Modeling diffuse reflectance from semi-infinite turbid media: application to the study of skin optical properties.
Diffuse reflectance spectroscopy in the visible and NIR spectral ranges is an effective and extensively used technique for the non-invasive study and characterization of various biological tissues. In this article, a short review of currently available modeling techniques for diffuse reflectance from semi-infinite turbid media is presented. Starting from the basic physical picture of the diffuse reflectance problem, a simple and practical model is then proposed for use with fiber optic probes. The validity of the model is tested on tissue phantoms and it is then applied to the analysis of diffuse reflectance spectra collected from human skin in vivo.


Cold-Active Lipases and Esterases: A Review on Recombinant Overexpression and Other Essential Issues.
Cold environments characterised by diverse temperatures close to or below the water freezing point dominate about 80% of the Earth's biosphere. One of the survival strategies adopted by microorganisms living in cold environments is their expression of cold-active enzymes that enable them to perform an efficient metabolic flux at low temperatures necessary to thrive and reproduce under those constraints. Cold-active enzymes are ideal biocatalysts that can reduce the need for heating procedures and improve industrial processes' quality, sustainability, and cost-effectiveness. Despite their wide applications, their industrial usage is still limited, and the major contributing factor is the lack of complete understanding of their structure and cold adaptation mechanisms. The current review looked at the recombinant overexpression, purification, and recent mechanism of cold adaptation, various approaches for purification, and three-dimensional (3D) crystal structure elucidation of cold-active lipases and esterase.


Refractory candidal meningitis in an immunocompromised patient cured by caspofungin.
Candidal meningitis is a rare infectious disease that usually leads to substantial morbidity and mortality. We present a case of candidal meningitis refractory to systemic antifungal therapy (amphotericin B and fluconazole). A 63-year-old female with lymphoblastic lymphoma and myelodysplasia with leukemia transformation developed prolonged fever and headache on the seventh day following intrathecal prophylactic chemotherapy. A lumbar puncture showed neutrophilic pleocytosis, and a cerebrospinal fluid culture yielded Candida albicans. The clinical course was complicated by brain edema, subarachnoid hemorrhage, and hydrocephalus. Parenteral therapy with amphotericin B alone or amphotericin B in combination with fluconazole or intrathecal administration of amphotericin B failed to eradicate C. albicans in the cerebrospinal fluid. After 7 days of caspofungin therapy, however, the cerebrospinal fluid became sterile and the patient gradually regained consciousness. She was discharged 1 month after completing 4 weeks of caspofungin therapy. There were two critical issues we thought to be relevant to the favorable outcome of this case. First, isolation of C. albicans was achieved by inoculating enriched liquid medium with cerebrospinal fluid. Second, there is a potential therapeutic benefit of caspofungin in treating a fungal infection of the central nervous system.


Centromere mapping functions for aneuploid meiotic products: Analysis of rec8, rec10 and rec11 mutants of the fission yeast Schizosaccharomyces pombe.
Recent evidence suggests that the position of reciprocal recombination events (crossovers) is important for the segregation of homologous chromosomes during meiosis I and sister chromatids during meiosis II. We developed genetic mapping functions that permit the simultaneous analysis of centromere-proximal crossover recombination and the type of segregation error leading to aneuploidy. The mapping functions were tested in a study of the rec8, rec10, and rec11 mutants of fission yeast. In each mutant we monitored each of the three chromosome pairs. Between 38 and 100% of the chromosome segregation errors in the rec8 mutants were due to meiosis I nondisjunction of homologous chromosomes. The remaining segregation errors were likely the result of precocious separation of sister chromatids, a previously described defect in the rec8 mutants. Between 47 and 100% of segregation errors in the rec10 and rec11 mutants were due to nondisjunction of sister chromatids during meiosis II. In addition, centromere-proximal recombination was reduced as much as 14-fold or more on chromosomes that had experienced nondisjunction. These results demonstrate the utility of the new mapping functions and support models in which sister chromatid cohesion and crossover position are important determinants for proper chromosome segregation in each meiotic division.


Pedometer use and self-determined motivation for walking in a cardiac telerehabilitation program: a qualitative study.
Exercise-based cardiac rehabilitation reduces morbidity and mortality. Walking is a convenient activity suitable for people with cardiac disease. Pedometers count steps, measure walking activity and motivate people to increase physical activity. In this study, patients participating in cardiac telerehabilitation were provided with a pedometer to support motivation for physical activity with the purpose of exploring pedometer use and self-determined motivation for walking experienced by patients and health professionals during a cardiac telerehabilitation program. A qualitative research design consisting of observations, individual interviews and patient documents made the basis for a content analysis. Data was analysed deductively using Self Determination Theory as a frame for analysis and discussion, focusing on the psychological needs of autonomy, competence and relatedness. Twelve cardiac patients, 11 health professionals, 6 physiotherapists and 5 registered nurses were included. The pedometer offered independence from standardised rehabilitation since the pedometer supported tailoring, individualised walking activity based on the patient's choice. This led to an increased autonomy. The patients felt consciously aware of health benefits of walking, and the pedometer provided feedback on walking activity leading to an increased competence to achieve goals for steps. Finally, the pedometer supported relatedness with others. The health professionals' surveillance of patients' steps, made the patients feel observed, yet supported, furthermore, their next of kin appeared to be supportive as walking partners. Cardiac patients' motivation for walking was evident due to pedometer use. Even though not all aspects of motivation were autonomous and self determined, the patients felt motivated for walking. The visible steps and continuous monitoring of own walking activity made it possible for each individual patient to choose their desired kind of activity and perform ongoing adjustments of walking activity. The immediate feedback on step activity and the expectations of health benefits resulted in motivation for walking. Finally, pedometer supported walking made surveillance possible, giving the patients a feeling of being looked after and supported. Current study is a part of The Teledi@log project.


Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis.
Disease progression in amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons (MN) and their axons, but is also influenced by neighboring cells such as astrocytes and microglial cells. The role of microglia in ALS is complex as it switches from an anti-inflammatory and neuroprotective phenotype in early disease to a proinflammatory and neurotoxic phenotype in later stages. Our previous studies in models of neurodegeneration identified rho kinase (ROCK) as a target, which can be manipulated to beneficially influence disease progression. Here, we examined the neuroprotective potential of the ROCK inhibitor Fasudil to target the central pathogenic features of ALS. Application of Fasudil to kainic acid-lesioned primary MN in vitro resulted in a strong prosurvival effect. In vivo, SOD1(G93A) mice benefited from oral treatment with Fasudil showing prolonged survival and improved motor function. These findings were correlated to an improved survival of motor neurons and a pronounced alteration of astroglial and microglial cell infiltration of the spinal cord under Fasudil treatment. Modeling a proinflammatory microglial phenotype by stimulation with LPS in vitro, Fasudil decreased the release of proinflammatory cytokines and chemokines TNFα, Il6, CCL2, CCL3, and CCL5 while CXCL1 release was only transiently suppressed. In sciatic nerve motor axons, neuromuscular junction remodeling processes were increased. In conclusion, we provide preclinical and neurobiological evidence that inhibition of ROCK by the clinically approved small molecule inhibitor Fasudil may be a novel therapeutic approach in ALS combining both neuroprotection and immunomodulation for the cure of this devastating disease.


CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions.
Surface molecules that are differentially expressed on Th1 and Th2 cells may be useful in regulating specific immune responses in vivo. Using a panel of mAbs, we have identified murine CD226 as specifically expressed on the surface of differentiated Th1 cells but not Th2 or Th0 cells. Although CD226 is constitutively expressed on CD8 cells, it is up-regulated on CD4 cells upon activation. Th1 differentiation results in enhanced CD226 expression, whereas expression is down-regulated upon Th2 polarization. We demonstrate that CD226 is involved in the regulation of T cell activation; in vivo treatment with anti-CD226 results in significant reduction of Th1 cell expansion and in the induction of APCs that inhibit T cell activation. Furthermore, anti-CD226 treatment delays the onset and reduces the severity of a Th1-mediated autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest that CD226 is a costimulatory molecule that plays an important role in activation and effector functions of Th1 cells.


Plant-Based Diets and Hypertension.
Hypertension is a global epidemic and a risk factor for many adverse outcomes, including cardiovascular disease, kidney disease, and death. Lifestyle plays a significant role in the development and maintenance of hypertension, and guidelines from several organizations recommend lifestyle modifications as first-line intervention for hypertensive patients. Data supporting the use of plant-based diets in the treatment of hypertension goes back almost a century. More recently, clinical trial data, including randomized controlled trials, have established plant-based diets as an effective lifestyle intervention for high blood pressure (BP). Plant-based diets differ from the standard American diet in a myriad of ways, with some substances being present in either substantially higher or lower amounts. Although the precise mechanism of a plant-based diet's beneficial effects on BP is unknown, many of these differences may be responsible. Attributes of a plant-based diet that may lower BP include a lower energy content leading to weight loss, a lower sodium content, an increased potassium content, reduced oxidative stress, higher bioavailability of the vasodilator nitric oxide, and beneficial effects on the microbiome. The evidenced-based benefits of plant-based diets in treating hypertension should lead providers to advocate for this dietary pattern for their patients.


