Quantifying axon diameter and intra-cellular volume fraction in excised mouse spinal cord with q-space imaging.
Q-space magnetic resonance imaging (QSI) can quantify white matter (WM) axonal architecture at the cellular level non-destructively, unlike histology, but currently has several limitations. First, current methodology does not differentiate between diffusing molecules occupying extra- or intra-cellular spaces (ECS and ICS, respectively). Second, accurate assessment of axonal architecture requires high-gradient amplitudes not clinically available. Third, the only direct QSI marker of axonal architecture has been mean axon diameter (MAD), even though other direct markers would be valuable as well. The objective was to investigate three QSI-based methods that address the above limitations. Method 1 employs a two-compartment model to account for signal from ECS and ICS. Method 2 uses data only from low q-values thereby obviating the need for high-gradient amplitudes. Method 3 empirically estimates ICS volume fraction and provides an additional metric of axonal architecture. We implemented each method on data from excised healthy adult mouse spinal cords collected previously using a home-built 50T/m z-gradient yielding sub-micron displacement resolution. Through comparison with histology, each method was evaluated for accuracy in assessing axonal architecture. MAD measured with Methods 1 and 2 showed good correlation with histology (R(2)=0.99 (p<0.0001), and 0.77 (p<0.01), respectively) and Bland-Altman analysis indicates that measurements from the two methods are not significantly different from histology. The third method measured ICS volume fractions (0.64+/-0.07) that were highly correlated (R(2)=0.92, p<0.05) with measurements from histology (0.68+/-0.07). These methods may provide insight into axonal architecture in normal and abnormal WM tissue but additional validation with more samples will be needed.


Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons.
Listeria monocytogenes (L. monocytogenes) is a food-borne bacterial pathogen. Innate immunity to L. monocytogenes is profoundly affected by type I interferons (IFN-I). Here we investigated host metabolism in L. monocytogenes-infected mice and its potential control by IFN-I. Accordingly, we used animals lacking either the IFN-I receptor (IFNAR) or IRF9, a subunit of ISGF3, the master regulator of IFN-I-induced genes. Transcriptomes and metabolite profiles showed that L. monocytogenes infection induces metabolic rewiring of the liver. This affects various metabolic pathways including fatty acid (FA) metabolism and oxidative phosphorylation and is partially dependent on IFN-I signaling. Livers and macrophages from Ifnar1-/- mice employ increased glutaminolysis in an IRF9-independent manner, possibly to readjust TCA metabolite levels due to reduced FA oxidation. Moreover, FA oxidation inhibition provides protection from L. monocytogenes infection, explaining part of the protection of Irf9-/- and Ifnar1-/- mice. Our findings define a role of IFN-I in metabolic regulation during L. monocytogenes infection. Metabolic differences between Irf9-/- and Ifnar1-/- mice may underlie the different susceptibility of these mice against lethal infection with L. monocytogenes.


A longitudinal analysis of stress among incoming college freshmen.
The objectives of this study were to: (1) examine changes in stress during first semester among freshmen undergraduates and (2) identify predictors of stress (coping strategies, emotional states, and quality of sleep). One hundred ninety-seven freshmen students were recruited for a 10-week study during first quarter (October-December, 2015). Students completed weekly self-report surveys on stress, coping strategies, emotions, and quality of sleep. A generalized linear mixed model was used for analyses. Stress was elevated during examinations periods. Women reported a greater stress level than men. Increased stress level was significantly associated with lower sleep quality and greater negative emotions (fear, anger). Exercise was an effective stress coping strategy, while other coping methods (Internet usage, meditation, and self-isolation) were associated with higher stress. Social media usage did not influence stress level. Future stress management programs for freshmen need to consider gender differences and may focus on sleep, exercise, and decreased general Internet usage.


Azoospermia and segmentation abnormalities of the cervicothoracic spine ('MURCS in the male').
The MURCS association is traditionally regarded as a disorder limited to the female sex. It has been hypothesized that men displaying the combination of azoospermia, segmentation abnormalities of the cervicothoracic spine and renal anomalies may have a male analogue of MURCS. Here we describe a patient with non-obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this may represent another case of 'MURCS in the male'.


Solvothermal synthesis of TiO2nanospheres for non-volatile memory and synaptic learning applications.
In this study, we used the one-pot solvothermal method to synthesize the TiO2nanospheres (NSs) and used them for non-volatile memory and neuromorphic computing applications. Several analytical tools were used to understand the structural, optical, morphological, and compositional characteristics of synthesized TiO2NSs. The tetragonal crystal structure of anatase TiO2was formed, according to the Rietveld refined x-ray diffraction results. The NS morphology was confirmed by field emission scanning electron microscopy and transmission electron microscopy images. X-ray photoelectron spectroscopy was probed to understand the elemental composition and electronic states of the TiO2NSs. We specifically looked at the impact of reaction time on the structural, optical, morphological, compositional, and resistive switching (RS) properties of TiO2NSs. The fabricated devices (Ag/TiO2NSs/FTO) exhibit bipolar RS behavior. The optimized RS device shows good endurance (5000 cycles) and memory retention (5000 s) properties. Moreover, fabricated devices showed double-valued charge-flux characteristics, whereas charge transport was caused by the Ohmic and space charge-limited current mechanisms. Additionally, the optimized device can mimic various synaptic characteristics including potentiation-depression, excitatory post-synaptic current, and paired-pulse facilitation.


An experimental model of ischemia in rabbit hindlimb.
This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia.


Multiple bradykinin-related peptides from the skin of the frog, Rana temporaria.
The skin of the European common frog, Rana temporaria, contains a very high concentration of bradykinin (BK) but the mode of biosynthesis of the peptide is unknown. In addition to BK, we have isolated from an extract of R. temporaria skin the metabolites [des-Arg9]BK and [hydroxyprolyl3]BK. Peptides were also isolated that represent partially processed intermediates in the biosynthetic pathway to BK and comprise BK extended from its N-terminus by -Gly-Val-Ile-Pro-Leu-Leu and three peptides comprising BK extended from its C-terminus by -Ile-Ala, by -Ile-Ala-Pro-Ala-Ser-Thr-Leu, and by -Ile-Ala-Pro-Ala-Ser-Ile-Leu. The isolation of two C-terminally extended BK-containing peptides differing by a single amino substitution indicates that the biosynthetic precursor of frog skin BK may contain more than one copy of the BK sequence and/ or more than one gene encoding BK is expressed. The structures of the biosynthetic intermediates suggest that BK in frog skin is generated by the action of cellular endoproteinase(s) cleaving at the site of monobasic residues rather than by the action of the kallikrein-kinin system.


Ant allergy in Asia and Australia.
Anaphylaxis due to ant sting is increasingly being recognized as a significant problem. Severe allergic reactions to ants are well described in the south-eastern United States, but have only been recognized in recent years as being important in other parts of the world. There are many different ant species and their distribution around the world varies. The purpose of this review is to familiarize the reader with the epidemiology and clinical characteristics of ant allergy in Asia and Australia. In Korea, allergy to Pachycondyla chinensis (subfamily Ponerinae) has been well described. In an ant-endemic area, sensitization was 23%, with about 1% having anaphylactic reactions. There were at least eight IgE-binding proteins in P. chinensis venom, with 1 major allergen binding 85% of patient sera. P. chinensis venom was also found to be possibly crossreactive with bee venom, but not with imported-fire-ant venom. In Australia, anaphylactic reactions to ant stings are usually caused by the 'jack jumper' ant (Myrmecia pilosula) or the bull ant (Myrmecia pyriformis). A recent study showed promising results for immunotherapy with M. pilosula venom. There have been reports of stings by other ant species in Asia and Australia, but these reports are few and sporadic. The study of ant allergy in Asia is in its infancy. Clinicians in Asia need to be aware of ant stings as a cause of severe allergic reactions. Certain species that cause allergic reactions are unique to Asia and Australia and deserve further research. The allergens in the venom of the different ant species need to be identified. We should aim for improved understanding of the epidemiology of ant-sting anaphylaxis, formulation of better diagnostic tests and possibly the introduction of immunotherapeutic strategies.


Effect of cadmium on the growth of Chlorella vulgaris and Stichococcus bacillaris.
The growth of Chlorella vulgaris and Stichococcus bacillaris cultures in media containing from 20 to 100 mg Cd/l was studied. The examined strains were found to be highly resistant to the action of cadmium since the highest concentration of the metal used limited the production of dry weight (during 5 days of cultivation) by less than 50%. The lower production of chlorophyll a by S. bacillaris cultures in media containing from 60 to 100 mg Cd/l and 2-fold elongation of the cells point to lower tolerance of the strain to cadmium than that shown by C. vulgaris.


A Critical Review of Analytical Methods for Quantification of Cefotaxime.
Bacterial resistance to antibiotics is a growing phenomenon in the world. Considering the relevance of antimicrobials for population and the reduction in the registration of new antimicrobials by regulatory, proper quality control is required in order to minimize the spread of bacterial resistance and ensure the effectiveness of a treatment, as well as safety for the patient. Among the antimicrobials is cefotaxime, a drug belonging to third-generation cephalosporins, which is highly active against Gram-negative bactéria and is used to treat central nervous system infections such as meningitis and septicemia. Due to the critical importance of quality control in regard to drugs and pharmaceutical products, combined with bacterial resistance to antibiotics, this study aims to conduct a detailed review of analytical methods for cefotaxime. Using a critical review of literature, this paper describes the analytical methods published to quantify cefotaxime in different matrices; a large number of methods by HPLC and spectrophotometry were observed. Despite the advantages of the techniques, most methods reported have large environment and occupational impact, which enfatizes the need to adopt green procedures in quantifying cefotaxime.


