, exhibited varying keratinization similarities to TK. The most similar case showed changes almost identical to intrinsic TK. Electron microscopy revealed uneven and somewhat interdigitating borders between the keratinized and the keratinizing cells, with a few ladder-like membrane coating granules. It is postulated that there may be TK or TK-like keratinization without any relationship to the outer root-sheath of the hair follicle. We propose the concept of pseudo-TK to distinguish this type of keratinization from intrinsic TK.


[Arrhythmia as a major manifestation of Lyme borreliosis].
The submitted case-history is focused on one of the leading manifestations of cardiac affection in Lyme borreliosis. The authors recapitulate and analyze the patient's complaints, her electrocardiographic and other findings and confront them with data from the literature on this "new" nosological unit.


[Preliminary studies on the mechanisms of a new anti-tumor agent PH II-7 with special preference to multidrug resistant tumor cells].
To determine the anti-tumor activity of PH II-7 in vitro and explore preliminarily its mechanisms. The anti-tumor activity was measured using colorimetric MTT assay. Apoptosis was determined with fluorescence-activated cell sorter (FACS), electron microscopy and agarose gel electrophoresis. The expressions of mdr1 and sorcin genes were determined by Northern blot assay. PH II-7 inhibited the proliferation of various human tumor cells derived from different tumor cell lines. The IC50 values varied from 0.34-18.61 mumol/L. Especially, PH II-7 had strong inhibitory effect on multidrug resistant tumor cells, whereas adriamycin (ADR) was resistant. Apoptosis was induced in HL60 and HL60/ADR cells treated with 1 microgram/ml PH II-7, while PH II-7 inhibited the expressions of mdr1 and sorcin genes. PH II-7 is a new potential agent which has strong inhibitory effect on both multidrug resistant cells and their parental cells. PH II-7 may increase the intracellular drug concentration in MDR cells by inhibiting the expressions of the MDR-related genes mdr1 and sorcin and induce the apoptosis of MDR cells and their parental tumor cells.


Oxygen toxicity during one-lung ventilation: is it time to re-evaluate our practice?
Lung cancer remains one of the leading causes of cancer-related mortality. Surgical resection remains the mainstay of non-small cell lung cancer therapy, but an increasing number of patients receive preoperative adjuvant chemotherapy that may predispose these patients to unique organ toxicities. This chemotherapy, along with exposure to high oxygen concentrations, may combine to increase the risk of reactive oxygen species-mediated lung injury. Continued efforts are needed to improve overall outcome in these patients, including a reevaluation of our management of oxygen therapy.


The expression of antioxidant enzymes in a mouse model of fetal alcohol syndrome.
Superoxide dismutase, glutathione peroxidase, and catalase prevent cellular damage produced by free radicals. Our objective was to evaluate if prenatal alcohol exposure decreased the expression of antioxidant enzymes in the brain, liver, or placenta of fetal mice. Timed, pregnant C57BL6/J mice were treated on gestational day 8 with intraperitoneal injection of alcohol (0.03 mL/g) or saline (control). Fetuses were harvested on gestational day 18. Fetal brain, liver, and placenta were analyzed for mRNA expression of superoxide dismutase, glutathione peroxidase, and catalase by real-time polymerase chain reaction, with 18S RNA used as reference. Superoxide dismutase, glutathione peroxidase, and catalase expression was lower in fetal brains exposed to alcohol with no differences detected in the liver or placenta between the 2 groups. Maternal alcohol consumption causes a decrease in superoxide dismutase, glutathione peroxidase, and catalase expression in the fetal brain. This may explain the long-term neurologic findings in fetal alcohol syndrome.


Milder forms of α-sarcoglicanopathies diagnosed in adulthood by NGS analysis.
Sarcoglycanopathies (LGMD 2C2F) are a subgroup of limb-girdle muscular dystrophies (LGMD), caused by mutations in sarcoglycan genes. They usually have a childhood onset and rapidly progressive course with loss of ability to walk over 12-16 years. Next generation sequencing (NGS) targeted gene panel was performed in three adult patients with progressive muscle weakness in which routine muscle histology and immunohistochemistry were not diagnostic. Genetic analysis revealed homozygous or compound heterozygous mutations in SGCA gene and Western Blot demonstrated protein reduction confirming the diagnosis of α-sarcoglicanopathy. Our cases evidence that the diagnosis of mild forms of alfa sarcoglicanopathy could be a challenge and suggest the possibility that they could be underdiagnosed. The use of Next generation Sequencing targeted gene panels is very helpful in the diagnosis of these patients.


Options for preserving fertility in women undergoing gonadotoxic treatment.
Cancer chemotherapy and radiotherapy can be toxic to the ovaries, but women can improve their chances of preserving their fertility. Three options are available: gonadotropin-releasing hormone (GnRH) analogues, oocyte cryopreservation, and ovarian tissue cryopreservation. A fourth option, ovarian transposition, is valid for patients undergoing pelvic radiation but is not useful in patients undergoing chemotherapy.


Application of morphological characteristics of radiofrequency lesions to individual parameters of thermal rhizolysis for trigeminal neuralgia.
Thermic rhizolysis is a reliable therapy for pharmaco-resistant trigeminal neuralgia (TN). Temperature, duration of electrocautery and needle location can influence the efficacy and complications of the therapy. We performed experimental thermocautery on egg white with increasing parameters of time (30-120 s) and temperature (60-95°C); we analysed the shape, size and volume of the thermic lesions produced. We developed a surgical procedure to assess peroperatively the probable thermocoagulation field and its geometric relations with the trigeminal roots and other anatomical structures of Meckel's cave, and we individually adapted the parameters of rhizolysis to optimize the results. This procedure was applied on 22 patients with TN. The volume of the lesions produced by rhizolysis on egg white had a spheroidal shape and increased linearly with the level of temperature and the time of electrocautery from 1.595 mm3 (SD 0.38) to 54.454 mm3 (SD 10.41); higher temperatures induced larger thermocoagulation fields than longer time periods. The calculated volumes measured at all levels of temperature and time were applied in vivo on the patient stereotactic planning during the thermocoagulation procedure in order to select the optimal parameters for rhizolysis. The median values used were 75°C (range 70-85°C) and 60 s (range 45-60 s). At 6-month follow-up, pain outcome was Barrow-Neurological-Institute class-I for 72.7%, IIIa for 22.7% and IIIb for 4.6%; the only complication due to rhizolysis was mild facial numbness in 13 subjects (59%) at 6-month follow-up. We conclude that geometric analysis of the position of the electrode before trigeminal thermocoagulation with morphometric-related individual adaptation of treatment parameters could avoid serious injuries and optimize pain control. We have adapted the technique of radiofrequency rhizolysis for TN. Our procedure allows individual peroperative adaptation of the parameters of thermocoagulation, according to the specific position of the electrode during rhizolysis. Preliminary results on a series of 22 patients have shown promising results.