New Triplet Sensitization Routes for Photon Upconversion: Thermally Activated Delayed Fluorescence Molecules, Inorganic Nanocrystals, and Singlet-to-Triplet Absorption.
Photon upconversion based on triplet-triplet annihilation (TTA-UC) has attracted much interest because of its possible applications to renewable energy production and biological fields. In particular, the UC of near-infrared (NIR) light to visible (vis) light is imperative to overcome the Shockley-Queisser limit of single-junction photovoltaic cells, and the efficiency of photocatalytic hydrogen production from water can also be improved with the aid of vis-to-ultraviolet (UV) UC. However, both processes have met limitations in the wavelength range, efficiency, and sensitivity for weak incident light. This Account describes recent breakthroughs that solve these major problems, new triplet sensitization routes to significantly enlarge the range of conversion wavelength by minimizing the energy loss during intersystem crossing (ISC) of triplet sensitizers or bypassing the ISC process. The photochemical processes of TTA-UC in general start with the absorption of longer wavelength incident light by triplet sensitizers, which generate the triplet states via ISC. This ISC inevitably accompanies the energy loss of hundreds of millielectronvolts, which significantly limits the TTA-UC with large anti-Stokes shifts. The small S1-T1 gap of molecules showing thermally activated delayed fluorescence (TADF) allows the sensitization of emitters with the highest T1 and S1 energy levels ever employed in TTA-UC, which results in efficient vis-to-UV UC. As alternatives to molecular sensitizers in the NIR region, inorganic nanocrystals with broad NIR absorption bands have recently been shown to work as effective sensitizers for NIR-to-vis TTA-UC. Their small exchange splitting minimizes the energy loss during triplet sensitization. The modification of nanocrystal surfaces with organic acceptors via coordination bonds allows efficient energy transfer between the components and succeeding TTA processes. To remove restrictions on the energy loss during ISC, molecules with direct singlet-to-triplet (S-T) excitation are employed as triplet sensitizers. Although the S-T absorption is spin forbidden, large spin-orbital coupling occurs for appropriately designed metal complexes, which allow S-T absorption in the NIR region with large absorption coefficients. While the triplet lifetime of such S-T absorption sensitizers is often short (less than microsecond), the integration of the molecular sensitizers with emitter assemblies allows facile Dexter energy transfer to the surrounding emitter molecules, leading to efficient NIR-to-vis UC emission through triplet energy migration (TEM) in the condensed state. By judicious modification of the chromophore structures, the first example of NIR-to-blue UC has also been achieved. It is essential to combine these new triplet sensitization routes with an upconverted energy collection (UPCON) approach in molecular assemblies to effectively populate emitter triplets and to overcome remaining issues including back energy transfer. We propose two overall materials designs for the TEM-UPCON strategy, core-shell-shell structures and trilayer structures composed of triplet donor, acceptor, and energy collector. The fusion between triplet science and chemistry of self-assembly would overcome previous difficulties of NIR-to-vis and vis-to-UV TTA-UC toward real-world applications ranging from energy to biology.


Polymeric nanomedicine for cancer MR imaging and drug delivery.
Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (<200 nm). Currently, several nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.


Leukocytoclastic vasculitis masking chronic vascular changes in previously undiagnosed erythropoietic protoporphyria.
A 31-year old man presented with swelling and purpura of the dorsum of the hands following sun exposure. There was a preceding lifelong history of photosensitivity, but this episode, which occurred after the recent commencement of oral iron therapy, and after recent alcohol ingestion, was much more severe than any preceding episode. Skin biopsy performed 48 h after the onset of symptoms showed features consistent with the early stages of leukocytoclastic vasculitis. Direct immunofluorescence showed homogeneous thick staining of the vessel walls with IgG, IgM and IgA, together with abundant perivascular fibrinogen. A subsequent periodic acid-Schiff (PAS) stain on the skin biopsy revealed thickening of the walls of dermal vessels, which was not discernible in routinely stained (hematoxylin/eosin) sections. The diagnosis of erythropoietic protoporphyria (EPP) was confirmed by significantly elevated erythrocyte protoporphyrin levels and positive plasma fluorimetry. The diagnosis of porphyria may have been missed by routine skin microscopy if not for the additional information provided by clinical history, direct immunofluorescence and PAS stain. The pathogenesis and histopathology of acute and chronic vascular changes in EPP are reviewed.


Molecular characterization and expression pattern of four chemosensory proteins from diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).
Some chemosensory proteins (CSPs) expressed in insect sensory appendages are thought to be involved in chemical signaling in moths. We cloned and characterized four CSP genes from Plutella xylostella. The deduced amino acid sequences of PxylCSP1, PxylCSP2, PxylCSP3 and PxylCSP4 revealed open reading frames of 152, 128, 126 and 126 amino acids, respectively, with four conserved cysteine residues. The expression patterns of the four PxylCSP genes were further investigated by reverse transcription (RT) PCR and real-time PCR. PxylCSP1 and PxylCSP2 genes were expressed in all the tested tissues with the highest expression level in the antennae and heads (without antennae) whereas PxylCSP3 and PxylCSP4 mRNA were distributed extensively in all the tested tissues without apparent quantitative differences. The transcription levels of these CSP genes depended on sex, age, mating and the genes. Fluorescence quenching with Rhodojaponin-III (R-III) and homology modelling studies indicated that PxylCSP1 was able to bind non-volatile oviposition deterrents, such as R-III. These ubiquitous proteins might have the role of extracting non-volatile compounds (oviposition deterrents or antifeedants) dispersed in the environment and transporting them to their receptor.


Developmental regulation of calmodulin, actin, and tubulin RNAs during rat testis differentiation.
Postnatal testis differentiation involves transition through neonatal, pre-meiotic, meiotic, haploid, and mature stages. We have examined the qualitative and quantitative changes in rat testis RNAs that specifically hybridize to cDNAs encoding the cytoskeletal proteins, calmodulin, beta-actin, alpha- and beta-tubulin at ages corresponding to each of these developmental periods. We compared the species and relative levels of specific RNAs from testes of animals engaged in normal spermatogenesis with RNA from germ cell-depleted, Sertoli cell-enriched (SCE) testis. Distinct developmental patterns of expression of the specific RNAs were found with each of the cDNAs in the two animal models. A 2.2 kb (kilobase) actin RNA and a 2.7 kb beta-tubulin RNA are maximal at 5-10 days of age, suggesting these RNAs are required by somatic and germ cells in the postnatal phase prior to puberty. Between 19 and 29 days, when pachytene spermatocytes appear in significant numbers, there is a slight increase in the 2.2-kb actin RNA, but a 4- to 10-fold increase in RNAs hybridizing to cDNAs for calmodulin, alpha- and beta-tubulin. These changes are much less pronounced in the SCE testis than in the normal testis, indicating increases in these RNAs are related to germinal cell maturation. The germ cell-related increase in 1.8-kb beta-tubulin RNA appears to reflect a developmental "switch" in the gene from which the RNA is derived. This hypothesis is based on the observation that the ratio of hybridization of a chicken brain beta-tubulin cDNA versus a rat spleen beta-tubulin cDNA to the 1.8-kb RNA band increases more than 40-fold between 5 and 29 days of age in normal testis, but is constant in SCE testis. These data suggest that a specific beta-tubulin gene is activated in maturing germ cells. Analogously, a 2.1-kb alpha-tubulin RNA is found only in maturing normal testis and increases as spermatids are produced. A 2.0-kb beta-tubulin RNA, not found in normal testes, is maximal in maturing SCE testes, suggesting this RNA is of somatic cell origin. All of the RNA species studied, except the 2.0-kb beta-tubulin RNA, decrease between 5 and 19 days in SCE testes, as Sertoli cell mitotic activity wanes, indicating that their levels may be regulated by the developmental signals that influence mitosis.


Decisions from experience: adaptive information search and choice in younger and older adults.
In real-world decision making, choice outcomes, and their probabilities are often not known a priori but must be learned from experience. The dopamine hypothesis of cognitive aging predicts that component processes of experience-based decision making (information search and stimulus-reward association learning) decline with age. Many existing studies in this domain have used complex neuropsychological tasks that are not optimal for testing predictions about specific cognitive processes. Here we used an experimental sampling paradigm with real monetary payoffs that provided separate measures of information search and choice for gains and losses. Compared with younger adults, older adults sought less information about uncertain risky options. However, like younger adults, older participants also showed evidence of adaptive decision making. When the desirable outcome of the risky option was rare (p = 0.10 or 0.20), both age groups engaged in more information search and made fewer risky choices, compared with when the desirable outcome of the risky option was frequent (p = 0.80 or 0.90). Furthermore, loss options elicited more sampling and greater modulation of risk taking, compared with gain options. Overall, these findings support predictions of the dopamine hypothesis of cognitive aging, but they also highlight the need for additional research into the interaction of age and valence (gain vs. loss) on experience-based choice.


Radiation-Induced Skin Fibrosis: Pathogenesis, Current Treatment Options, and Emerging Therapeutics.
Radiotherapy (RT) has become an indispensable part of oncologic treatment protocols for a range of malignancies. However, a serious adverse effect of RT is radiodermatitis; almost 95% of patients develop moderate to severe skin reactions following radiation treatment. In the acute setting, these can be erythema, desquamation, ulceration, and pain. Chronically, soft tissue atrophy, alopecia, and stiffness can be noted. Radiodermatitis can delay oncologic treatment protocols and significantly impair quality of life. There is currently a paucity of effective treatment options and prevention strategies for radiodermatitis. Importantly, recent preclinical and clinical studies have suggested that fat grafting may be of therapeutic benefit, reversing detrimental changes to soft tissue following RT. This review outlines the damaging effects of RT on the skin and soft tissue as well as discusses available treatment options for radiodermatitis. Emerging strategies to mitigate detrimental, chronic radiation-induced changes are also presented.