Inhibition of transcription by bisPNA-peptide conjugates.
Homopyrimidine bisPNAs have been reported to arrest transcription elongation by invading double-stranded DNA and forming a stable (PNA)2/DNA complex. We previously reported that attachment of a designed cationic peptide to the bisPNA enhances the efficiency of strand invasion. Here we investigate whether conjugation to cationic peptides can also improve inhibition of transcription. We observe that a conjugate between a bisPNA and a peptide containing eight lysines is a superior agent for inhibition of transcription, but that inhibition of transcription is reduced as pH and the concentration of magnesium are increased. Our studies provide useful characterization of bisPNAs as agents for inhibiting transcription.


Analysis of recorded biomedical book and journal use in the Yale Medical Library. I. Date and subject relations.
Analysis of book and journal circulation is based on cancelled charge slips collected over a one-year period in the Yale Medical Library. About two-fifths of material circulated were monographs. Books and journals in seven subject fields provided over half of the circulation. Approximately two-thirds of both books and journals used had been published during the most recent nine years. A subject-by-subject examination of the ratio of books to journals circulating revealed that, in subjects where proportionally more journals than books were taken out of the Library, books were of more recent imprint dates than were journals, contrary to the overall pattern. Date distribution of books and journals by subject was also studied. Results are illustrated with graphs and tables.


Coat condition of ringtailed lemurs, Lemur catta, at Berenty Reserve, Madagascar: II. Coat and tail alopecia associated with Leucaena leucocepahala, 2001-2006.
Fur condition in wild ringtailed lemurs, Lemur catta, was recorded during September-November birth seasons 2001-2006 at Berenty Reserve, Madagascar. Body coat condition was scored on a scale from BS 0: full, smooth coat with guard hairs, to BS5: half or more of back and limbs hairless. Tail condition was scored from TS 0: full, to TS 5: half or more hairless. Where troop core areas included stands of Leucaena leucocephala, alopecia was dramatically more frequent than in similar areas without leucaena, including many animals with score BS5 or TS5, "bald lemur syndrome." Females' coats were worse than males', possibly related to female dominance and access to this preferred food. Tails in non-leucaena-feeding females tend to remain full, even if coats deteriorate, but with leucaena-feeding female tails are highly correlated with coat condition and equally bare. Coat and tail condition in L. catta reflected not only the dietary toxin but individual differences as well as differences between adjacent troops that may result from territorially mediated access to the environment. Leucaena contains the non-protein amino acid mimosine, a known cause of alopecia, wasting, and organ damage in livestock, although the effects are usually reversible. This is the first case of its effect in wildlife. Leucaena is an agroforestry tree introduced throughout the tropics. In high dietary concentrations leucaena might potentially affect any browsing mammal.


Fluorescent Image-Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real Time.
The inability to visualize cancer during prostatectomy contributes to positive margins, cancer recurrence, and surgical side effects. A molecularly targeted fluorescent probe offers the potential for real-time intraoperative imaging. The goal of this study was to develop a probe for image-guided prostate cancer surgery. An antibody fragment (cys-diabody, cDb) against prostate stem cell antigen (PSCA) was conjugated to a far-red fluorophore, Cy5. The integrity and binding of the probe to PSCA was confirmed by gel electrophoresis, size exclusion, and flow cytometry, respectively. Subcutaneous models of PSCA-expressing xenografts were used to assess the biodistribution and in vivo kinetics, whereas an invasive intramuscular model was utilized to explore the performance of Cy5-cDb-mediated fluorescence guidance in representative surgical scenarios. Finally, a prospective, randomized study comparing surgical resection with and without fluorescent guidance was performed to determine whether this probe could reduce the incidence of positive margins. Cy5-cDb demonstrated excellent purity, stability, and specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 6 hours. In mice carrying PSCA(+) and negative (-) dual xenografts, the mean fluorescence ratio of PSCA(+/-) tumors was 4.4:1. In surgical resection experiments, residual tumors <1 mm that were missed on white light surgery were identified and resected using fluorescence guidance, which reduced the incidence of positive surgical margins (0/8) compared with white light surgery alone (7/7). Fluorescently labeled cDb enables real-time in vivo imaging of prostate cancer xenografts in mice, and facilitates more complete tumor removal than conventional white light surgery alone.


The CAREFALL Triage instrument identifying risk factors for recurrent falls in elderly patients.
To validate the CAREFALL Triage Instrument (CTI), a self-administered questionnaire concerning modifiable risk factors for recurrent falls in elderly patients who experienced fall. This study in patients 65 years or older who experienced fall was performed at the accident and emergency department of a tertiary university hospital in the Netherlands. The construct validity was determined in 200 patients and 100 matched controls. The test-retest reliability was determined in 27 patients who answered the CTI twice. The clinical validity was determined in 111 high-risk patients who visited the Fall Prevention Clinic (FPC). The risk factors were as follows: medication, balance and mobility, fear of falling, orthostatic hypotension, mood, high risk of osteoporosis, impaired vision, and urinary incontinence. Construct Validity Recurrent falls correlated with more risk factors. Age, female gender, and 6 risk factors correlated with recurrent falls. Clinical validity: the agreement between the CTI and FPC was fair for balance and mobility, orthostatic hypotension, and urinary incontinence, moderate for mood, fear of falling, and high risk of osteoporosis, and substantial for "medication and impaired vision. Test-retest reliability: the agreement between the 2 CTIs was substantial for medication, high risk of osteoporosis, moderate for balance and mobility, mood, fair for orthostatic hypotension, impaired vision, and urinary incontinence, and poor for fear of falling. The CTI is reliable and valid in assessing risk factors for recurrent falls in elderly patients who experienced fall.


The mouse antibody response to Trichinella spiralis defines a single, immunodominant epitope shared by multiple antigens.
Immunoblot analysis was used to characterize the Trichinella spiralis L1 larval Ag recognized by antisera from T. spiralis-infected AKR/J mice. Antisera were analyzed for reactivity with crude worm extract, excretory/secretory proteins and cuticle proteins from L1 larvae. The response was biphasic; antibodies against one set of Ag were detected 13 days after infection (group I Ag), and antibodies against a different set of Ag were detected 35 days after infection (group II Ag). Excretory/secretory and cuticle proteins were recognized only by antibodies produced late in infection. The predominant isotype in day 42 antiserum was IgG1, and 80% of these IgG1 antibodies reacted with a stage-specific determinant shared by virtually all group II Ag. A mAb reactive with the shared determinant was used to purify the group II Ag from L1 larval extract. Such affinity-purified Ag were protective when used to immunize mice against subsequent infection, and T cells from infected mice proliferated when cultured with these Ag in vitro. Other mouse strains also made a strong serum antibody response to the group II Ag. We hypothesize that immune responses to the shared epitope play an important role in determining the outcome of the host-parasite interaction during infection.


Stone's views of 25 years ago have now shifted incrementally.
Twenty-five years ago, a major article by Professor Alan Stone on ethics in forensic psychiatry was published. It caused reverberations on a national scale. After the seismic shocks that he had provoked settled down, several thoughtful forensic psychiatrists set out to take serious stock of his critique and to articulate ways in which corrective actions could be taken. Indeed, slightly more than a decade later, I critiqued Stone's ideas in my Presidential Address to the Annual Meeting of the American Academy of Psychiatry and the Law. It is a unique privilege now to evaluate what Stone currently says about ethics in forensic psychiatry. While his present positions are slightly different from his arguments of 25 years ago, Stone still holds dearly to his ivory tower, which remains almost impermeable to the voices of those working in the trenches.


Guarana: Paullinia cupana, P. sorbilis; also known as Brazilian cocoa and 'zoom'.
The main constituent of guarana is caffeine, with smaller quantities of theophylline and theobromine. There is no evidence that the berries or extracts contain anything else that is therapeutically useful.Guarana is associated with many therapeutic properties, but there is no evidence to support these other than effects that can be attributed to caffeine. Guarana is widely available in herbal products and energy drinks. Excessive intake can cause the same effects as too much caffeine. It is not widely recognised that guarana has a high caffeine content and the labelling on some products is misleading.Although not specifically studied, guarana would be expected to exhibit the same range of adverse effects and drug interactions as those associated with caffeine.


Metabolic acidosis and renal tubular injury due to pure toluene inhalation.
A 22-y-old woman was hospitalized for muscle weakness of her lower extremities after she sniffed approximately 6 l of pure toluene during the month prior to admission. The examinations on serum and urine revealed mixed hyperchloremic and high anion gap metabolic acidosis accompanied by impaired urinary acidification. Histopathological changes of the kidney were patchy areas of tubular injury. Acidosis normalized on the fourth day of admission, but both proximal and distal tubular dysfunction persisted. These findings indicate that toluene is a tubular toxin and may contribute to the development of distal renal tubular acidosis.


Restoration of E-cadherin cell-cell junctions requires both expression of E-cadherin and suppression of ERK MAP kinase activation in Ras-transformed breast epithelial cells.
E-cadherin is a main component of the cell-cell adhesion junctions that play a principal role in maintaining normal breast epithelial cell morphology. Breast and other cancers that have up-regulated activity of Ras are often found to have down-regulated or mislocalized E-cadherin expression. Disruption of E-cadherin junctions and consequent gain of cell motility contribute to the process known as epithelial-to-mesenchymal transition (EMT). Enforced expression of E-cadherin or inhibition of Ras-signal transduction pathway has been shown to be effective in causing reversion of EMT in several oncogene-transformed and cancer-derived cell lines. In this study, we investigated MCF10A human breast epithelial cells and derivatives that were transformed with either activated H-Ras or N-Ras to test for the reversion of EMT by inhibition of Ras-driven signaling pathways. Our results demonstrated that inhibition of mitogen-activated protein kinase (MAPK) kinase, but not PI3-kinase, Rac, or myosin light chain kinase, was able to completely restore E-cadherin cell-cell junctions and epithelial morphology in cell lines with moderate H-Ras expression. In MCF10A cells transformed by a high-level expression of activated H-Ras or N-Ras, restoration of E-cadherin junction required both the enforced reexpression of E-cadherin and suppression of MAPK kinase. Enforced expression of E-cadherin alone did not induce reversion from the mesenchymal phenotype. Our results suggest that Ras transformation has at least two independent actions to disrupt E-cadherin junctions, with effects to cause both mislocalization of E-cadherin away from the cell surface and profound decrease in the expression of E-cadherin.