[Impact of the COVID-19 pandemic on cannabis use in young adults and general population: a systematic review].
The first COVID-19 lockdown was a very restrictive situation that may have impacted on the prevalence and patterns of cannabis use. The aim of this systematic review was to assess the evidence on cannabis use and reasons for use in different countries during first lockdown in young adults and general population. This study followed PRISMA guidelines, and the review protocol was registered in PROSPERO (registration CRD42022303181). The search was carried out in PubMed, Scopus, Web of Science y Embase databases. Inclusion criteria were: cross-sectional or cohort studies; population ≥16 years; exploring cannabis use during lockdown; and English or Spanish language. Thirty studies, conducted in European countries (n=17), North America (n=12) and rest of the world (n=1), were analysed. The overall prevalence of cannabis use was found to be largely unchanged, but regular users tended to maintain (between 39.5% and 96.8% of the sample) or increase cannabis use (between 2.9% and 51.6%). The main decreases were among occasional users. Some reasons for the increase were boredom, loneliness, stress, coping and depressive symptoms. In addition, young people were the heaviest users, and being younger, live without family, financial problems and a low educational level were significantly (p-value<0.05) associated with increased use. Most regular users maintained or slightly increased their use, with young people being the main users. Concerning reasons for use like coping and depressive symptoms were found. Cannabis use needs to be addressed with strategies focused on the young population, considering occasional and regular use, as well as motivations.


Upregulation of MED7 was associated with progression in hepatocellular carcinoma.
MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC. In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored. High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels. MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.


Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments.
Helicobacter pylori is closely related to upper gastrointestinal diseases, and the precise evaluation of H. pylori infection is necessary for the treatment of these diseases. The aim of the present study was to establish a method for the quantitative detection of H. pylori. We applied a competitive PCR method using various amounts of synthetic DNA fragments containing the same primer-binding and a subset of the same template sequences as the target competing for primer binding and amplification in order to quantify H. pylori in gastric mucus. The results obtained by this method were compared with the results of histological examination, the rapid urease test, bacterial culture, the [13C]urea breath test, and urea and ammonia measurements in gastric juice. As the quantity of H. pylori in gastric mucus increased, the rates of positivity of histological examination, the rapid urease test, and bacterial culture increased. The quantity of H. pylori in gastric mucus was also significantly correlated with the results of the [13C]urea breath test and was negatively correlated with the urea/ammonia ratio in gastric juice. The competitive PCR method provides an objective measure of the quantity of H. pylori and makes it possible to distinguish true negatives from false negatives due to incomplete PCR and true positives from false positives due to contamination. This method is very useful for the precise evaluation of gastric H. pylori infection.


Enhanced light absorption in thin-film solar cells with light propagation direction conversion.
Enhancement of optical absorption in thin-film solar cells (TF-SCs) has been the long-lasting issue to achieve high efficiencies. Grating couplers have been studied for the conversion of incident light into guided modes propagating along TF-SCs to extend optical path for higher optical absorption. However the wavelength band for the efficient conversion remained relatively narrow and the overall improvement of TF-SC efficiencies has been limited. This paper demonstrates that the grating height design as well as the phase matching condition is important for the enhancement of optical absorption in TF-SCs with the calculation of short-circuit currents as a figure of merit for optimization. The influence of the light absorption coefficients and grating coupling strengths on the light absorption bandwidth is also discussed.


Intraoperative infusion of acetated Ringer solution containing glucose and ionized magnesium reduces ketogenesis and maintains serum magnesium.
The effect of glucose infusion during surgery on glucose metabolism has not been investigated sufficiently. We, therefore, examined the effect after the infusion of 1% glucose acetated Ringer solution containing Mg2+ during surgery on ketogenesis and serum Mg2+ concentrations. Patients, classified as ASA I-II, age 51-80 years, were randomly assigned to receive infusion of acetated Ringer solution. The G/Mg group received infusion with 1% glucose, Na+ 140mEq/L, Mg2+ 2 mEq/L, and the C group received infusion with glucose free solution containing Na+ 130 mEq/L without Mg2+. Both solutions were infused at a rate of 25 mL/kg for the first hour, and main-tained at 4 mL/kg/hr thereafter. Blood samples were collected three times: before infusion and at 1 hour and 4 hours after the start of infusion. Electrolytes and glucose metabolism were evaluated at each sampling. After rapid infusion, blood glucose level significantly increased to 170+/-19mg/dL in the G/Mg group, but it returned to close to baseline after 4 hours and serum ketone bodies did not increase during infusion. In the C group, however, blood glucose never increased beyond 110 mg/dL, but both acetoacetic and hydroxybutyric acids increased significantly at the third measurement.


Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells.
Previous studies have shown that angiotensin II stimulates the synthesis of plasminogen activator inhibitor-1 in cultured vascular cells, which suggests that activation of the renin-angiotensin system may impair fibrinolysis. We have investigated the effects of angiotensin II and of valsartan, a recently developed angiotensin II antagonist that is highly specific and selective for the angiotensin II subtype 1 receptor, on plasminogen activator inhibitor-1 secretion by smooth muscle cells isolated from rat and human vessels. Angiotensin II induced a time- and concentration-dependent increase of plasminogen activator inhibitor activity in supernatants of rat aortic cells, which reached a plateau after 6 hours of incubation with 100 nmol/L angiotensin II (2.4+/-0.6-fold over control value; P:<0.001). The angiotensin II-induced plasminogen activator inhibitor activity was inhibited, in a concentration-dependent manner, by valsartan with an IC(50) value of 21 nmol/L. Valsartan fully prevented the angiotensin II-induced increase in plasminogen activator inhibitor-1 protein and mRNA. Furthermore, angiotensin II doubled the secretion of plasminogen activator inhibitor-1 by smooth muscle cells obtained from human umbilical and internal mammary arteries, and valsartan fully prevented it. Angiotensin II did not affect the secretion of tissue plasminogen activator antigen by any of the cell systems tested. Thus, valsartan effectively inhibits angiotensin II-induced plasminogen activator inhibitor-1 secretion without affecting that of tissue plasminogen activator in arterial rat and human smooth muscle cells.


Rotational control of unstable subcapital fractures. An experimental study.
An experimental evaluation of the stability of rotational fixation of unstable, subcapital femoral-neck fractures as provided by either the multiple pin and side-plated Deyerle device or the heavy duty Jewett triflanged nail showed no significant difference between the two devices. The determination of moment versus deformation behavior included study of two torsional axis orientations and superposition of simulated body-weight and muscular-force impaction loadings.


Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management.
Surgical ligation of patent ductus arteriosus (PDA) is widely practised in preterm infants despite no clear evidence that this improves outcomes. Geographical isolation meant that ductal ligation was not an option in King Edward Memorial Hospital until recently. A retrospective data analysis to test the hypothesis that outcomes of infants with persistent PDA were no worse than those of infants with no significant duct or a duct that closed after medical treatment. A total of 252 infants (gestation < or =28 weeks) born between 1 January 2000 and 30 June 2002 were divided into three groups: group 1, no significant PDA (n = 154); group 2, significant PDA which closed after medical treatment (n = 65); group 3, significant PDA remaining patent after medical treatment (n = 33). A significant PDA was defined by a left atrium to aortic root ratio of >1.4 or a ductal diameter >1.5 mm with a left to right shunt. Twenty four (10%) infants died at median (interquartile range) 15.5 (9-35) days. After adjustment for gestational age, relative to group 1, the infants from group 3 were at a 4.02 times increased risk of death (95% confidence interval 1.12 to 14.51). There was no significant difference between groups in the incidence of chronic lung disease, chronic lung disease or death, necrotising enterocolitis, intraventricular haemorrhage, duration of oxygen, or hospital stay. Mortality was higher in infants with a persistent PDA, but other morbidities were not significantly different. A randomised trial is needed to determine whether surgical ligation will reduce mortality in such infants.


Making contact: rooting out the potential for exposure of commercial production swine facilities to feral swine in North Carolina.
Despite North Carolina's long history with feral swine, populations were low or absent in eastern counties until the 1990s. Feral swine populations have since grown in these counties which also contain a high density of commercial production swine (CPS) facilities. Sixteen of the highest swine producing U.S. counties also populated with feral swine are in North Carolina. Disconcertingly, since 2009, positive tests for exposure to swine brucellosis or pseudorabies virus have been found for feral swine. We surveyed 120 CSP facilities across four eastern counties to document the level and perception of feral swine activity around CSP facilities and to identify disease transmission potential to commercial stock. Nearly all facility operators (97%) recognized feral swine were in their counties. Far fewer said they had feral swine activity nearby (18%). Our inspections found higher presence than perceived with feral swine sign at 19% of facilities where operators said they had never observed feral swine or their sign. Nearly 90% expressed concern about feral to domestic disease transmission, yet only two facilities had grain bins or feeders fenced against wildlife access. Due to increasing feral swine populations, recent evidence of disease in feral populations, the importance of swine production to North Carolina's economy and the national pork industry, and potential for feral-domestic contact, we believe feral swine pose an increasing disease transmission threat warranting a stringent look at biosecurity and feral swine management at North Carolina CPS facilities.


Posttraumatic stress disorder: a primer for trauma surgeons.
In 1980, posttraumatic stress disorder (PTSD) officially became classified as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition. Since then, there has been increasing recognition that PTSD is a prevalent disorder that may have significant impact on the quality of life for survivors of traumatic events. More recently, methodologically sound research has begun to provide important insight into this disorder. The following review serves to provide the trauma surgeons information on PTSD in terms of its diagnosis, prevalence, risk factors, treatment strategies, and outcomes, with the goal of minimizing the sequelae of PTSD and maximizing postinjury quality of life.


Shrinkage-induced protein tyrosine phosphorylation in Chinese hamster ovary cells.
To investigate the signal transduction of osmotic stress, we examined hypertonicity-induced tyrosine phosphorylations in Chinese hamster ovary cells. Hyperosmosis elicited characteristic phosphotyrosine accumulation in at least 3 proteins (approximately 42, approximately 85, and approximately 120 kDa). The most prominent response occurred in the 85-kDa band (p85) whose phosphorylation was rapid, sustained, apparent already at mild hypertonicity (350 mosM), proportional to the extracellular osmotic concentration, and reversible. Hyperosmotic environment could not induce tyrosine phosphorylation if cell shrinkage was prevented by nystatin and appropriately composed media. Conversely, isotonic shrinkage caused strong tyrosine phosphorylation. Thus, the initial signal is a decrease in cell volume and not an increase in the intra- or extracellular osmotic concentration, or a rise in cytosolic K+ and Cl- levels. Tyrosine phosphorylation of p85 was not due to the hypertonicity-induced protein kinase C-dependent stimulation of the extracellular signal-regulated protein kinase, nor to the activation of stress-activated protein kinases. Tonicity-responsive proteins interacted with Grb2-glutathione S-transferase fusion proteins: the 120-kDa protein complexed with the SH2 and both SH3 domains, whereas p85 associated with the SH2 and the N-terminal SH3 domains of the adapter. Tyrosine phosphorylation of p85 is a sensitive indicator of reduced intracellular hydration and might signify a hitherto unrecognized, early volume-dependent signaling event.


Three-photon absorption in semiconductor quantum dots: experiment.
The four-band model, derived under the effective-mass approximation for cubic semiconductor quantum dots (QDs), is compared with experimental measurements on frequency degenerate three-photon absorption (3PA) in CdSe QDs and ZnS QDs. Qualitatively, the model provides the correct prediction on the magnitude of the 3PA cross-sections, which are in the range from 10(-79) to 10(-77) cm(6)s(2)photon(-2) in the light frequency region of interest. More noticeably, the theoretical conclusion of an increasing tendency in the 3PA cross-sections with increasing dot-size is in agreement with the experiment. The discrepancy is also found for smaller QDs (dot-radius is less than one-third of the exciton Bohr radius), which is attributed to neglecting the mixing among the three valence bands in the theory.


Exploring the cultural appropriateness of a psychosocial intervention, the Thinking Healthy Programme-Peer delivered (THPP), for perinatal depression in Lilongwe, Malawi.
Perinatal depression is a common and disabling mental health problem in Malawi and other Low- and middle-income countries. There is evidence for effective psychosocial interventions for perinatal depression, but no such intervention has been developed for use in Malawi. The broad aim of this study was to explore the cultural appropriateness of a psychosocial intervention for perinatal depression called the Thinking Healthy Programme-Peer delivered for adaptation and use in Lilongwe, Malawi. A qualitative exploratory design was used. Data were collected through conducting five Focus Group Discussions, involving thirty-eight purposefully selected participants including pregnant women, community volunteers and their supervisors, the Health Surveillance Assistants and maternal health care workers at implementation and policy level following observations of video recorded role plays of the Thinking Healthy Programme-Peer delivered sessions in theatre testing. A content analysis approach was used to analyse data. Six main themes were generated regarding the appropriateness of the content and delivery of the Thinking Healthy Programme-Peer delivered intervention, including: 1) Focus of the intervention; 2) Cultural appropriateness of the content; 3) Language used; 4) Context; 5) Provider of the intervention; and 6) Flexibility in the delivery of the intervention. The Thinking Healthy Programme-Peer delivered intervention was deemed appropriate for the target population, though with recommendations to: review illustrations to enhance clarity, use culturally appropriate stories and idioms, use daily spoken language, and adapt the number and duration of sessions to meet the needs of individual clients. These findings highlight important areas to inform adaptation of the Thinking Healthy Programme-Peer delivered and add to the growing evidence of cultural adaptation of psychosocial interventions for perinatal depression.


Diffuse optical multipatch technique for tissue oxygenation monitoring: clinical study in intensive care unit.
Diffuse optical multipatch technique is used to assess spatial variations in absorption and scattering in biological tissue, by monitoring changes in the concentration of oxyhemoglobin and deoxyhemoglobin. In our preliminary study, the temporal tracings of tissue oxygenation are measured using diffuse optical multipatch measurement and a venous occlusion test, employing normal subjects and ICU patients suffering from sepsis and heart failure. In experiments, obvious differences in tissue oxygenation signals were observed among all three groups. This paper discusses the physiological relevance of tissue oxygenation with respect to disease.


Outcomes of atherosclerotic renal artery stenosis managed without revascularization.
To determine how often patients with renal artery stenosis (RAS) managed without revascularization progress to accelerated hypertension and/or renal failure. We examined the outcomes of 68 patients (mean +/- SEM age, 71.8 +/- 0.9 years) with high-grade (>70%) RAS identified between 1989 and 1993 who were treated without renal revascularization for at least 6 months after angiography. The time to last follow-up averaged 38.9 +/- 2.8 months. Other vascular beds were affected in 66 of the 68 patients. End points were revascularization, nephrectomy, dialysis, or death. The mean +/- SEM serum creatinine level rose from 1.4 +/- 0.1 to 2.0 +/- 0.2 mg/dL (P<.001). Mean +/- SEM blood pressure did not change (157 +/- 3/83+/-2 vs 155 +/- 3/79 +/- 2 mm Hg), but the need (mean +/- SEM) for medication increased from 1.6+/-0.1 to 1.9+/-0.1 drugs (P=.02). Four patients (5.8%) eventually underwent renal revascularization for refractory hypertension (1 patient), for progressive stenosis (1 patient), and during aortic reconstruction (2 patients). One additional patient underwent nephrectomy to improve blood pressure control. Five others (7.4%) developed end-stage renal disease (ESRD) for reasons other than progressive vascular disease, namely, diabetes (3 patients), atheroemboli (1 patient), and contrast toxicity without RAS progression (1 patient). In 1 further case, the reason for ESRD was unknown, and it may have been caused by vascular occlusion. During follow-up, 19 patients died of unrelated causes, including myocardial infarction and stroke. These data indicate that antihypertensive medication requirements increased and renal function deteriorated modestly in a subset of patients with atherosclerotic RAS managed initially without vascular intervention. Many achieved stable blood pressure for many years. Deterioration of renal function and mortality risk were greatest in patients with bilateral stenosis or stenosis to a solitary functioning kidney. These results reinforce the need for meticulous follow-up for disease progression but underscore the role of competing risks and high mortality from other cardiovascular diseases, which primarily determine the outcomes in patients with RAS and widespread atherosclerotic disease.


A Population-Based Assessment of Emergency Department Observation Status for Older Adults With Cancer.
Background: Hospitals' use of observation status for patients with cancer presenting to the emergency department (ED) is not well understood. This model of care delivery may be a viable alternative to inpatient admission for patients with cancer presenting with certain conditions. Our objective was to assess the use of observation status among Medicare beneficiaries with and without cancer. Methods: Population-based SEER-Medicare data were used to assess differences in the use of observation status between Medicare beneficiaries aged ≥66 years with and without cancer using a matched analysis (n=151,183 per cohort). We assessed the ratio of observation unit use to inpatient admission, between cancer and noncancer cohorts, and for patients diagnosed with breast, colon, lung, and prostate cancers. Poisson regression models were used to calculate observation rate estimates and 95% CIs while adjusting for selected patient characteristics. Results: When considering the volume of hospitalizations, observation status is used less frequently among beneficiaries with cancer than those without (43 vs 69 observation status visits per 1,000 inpatient admissions, respectively). The estimated observation rate per 1,000 inpatient admissions was higher for beneficiaries aged <75 years versus those aged ≥75 years, those with a Charlson comorbidity index of 0 vs 1 or ≥2, and those without a prior hospitalization versus those with ≥1 prior hospitalizations. Patients with breast and prostate cancers had higher adjusted and unadjusted observation rates per 1,000 inpatient admissions compared with those with colon and lung cancers. Conclusions: Observation status is used proportionately less for beneficiaries with cancer than those without. There may be opportunities to develop standards for ED staff to manage certain conditions for patients with cancer in observation status, and to reserve hospital resources for those who need it most.


Functional hyperemia drives fluid exchange in the paravascular space.
The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that directional fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to examine if arteriolar pulsations and dilations can drive directional CSF flow in the PVS and found that arteriolar wall movements do not drive directional CSF flow. We propose an alternative method of metabolite clearance from the PVS, namely fluid exchange between the PVS and the subarachnoid space (SAS). In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable fluid exchange between the PVS and the SAS. However, when the arteriole dilated, as seen during functional hyperemia, there was a marked exchange of fluid. Simulations suggest that functional hyperemia may serve to increase metabolite clearance from the PVS. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. These measurements showed that brain deforms in response to pressure changes in PVS, consistent with our simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.


Ectopic pregnancy rate increases with the number of retrieved oocytes in autologous in vitro fertilization with non-tubal infertility but not donor/recipient cycles: an analysis of 109,140 clinical pregnancies from the Society for Assisted Reproductive Technology registry.
To study the impact of controlled ovarian stimulation on ectopic pregnancy (EP) rate as a function of the number of oocytes retrieved, using donor IVF cycles as a control. Retrospective cohort study using a large national database. Not applicable. Data from 109,140 cycles from the 2008-2010 SART registry, including 91,504 autologous cycles and 17,636 donor cycles in patients with non-tubal infertility. Varying amounts of oocytes retrieved in autologous and donor IVF. Ectopic pregnancy rates. In autologous cycles, the EP rate significantly increased as oocyte yield increased. This association was not found in oocyte recipients. In autologous IVF cycles, increasing oocyte yield is correlated with a significantly increased EP rate. This association is not found in oocyte recipients, indicating that the increased EP rate may be due to the supraphysiologic hormone levels achieved with controlled ovarian hyperstimulation.