[Construction of wild-type and mutant SPAST vectors for the study of molecular mechanism of hereditary spastic paraplegia].
To construct wild-type and mutant pEGFP SPAST vectors and to explore the molecular mechanism of hereditary spastic paraplegia. Mutant SPAST vector was constructed using overlap PCR method following construction of wild-type SPAST vector. Wild-type and mutant constructs were transfected to COS7 cells and subcellular localization of spastin was observed. Co-localizations of spastin and microtubule, spastin and mitochondria were viewed by immunofluorescence staining. Wild-type spastin is localized in plasma, and mutant spastin did not change its cellular localization. Wild-type and mutant spastins did not co-localize with microtubules and mitochondria by immunofluorescence analysis. Wild-type and mutant SPAST constructs were successfully generated. Mutant spastin did not change its localization in cells. Spastin does not co-localize with microtubules and mitochondria. This study may facilitate further studies on molecular mechanism of hereditary spastic paraplegia.


Comprehensive genomic analysis of a BRCA2 deficient human pancreatic cancer.
Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function.


Human helper T cell factor(s) (ThF). I. Partial purification and characterization.
T cells obtained from pleural effusion of patients with tuberculous pleurisy were stimulated in vitro with PPD. The culture supernatant was shown to be substituted for T cells in PWM-induced IgG production by human B cells. As many as 0.5 to 3 x 10(9) lymphocytes were obtained from 1 patient, and about 85% of them were E-rosette positive, making it possible to purify human helper T cell factor(s) (ThF). Helper activity was sensitive to heating at 70 degrees C for 5 min and treatment with trypsin. ThF did not have conventional Ig determinants and was recovered in the 50 to 67% ammonium sulfate fraction. The purification was done by successive DEAE-Sephadex and CM-Sephadex ion-exchange chromatography, Sephadex G-100 gel filtration, and isoelectric focusing. It was shown that ThF activity was eluted by gel filtration in the fraction with a m.w. of about 20,000. Isoelectric focusing of this fraction revealed that ThF activity distributed in the pl range of 6.5 to 8.0, whereas TCGF activity was focused in a single peak at pI of 6.5, indicating the existence of a helper factor without TCGF activity.


Dynamic Control of Intramolecular Rotation by Tuning the Surrounding Two-Dimensional Matrix Field.
The intramolecular rotation of 4-farnesyloxyphenyl-4,4-difluoro-4-bora-3a,4a-diaza- s-indacene (BODIPY-ISO) was controlled by tuning its local physical environment within a mixed self-assembled monolayer at an air-water interface. Intramolecular rotation was investigated by considering the twisted intramolecular charge transfer (TICT) fluorescence of BODIPY-ISO, which increases in intensity with increasing viscosity of the medium. In situ fluorescence spectroscopy was performed on mixed monolayers of BODIPY-ISO with several different lipids at the air-water interface during in-plane compression of the monolayers. Depending on the identity of the lipid used, the fluorescence of the mixed monolayers could be enhanced by mechanical compression, indicating that the rotation of BODIPY-ISO can be controlled dynamically in mixtures with lipids dispersed at the air-water interface. Taken together, our findings provide insight into strategies for controlling the dynamic behavior of molecular machines involving mechanical stimuli at interfaces.


Treatment and control of scabies.
The treatment of individual patients with scabies and its control in institutional and community settings remains challenging, with relatively few treatment choices available. In this review, evidence of the efficacy of available treatments will be discussed, and possible emerging drug resistance and new therapeutic directions outlined. Although there has been attention on the use of ivermectin for the treatment of ordinary scabies and for mass drug administration, evidence supporting its superiority for both indications over alternative treatment is inconclusive. This is particularly true in light of several case reports of drug resistance in human and veterinary settings when the drug has been intensively used. When used correctly, topical agents such as permethrin and benzyl benzoate are effective. Little research on the development of new and more effective acaricides suitable for human use is underway. While the in-vitro acaricidal properties of several natural products have been documented, these are yet to be evaluated in animal studies or clinical trials. When properly administered, chemotherapy for scabies remains effective in most situations. However, with reports of drug resistance increasing and with the need for therapies suitable for use in interventions to control community outbreaks, there is a need to develop new therapies.


Critical traumatic brain injury is associated with worse coagulopathy.
As thromboelastography (TEG) becomes the standard of care in patients with hemorrhagic shock (HS), an association between concomitant traumatic brain injury (TBI) and coagulopathy by TEG parameters is not well understood and is thus investigated. Retrospective analysis of trauma registry data at a single level 1 trauma center of 772 patients admitted with head Abbreviated Injury Scale (AIS) score of 3 and TEG studies between 2014 and 2017. Patients were stratified to moderate-severe TBI by head AIS scores of 3 and 4 (435 patients) and critical TBI by head AIS score of 5 (328 patients). Hemorrhagic shock was defined by base deficit of 4 or shock index of 0.9. Statistical analysis with unpaired t tests compared patients with critical TBI with patients with moderate-severe TBI, and patients were grouped by presence or absence of HS. A comparison of TBI data with conventional coagulation studies was also evaluated. In the setting of HS, critical TBI versus moderate-severe TBI was associated with longer R time (p = 0.004), longer K time (p < 0.05), less acute angle (p = 0.001), and lower clot strength and stability (maximum amplitude [MA]) (p = 0.01). Worse TBI did not correlate with increased fibrinolysis by clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (p = 0.3). Prothrombin time and international normalized ratio failed to demonstrate more severe coagulopathy, while partial thromboplastin time was found to correlate with severity of TBI (p = 0.01). In patients with critical TBI, the presence of HS correlated with a statistically significant worsening of all parameters (p < 0.05) except for clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (LY-30). Thromboelastography demonstrates that, with and without hemorrhagic shock, critical TBI correlates with a significant worsening of traumatic coagulopathy in comparison with moderate/severe TBI. In HS, critical TBI correlates with impaired clot initiation, impaired clot kinetics, and impaired platelet-associated clot strength and stability versus parameters found in moderate-severe TBI. Hemorrhagic shock correlates with worse traumatic coagulopathy in all evaluated patient groups with TBI. Conventional coagulation studies underestimate TBI-associated coagulopathy. Traumatic brain injury-associated coagulopathy is not associated with fibrinolysis. Prognostic/epidemiological, level IV; prognostic/epidemiological, level III.


Chronic Chagas' disease: possible mechanism of sinus bradycardia.
To determine the cause of sinus bradycardia in patients with chronic Chagas' disease by studying their sinus node function with pharmacological agents. Cohort study. Referral tertiary care hospital in Cordoba, Argentina. Thirty-seven chagasic patients (19 females and 18 males, mean age 41 +/- 12 years) were divided into three groups: group 1, 14 patients with positive serology for Chagas' disease but no evidence of cardiac involvement; group 2, 14 patients with Chagas' disease and electrocardiographic abnormalities but without signs or symptoms of congestive heart failure or cardiomegaly; and group 3, nine patients with Chagas' disease and evidence of cardiomegaly and congestive heart failure. Six healthy volunteers with no evidence of heart disease were used as controls. All subjects received 0.04 mg/kg intravenous atropine sulphate followed 3 mins later by 0.2 mg/kg intravenous propranolol slowly injected. The resultant heart rate obtained with this total autonomic blockade (TAB) was considered to be the intrinsic heart rate observed (IHRo). The mean increase of heart rate after atropine was +68 beats/min in controls, +45 beats/min in group 1, +45 beats/min in group 2 and +32 beats/min in group 3. The change from the basal heart rate to the IHRo after TAB with atropine and propranolol was +29 beats/min in controls, +17 beats/min in group 1, +17 beats/min in group 2 and +5 beats/min in group 3. The observed response to atropine in patients with Chagas' disease suggests abnormality in the innervation of the sinus node. The difference found in the IHRo after TAB indicates involvement of the automaticity of the sinus node. These findings may explain the bradycardia reported in this disease.


Performance of a Breast Cancer Detection AI Algorithm Using the Personal Performance in Mammographic Screening Scheme.
Background The Personal Performance in Mammographic Screening (PERFORMS) scheme is used to assess reader performance. Whether this scheme can assess the performance of artificial intelligence (AI) algorithms is unknown. Purpose To compare the performance of human readers and a commercially available AI algorithm interpreting PERFORMS test sets. Materials and Methods In this retrospective study, two PERFORMS test sets, each consisting of 60 challenging cases, were evaluated by human readers between May 2018 and March 2021 and were evaluated by an AI algorithm in 2022. AI considered each breast separately, assigning a suspicion of malignancy score to features detected. Performance was assessed using the highest score per breast. Performance metrics, including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), were calculated for AI and humans. The study was powered to detect a medium-sized effect (odds ratio, 3.5 or 0.29) for sensitivity. Results A total of 552 human readers interpreted both PERFORMS test sets, consisting of 161 normal breasts, 70 malignant breasts, and nine benign breasts. No difference was observed at the breast level between the AUC for AI and the AUC for human readers (0.93% and 0.88%, respectively; P = .15). When using the developer's suggested recall score threshold, no difference was observed for AI versus human reader sensitivity (84% and 90%, respectively; P = .34), but the specificity of AI was higher (89%) than that of the human readers (76%, P = .003). However, it was not possible to demonstrate equivalence due to the size of the test sets. When using recall thresholds to match mean human reader performance (90% sensitivity, 76% specificity), AI showed no differences inperformance, with a sensitivity of 91% (P =. 73) and a specificity of 77% (P = .85). Conclusion Diagnostic performance of AI was comparable with that of the average human reader when evaluating cases from two enriched test sets from the PERFORMS scheme. © RSNA, 2023 See also the editorial by Philpotts in this issue.