Stereotactic microsurgical craniotomy for the treatment of third ventricular colloid cysts.
The treatment of colloid cysts remains controversial. This article reports on 18 patients with colloid cysts of the third ventricle who presented to the University of Michigan between January 1990 and June 1995. Two patients had conventional transcortical-transventricular approaches; the remaining 16 patients underwent a stereotactic modification of the transcortical approach, using a specially designed cylindrical retractor, for the resection of their colloid cysts. Minor morbidity and no mortality have been associated with this technique. There have been no instances of recurrence during the period of this report. The mean operative time for the two conventional craniotomies was 233 minutes, compared with 129 minutes for the stereotactic craniotomies. Our technique allows for a limited craniotomy and limited cortical disruption. It is not dependent on ventricular size. Localization of the colloid cyst is trivial because of modern stereotactic technology, and all standard microsurgical techniques can be used. The retractor is readily adaptable to any Leksell system. This technique shortens operative time, compared with conventional craniotomy, and allows for definitive treatment of the lesion.


Down-regulation of miR-29b is essential for pathogenesis of uterine leiomyoma.
Uterine leiomyomata (LMs) are the most common tumor affecting the female reproductive organs. The most notable pathophysiologic feature of this tumor is the excessive accumulation of rigid extracellular matrix (ECM) composed mainly of collagen types I and III. It is believed that the rigidity of the collagen-rich ECM causes symptoms such as abnormal bleeding and pelvic pain/pressure. However, the molecular pathogenesis for this ECM-rich tumor has yet to be elucidated. We have established that miR-29b was consistently down-regulated in LM compared with myometrium (MM). Hence, the function of miR-29b in LM was examined in vivo using adult female ovariectomized NOD-scid IL2Rγ(null) mice for subrenal xenograft models. In LM xenografts, restoring miR-29b inhibited the accumulation of ECM and the development of solid tumors. Although the miR-29b knockdown in MM cells increased the expression of collagens, it did not transform MM cells into tumorigenic, indicating that the down-regulation of miR-29b is essential but not sufficient for LM tumorigenesis. In addition, 17β-estradiol and progesterone down-regulated miR-29b and up-regulated mRNAs for multiple collagens in LM xenografts. Thus, we conclude that ECM production in LMs is regulated by steroid hormones via down-regulation of miR-29b, which is one of the mechanisms underlying the excessive accumulation of ECM.


Antibiotic policies for short-term catheter bladder drainage in adults.
Urinary tract infections account for about 40% of hospital-acquired (nosocomial) infections, and about 80% of urinary tract infections acquired in hospital are associated with urinary catheters. To determine if certain antibiotic policies are better than others in terms of prevention of urinary tract infections, complications, quality of life and cost-effectiveness in short-term catheterised adults. We searched the Cochrane Incontinence Group Specialised Register (searched 20 December 2004). Additionally, we examined all reference lists of identified trials. All randomised and quasi-randomised trials comparing antibiotic policies for short-term (up to and including 14 days) catheterization in adults. Data were extracted by both reviewers independently and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. If data had not been fully reported, clarification was sought directly from the authors of the trial. Six parallel-group randomised controlled trials met the inclusion criteria. In one trial comparing antibiotic prophylaxis with giving antibiotics when clinically indicated amongst female surgical patients who had a urethral catheter for more than 24 hours, symptomatic urinary tract infection was less common in the prophylaxis group (RR 0.20, 95% CI 0.06 to 0.66). Five trials compared antibiotic prophylaxis with giving antibiotics when microbiologically indicated, bacteriuria, pyuria and gram-negative isolates in patients' urine were less common in the prophylaxis group amongst surgical patients with bladder drainage for at least 24 hours postoperatively. Bacteriuria rates were also about five-fold lower in the prophylaxis group in trials involving urological surgery patients and non-surgical patients. No trial compared giving antibiotics when microbiologically indicated with giving antibiotics when clinically indicated. There was weak evidence that antibiotic prophylaxis compared to giving antibiotics when clinically indicated reduced the rate of symptomatic urinary tract infection in female patients with abdominal surgery and a urethral catheter for 24 hours. The limited evidence indicated that receiving antibiotics during the first three postoperative days or from postoperative day two until catheter removal reduced the rate of bacteriuria and other signs of infection such as pyuria and gram-negative isolates in patients urine in surgical patients with bladder drainage for at least 24 hours postoperatively. There was also limited evidence that prophylactic antibiotics reduced bacteriuria in non-surgical patients.


Transient triglyceridemia in healthy normolipidemic men increases cellular processing of large very low density lipoproteins by fibroblasts in vitro.
Exaggerated and prolonged postprandial triglyceridemia is a characteristic of patients with precocious coronary heart disease. Although large very low density lipoprotein (VLDL) particles accumulate during alimentary lipemia, the biological properties of the postprandial VLDL remain unknown. In the present study, an intravenous infusion of a chylomicron-like emulsion was given to healthy normolipidemic men to examine the effects of transient triglyceridemia in vivo on compositional and cell biological characteristics of VLDL. The postinfusion large(Svedberg flotation rate (Sf) (60-400) VLDL was found to have increased capacity to inhibit low density lipoprotein (LDL) binding to the LDL-receptor and a greater ability to suppress the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity of cultured fibroblasts compared to VLDL isolated from fasting plasma. These alterations in cellular interactions were accompanied by increases in the number of apolipoprotein (apo) E, C-I, and C-III molecules per large VLDL particle and loss of apoC-II, compositional changes similar to those observed after an oral fat load. The increase in number of apoE molecules per large VLDL particle correlated positively and significantly with the increase in the capacity of large VLDL to inhibit LDL binding to the LDL receptor (r = 0.76, P = 0.01, n = 10). In contrast, the composition of the small (Sf 20-60) VLDL particles did not change significantly, nor was the LDL receptor-mediated processing of these particles altered consistently. These observations indicate that large VLDL particles that accumulate during alimentary lipemia undergo compositional changes that render them more prone to cellular binding and uptake.


Depressive mood accompanies hypercholesterolemia in young Japanese adults.
Screening of young hypercholesterolemics is important because they are highly susceptible to atherosclerotic diseases. However, in some cases, serum cholesterol level may be elevated temporarily due to stress or other psychological factors. This study examined the effects of mood states on 'persistent' hypercholesterolemia in comparison with 'temporary' hypercholesterolemia among students entering a university. The subjects were 114 untreated first-year students aged 18 to 20 years old. All had been screened positive for hypercholesterolemia (serum total cholesterol > or = 220 mg/dl) upon enrolling in the university. Three months after the screening, they were divided into two groups according to the re-examined serum total cholesterol level; a persistent hypercholesterolemic group (n=41) with >220 mg/dl and a temporary hypercholesterolemic group (n=73) with <220 mg/dl. At that time, they completed the Profile of Mood States (POMS) with tension-anxiety, depression, anger-hostility, vigor, fatigue and confusion scales. The POMS depression scores and the female ratio were higher (both p<0.01) and body mass index was lower (p<0.05) in the persistent hypercholesterolemic subjects than in the temporary hypercholesterolemic subjects; the POMS depression scores were still higher (p<0.05) after controlling for the effects of gender, body mass index, and other POMS scales by multiple logistic regression analysis. Depressive mood appeared to relate to hypercholesterolemia when the university students were screened. Assessment of mood states may be important in screening young hypercholesterolemic patients.


Role of spirituality in patients with sickle cell disease.
Patients with sickle cell disease cope with their disease in various ways, such as psychological counseling, hypnosis, medication, and prayer. Spirituality is a coping mechanism in a variety of diseases. This study evaluates the role of spirituality in patients coping with the pain of sickle cell disease. Seventy-one patients from the Georgia Sickle Cell Clinic completed a questionnaire addressing their ability to cope with the pain of sickle cell disease and their degree of spirituality. A descriptive cross-sectional design was used. Correlation and multiple regression analyses were calculated for the relation between coping with the pain of sickle cell disease and spirituality. The questionnaire provided several scales with high internal consistency for measuring spiritual well-being and its two components, existential well-being and religious well-being, that show a correlation between high levels of spirituality and life control. The study population exhibited high levels of spirituality and religiosity, but the influence of these feelings on coping with sickle cell disease was variable. Spiritual well-being was correlated with life-control but not with perceived pain severity. Existential well-being was associated with general coping ability. Spiritual well-being is important for some patients who must cope with the pain of sickle cell disease.


EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.
The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1beta and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.


Releasing the Brake on the Immune System: The PD-1 Strategy for Hematologic Malignancies.
Manipulation of the immune system as a viable cancer treatment strategy has re-emerged. The programmed death 1 (PD-1) pathway is an important, physiologic immune checkpoint necessary to limit autoimmune processes but co-opted by tumors to suppress the antitumor response and allow tumor escape. Blockade of the PD-1 pathway through the use of PD-1 or PD ligand 1(PD-L1) antibodies releases this brake on the immune response. The anti-PD-1 antibodies have produced encouraging results across a broad range of malignancies. Many hematologic malignancies have usurped the PD-1 pathway. Recent investigations have explored the use of anti-PD-1 therapy in hematologic malignancies, with encouraging results. Incorporation of PD-1 blockade into the treatment algorithms for hematologic malignancies is currently being pursued in multiple active clinical trials. Here we review the data on anti-PD-1 monoclonal antibodies to date and discuss ongoing and future clinical trials.


Lunar maria: structure and evolution.
The lunar maria are considered to have evolved as homologous, transient, gravity-wave systems from large impact craters on a crustal layer 50 kilometers thick, fluidized from beneath by prompt, shock-induced melting inside an initially hot moon.