[Current status of extracorporeal shock wave lithotripsy in urinary lithiasis.]
Over the last decade, urinary lithiasis' prevalence has dramatically increased due to diet and lifestyle changes, growing 10.6% and 7.1% in men and women respectively. Extracorporeal shock wave lithotripsy has lost relevance in current practice due to endoscopic device development and unpredictability of results. Instrument miniaturization is leading to an increase of the percutaneous approach of increasingly smaller stones, while most flexible ureteroscopes durability and digitalization has allowed urologists to address larger stones. So that, decision algorithm is now impossible to define, but what is clear is that ESWL has declined worldwide. Can it disappear as a urinary lithiasis treatment modality? If we don't improve appropriate candidate selection and optimize disintegration efficiency, guidelines are going to replace the more "boring" ESWL by popular and more attractive endoscopes. Shock wave technology has evolved in the last two decades, however lithotripsy fundamental principle has not changed. ESWL has passed the test of time and centers dedicated to stone treatment should have a lithotripter in order to offer an appropriate balance in different options for different clinical situations. New developments will be focused on improvements in location (in-line navigation systems; Vision track system) and automatic ultrasound location on a robotic arm; monitoring and stone fixation, implementation of different focal sizes with new acoustic lenses, multitask working stations that allow endourological approach, coupling control (avoiding microbubbles) and low cost devices for different applications. On the other hand, optimizing outcomes by: slower pulse rates, ramping strategies and patient selection with soft stones, short stone-skin distance, low BMI and favorable collecting system anatomy, allow us to achieve better outcomes in shock wave treatments. SWL still represents a unique non invasive method of stone disease treatment with no anesthesia and low complication rates; and a high proportion of stones could still be treated with shock waves and remains among patient's first options. This update objective has been to review the evolution, identify shock wave new developments and clarify their impact on our daily practice in urinary stones treatment.


In vitro assessment of anti-proliferative effect induced by α-mangostin from Cratoxylum arborescens on HeLa cells.
Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing.


A Predictive Model to Classify Undifferentiated Fever Cases Based on Twenty-Four-Hour Continuous Tympanic Temperature Recording.
Diagnosis of undifferentiated fever is a major challenging task to the physician which often remains undiagnosed and delays the treatment. The aim of the study was to record and analyze a 24-hour continuous tympanic temperature and evaluate its utility in the diagnosis of undifferentiated fevers. This was an observational study conducted in the Kasturba Medical College and Hospitals, Mangaluru, India. A total of ninety-six (n = 96) patients were presented with undifferentiated fever. Their tympanic temperature was recorded continuously for 24 hours. Temperature data were preprocessed and various signal characteristic features were extracted and trained in classification machine learning algorithms using MATLAB software. The quadratic support vector machine algorithm yielded an overall accuracy of 71.9% in differentiating the fevers into four major categories, namely, tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases. The area under ROC curve for tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases was found to be 0.961, 0.801, 0.815, and 0.818, respectively. Good agreement was observed [kappa = 0.618 (p < 0.001, 95% CI (0.498-0.737))] between the actual diagnosis of cases and the quadratic support vector machine learning algorithm. The 24-hour continuous tympanic temperature recording with supervised machine learning algorithm appears to be a promising noninvasive and reliable diagnostic tool.


Reactive lymphoid hyperplasia one month after LASIK surgery.
To describe a case of reactive lymphoid hyperplasia following laser assisted in situ keratomileusis (LASIK). This observational case report describes a 31-year-old man who underwent LASIK and presented 1 month later with a fleshy, conjunctival (plical) tumour in the left eye. An excisional biopsy of the tumour was performed. Histopathology of the excised tumour revealed reactive lymphoid hyperplasia involving the left conjunctiva. Conjunctival lymphomas can masquerade as chronic conjunctivitis and can be preceded by reactive lymphoid hyperplasia. It is important to identify and differentiate these tumours. This report describes the unusual occurrence of a lymphoid conjunctival tumour after LASIK eye surgery.


Mycological aspects of gastrointestinal microflora.
There are two aspects about the presence of Candida in the human orointestinal tract: (i) it is a part of normal human flora and (ii) it is a risk factor for immunocompromised patients. The orointestinal tract can be considered a reservoir for Candida species, several of which are from the oral cavity, stomach, duodenal juice and faeces. Their germ counts in normal small and large bowel do not exceed 10(4) cfu/ml resp.g. The input of Candida to a well-developed faecal flora system under continuous flow culture conditions did not lead to a multiplication of the yeast. The take in of faecal flora into a Candida continuous flow culture diminish Candida germ counts. If, however, the faecal flora was destroyed, e.g. by antibiotics, we found the yeasts multiplying, with the formation of germ tubes and mycelial structures. Colonization by Candida has to be seen as a starting-point of the development of subsequent candidosis in immunosuppressed or intensive care patients. The best protection against Candida colonization in the gut is the existence of a normal bacterial flora. Lactulose, which promotes the Gram-positive potential of faecal flora, may protect indirectly by supporting the indigenous flora.


Forming Quality Analysis on the Cold Roll Forming C-channel Steel.
Cold roll forming, as a metal plastic forming process, is still mainly used in industrial production by the trial-and-error method, which wastes a lot of time and materials. In this paper, the C-channel steel is taken as the research object. First, the empirical equations of forming passes are verified and analyzed, then the cold roll forming model of C-channel steel is established, the forming quality of each pass and the stress-strain distribution of the whole sheet metal are analyzed, and the validity of the model is verified by experiments. The residual stresses of the web zone and flange of the finished product were measured. The results show that the empirical formulas are still not universal and the forming quality of the bite zone is poor. It needs to be adjusted by improving the distribution of deformation. The external surface of the C-channel steel is undertensile stress, while the internal surface is undercompressive stress, and the residual stresses of the flange are far greater than those of the web zone. The research provides a reference for the design of the bite zone and the number of forming passes.


Impact of endoscopic ultrasonography (EUS) on surgical decision-making in upper gastrointestinal tract cancer: an international multicenter study.
Endoscopic ultrasonography (EUS) is an integrated part of the pretherapeutic evaluation program for patients with upper gastrointestinal (GI) tract cancer. Whether the clinical impact of EUS differs between surgeons from different countries is unknown. The same applies to the potential clinical influence of EUS misinterpretations. The aim of this study was to evaluate the interobserver agreement on predefined treatment strategies between surgeons from four different countries, with and without EUS, and to evaluate the clinical consequences of EUS misinterpretations. One hundred patients with upper GI tract cancer were randomly selected from all upper GI tract cancer patients treated at Odense University Hospital between 1997 and 2000. Based on patient records and EUS database results, a case story was created with and without the EUS result for each patient. Four surgeons were asked to select the relevant treatment strategy in each case, at first without knowledge of the EUS and thereafter with the EUS result available. Interobserver agreement and impact of EUS misinterpretations were evaluated using the actual final treatment of each patient as reference. Three of four or all four surgeons agreed on the same treatment strategy for nearly 60% of the patients with and without the EUS results. Treatment decisions were changed in 34% based on the EUS results, and the majority of these changes were toward nonsurgical and palliative treatments (85%). Interobserver agreement was relatively low, but overall EUS increased kappa values from 0.16 ("poor") to 0.33 ("fair"), thus indicating increased overall agreement after the EUS results were available. EUS conclusion regarding stage or resectability was wrong in 17% of the cases, but only one serious event would have been the clinical result of EUS misinterpretations. Despite being used in different ways by different surgeons, EUS did change patient management in one third of the cases. The impact of EUS misinterpretations seemed very low, and this study confirmed one of the strongest clinical possibilities of EUS, i.e., the ability to detect nonresectable cases. EUS is an important imaging modality for oncosurgeons from different countries.


What questions can large, simple trials answer?
Large, simple trials can provide reliable evidence on the balance of risk and benefit of widely practicable treatments that have moderate effects on major clinical outcomes. Treatments for stroke will potentially be used extensively world-wide. Each year about 8,000,000 people have an acute stroke, with about 5,000,000 being ischaemic. Of these, perhaps 1,000,000 receive medical attention within the first few hours of stroke onset. If reliable decisions about the treatment of such large numbers of patients are to be made, we need to be certain about the effects of treatment on death from any cause (and on other important outcomes) and in many different types of patient. Generally, such reliable evidence on whether to treat and on whom to treat, will only come from large, randomised trials recruiting many thousands of patients. Such trials are only feasible and affordable if they are simple.


How long is your arm? Using multisensory illusions to modify body image from the third person perspective.
Updating body representations from the 3rd person perspectives (3PP) seems to require viewing the real body, unlike when viewing from a 1st person perspective. Here, 3PP updating was investigated through induction of a physically impossible multisensory illusion in which participants viewed real-time 3PP video of themselves having their arm pulled until it stretched to twice its normal length. The illusion elicited the subjective experience that the participant's own arm had been stretched and caused an overestimation of reaching distance, although actual reaches were unaffected. Multisensory illusions from the 3PP can alter body image when applied to real bodies.


"A ubiquitous sex difference in dreams" revisited.
Males dream more often of males than females do. This sex difference was found in 29 comparisons of male and female dreams. It holds for children, adolescents, college students, and adults in all parts of the world; and for dreams collected in the laboratory, as well as dreams reported under nonlaboratory conditions. Various explanations for this ubiquitous sex difference are discussed.