Prognostic factors for a favorable outcome after varicocele repair in adolescents and adults.
The effect of varicocele repair on male fertility remains controversial. It would be helpful to determined which men would benefit most from varicocele repair, and target repair efforts at those individuals. A detailed review of the literature on prognostic factors for varicocele repair was performed using the PubMed NLM database. We found that the best predictor of postvaricocelectomy semen parameters is the preoperative semen parameters. The greatest improvements in semen parameters were found in men with larger varicoceles. While there is controversy, higher testosterone, younger age and larger testis size, in some studies predict for improvements in semen parameters postvaricocelectomy. A nomogram has been developed to predict the postvaricocelectomy semen parameters based on the preoperative semen parameters, varicocele grade and the age of the man (www.fertilitytreatmentresults.com). Limited data consistently demonstrates the greatest improvements in DNA fragmentation rates in men with higher baseline DNA fragmentation rates. With respect to reproductive outcomes, higher baseline sperm density consistently predicts for natural pregnancy or assisted reproductive technology (ART) pregnancy rates. In addition, varicocele repair does seem to reduce the need for more invasive modalities of ART. In conclusion, we can now start to use specific parameters such as baseline semen quality, varicocele grade and patient age to predict post-repair semen quality and fertility potential following varicocelectomy.


The relationship between weight and smoking in a national sample of adolescents: Role of gender.
This study sought to investigate the role of weight status and body mass index percentile in risky smoking behaviors in male and female adolescents. Analyses of the data obtained in the 2011 Youth Risk Behavior Surveillance System were conducted. The national sample size included 15,425 adolescents. Questions addressing weight status and smoking behaviors were used in analyses. Significant effects of perceived weight status, weight change status, and body mass index percentile on smoking behaviors were found for both genders. The current findings indicate the importance of accounting for both gender and weight status when developing prevention and cessation programs targeting smoking behaviors.


RBD class 1 and 2 antibody epitopes elicit around 70% neutralizing capacity against SARS-CoV-2 virus following boosting with inactivated virus vaccine.
A third dose of inactivated virus vaccine (IVV) boosts neutralizing antibodies, reducing SARS-CoV-2 transmission rate and COVID-19 severity. However, the impact of RBD-elicited antibodies and their neutralizing activity by the boost of IVV is unknown. We investigated the impact of IVV's boost shot on RBD-elicited antibodies and their neutralizing activity in 18 subjects receiving the second and third IVV doses. Using an RBD antibodies depletion assay, we assessed the neutralizing activity of RBD-elicited antibodies. After the second dose, RBD-antigen elicitation accounted for ∼60% of neutralizing activity, which increased to 82% after the IVV boost against ancestral SARS-CoV-2. Depleting class 3 and class 4-specific antibodies with the Beta-RBD protein revealed that NAbs targeting RBD class 1 and class 2 subdomains increased from 57% to 75% post-boost. These findings highlight the significant enhancement of RBD-specific antibodies, especially against RBD class 1 and class 2, with IVV booster doses. Our study offers valuable insights for optimizing COVID-19 vaccine strategies.


Docosahexaenoic acid (DHA), an omega-3 fatty acid, inhibits tumor growth and metastatic potential of ovarian cancer.
Omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish oil, are thought to have anti-tumorigenic effects and may help to treat and prevent cancer, including ovarian cancer. Thus, we aimed to evaluate the potential of docosahexaenoic acid (DHA), an omega-3 PUFA, as a therapeutic agent in ovarian cancer cell lines and a transgenic mouse model of ovarian cancer. DHA significantly inhibited cellular proliferation, induced cell cycle arrest and caused apoptosis in Hey and IGROV-1 cells. Pre-treatment with the anti-oxidant, N-acetylcysteine (NAC), reversed DHA-induced caspase 3 activity and prevented DHA-reduced cell proliferation. DHA also induced cellular reactive oxygen species (ROS) and inhibited adhesion and invasion in IGROV-1 and Hey cells. Furthermore, treatment with DHA demonstrated anti-tumorigenic and anti-invasive activity in a K18-gT121 +/-; p53fl/fl; Brca1fl/fl mouse model of ovarian cancer including downregulation of Ki67 and VEGF expression. The data provide a preclinical rationale for applying DHA for dietary intervention and therapeutic adjunct in patients with ovarian cancer.


The impact of hepatitis B on heart transplantation: 19 years of national experience in Korea.
Hepatitis B virus (HBV) infection is endemic in Korea. With an increasing number of heart transplantation, problems associated with hepatitis B reactivation are becoming an important issue. We aimed to evaluate the functional significance of HBV infection on outcomes of heart transplantation. We reviewed all medical records of overall national heart transplantation recipients and donors who had HBV hepatitis at the time of the transplantation, from March 1994 to May 2013. We investigated the HBV serology status, HBV-DNA level of donors and recipients, liver function test, immunosuppressive agent and antiviral agent prescription, and hepatitis morbidity and mortality. 1) There were 12 HBsAg (+) recipients and 6 HBsAg (+) donors. Median duration of follow-up was 1715 days (minimum 162 days to maximum 6553 days). 2) Nine HBsAg (+) recipients (75%), who continued antiviral treatment, have survived without any hepatic event. Reactivation of HBV developed in 3 recipients at a median duration of 238 days after transplantation. They died of fulminant hepatitis despite antiviral rescue therapy. 3) In contrast, 6 recipients with immunity to HBV before the transplantation, who had received heart from HBV (+) donors, have survived without any liver-related event. HBV (+) recipients have perioperative results and long-term survival rates comparable to HBV (-) recipients. However, absence or cessation of antiviral prophylaxis indiscriminately brought reactivation of HBV, which rapidly progressed to hepatic failure and death. In contrast, HBV (+) hearts transplanted to HBV-immune recipients were maintained without hepatitis reactivation. Nineteen years of national experience strongly suggests that long-term antiviral prophylaxis is necessary for HBV (+) recipients.


NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling.
The activity-dependent remodeling of postsynaptic structure is a fundamental process underlying learning and memory. Insulin receptor substrate p53 (IRSp53), a key player in cytoskeletal dynamics, is enriched in the postsynaptic density (PSD) fraction, but its significance in synaptic functions remains unclear. We report here that IRSp53 is accumulated rapidly at the postsynaptic sites of cultured hippocampal neurons after glutamate or NMDA stimulation in an actin cytoskeleton-dependent manner. Pharmacological profiles showed that a PKC inhibitor, but not other kinase inhibitors, specifically suppressed the synaptic translocation of IRSp53 in response to NMDA, and the selective activation of PKC with phorbol ester markedly induced the synaptic translocation. Reverse transcriptase-PCR and Western blotting showed that IRSp53-S is the major isoform expressed in cultured hippocampal neurons. The synaptic targeting of IRSp53-S was found to be mediated through N-terminal coiled-coil domain and the PDZ (PSD-95/Discs large/zona occludens-1)-binding sequence at its C-terminal end and regulated by the PKC phosphorylation of its N terminus. In electrophysiological experiments, overexpression of IRSp53-S wild type and IRSp53-S mutant that is spontaneously accumulated at the postsynaptic sites enhanced the postsynaptic function as detected by an increased miniature EPSC amplitude. These data suggest that IRSp53 is involved in NMDA receptor-linked synaptic plasticity via PKC signaling.


Therapeutic Argentine Tango Dancing for People with Mild Parkinson's Disease: A Feasibility Study.
Individuals living with Parkinson's disease (PD) can experience a range of movement disorders that affect mobility and balance and increase the risk of falls. Low health-related quality of life, depression, and anxiety are more common in people with PD than age-matched comparisons. Therapeutic dance is a form of physical activity believed to facilitate movement and therapy uptake. As well as being enjoyable, dancing is thought to improve mobility, balance, and well-being in some people living with PD. The primary objective of this study was to evaluate the feasibility and safety of a 4-week Argentine tango dance program for people with PD. Six community dwelling individuals with mild to moderate PD were recruited from Parkinson's support groups, movement disorder clinics, and the PD association in Australia. To minimize falls risk, participants were required to be <75 years of age and physically independent (Hoehn and Yahr stages I-III). They were also required to speak English. Participants attended a 1-hour dance class at a dance studio twice per week for 4 weeks. A professional dance instructor led and choreographed the Argentine tango dance classes. Physiotherapists were present to assist participants during the class and served as dance partners as necessary. The primary outcome was feasibility, which was determined by measures of recruitment, adherence, attrition, safety (falls, near misses and adverse events), and resource requirements. Secondary measures included the Beck Depression Inventory and the Euroqol-5D, administered at baseline and post intervention. Therapy outcomes pre- and post-intervention were analyzed descriptively as medians and interquartile ranges and using Wilcoxon matched pair signed-rank tests. The Argentine tango dance intervention was shown to be safe, with no adverse events. Adherence to the dance program was 89%. Depression scores improved after intervention (p = 0.04). Some challenges were associated with the need to quickly recruit participants and physiotherapists to act as dance partners during classes and to monitor participants. The 4-week, twice weekly Argentine tango dancing program was shown to be feasible and safe for people with mild-to-moderately severe PD.