Myocardial mechanics in aortic and mitral valvular regurgitation: the concept of instantaneous impedance as a determinant of the performance of the intact heart.
The effects on myocardial mechanics of acute, artificial aortic and mitral regurgitation were studied in the dog to determine the manner in which the changes in load induced by valvular regurgitation alter ventricular performance. With mitral and aortic regurgitant volumes of approximately the same magnitude as the forward stroke volume, immediate increases occurred in total stroke volume, left ventricular enddiastolic pressure, and peak ejection velocity, whereas contractility remained unchanged. Although calculated myocardial fiber tension rose, the rate of decline of tension during ejection was accelerated with regurgitation due to the more rapid decrease in ventricular size. Average tension therefore decreased relative to average pressure. As a consequence of the increased fiber length and this unloading, contractile element velocity, work, and power were increased. Despite unchanged contractility of the myocardium, the ejection fraction rose with both aortic and mitral regurgitation.When regurgitant beats were compared with control beats at a constant end-diastolic volume, ventricular stroke volume, work, power, and ejection fraction, as well as contractile element velocity, work, and power consistently increased. Thus, reduction of instantaneous impedance to ejection allowed the ventricle to empty further, reducing ventricular wall tension with a resultant increase in the velocity of shortening. External energy output was increased despite unchanged contractility and diastolic fiber length. It is concluded that the impedance to ejection and myocardial fiber tension during ejection govern the velocity and extent of contractile element shortening, and hence affect stroke volume, peak aortic flow rate, and ejection fraction. The alterations of ventricular function accompanying valvular regurgitation can be explained by an evaluation of the effects of these lesions on the instantaneous impedance to left ventricular ejection.


Alteration of tissue disposition of cadmium by chelating agents.
The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. The effects of increasing the time interval between Cd administration and initiation of chelation therapy was determined by using a single administration of DTPA, EDTA, and DMSA. Mice treated immediately after Cd administration excreted approximately 50% of the administered dose of Cd compared to 0.2% in controls. Treatment with chelator at later times significantly increased Cd excretion but the magnitude of the effect was much less than that seen in mice treated immediately after Cd. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal.


Formation of flower- or cake-shaped stereocomplex particles from the stereo multiblock copoly(rac-lactide)s.
Flower- or cake-shaped particles with uniform particle size ranging from nanometers to micrometers were prepared from the stereo multiblock copoly(rac-lactide)s (smb-PLAs) by precipitating the polymer from its solution in methylene chloride/ethanol via three different methods: slowly lowering the solution temperature, slowly evaporating the solvent, and slowly adding a nonsolvent. Under the same condition, sheet-shaped crystals in 10 mum size but not particles were obtained from the pure PLLA with almost the same molecular weight. Electron diffraction and WAXD data demonstrated that the stereocomplex particles belonged to the monoclinic system. All three methods resulted in particles with identical morphology and almost the same particle size. At a given stereoregularity of 88%, as the molecular weight of the polymer increased from 8700 to 23,200 Da, the crystallinity decreased, the particle morphology changed from flower-shaped to cake-shaped, and the diameter and height of the particles increased from 0.8 and 0.45 to 3.6 microm and 2.0 microm, respectively. The initial concentration of the polymer solution influenced the particle size slightly but affected the morphology markedly. On the basis of the above experimental observations, it was proposed that the smb-PLA particles of flower- or cake-shape were formed in four steps: (1) complexation in solution of the smb-PLA chains; (2) particle nucleation; (3) particle growth in the width direction; and (4) particle growth in the height direction. The curvature of the paired smb-PLA chains and the inner stress governed the particle size, and the interconnection between the neighboring particles determined the layered structure and the package density of the particles formed.


From the tetra(amino) phosphonium cation, [P(NHPh)4]+, to the tetra(imino) phosphate trianion, [P(NPh)4]3-, two-faced ligands that bind anions and cations.
The tetraanilino phosphonium cation, [P(N(H)Ph)4]+, 1+, is sequentially deprotonated by Bu(n)Li in thf. The deprotonation reaction of the chloride derivative, Cl, was monitored by (31)P NMR, which revealed the successive formation of the neutral [P(N(H)Ph)3(NPh)], 2, the monoanionic [P(N(H)Ph)2(NPh)2]-, 3-, the dianionic [P(N(H)Ph)(NPh)3]2-, 4(2-), and finally the trianionic species [P(NPh)(4)](3-), (3-). Considering the isoelectronic relationship of oxo, =O, and imino groups, =NR, as well as hydroxy, -OH, and amino groups, -N(H)R, the neutral complex corresponds to phosphoric acid, H3PO4, whereas the anions 3-, 4(2-) and 5(3-) are analogues of dihydrogen phosphate, H2PO4-, monohydrogenphosphate, HPO4(2-), and orthophosphate ions, PO4(3-), respectively. Solid state structures were obtained of 1Cl, 2LiCl(thf)(2), 3Li(thf)(3.5), 3Li(2)Cl(thf)(4.25), 3Li(2)Cl(thf)(6) and 5Li(4)Cl(thf)(4). All systems provide two separate N-P-N chelation sites at opposite ligand faces, either consisting of the di(amino) arrangement P(NH)(2), acting as a double H-bond donor, the di(imino) arrangement PN(2), donating two electron pairs, or the mixed amino imino arrangement P(N)(NH), which supplies both electron pair and H-donor site. Interesting in this aspect is the mixed amino imino derivative 3- which has the ability to chelate a Lewis acid, such as a metal ion, at one face and a Lewis base, such as an anionic or neutral donor at the opposite ligand face. The formation of 1-D aggregates and the entrapment of lithium chloride are key characteristics of the supramolecular structures of the discussed complexes.


Neuroendocrine control in social relationships in non-human primates: Field based evidence.
Primates maintain a variety of social relationships and these can have fitness consequences. Research has established that different types of social relationships are unpinned by different or interacting hormonal systems, for example, the neuropeptide oxytocin influences social bonding, the steroid hormone testosterone influences dominance relationships, and paternal care is characterized by high oxytocin and low testosterone. Although the oxytocinergic system influences social bonding, it can support different types of social bonds in different species, whether pair bonds, parent-offspring bonds or friendships. It seems that selection processes shape social and mating systems and their interactions with neuroendocrine pathways. Within species, there are individual differences in the development of the neuroendocrine system: the social environment individuals are exposed to during ontogeny alters their neuroendocrine and socio-cognitive development, and later, their social interactions as adults. Within individuals, neuroendocrine systems can also have short-term effects, impacting on social interactions, such as those during hunting, intergroup encounters or food sharing, or the likelihood of cooperating, winning or losing. To understand these highly dynamic processes, extending research beyond animals in laboratory settings to wild animals living within their natural social and ecological setting may bring insights that are otherwise unreachable. Field endocrinology with neuropeptides is still emerging. We review the current status of this research, informed by laboratory studies, and identify questions particularly suited to future field studies. We focus on primate social relationships, specifically social bonds (mother-offspring, father-offspring, cooperative breeders, pair bonds and adult platonic friendships), dominance, cooperation and in-group/out-group relationships, and examine evidence with respect to the 'tend and defend' hypothesis.


Primary immunization of infants with an acellular pertussis vaccine in a double-blind randomized clinical trial.
The rate of adverse reactions and the immunogenicity of a two-component acellular pertussis vaccine as compared with a plain whole-cell vaccine and a placebo were evaluated for primary immunization in 319 6-month-old infants in a double-blind randomized clinical trial. The acellular vaccine produced few and mild systemic and local reactions. Fever (greater than or equal to 38 degrees C) occurred in 6% to 8% of acellular vaccinees as opposed to 25% to 37% of whole-cell vaccinees. Redness (greater than or equal to 1 cm) appeared in 2% to 13% of the acellular vaccine and 24% to 32% of the whole-cell vaccine recipients. Antibody response to pertussis toxin measured in a neutralization test was obtained in 97% to 100% of the infants receiving either two or three doses of the acellular vaccine as compared to 59% after three doses of whole-cell vaccine.


The RhHB1/RhLOX4 module affects the dehydration tolerance of rose flowers (Rosa hybrida) by fine-tuning jasmonic acid levels.
Phytohormones are key factors in plant responsiveness to abiotic and biotic stresses, and maintaining hormone homeostasis is critically important during stress responses. Cut rose (Rosa hybrida) flowers experience dehydration stress during postharvest handling, and jasmonic acid (JA) levels change as a result of this stress. However, how JA is involved in dehydration tolerance remains unclear. We investigated the functions of the JA- and dehydration-induced RhHB1 gene, which encodes a homeodomain-leucine zipper I γ-clade transcription factor, in rose flowers. Silencing RhHB1 decreased petal dehydration tolerance and resulted in a persistent increase in JA-Ile content and reduced dehydration tolerance. An elevated JA-Ile level had a detrimental effect on rose petal dehydration tolerance. RhHB1 was shown to lower the transient induction of JA-Ile accumulation in response to dehydration. In addition to transcriptomic data, we obtained evidence that RhHB1 suppresses the expression of the lipoxygenase 4 (RhLOX4) gene by directly binding to its promoter both in vivo and in vitro. We propose that increased JA-Ile levels weaken the capacity for osmotic adjustment in petal cells, resulting in reduced dehydration tolerance. In conclusion, a JA feedback loop mediated by an RhHB1/RhLOX4 regulatory module provides dehydration tolerance by fine-tuning bioactive JA levels in dehydrated flowers.