Consultations between patients with breast cancer and surgeons: a pathway from patient-centered communication to reduced hopelessness.
Patient-centered communication (PCC) affects psychosocial health outcomes of patients. However, these effects are rarely direct, and our understanding of such effects are largely based on self-report (v observational) data. More information is needed on the pathways by which concrete PCC behaviors affect specific psychosocial outcomes in cancer care. We hypothesized that PCC behaviors increase the satisfaction of patients with surgeons, which, in turn, reduces the postconsultation hopelessness of patients. In Portland, OR, we videotaped consultations between 147 women newly diagnosed with breast cancer and nine surgeons and administered surveys to participants immediately preconsultation and postconsultation. Consultations were coded for PCC behaviors. Multivariate regression models analyzed the association between PCC and the satisfaction of patients and between satisfaction and hopelessness. Levels of hopelessness of patients significantly decreased from preconsultation to postconsultation (P < .001). Two PCC behaviors (ie, patient asserting treatment preference [odds ratio {OR}, 1.50/log unit; 95% CI, 1.01 to 2.23/log unit; P = .042] and surgeon providing good/hopeful news [OR, 1.62/log unit; 95% CI, 1.01 to 2.60/log unit; P = .047]) were independently significantly associated with the satisfaction of patients with surgeons, which, in turn, independently predicted reduced levels of postconsultation hopelessness (linear change, -0.78; 95% CI, 1.44 to -0.12; P = .02). Although additional research is needed with larger and more-diverse data sets, these findings suggest the possibility that concrete and trainable PCC behaviors can lower the hopelessness of patients with breast cancer indirectly through their effects on patient satisfaction with care.


Brazilian Consensus on Endoscopic Sleeve Gastroplasty.
Bariatric endoscopy is a less invasive approach for obesity management, with better efficacy than pharmacological treatment and low morbidity. Endoscopic sleeve gastroplasty (ESG) is the remodeling of the stomach using a suturing device showing technical feasibility, safety, and sustained weight loss. With growing numbers of procedures worldwide, there is a need to standardize the procedure. A consensus meeting was held in São Caetano do Sul-SP, Brazil, in June 2019, bringing together 47 Brazilian endoscopists with experience in ESG from all regions of the country. Topics on indications and contraindications of the procedure, pre-procedure evaluation and multidisciplinary follow-up, technique and post-procedure follow-up, and training requirements were discussed. An electronic voting was carried, and a consensus was defined as ≥ 70% agreement. The panel's experience consisted of 1828 procedures, with a mean percentage total body weight loss (TBWL) of 18.2% in 1 year. Adverse events happened in 0.8% of the cases, the most common being hematemesis. The selected experts discussed and reached a consensus on several questions concerning patient selection, contraindications for the procedure, technical details such as patient preparation, procedure technique, and patient follow-up. This consensus establishes practical guidelines for performance of ESG. The experience of 1828 procedures shows the expertise of the selected specialists participating in this consensus statement. The group's experience has a satisfactory weight loss with low adverse events rate. The main points discussed in this paper may serve as a guide for endoscopists performing ESG. Practical recommendations and technique standardization are described.


Identification and evaluation of LPS antigen for serodiagnosis of uveitis associated with leptospirosis.
Leptospirosis is a widespread zoonotic disease that affects all mammals in different parts of the world. Though there are many commercial kits available for the diagnosis of systemic leptospirosis, the nature of the antigen has not been described. Therefore, identification of a specific antigen is important. Since ocular involvement in leptospirosis has been reported, there is a need to identify and characterize the leptospiral antigen for diagnosis of uveitis associated with past leptospiral infection (leptospiral uveitis) and for confirming the clinical diagnosis. Seven-day-old culture of Leptospira biflexa serovar Patoc was used for preparing the antigen. The present study included serum samples from 81 patients with clinical criteria for leptospiral uveitis, 15 cataract controls and 15 non-leptospiral uveitis controls. Serum samples were assayed by ELISA using our antigenic preparation and by a microscopic agglutination test (MAT) using 19 serovars. The antigen prepared had 280 micro g LPS ml(-1) and no detectable amount of protein. Silver-staining of SDS-PAGE for protein and LPS, dot blot and Western blot analysis and proteinase K and periodate treatment showed that LPS (13-21 kDa and 28 kDa) in our preparation was the relevant antigen for serodiagnosis. IgG antibodies showed reactivity in both leptospiral uveitis patients and controls. However, on the basis of IgM response to LPS, 48 % of the leptospiral uveitis patients were significantly positive compared with controls; 58 % of leptospiral uveitis patients and none of the controls were positive for MAT. When MAT and IgM ELISA results were considered together, 77 % were significantly positive. LPS is identified as a candidate antigen for serodiagnosis of leptospiral uveitis and has sensitivity and specificity of 48 and 90 %, respectively, in ELISA for IgM antibodies. Confirmation of clinical diagnosis with a specific laboratory test would help to initiate the most appropriate treatment for leptospiral uveitis.


Prevalence of hepatitis E and hepatitis B dual infection in North India (Delhi).
The prevalence of dual infection was 2.8% (26/927). Majority of these patients had presented with acute flare of a chronic liver disease (42.3%) followed by acute jaundice (38.5%).We found HEV infection to be was highly prevalent among 20 to 40 years of age group. In the case of HBV only 5.37% (5/93) children were affected in the age group 0-10 years. Serum samples from 1147 proven HEV infection suspected were collected and tested for HBsAg and HEV (IgM) antibodies using enzyme linked immunosorbent assay kits (bio Merieux, France). There were the 32.16% (367/1141) HEV positive cases. We found maximum HEV positivity in the age group of 21-30 years. There were 2.8% (26/927) HEV and HBV dully infected patients. The total 44.68% (273/611) suspected of acute hepatitis/jaundice were HEV positive. The HEV found to be was highly prevalent among 20 to 40 years of age group. The males were more frequent than females for HEV and HBV infection. In the children's, there were lower attack of both HEV and HBV. The maximum patients were having acute hepatitis/jaundice in both HEV and HBV infection. There were 26 dually infected patients in 12 months.


Understanding the nano-photonics absorption limit in both front-side and front/rear-side textured slabs.
Surface texturing is one of the main techniques to enhance light absorption in solar cells. In thin film devices, periodic texturing can be used to excite the guided resonances supported by the structure. Therefore, total absorption is enhanced largely due to the excitation of these resonances. Although the maximum absorption enhancement limit in both bulk and photonic structures is known already, the weight of each resonance type in this limit is not yet clear. In this contribution, we extend the temporal couple-mode theory, deriving a closed formula to distinguish the contribution of Fabry-Perot and wave-guided modes within the absorption limit for 1-D grating structures. Secondly, using this analytical approach, we can clearly address cases of bulk and thin absorber thicknesses. Our results, supported by rigorous electromagnetic calculation, show that absorption enhancement in a 1-D grating structure can be much higher than the nano-photonic limit (2πn) reported by Yu et al. Thirdly, beyond the framework put forward by Yu et al., we extended our theory to describe the absorption enhancement in double side textured slabs. We have found that when the periods of top and bottom gratings are aliquant, absorption is enhanced in a wider frequency range. We provide rigorous numerical calculations to support our theoretical approach.


Circulating markers of neutrophil activation and lung injury in pediatric pneumonia in low-resource settings.
Diagnostic biomarkers for childhood pneumonia could guide management and improve antibiotic stewardship in low-resource settings where chest x-ray (CXR) is not always available. In this cross-sectional study, we measured chitinase 3-like protein 1 (CHI3L1), surfactant protein D (SP-D), lipocalin-2 (LCN2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in Ugandan children under the age of five hospitalized with acute lower respiratory tract infection. We determined the association between biomarker levels and primary end-point pneumonia, indicated by CXR consolidation. We included 89 children (median age 11 months, 39% female). Primary endpoint pneumonia was present in 22 (25%). Clinical signs were similar in children with and without CXR consolidation. Broad-spectrum antibiotics (ceftriaxone) were administered in 83 (93%). Levels of CHI3L1, SP-D, LCN2 and TIMP-1 were higher in patients with primary end-point pneumonia compared to patients with normal CXR or other infiltrates. All markers were moderately accurate predictors of primary end-point pneumonia, with area under receiver operator characteristic curves of 0.66-0.70 (p<0.05 for all markers). The probability of CXR consolidation increased monotonically with the number of markers above cut-off. Among 28 patients (31%) in whom all four markers were below the cut-off, the likelihood ratio of CXR consolidation was 0.11 (95%CI 0.015 to 0.73). CHI3L1, SP-D, LCN2 and TIMP-1 were associated with CXR consolidation in children with clinical pneumonia in a low-resource setting. Combinations of quantitative biomarkers may be useful to safely withhold antibiotics in children with a low probability of bacterial infection.


CLINICAL AND PATHOLOGIC FINDINGS OF AN OUTBREAK OF VITAMIN D3-RESPONSIVE METABOLIC BONE DISEASE IN HERON AND EGRET (FAMILY ARDEIDAE) CHICKS FED CAPELIN (MALLOTUS VILLOSUS).
An increase in cases of metabolic bone disease (MBD) in chicks of six species of heron and egret (family Ardeidae) was identified at a wildlife rehabilitation center in the spring and summer of 2018. The outbreak affected 34.3% of birds in care for four or more days during the first 3 mo of the study and was the most common reason for euthanasia during that time. Cases were characterized by lameness, increased flexibility of multiple long bones, angular deformities, and bone fractures. Gross postmortem examinations were conducted on 145 nestlings and fledglings that died or were euthanatized either because of MBD or for unrelated conditions. Histology was performed in four cases and three controls. Histologic findings were characterized by multiple lesions in the appendicular long bones, including variable elongation of the physis, retention of cartilage cores in the metaphyseal primary spongiosa, poorly mineralized osteoid seams within the primary spongiosa, thinning or lack of diaphyseal cortical bone compaction, and folding fractures typically propagating through the physis-metaphyseal interface. Folding fractures were often associated with focal metaphyseal fibroplasia. The parathyroid gland diameter of birds diagnosed postmortem with MBD in care was significantly larger than that of unaffected birds. The authors hypothesized that a dietary deficiency of vitamin D3 because of low levels in the bird's captive diet of capelin (Mallotus villosus) was the cause of the MBD. Starting in mid-July every chick's diet was supplemented with 714 IU oral vitamin D3/kg body weight per day, after which the number of birds developing MBD declined to a rate of 4.3%. This study characterizes the clinical, gross, radiographic, and histologic features of vitamin D3-responsive MBD in young herons and egrets and provides evidence to support the recommendation that captive birds on a diet of capelin be supplemented with vitamin D3, especially during growth.