Rapid Isolation of Staphylococcus aureus Pathogens from Infected Clinical Samples Using Magnetic Beads Coated with Fc-Mannose Binding Lectin.
Here we describe how Staphylococcus aureus bacteria can be rapidly isolated from clinical samples of articular fluid and synovial tissue using magnetic beads coated with the engineered chimeric human opsonin protein, Fc-mannose-binding lectin (FcMBL). The FcMBL-beads were used to capture and magnetically remove bacteria from purified cultures of 12 S. aureus strains, and from 8 articular fluid samples and 4 synovial tissue samples collected from patients with osteoarthritis or periprosthetic infections previously documented by positive S. aureus cultures. While the capture efficiency was high (85%) with purified S. aureus strains grown in vitro, direct FcMBL-bead capture from the clinical samples was initially disappointing (< 5% efficiency). Further analysis revealed that inhibition of FcMBL binding was due to coating of the bacteria by immunoglobulins and immune cells that masked FcMBL binding sites, and to the high viscosity of these complex biological samples. Importantly, capture of pathogens using the FcMBL-beads was increased to 76% efficiency by pretreating clinical specimens with hypotonic washes, hyaluronidase and a protease cocktail. Using this approach, S. aureus bacteria could be isolated from infected osteoarthritic tissues within 2 hours after sample collection. This FcMBL-enabled magnetic method for rapid capture and concentration of pathogens from clinical samples could be integrated upstream of current processes used in clinical microbiology laboratories to identify pathogens and perform antibiotic sensitivity testing when bacterial culture is not possible or before colonies can be detected.


Histamine and histamine type-2 receptor antagonists in psoriasis. Mechanisms and speculations.
The findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raise the possibility that cellular immune processes may play a major role in the pathogenesis of this disease. It is broadly agreed that histamine released by mast cells is one of the molecules involved in the pathogenesis. This is supported by the findings that CsA and methotrexate (Mxt) reduce formation and release of histamine. However, the well known side-effects of CsA and Mxt may argue potential use of other agents acting on formation and action of histamine. Such agents may be the histamine-2 receptor antagonists, previously reported to have a clinical effect on psoriasis. But randomised short-term studies have disclosed that these drugs have no beneficial or even an aggravating effect on the disease. This article reports on recent findings of improvement in psoriasis using high doses of the histamine-2 receptor antagonist ranitidine in long-term studies. Also presented are a hypothetical action of histamine in development of psoriasis and a rationale for ranitidine as a potential agent in the therapy of psoriasis.


A comparison of two types of vacuum drainage after cholecystectomy.
Following cholecystectomy, 50 patients were randomly allocated for suction drainage by small (2.5 mm) Redivac or large calibre (6 mm) Redivac drains. There were 25 patients in each group. Subhepatic collection was detected by ultrasonic examination in 5 patients on the seventh postoperative day. The smaller drain was used in all of these patients. Of these 5 patients, one developed pulmonary infection, a second had internal bleeding requiring laparotomy, while the remaining 3 were asymptomatic. Subhepatic fluid was not detected in any patient who had the larger drain.


Slender Stalk with Combined Features of Saccular Limited Dorsal Myeloschisis and Congenital Dermal Sinus in a Neonate.
Limited dorsal myeloschisis (LDM) and congenital dermal sinus (CDS) originate from incomplete disjunction between the cutaneous and neural ectoderms. Some LDM stalks have been found to have elements of a CDS or dermoid cyst. We surgically treated a saccular lesion in the lumbosacral region of a 7-day-old male neonate. Although fetal magnetic resonance imaging (MRI) failed to reveal a stalk, postnatal MRI including three-dimensional heavily T2-weighted imaging demonstrated a stalk originating from the lumbar cord and extending caudally to enter the lumbosacral meningocele sac. During untethering surgery, we found that the stalk was slender, with a diameter of 0.7-0.8 mm, but otherwise appeared to be a typical LDM stalk. Histopathological examination revealed that the fibrocollagenous stalk contained glial fibrillary acidic protein-immunopositive neuroglial tissues and stratified squamous epithelium. The present report describes the first documented case of a stalk with combined features of saccular LDM and CDS in a neonate. Since cutaneous ectodermal tissue is likely to remain in the remnant stalk, this patient requires careful monitoring to detect the potential development of a dermoid cyst.


[Use of SPIO-enhanced T1- and T2-weighted images for the differentiation of liver lesions: an ROC analysis].
The superparamagnetic iron oxide (SPIO) Resovist is a contrast media with shortening of both T(1) and T(2) relaxation time. This study evaluates the impact of SPIO-enhanced T(1)- and T(2)-weighted images for the differentiation of liver lesions. SPIO-enhanced MRI examinations (1.5 T, Symphony Quantum) of 61 patients were analyzed. Thirty-seven patients had malignant liver lesions (metastases n = 32, HCC n = 5) proven by biopsy or laparotomy, 11 patients had benign liver lesions (FNH n = 2, hemangiomas n = 4, benign cysts n = 5, normal liver on laparoscopy n = 13). After unenhanced T(1)- and T (2)-weighted imaging, a bolus injection of 1.4 ml SPIO (Resovist) was given, followed by T(1)-weighted imaging at 20 s, 60 s, and 5 min and T(2)-weighted imaging at 10 min post injection. A score from 1 (benign) to 5 (malignant) was used by three blinded radiologist for the ROC analysis of the unenhanced T(1)-/T(2)-weighted images (set 1) and of the combinations of unenhanced T(1)/T(2)-weighted and SPIO T(1)-weighted images (set 2), unenhanced T(1)/T(2) and SPIO T(2)-w images (set 3) and all images (set 4). The accuracy of plain MRI (set 1: 56 %) was increased by SPIO-enhanced T(1)-weighted images (set 2: 81 %) and SPIO-enhanced T(2)-weighted images (set 3: 90 %). Best results were obtained using unenhanced T(1)-weighted, unenhanced T(2)-weighted and both SPIO T(1)-weighted and T(2)-weighted images (set 4: 93%). The accuracy of predicting histopathologic diagnosis was 91%. For the differentiation of liver lesions, SPIO-enhanced T(2)-weighted images had a greater impact on the accuracy of MRI than T (1)-weighted images, but SPIO-enhanced T(1)-weighted images provided additional information in some patients and should not be deleted.


Economic impact of a noncomprehensive smoke-free air law.
Many stakeholders were interested in the potential economic impact of Pennsylvania's 2008 Clean Indoor Air Act (CIAA). This study focused on the examination of economic change subsequent to CIAA and, because CIAA allows certain venue exemptions among eating and drinking establishments, if the allowance of exemptions influenced that impact. Policy analysis. Prais-Winsten regressions were employed to assess effects of CIAA and law exemptions on county-level quarterly taxable sales in restaurants and drinking establishments. Regressions controlled for general economic activity, trends in eating/drinking establishment sales, seasonality, and county characteristics. Across models, CIAA had no significant negative effects on taxable sales in full-/limited-service restaurants or drinking establishments and some positive effects. CIAA exemptions for drinking establishments do not offer a clear economic benefit. Restaurant and drinking establishment taxable sales were strongly related to overall economic conditions and seasonality. After controlling for confounding factors, and consistent with the weight of the evidence from literature on the economic impact of smoke-free policies, our study concludes that the Pennsylvania CIAA had no negative effects on per capita restaurant and drinking establishment taxable sales. High rates of drinking establishment exemptions were not economically beneficial. This study can inform efforts to make smoke-free laws more comprehensive.


Mutations conferring new patterns of sensitivity to volatile anesthetics in Caenorhabditis elegans.
We previously described the use of the nematode Caenorabditis elegans as a genetic model for studying the mechanism of action of volatile anesthetics. All previous strains of C. elegans with altered responses to anesthetics have been identified by screening the response to halothane. The current study was designed to identify classes of mutations by screening for alterations in sensitivity to enflurane, isoflurane, and diethylether. Nematodes were mutated and the resulting mutant strains were screened for immobility in low doses of enflurane, isoflurane, or diethylether. Concentrations of halothane, enflurane, isoflurane, and diethylether that anesthetized 50% of the animals were determined in all mutations. Interactions of some new mutations with previously identified mutations were determined by construction of double mutants. Mutations in six genes were identified and were divided into two classes. One class primarily affected sensitivity to enflurane and isoflurane; a second class affected sensitivity to all of the volatile anesthetics studied. The effects of the latter group dominated the effects of previously identified mutations. The interaction of these mutations indicates that multiple sites of anesthetic action exist and that there are at least three such sites. A pathway for control of sensitivity to volatile anesthetics is proposed.


Geological setting and age of Australopithecus sediba from southern Africa.
We describe the geological, geochronological, geomorphological, and faunal context of the Malapa site and the fossils of Australopithecus sediba. The hominins occur with a macrofauna assemblage that existed in Africa between 2.36 and 1.50 million years ago (Ma). The fossils are encased in water-laid, clastic sediments that were deposited along the lower parts of what is now a deeply eroded cave system, immediately above a flowstone layer with a U-Pb date of 2.026 +/- 0.021 Ma. The flowstone has a reversed paleomagnetic signature and the overlying hominin-bearing sediments are of normal polarity, indicating deposition during the 1.95- to 1.78-Ma Olduvai Subchron. The two hominin specimens were buried together in a single debris flow that lithified soon after deposition in a phreatic environment inaccessible to scavengers.


Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia.
Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP) has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT). A 55-year-old man with chronic lymphocytic leukemia (CLL) received a cord blood transplant for relapsed refractory disease with high risk cytogenetics. On day 221, patient presented with skin rash, tingling in both lower extremites, and ascending paralysis that progressed rapidly over the course of 2 days. The workup resulted in a diagnosis of AIDP and administration of intravenous immunoglobulins plus steroids was initiated. Motor and sensory powers were fully recovered and his chronic GVHD was managed for several months with single agent sirolimus.