Amoebic liver abscesses complicated by inferior vena cava and right atrium thrombus.
Amoebiasis is a common protozoal infection that is endemic in South Asia. Hepatic involvement that manifests as abscess formation occurs in approximately 10% of all patients. Identified expeditiously, this can be treated with metronidazole. We present a case of multiple, large amoebic liver abscesses, that were complicated by thrombus formation in the inferior vena cava extending to the right atrium, requiring surgical removal.


Digital quantitative measurements of gene expression.
One of the primary goals of functional genomics is to provide a quantitative understanding of gene function. However, the success of this enterprise is dependent on the accuracy and precision of the functional genomic data. A novel approach, digital analysis of gene expression (DAGE) described herein, is an accurate and precise technology for measuring digital gene expression on a relative or absolute scale by simply counting the number of transcripts of a gene being expressed at a given time. The result is a greatly improved technology sensitive enough for identifying and quantifying small (but biologically important and statistically relevant) changes in gene expression. Fourteen genes involved in galactose metabolism in Saccharomyces cerevisiae were analyzed for their expression levels in glucose and galactose minimal media. The quantitative expression results were characterized in terms of distributional and accuracy attributes; they were also in general agreement (in terms of direction of change) with corresponding results obtained using microarray technology. DAGE is likely to have profound implications in the field of functional genomics because the gene expression measurements are digital in nature and therefore more accurate than any other technologies.


Members of the Arabidopsis HRT/RPP8 family of resistance genes confer resistance to both viral and oomycete pathogens.
Turnip crinkle virus (TCV) inoculation onto TCV-resistant Arabidopsis leads to a hypersensitive response (HR) controlled by the dominant gene HRT. HRT is a member of the class of resistance (R) genes that contain a leucine zipper, a nucleotide binding site, and leucine-rich repeats. The chromosomal position of HRT and its homology to resistance gene RPP8 and two RPP8 homologs indicate that unequal crossing over and gene conversion may have contributed to HRT evolution. RPP8 confers resistance to an oomycete pathogen, Peronospora parasitica. Despite very strong similarities within the HRT/RPP8 family, HRT and RPP8 are specific for the respective pathogens they detect. Hence, the HRT/RPP8 family provides molecular evidence that sequence changes between closely related members of multigene families can generate novel specificities for radically different pathogens. Transgenic plants expressing HRT developed an HR but generally remained susceptible to TCV because of a second gene, RRT, that regulates resistance to TCV. However, several transgenic plants that overexpressed HRT produced micro-HRs or no HR when inoculated with TCV and were resistant to infection. Expression of the TCV coat protein gene in seedlings containing HRT resulted in massive necrosis and death, indicating that the avirulence factor detected by the HRT-encoded protein is the TCV coat protein.


Nanoscale morphology revealed at the interface between colloidal quantum dots and organic semiconductor films.
The degree of interpenetration at the interface between colloidal quantum dots (QDs) and organic semiconductor molecules commonly employed in hybrid light-emitting devices (QD-LEDs) has been examined using tapping-mode atomic force microscopy. Both phase separation-driven and Contact Printing-enabled QD/semiconductor heterojunction fabrication methodologies lead to significant QD embedment in the underlying organic film with the greatest degree of QD penetration observed for QD monolayers that have been contact printed. The relative performance of QD-LEDs fabricated via three different methods using the same materials set has also been investigated.


Detection of Intestinal Protozoa in Trichrome-Stained Stool Specimens by Use of a Deep Convolutional Neural Network.
Intestinal protozoa are responsible for relatively few infections in the developed world, but the testing volume is disproportionately high. Manual light microscopy of stool remains the gold standard but can be insensitive, time-consuming, and difficult to maintain competency. Artificial intelligence and digital slide scanning show promise for revolutionizing the clinical parasitology laboratory by augmenting the detection of parasites and slide interpretation using a convolutional neural network (CNN) model. The goal of this study was to develop a sensitive model that could screen out negative trichrome slides, while flagging potential parasites for manual confirmation. Conventional protozoa were trained as "classes" in a deep CNN. Between 1,394 and 23,566 exemplars per class were used for training, based on specimen availability, from a minimum of 10 unique slides per class. Scanning was performed using a 40× dry lens objective automated slide scanner. Data labeling was performed using a proprietary Web interface. Clinical validation of the model was performed using 10 unique positive slides per class and 125 negative slides. Accuracy was calculated as slide-level agreement (e.g., parasite present or absent) with microscopy. Positive agreement was 98.88% (95% confidence interval [CI], 93.76% to 99.98%), and negative agreement was 98.11% (95% CI, 93.35% to 99.77%). The model showed excellent reproducibility using slides containing multiple classes, a single class, or no parasites. The limit of detection of the model and scanner using serially diluted stool was 5-fold more sensitive than manual examinations by multiple parasitologists using 4 unique slide sets. Digital slide scanning and a CNN model are robust tools for augmenting the conventional detection of intestinal protozoa.


Effects of combined postischemic hypothermia and delayed N-tert-butyl-alpha-pheylnitrone (PBN) administration on histopathologicaland behavioral deficits associated with transient global ischemia in rats.
Previous cerebral ischemia studies have reported the limitations of restricted periods of postischemic hypothermia in producing long-term neuroprotection. The present experiment attempts to determine whether delayed treatment with the free radical scavenger N-tert-butyl-a-phenylnitrone (PBN) is protective at 2 months following transient global forebrain ischemia, and whether additive effects can be observed when PBN is administered in combination with moderate hypothermia. For this aim rats were subjected to 10 min of two-vessel forebrain ischemia followed by (a) 3 h of postischemic normothermia (37 degrees C); (b) 3 h of postischemic hypothermia (30 degrees C); (c) normothermic procedures combined with delayed injections of PBN (100 mg/kg) on days 3, 5 and 7 post-insult; (d) postischemic hypothermia combined with delayed PBN treatment; or (e) sham procedures. Outcome measures included cognitive behavioral testing and quantitative histopathological analysis at 2 months. Postischemic PBN injections induced a systemic hypothermia (1.5 degrees C-2.0 degrees C) that lasted for 2-2.5 h. Water maze testing revealed significant performance deficits relative to shams in the normothermic ischemic group, with the postischemic hypothermia and PBN groups showing intermediate values. A significant attenuation of cognitive deficits was observed in the animal group receiving the combination postischemic hypothermia and delayed PBN treatment. Quantitative CA1 hippocampal cell counts indicated that each of the ischemia groups exhibited significantly fewer viable CA1 neurons compared to sham controls. However, in rats receiving either delayed PBN treatment or 3 h of postischemic hypothermia, significant sparing of CA1 neurons relative to the normothermic ischemia group was observed. These data indicate that hypothermia combined with PBN treatment provides long-term cognitive improvement compared to nontreatment groups. PBN-induced mild hypothermia could contribute to the neuroprotective effects of this pharmacological strategy.


Microvascular invasion in hepatocellular carcinoma: is it predictable with quantitative computed tomography parameters?
To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI. Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively). Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC.


Two Cases of Subvesical Bile Duct Injury Detected and Repaired Simultaneously during Laparoscopic Cholecystectomy.
Subvesical bile duct (SVBD) injury is a secondary major cause of minor bile duct injury after laparoscopic cholecystectomy (LC). However, this injury is usually not recognized intraoperatively, but postoperatively. Case 1: the patient was an 84-year-old female, preoperatively diagnosed with acute cholecystitis. During LC, a tiny hole in the gallbladder fossa from which bile juice oozing was confirmed. Suturing was performed laparoscopically. Case 2: the patient was an 81-year-old male, preoperatively diagnosed with cholelithiasis. Because of a previous history of gastrectomy, laparoscopic adhesiolysis around the gallbladder was performed. During dissection, a small amount of bile was oozing from the surface of the liver adjacent to the gallbladder fossa. Suturing was performed laparoscopically. If a small amount of bile juice was detected, meticulous observation not only around the cystic duct stump but also the gallbladder fossa should be performed. Simultaneous laparoscopic suturing was feasible, and an ideal procedure against SVBD injury developed during LC.


Association of IGF1 with glycemic control and occurrence of severe hypoglycemia in patients with type 1 diabetes mellitus.
GH is implicated in the counter-regulatory response to hypoglycemia. We tested whether IGF1 levels are associated with occurrence of severe hypoglycemic events in patients with type 1 diabetes and whether the IGF1 concentration is influenced by glycemic control. A total of 228 outpatients with type 1 diabetes were included in a post hoc analysis of a 1-year observational study on severe hypoglycemia. Serum total IGF1 was measured at entry into the study. The occurrence of severe episodes of hypoglycemia, mild symptomatic, and biochemical as well as hypoglycemia awareness status was assessed. Also patients were included in a multiple regression analysis to investigate the role of HbA1c in the IGF1 concentration. IGF1 levels were associated with neither severe hypoglycemia in the entire cohort (P=0.30) nor in any gender nor when confining the analysis to those with long-standing diabetes (>20 years) (n=112, P=0.68) and those with both long-standing diabetes and undetectable C-peptide (n=51, P=0.067). Levels of IGF1 were associated with neither mild symptomatic hypoglycemia (P=0.24) nor biochemical hypoglycemia (0.089) nor hypoglycemia awareness (P=0.16). At a multiple regression analysis, HbA1c was negatively associated with IGF1 (P=0.001). In type 1 diabetes, circulating IGF1 levels are negatively associated with glycemic control. However, IGF1 levels were not associated with occurrence of hypoglycemia or hypoglycemia awareness in these patients.