MMPI scales for diagnosing acute and chronic PTSD in civilians. Minnesota Multiphasic Personality Inventory.
To develop new Minnesota Multiphasic Personality Inventory (MMPI) scales for diagnosing acute and chronic posttraumatic stress disorder (PTSD), 237 civilians with PTSD or panic disorder (controls) completed the MMPI-R. All 399 items were submitted to chi-square analysis to select those differentiating acute or chronic PTSD from controls. The analyses yielded an MMPI Acute PTSD scale (32 items) and a MMPI Chronic PTSD scale (41 items). Discriminating between acute PTSD and controls, the MMPI Acute PTSD scale had a hit rate of 83% and the MMPI Chronic PTSD scale produced a hit rate of 75% to 80%. Cross-validation produced similar hit rates. These scales scores were not substantially influenced by gender or types of traumatic events, and only the MMPI Acute PTSD scale seemed to not be sensitive to co-morbidity.


Mechanisms of wheat (Triticum aestivum) grain storage proteins in response to nitrogen application and its impacts on processing quality.
Basis for the effects of nitrogen (N) on wheat grain storage proteins (GSPs) and on the establishment of processing quality are far from clear. The response of GSPs and processing quality parameters to four N levels of four common wheat cultivars were investigated at two sites over two growing seasons. Except gluten index (GI), processing quality parameters as well as GSPs quantities were remarkably improved by increasing N level. N level explained 4.2~59.2% and 10.4~80.0% variability in GSPs fractions and processing quality parameters, respectively. The amount of N remobilized from vegetative organs except spike was significantly increased when enhancing N application. GSPs fractions and processing quality parameters except GI were only highly and positively correlated with the amount of N remobilized from stem with sheath. N reassimilation in grain was remarkably strengthened by the elevated activity and expression level of glutamine synthetase. Transcriptome analysis showed the molecular mechanism of seeds in response to N levels during 10~35 days post anthesis. Collectively, we provided comprehensive understanding of N-responding mechanisms with respect to wheat processing quality from N source to GSPs biosynthesis at the agronomic, physiological and molecular levels, and screened candidate genes for quality breeding.


Optimization of process conditions for effective ohmic heating of greater lizardfish (saurida tumbil) sausage via response surface methodology.
In current research, the optimization of ohmic heating on greater lizardfish (Saurida tumbil) sausage variables was carried out using response surface methodology-central composite design (RSM-CCD). The effect of process variables including voltage gradient (15-60 V/cm), time (1-15 min), and temperature (60-90°C) on the microbial properties, pH, peroxide value, water holding capacity (WHC), and cooking loss of the sausages was evaluated. The results showed that the characteristics of the sausages were dependent on the ohmic heating conditions and these properties can be modulated. As per the results, the voltage gradient and temperature has a significant effect on the total plate count (p < 0.05). The increase in voltage gradient was the most effective on pH (5.63-6.91). The interaction terms of all items had a significant effect (p < 0.05) on the peroxide value of the fish sausages. Higher amount of temperature and process time were resulted in the more cooking loss. Increasing the voltage gradient was more effective on WHC compared to the temperature. Finally, the process was optimized and the optimized condition was achieved by setting the voltage gradient at 30 V/cm, process time at 4 min, and temperature at 66 °C. Also, it was compared with conventional heating. The results were shown that the differences between the mean values of all responses were statistically significant (p < 0.05) except for pH. Therefore, ohmic method was carried out faster, with lower temperature and obtaining the highest WHC and lowest total plate count, peroxide value, cooking loss, and optimized pH. Generally, this study suggested that the ohmic heating can be used as a rapid and homogeneous cooking method for the preparation of sausages from greater lizardfish as a commercial low-valued fish.


Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells.
Hepatocytes polarize by forming functionally distinct sinusoidal (basolateral) and canalicular (apical) plasma membrane domains. Two distinct routes are used for delivery of membrane proteins to the canaliculus. Proteins having glycosylphosphatidylinositol anchors or single transmembrane domains are targeted to the sinusoidal plasma membrane from where they transcytose to the canalicular domain. In contrast, apical ATP-binding-cassette (ABC) transporters, which are required for energy-dependent biliary secretion of bile acids (ABCB11), phospholipids (ABCB4), and nonbile acid organic anions (ABCC2), lack initial residence in the basolateral plasma membrane and traffic directly from Golgi membranes to the canalicular membrane. While investigating mechanisms of apical targeting in WIF-B9 cells, a polarized hepatic epithelial cell line, we observed that rab11a is required for canalicular formation. Knockdown of rab11a or overexpression of the rab11a-GDP locked form prevented canalicular formation as did overexpression of the myosin Vb motorless tail domain. In WIF-B9 cells, which lack bile canaliculi, apical ABC transporters colocalized with transcytotic membrane proteins in rab11a-containing endosomes and, unlike the transcytotic markers, did not distribute to the plasma membrane. We propose that polarization of hepatocytes (i.e., canalicular biogenesis) requires recruitment of rab11a and myosin Vb to intracellular membranes that contain apical ABC transporters and transcytotic markers, permitting their targeting to the plasma membrane. In this model, polarization is initiated upon delivery of rab11a-myosin Vb-containing membranes to the surface, which causes plasma membrane at the site of delivery to differentiate into apical domain (bile canaliculus).


Neural expression and regulation of NSSR1 proteins.
Neural salient serine-/arginine-rich protein 1 (NSSR1) is a newly identified SR protein that regulates pre-mRNA splicing. In the present study, we demonstrated the neural specialization of NSSR1 protein expression in humans and mice. Strong immunoreactive signals to NSSR1 were observed in mouse cerebral neurons, cerebellar Purkinje cells, pyramidal neurons in CA1, CA2 and CA3 regions of the hippocampus and granule cells in the dentate gyrus. In primarily cultured mouse neural progenitor cells (NPCs), at the undifferentiated status, NSSR1 transcripts were detected, but not the proteins. In comparison, in differentiated NPCs both NSSR1 transcripts and proteins were expressed and significantly up-regulated. The results suggest that NSSR1 is important in regulation of brain function and neural differentiation, possibly via regulating the neural-specific alternative splicing of genes.


[Study on TCM syndrome differentiation rules in coronary artery bypass grafting patients during peri-operation period].
To study the TCM syndrome differentiation rules in coronary artery bypass grafting (CABG) patients during peri-operation period. According to the Guideline for Clinical Trail of Traditional Chinese New Drugs and experience of Professor DENG Tie-tao, the standard of TCM syndrome differentiation for CABG patients was established, with which 161 CABG patients were classified before and two weeks after CABG operation. Before CABG, the qi stagnation and blood stasis syndrome type was the type most commonly seen (46.0%), the next in turn was the phlegm stagnation type (24.8%), the yang-qi deficiency type (15.5%), and the yin-blood deficiency type (13.7%). While after CABG, the phlegm stagnation syndrome type was the most frequently occurred one (35.9%), then in turn was the yang-qi deficiency type (30.8%), the yin-blood deficiency type (21.2%) and the qi stagnation with blood stasis type (12.2%). For patients before CABG, the pathological characteristic is mostly the deficiency in root with excess in superficiality, and the commonest syndrome is the qi stagnation with blood stasis type. For patients after CABG, both deficiency and excess is the pathological characteristic, the Xin-qi and Xin-yang deficiency syndrome the commonest type, and with phlegm as the main pathologic factor.


Melanosomal proteins as melanoma-specific immune targets.
Pigmentation of our skin, hair and eyes is essential for photoprotection, embryological development, detoxification and protective/cosmetic coloration. A number of proteins important to the production of melanin within melanosomes have now been identified including enzymatic and structural proteins encoded at the murine albino, brown, pinkeyed-dilution, MART1, slaty and silver loci. Interestingly, many of those melanosomal proteins (including epitopes derived from tyrosinase, TRP1/gp75, silver/gp100 and MART1/melan-A) function in vivo as targets of humoral and cellular autoimmune responses directed specifically against normal or transformed melanocytes. These findings have provided new impetus to research on immune responses to melanoma and, perhaps more importantly, examining why they are insufficient to provide protection against tumour growth and what type of immune therapy can be designed to correct that. The melanosome must now be considered beyond its function in pigmentation, and assumes the role of a valuable source for specific immune targets for malignant melanoma.


Real-world effectiveness of sofosbuvir-based treatment regimens for chronic hepatitis C genotype 3 infection: Results from the multicenter German hepatitis C cohort (GECCO-03).
There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. Three hundred forty-two chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37.1%], 38 HCV/HIV co-infected patients [11.1%]). SVR12 rates in the "intention-to-treat" analysis were as follows: sofosbuvir/ribavirin 69.4% (75/108), sofosbuvir/peginterferon/ribavirin 80.6% (58/72), sofosbuvir/daclatasvir ± ribavirin for 12 weeks 88.3% (53/63), sofosbuvir/daclatasvir ± ribavirin for 24 weeks 79.3% (23/29), sofosbuvir/ledipasvir ± ribavirin for 12 weeks 71.4% (10/14), and sofosbuvir/ledipasvir ± ribavirin for 24 weeks 86.7% (26/30). Forty patients were lost to follow-up, 23 patients had a relapse, 4 patients stopped treatment prematurely and 1 patient died. Female sex (P = 0.038) and treatment with two different DAAs (P = 0.05) were predictors for SVR12 in the multivariate analysis. In conclusion, sofosbuvir/daclatasvir ± ribavirin for 12 weeks and sofosbuvir/ledipasvir ± ribavirin for 24 weeks are effective for the treatment of HCV genotype 3 infected patients including cirrhotic, treatment-experienced or HIV/HCV co-infected patients.


Unusual Presentation of Cutaneous Spindle Cell Squamous Cell Carcinoma: A Case Report.
Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare and often aggressive subtype of squamous cell carcinoma (SCC), which usually appears in sun-exposed areas, in areas that have received prior ionizing radiation, or in immunosuppressed individuals. SpSCCs are histologically characterized by keratinocytes infiltrating the dermis as single cells with elongated nuclei rather than as cohesive nests or islands and, in contrast to conventional SCC, are lacking features of keratinization. Immunohistochemical studies are useful to distinguish SpSCC from other spindle cell neoplasms, such as spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, and atypical fibroxanthoma. We present a rare case of a patient with SpSCC in the gluteal region with regional lymph node metastasis. The patient was treated with wide excision of the tumor, inguinal lymph node dissection, and adjuvant radiotherapy. Cutaneous SpSCC is clinically similar to conventional SCC but can demonstrate more aggressive behavior. This case is rare since it was localized in the gluteal region of an otherwise healthy man.


Antiarrhythmic Drug Therapy for Rhythm Control in Atrial Fibrillation.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and affects over 33 million people worldwide. AF is associated with stroke and systemic thromboembolism, unpleasant symptoms and reduced quality of life, heart failure, and increased mortality, and treatment of AF and its complications are associated with significant cost. Antiarrhythmic drugs (AADs) can suppress AF, allowing long-term maintenance of sinus rhythm, and have the potential to relieve symptoms and reverse or prevent adverse effects associated with AF. However, large randomized controlled studies evaluating use of AADs have not demonstrated a clear benefit to maintaining sinus rhythm, and AADs often have significant limitations, including a modest rate of overall success at maintaining sinus rhythm, frequent side effects, and potentially life-threatening toxicities. Although some of the currently available AADs have been available for almost 100 years, better tolerated and more efficacious AADs have recently been developed both for long-term maintenance of sinus rhythm and for chemical cardioversion of AF to sinus rhythm. Advances in automated AF detection with cardiac implantable electronic devices have suggested that AADs might be useful for suppressing AF to allow safe discontinuation of anticoagulation in select patients who are in sinus rhythm for prolonged periods of time. AADs may also have synergistic effects with catheter ablation of AF. This review summarizes the pharmacology and clinical use of currently available AADs for treatment of AF and discusses novel AADs and future directions for rhythm control in AF.


Combined tumor therapy by using radiofrequency ablation and 5-FU-laden polymer implants: evaluation in rats and rabbits.
To evaluate the use of 5-fluorouracil (5-FU)-laden polymer implants as an adjunct to radiofrequency (RF) ablation for tumor treatment. All animal studies were performed in compliance with the Case Western Reserve University Institutional Animal Care and Use Committee guidelines. Three studies were performed to investigate (a) in vitro dissolution of 5-FU-laden polymer implants in saline and bovine serum, (b) tissue distribution of 5-FU and its metabolite, 5-fluorouridine (5-FUrd), in the ablated liver tissue of rats (n = 4), and (c) efficacy of combined approach (n = 4) compared with that of ablation alone (n = 6) for VX2 liver tumor model in rabbits. Characterization of 5-FU release in vitro and distribution of 5-FU in rat liver tissue were analyzed by using high performance liquid chromatography; in vivo efficacy was assessed by using computed tomography and pathologic examination. Results of the in vitro dissolution study showed that a 75% release of 5-FU occurred in 2 days when exposed to bovine serum and in 9 days when exposed to phosphate-buffered saline. In the ablated rat liver, the 5-FU level was higher at the center and lower at the periphery of the tissue both at 24 hours (41.0 mg per kilogram tissue vs 15.0 mg per kilogram tissue, respectively) and at 48 hours (8.0 mg per kilogram tissue vs 2.0 mg per kilogram tissue, respectively). The 5-FUrd concentration was twofold higher peripherally than centrally and was higher at 48 hours than at 24 hours. In rabbits, local delivery of 5-FU immediately after RF ablation provided a significant (P < .05) reduction in tumor size compared with ablation alone (1.80 cm3 +/- 0.28 [standard error] vs 3.53 cm3 +/- 0.52, respectively; P = .034) and a more than 20-fold reduction in tumor size compared with the control (1.80 cm3 +/- 0.28 vs 41.95 cm3 +/- 11.58, respectively; P = .018). Combined treatment by using 5-FU polymer implants and RF ablation shows uniform sustained release of 5-FU for 48 hours at least 8 mm from the edge of the ablation zone and appears to be successful at controlling the growth of an experimental tumor in rabbits appreciably better than does ablation alone.


Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease.
Latest data suggest that placental growth factor (PLGF), growth differentiation factor-15 (GDF-15) and hepatic growth factor (HGF) are involved in hepatic fibrogenesis. Diagnostic performance of these markers for non-invasive liver fibrosis prediction was evaluated based on liver histology and stiffness. In total 834 patients were recruited. Receiver-operating-characteristics were used to define cut-offs for markers correlating to fibrosis stages. Odds-ratios were calculated for the presence/absence of fibrosis/cirrhosis and confirmed in the sub-group of patients phenotyped by elastography only. Logistic and uni- and multivariate regression analyses were used to test for association of markers with liver fibrosis stages and for independent prediction of liver histology and stiffness. Marker concentrations correlated significantly (P<0.001) with histology and stiffness. Cut-offs for liver fibrosis (≥F2) were PLGF = 20.20 pg/ml, GDF15 = 1582.76 pg/ml and HGF = 2598.00 pg/ml. Logistic regression confirmed an increase of ORs from 3.6 over 33.0 to 108.4 with incremental (1-3) markers positive for increased liver stiffness (≥12.8kPa; all P<0.05). Subgroup analysis revealed associations with advanced fibrosis for HCV (three markers positive: OR = 59.9, CI 23.4-153.4, P<0.001) and non-HCV patients (three markers positive: OR = 144, CI 59-3383, P<0.001). Overall, serum markers identified additional 50% of patients at risk for advanced fibrosis presenting with low elastography results. In conclusion, this novel combination of markers reflects the presence of significant liver fibrosis detected by elastography and histology and may also identify patients at risk presenting with low elastography values.


Do estimates of contemporary effective population size tell us what we want to know?
Estimation of effective population size (Ne ) from genetic marker data is a major focus for biodiversity conservation because it is essential to know at what rates inbreeding is increasing and additive genetic variation is lost. But are these the rates assessed when applying commonly used Ne estimation techniques? Here we use recently developed analytical tools and demonstrate that in the case of substructured populations the answer is no. This is because the following: Genetic change can be quantified in several ways reflecting different types of Ne such as inbreeding (NeI ), variance (NeV ), additive genetic variance (NeAV ), linkage disequilibrium equilibrium (NeLD ), eigenvalue (NeE ) and coalescence (NeCo ) effective size. They are all the same for an isolated population of constant size, but the realized values of these effective sizes can differ dramatically in populations under migration. Commonly applied Ne -estimators target NeV or NeLD of individual subpopulations. While such estimates are safe proxies for the rates of inbreeding and loss of additive genetic variation under isolation, we show that they are poor indicators of these rates in populations affected by migration. In fact, both the local and global inbreeding (NeI ) and additive genetic variance (NeAV ) effective sizes are consistently underestimated in a subdivided population. This is serious because these are the effective sizes that are relevant to the widely accepted 50/500 rule for short and long term genetic conservation. The bias can be infinitely large and is due to inappropriate parameters being estimated when applying theory for isolated populations to subdivided ones.


Prophylactic transcatheter angiographic embolization reduces Forrest IIa ulcer rebleeding: A retrospective study.
The application of transcatheter angiographic embolization (TAE) is controversial in the treatment of ulcer bleeding. This study aims to determine rebleeding risk factors and evaluate the efficacy of prophylactic TAE (p-TAE) following endoscopic hemostasis in rebleeding prevention of Forrest lla ulcers.The medical records of Forrest lla ulcer patients who underwent endoscopic hemostasis (E group) and endoscopic hemostasis plus p-TAE (E + p-TAE group) in West China Hospital from May 2009 to May 2018 were retrospectively reviewed. Baseline characteristics, clinical efficacy, and rebleeding risk factors were analyzed.As a result, a total of 102 patients were included, with 75 and 27 patients in E and E + p-TAE group, respectively. Most of the baseline data in E and E + p-TAE group were similar except for the proportion of protruded non-bleeding visible vessel (NBVV) (E group vs E + p-TAE group, 50.7% vs 74.1%, P = .035). The rebleeding rate of E + p-TAE group (3.7%) was significantly lower than E group (24.0%) (P = .02). The protruded NBVV (OR: 6.896, 95% confidence interval [CI]: 1.532-30.642, P = .01) and employment of p-TAE (OR: 0.038, 95% CI: 0.003-0.448, P = .009) were identified as independent risk factors for Forrest IIa ulcer rebleeding. Additionally, log-rank test indicated the rebleeding occurrence was greatly reduced by p-TAE in patients with protruded NBVVs (P = .006).In conclusion, the protruded NBVV and employment of p-TAE were the independent risk factors tightly associated with rebleeding of Forrest IIa ulcer. P-TAE following endoscopic hemostasis could effectively prevent Forrest IIa ulcer from rebleeding.


The platelet-rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing.
Platelet-rich plasma is autologous plasma that contains concentrated platelets compared to whole blood. It is relatively inexpensive to produce, can be easily isolated from whole blood, and can be administered while the patient is in the operating room. Further, because platelet-rich plasma is an autologous therapy, there is minimal risk for adverse reactions to the patient. Platelet-rich plasma has been used to promote bone regeneration due to its abundance of concentrated growth factors that are essential to wound healing. In this review, we summarize the methods for producing platelet-rich plasma and the history of its use in bone regeneration. We also summarize the growth factor profiles derived from platelet-rich plasma, with emphasis on those factors that play a direct role in promoting bone repair within the local fracture environment. In addition, we discuss the potential advantages of combining platelet-rich plasma with mesenchymal stem cells, a multipotent cell type often obtained from bone marrow or fat, to improve craniofacial and long bone regeneration. We detail what is currently known about how platelet-rich plasma influences mesenchymal stem cells in vitro, and then highlight the clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo.