[Basophil CD63 expression in the blood of the anaphylactic shock rat].
To explore the value of flow cytometry in anaphylactic shock diagnosis by CD63 expression being detected using flow cytometry to conform the activation of basophils. Sixteen rats were randomly divided into two groups: control group and anaphylactic shock group. The model of anaphylactic shock rat with ovalbumin injection was established. CD63, CD45 and CD203c antibody combination, flow cytometry was employed to detected blood basophil CD63 expression. Immunofluorescence method was employed to observe the CD63 immunofluorescence staining in the rat lung tissue. (1) Pure basophils were obtained by CD45 and CD203c gating. (2) The percentages of basophils CD63 were (17.34 +/- 2.04)% and (1.52 +/- 0.35)% in the experimental and control group, respectively. The differences between two groups were statistically significant (P < 0.01). (3) Compared with the control group, the expression of CD63 in basophils increased in anaphylactic shock lung tissue. The detection of CD63 by flow cytometry could be the supplement of vivo allergic reactions and have good clinical value.


Inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islet cells with anti-ICAM-1 antibodies.
Cognate recognition of antigen-presenting cells by antigen-specific T cells is critically dependent on non-cognate adhesive interactions. For instance, several studies have shown that in vivo anti-LFA-1 plus anti-ICAM-1 mAb treatment results in prolongation of allograft survival. We have developed a xenogeneic islet transplant model to investigate the role of various adhesion interactions in the xenogeneic response and study the effect of pretreating donor tissue with immunosuppressive drugs. Pancreatic islet cells were pretreated in vitro with anti-human ICAM-1 mAb, transplanted under the renal capsule of diabetic B6 mice in the absence of systemic immunosuppression and examined for long-term xenograft acceptance. The survival of human islets pretreated with anti-human ICAM-1 was significantly prolonged (MST = 53 days, with 40% of grafts surviving > 100 days). In contrast, the survival of human islets pretreated with the control antibody was similar to those of nontreated islets (MST = 7 days). A massive lymphocyte infiltrate into control xenografts was observed at 5 days post-transplant. In contrast, a lymphocyte infiltrate did not appear in the anti-ICAM-1-treated islets for at least 11 days. Only mAbs specific for the LFA-1 binding epitope of ICAM-1 were found to inhibit a mixed islet/lymphocyte reaction in vitro and block graft rejection in vivo. However, graft prolongation is not accompanied by systemic tolerance. Mice transplanted simultaneously with human islet cells treated with control Ig (left kidney) or anti-ICAM-1 (right kidney) rejected the control islets but not anti-ICAM-1-treated islets. These results suggest that the LFA-1/ICAM-1 interaction is a critical component for xenograft rejection and, more important, that pretreatment of islet tissue with anti-adhesion molecule antibodies can profoundly alter graft recognition and rejection in the absence of any systemic drug therapy. However, graft prolongation is not accompanied by systemic tolerance induction.


Frontoethmoidal mucocele presenting as progressive enophthalmos.
In this case report we describe a 27-year-old man who presented with progressive enophthalmos for 5 months without any other associated ocular symptoms such as pain, diplopia, or visual disturbance. Computed tomography showed that his progressive enophthalmos originated from a frontoethmoidal mucocele and this caused destruction of the lamina papyracea and shrinkage of the ethmoidal air cell. Finally the enlarged orbital space caused an inward deviation of the eyeball. Endoscopic marsupialization was successfully performed by an otolaryngologist and did not result in any ophthalmologic sequelae. Although frontoethmoidal sinus mucoceles mostly frequently originates from orbital mucoceles, enophthalmic manifestations are very rare. Enophthalmic conditions are not as responsive to surgical interventions as exophthalmic conditions.


An interview with Robert S. Lane, Ph.D. Interviewed by Vicki Glaser.
Dr. Robert Lane received a B.A. degree in psychology from the University of California at Berkeley (UCB), an M.A. degree in biology at San Francisco State College, and a Ph.D. in entomology at UCB. While employed as a California State public health biologist he began his long-standing studies of the biology of ticks and the ecology and epidemiology of tick-borne disease agents. In 1984, Dr. Lane joined the faculty of UCB as a medical entomologist, a position he has held until the present. The diseases he and his many co-workers have investigated include Colorado tick fever, human granulocytic anaplasmosis, relapsing fever, Rocky Mountain spotted fever, tularemia, and particularly Lyme disease. Findings from these studies have elucidated the basic transmission cycles of and risk factors for spotted fever-group rickettsiae and Lyme disease spirochetes in the far western United States. Bob is a Fellow of both the California Academy of Sciences and the American Association for the Advancement of Science, a recipient of a UCB Biology Faculty Research Award and the C.W. Woodworth Award from the Pacific Branch of the Entomological Society of America, and a member of the Council for the International Congresses of Entomology. Also, he has served as president of the Acarological Society of America, the International Northwestern Conference on Diseases in Nature Communicable to Man, the Northern California Parasitologists, and the Society for Vector Ecology, as well as the Chair of Section D (Medical/Veterinary Entomology), Entomological Society.


The cytology of micropapillary variant of colloid carcinoma of breast: A report of two cases.
Colloid carcinoma (pure mucinous carcinoma) is an uncommon variant of breast carcinoma with distinctive cytological and histological features. These tumors are characterised by islands of tumor cells floating in a sea of abundant extracellular mucin. We present the cytology of two cases of colloid carcinoma occurring in 80-year-old and 45-year-old females. The fine-needle aspiration cytology helps to subcategorize the tumor type, thereby enhancing the knowledge about the distinctive cytological features of special and uncommon variants of breast carcinoma, their course and prognosis. A distinctive micropapillary variant of pure mucinous carcinoma which is rarely described, is represented in one of the cases. Also we report, here, colloid carcinoma in a female of reproductive age, a relatively uncommon occurrence.


The clinical research on the effect of hydrogen-rich water on primary retinitis pigmentosa.
To investigate the feasibility and effectiveness of hydrogen in the treatment of retinitis pigmentosa (RP) patients through the drinking of hydrogen-rich water (HRW). RP patients clinically diagnosed in our hospital were selected and given HRW for drinking at 400-500 ml twice a day for four consecutive weeks. Changes in best corrected visual acuity (BCVA), intraocular pressure, the retinal thickness, and choroidal thickness, as well as the amplitude and peak time of visual electrophysiological examinations before and after HRW drinking were observed. Data were statistically analyzed. In total, 24 eyes of 13 patients with RP (3 males and 10 females aged-27-65 years old, were enrolled in the study. The BCVA after HRW drinking was 0.34 ± 0.25, which was statistically improved compared with that before (P < 0.05). There were no significant differences in intraocular pressure, retinal lhickness, or choroidal thickness before and after HRW drinking (all P > 0.05). The amplitudes of the b-wave in Dark-adaptation 0.01 response, a and b waves in Dark-adaptation 3.0 response, the Dark-adaptation Ops total wave, a and b waves in Light-adaptation 3.0 response, and the Light-adaptation Flicker response of electroretinogram (ERG) were significantly higher than those before HRW drinking (all P < 0.05). The corresponding peak times iwere mproved to some extent compared to those before HRW consumption (all P < 0.05). Six patients with RP (11 eyes) had a BCVAm ore than 20/200. The amplitude and peak time of the P100 -ave from the 1°p attern visual evoked potentials (PVEP) were not significantly different from those before HRW drinking (P > 0.05), while the data from the 15' PVEP were statistically different (P < 0.05). Seven patients with RP (13 eyes) had a BCVA less than. 20/200 No significant differences were found in the amplitude and peak time of the P2 wave from the 1.0 Hz flash visual evoked potentials (FVEP) and the amplitude from the 12 Hz FVEP compared with those before HRW drinking (all P > 0.05). Short-term HRW drinking slightly improved visual function in patients with primary RP, whereas no significant improvement was found in the thickness of the retina and choroid.


Caenorhabditis elegans as a model in developmental toxicology.
A number of practical advantages have made the nematode Caenorhabditis elegans a useful model for genetic and developmental biological research. These same advantages, along with conservation of disease and stress response pathways, availability of mutant and transgenic strains, and wealth of biological information, have led to the increased use of C. elegans in toxicological studies. Although the potential to study the mechanisms of developmental toxicology in C. elegans is promising, embryonic and larval growth tests to identify compounds that affect the nematode have remained the primary use of C. elegans in developmental toxicology. Here, we describe a C. elegans larval growth and development assay for medium- and high-throughput screening using the COPAS Biosort flow cytometer and provide descriptions of the data and subsequent analysis.


[Trabeculotomy and goniotomy in congenital glaucoma].
The authors evaluated efficiency of antiglaucomatous surgery in 73 eyes of 50 children, staying under clinical control in the years 1969-1991. It was showed that after trabeculectomy, as the primary procedure, intraocular pressure was normalized much more often (40.9%) than after goniotomy (20.2%). In cases operated many times using different technics, more effective was goniotomy. Better visual acuity was found in cases with intraocular pressure well controlled after one surgical procedure. The most common complications connected with surgery were discussed.


Effects of dexamethasone on pancreatic tissue and on serum amylase and lipase activities in dogs.
The effects of dexamethasone on the pancreas and on pancreatic amylase and lipase activities were determined in clinically normal dogs and in dogs with neurologic disease. Dexamethasone increased serum lipase activity without any histologic damage to the pancreas in either group of dogs. It decreased serum amylase activity in the normal dogs and had a variable effect in dogs with neurologic disease, with or without confirmed pancreatitis. It was suggested that high serum lipase activity in dexamethasone-treated dogs may not be attributable to pancreatitis and that the reasons are still unknown. It was concluded that high serum lipase activity is an unreliable basis for diagnosis of pancreatitis in dogs treated with dexamethasone. The data allowed no conclusion about an additive effect of dexamethasone and neurologic disease causing pancreatitis.


Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration.
A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO(2)) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1) (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for SO(2) with an accuracy in the latter in the range -6%-+7%.


Compliance of asthmatic families with a primary prevention programme of asthma and effectiveness of measures to reduce inhalant allergens--a randomized trial.
Compliance to and the effect of pre- and post-natal exposure reduction measures to prevent asthma in high-risk children from asthmatic families were studied. Families were randomized to a special care group (n=222) and a control group (n=221). Educational advice on measures to reduce their newborn's exposure to allergens and smoke was provided to the special care group during three visits (two pre-natal and one post-natal). The control group (n=221) received usual care. After the intervention, the special care group differed significantly (P<0.01) from the usual care group in: use of anti-mite encasings (parental: 88% vs. 14%; baby: 98% vs. 10%); keeping pets outside (51% vs. 19%); combined breast- and hypoallergenic formula feeding (55% vs. 22%); first solids postponement until after the sixth month (71% vs. 28%); maternal post-natal smoking (52% vs. 28%). Little or no compliance was found for other sanitary measures (cleaning habits, providing a smooth floor covering, ventilation/airing, pet removal), exclusive breastfeeding, pre-natal smoking and partner smoking. In spite of pre-existent low allergen levels in both groups, there was a significant reduction of mite, cat, and dog allergens on the mattresses and mite and cat allergens in the living room in the special care group and were significantly lower compared with the usual care group after 1 year. High compliance was found for the use of anti-mite encasings; substantial compliance for using hypoallergenic formula, solid food postponement, keeping pets outside and reported post-natal maternal smoking. There was no compliance for sanitary measures and the reduction of maternal pre-natal passive smoking. Mite and pet allergens on mattresses were strongly reduced by anti-mite encasings.


Somatic variation in living, wild ring-tailed lemurs (Lemur catta).
While understanding somatic variability among wild primates can provide insight into natural patterns of developmental plasticity, published data for living populations are rare. Here we provide such information for two distinct wild populations of Lemur catta. Variants observed include microtia, athelia, and female virilization. Dental variants observed include individuals with supernumerary teeth, rotated teeth, maxillary incisor agenesis, and severe malocclusion. There was a sex bias in incisor agenesis, with 5 of 7 examples (71%) found in males. The frequency of dental variants in our sample is lower than that seen in many other lemuriformes, as well as other primates. This may be a product of their less derived dental formula and/or their relatively fast dental development. Amassing such data is a critical first step to assess if wild primate populations are exhibiting normal variability or are being affected by potential inbreeding and/or environmental effects.


Haemolytic uraemic syndrome.
Haemolytic uraemic syndrome (HUS) is a heterogeneous group of diseases that result in a common pathology, thrombotic microangiopathy, which is classically characterised by the triad of non-immune microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. In this Seminar, different causes of HUS are discussed, the most common being Shiga toxin-producing Escherichia coli HUS. Identifying the underlying thrombotic microangiopathy trigger can be challenging but is imperative if patients are to receive personalised disease-specific treatment. The quintessential example is complement-mediated HUS, which once carried an extremely high mortality but is now treated with anti-complement therapies with excellent long-term outcomes. Unfortunately, the high cost of anti-complement therapies all but precludes their use in low-income countries. For many other forms of HUS, targeted therapies are yet to be identified.


Base of tongue salivary gland tumors.
Salivary tumors of the base of the tongue are encountered infrequently. A retrospective review of medical records from 1955 to 1985 was undertaken to determine the incidence of occurrence and to assess the outcome of the therapy provided. One hundred seventy-eight minor salivary gland tumors of the oral cavity and oropharynx were identified, of which 22 (13%) were located in the tongue base. All were malignant. The most common histologic type was mucoepidermoid carcinoma (10 patients), followed by adenocarcinoma (6 patients), and adenoid cystic carcinoma (6 patients). Thirteen patients were available for a mean follow-up of 5 years. Treatment was most often a combination of wide resection combined with postoperative radiation therapy. Ten patients (77%) are alive, one with persistent disease 8 years after diagnosis. Three patients died within 2 years of diagnosis, one with intercurrent disease. Improved control of disease in this series, when compared to previously reported series, is attributed to adequate surgical therapy and adjuvant radiotherapy. The deaths in our series occurred in patients who were unable to proceed with the recommended therapy. These unusual lesions require aggressive multimodality treatment for improved survival.


Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy.
Background Noninvasive identification of glioma subtypes is important for optimizing treatment strategies. Purpose To compare the in vivo neurochemical profiles between isocitrate dehydrogenase (IDH) 1-mutant 1p/19q codeleted gliomas and their noncodeleted counterparts measured by MR spectroscopy at 3.0 T with a point-resolved spectroscopy (PRESS) sequence optimized for D-2-hydroxyglutarate (2HG) detection. Materials and Methods Adults with IDH1-mutant gliomas were retrospectively included for this study from two university hospitals (inclusion period: January 2015 to July 2016 and September 2019 to June 2021, respectively) based on availability of 1p/19q codeletion status and a PRESS acquisition optimized for 2HG detection (echo time, 97 msec) at 3.0 T before any treatment. Spectral analysis was performed using LCModel and a simulated basis set. Metabolite quantification was performed using the water signal as a reference and correcting for water and metabolite longitudinal and transverse relaxation time constants. Concentration ratios were computed using total creatine (tCr) and total choline. A two-tailed unpaired t test was used to compare metabolite concentrations obtained in codeleted versus noncodeleted gliomas, accounting for multiple comparisons. Results Thirty-one adults (mean age, 39 years ± 8 [SD]; 19 male) were included, and 19 metabolites were quantified. Cystathionine concentration was higher in codeleted (n = 13) than noncodeleted (n = 18) gliomas when quantification was performed using the water signal or tCr as references (2.33 mM ± 0.98 vs 0.93 mM ± 0.94, and 0.34 mM ± 0.14 vs 0.14 mM ± 0.14, respectively; both P < .001). The sensitivity and specificity of PRESS to detect codeletion by means of cystathionine quantification were 92% and 61%, respectively. Other metabolites did not show evidence of a difference between groups (P > .05). Conclusion Higher cystathionine levels were detected in IDH1-mutant 1p/19q codeleted gliomas than in their noncodeleted counterparts with use of a PRESS sequence optimized for 2HG detection. Of 19 metabolites quantified, only cystathionine showed evidence of a difference in concentration between groups. Clinical trial registry no. NCT01703962 © RSNA, 2023 See also the editorial by Lin in this issue.


Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits.
Magnesium sulfate (MgSO4) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO4 in rabbits. Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO4 150-200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1-2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO4 was not different from that in the group without MgSO4. The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P < 0.001); there were no other significant differences among the groups. The reversal of sugammadex from a deep rocuronium-induced NMB during large pretreatment of MgSO4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose.


DNA Polymer Nanoparticles Programmed via Supersandwich Hybridization for Imaging and Therapy of Cancer Cells.
Spherical nucleic acid (SNA) constructs are promising new single entity materials, which possess significant advantages in biological applications. Current SNA-based drug delivery system typically employed single-layered ss- or ds-DNA as the drug carriers, resulting in limited drug payload capacity and disease treatment. To advance corresponding applications, we developed a novel DNA-programmed polymeric SNA, a long concatamer DNA polymer that is uniformly distributed on gold nanoparticles (AuNPs), by self-assembling from two short alternating DNA building blocks upon initiation of immobilized capture probes on AuNPs, through a supersandwich hybridization reaction. The long DNA concatamer of polymeric SNA enables to allow high-capacity loading of bioimaging and therapeutics agents. We demonstrated that both of the fluorescence signals and therapeutic efficacy were effectively inhibited in resultant polymeric SNA. By further modifying with the nucleolin-targeting aptamer AS1411, this polymeric SNA could be specifically internalized into the tumor cells through nucleolin-mediated endocytosis and then interact with endogenous ATP to cause the release of therapeutics agents from long DNA concatamer via a structure switching, leading to the activation of the fluorescence and selective synergistic chemotherapy and photodynamic therapy. This nanostructure can afford a promising targeted drug transport platform for activatable cancer theranostics.


Laser peripheral iridotomy versus laser peripheral iridotomy plus laser peripheral iridoplasty in the treatment of multi-mechanism angle closure: study protocol for a randomized controlled trial.
China has the largest burden of primary angle-closure glaucoma (PACG) worldwide. The mechanism of the angle closure is complex and includes pupillary block and non-pupillary block. Currently, opinion is that laser peripheral iridotomy (LPI) alone is not sufficient to prevent disease progression. Laser peripheral iridoplasty (LPIP) is an alternative and effective way of widening the angle recess in eyes that are affected by primary angle closure (PAC). However, it is not known if greater benefit would be achieved using LPI plus LPIP for PAC with multiple mechanisms (MAC). Thus, the aim of this study is to demonstrate if LPI plus LPIP would be more effective than single LPI in controlling the progression of PAC with multiple mechanisms, based on ultrasound biomicroscopy (UBM) classification. A secondary aim is to determine whether or not this would result in the use of less medication and/or prolong the time to antiglaucoma surgery. This multiple-mechanism angle-closure study will comprise a 3-year, multicenter, randomized, parallel-group, open-label, superiority trial, the aim of which will be to evaluate the safety and efficacy of LPI plus LPIP versus LPI for PAC. It is anticipated that 240 adults, diagnosed with PAC (the mechanism of angle closure will be assessed by UBM and it will be determined whether or not it involves multiple mechanisms) will be recruited from ten ophthalmic centers in China. Participants will be randomly allocated to receive either single LPI or LPI plus LPIP. Participant assessment will be designed to test the rate of disease progression and who will be followed up for 3 years. The primary outcome will be the disease progression rate and a comparison will be made between the LPI and LPI plus LPIP groups using Pearson's χ2 test. Logistic regression analysis will be performed to account for the central effect. If the LPI plus LPIP is found to significantly decrease the rate of PAC progression, this intervention could potentially be a standard therapy to be used to treat PAC when multiple mechanisms are involved in angle closure. Subsequently, this would have the potential to delay the rate of PAC progression to PACG and delay the time to the administration of antiglaucoma medication or trabeculectomy surgery. ClinicalTrials.gov, NCT02613013 . Registered on 24 November 2015. In fact, the study was due to start in late October 2015, however, there were no patients recruited in October, and when we registered at ClinicalTrials.gov on 5 November 2015, we received suggestions on the English translation of our protocol from the PRS Team at Clinicaltrial.gov, so the final successful registration date was on 24 November 2015.


Morphological, Pathogenic, and Molecular Characterization of Colletotrichum acutatum Isolates Causing Almond Anthracnose in Spain.
Almond anthracnose is a serious and emerging disease in several countries. All isolates causing almond anthracnose have been assigned to the Colletotrichum acutatum species complex, of which only C. fioriniae and C. godetiae have been associated with the disease to date. Here, we characterized Colletotrichum isolates from almond fruit affected by anthracnose in the Andalusia region. Two Colletotrichum isolates causing olive anthracnose were included for comparison. Morphological characteristics were useful for separating the isolates into groups based on colony morphology. Pathogenicity tests in almond, olive, and apple fruit showed differences in virulence and some degree of pathogenic specialization among isolates. Molecular characterization allowed clear identification of the Colletotrichum isolates tested. The olive isolates were identified as C. godetiae and C. nymphaeae, both previously identified in Andalusian olive orchards. Two phylogenetic species were identified among the almond isolates: C. godetiae, with gray colonies, which is well known in other countries, and C. acutatum, with pink-orange colonies. This species identification differs from those of pink-colony subpopulations described in other countries, which are C. fioriniae. Therefore, this study is also the first report of a new species of Colletotrichum causing almond anthracnose within the C. acutatum species complex.


Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine.
Cytotoxic drugs, such as nucleoside analogs and toxins, commonly suffer from off-target effects. One approach to mitigate this problem is to deliver the cytotoxic drug selectively to the intended site. While for toxins this can be achieved by conjugating the cell-killing moiety to a targeting moiety, it is not an option for nucleoside analogs, which rely on intracellular enzymes to convert them to their active triphosphorylated form. To overcome this limitation, and achieve site-targeted activation of nucleoside analogs, we fused the coding region of a prodrug-activating enzyme, deoxycytidine kinase (dCK), to affinity reagents that bind to the Her2 cell surface protein. We evaluated dCK fusions to an anti-Her2 affibody and Designed Ankyrin Repeat Protein (DARPin) for their ability to kill cancer cells by promoting the activation of the nucleoside analog fludarabine. Cell staining and flow cytometry experiments with three Her2 positive cancer cell lines (BT-474-JB, JIMT-1 and SK-OV-3) indicate dCK fusions binding and cellular internalization. In contrast, these reagents bind only weakly to the Her2 negative cell line, MCF-7. Cell proliferation assays indicate that SK-OV-3 and BT-474-JB cell lines exhibit significantly reduced proliferation rates when treated with targeting-module fused dCK and fludarabine, compared to fludarabine alone. These findings demonstrate that we have succeeded in delivering active dCK into the Her2-positive cells, thereby increasing the activation of fludarabine, which ultimately reduces the dose of nucleoside analog needed for cell killing. This strategy may help establish the therapeutic index required to differentiate between healthy tissues and cancer cells.


Body sway characteristics during static upright posture in healthy and disordered elderly.
This study aimed to compare body sway characteristics of the healthy elderly and the disordered elderly. The subjects were 38 healthy elderly and 24 disordered elderly with disequilibrium. The latter consisted of two groups: 12 elderly with vestibular organ or central nervous systems disorder (central nervous disorders), and 12 elderly with disorder in other systems (other disorders). The measurement device can calculate the center of foot pressure (CFP) of vertical loads from the values of three vertical load sensors, which are located at the corners of an isosceles triangle on a level surface. The data sampling frequency was 20 Hz. Four body sway factors with high reliability (unit time sway, front-back sway, left-right sway, and high frequency band power) were used to evaluate body sway. As compared with healthy people, central nervous disorders had larger unit time sway, high frequency band power, and left-right sway factors. Other disorders were larger in unit time sway and high frequency band power factors. Central nervous disorders, as compared with other disorders, had larger unit time sway and left-right sway factors. Disorders produced large and fast sway, and central nervous disorders in particular showed a marked sway in the left-right direction. The existence of disease influenced body sway more than decline in various functions related to posture control with aging, because even with the same elderly, disorders showed a larger body sway.


Determination of isopropyl thioxanthone (ITX) in fruit juices by pressurized liquid extraction and liquid chromatography-mass spectrometry.
A rapid LC-MS method, which compares different mass analyzers-single quadrupole, ion trap, and triple quadrupole-was developed for the quantitative determination of isopropyl thioxanthone (ITX) in fruit juices. ITX, a photoinitiator in UV-cured inks that can reach foods from the cartons for beverages in which they are used, was extracted from fruit juice samples with acetone/hexane (50:50) using pressurized liquid extraction. This method gave detection limits of 3, 3, and 0.01 microg/L and quantification limits of 10, 10, and 0.05 microg/L using single quadrupole, ion trap, and triple quadrupole, respectively. Five replicate fortifications of different fruit juices at the quantification limit gave recoveries oscillating between 68 and 72% with CV varying between 14 and 18%. This is the first report of a positive mass spectrometric identification and quantification of ITX in fruit juice samples packed in TetraPack. The sensitivity and specificity of the LC-MS/MS analysis using the triple quadrupole enables it to be the method of choice for risk assessment and monitoring. The method was applied to apricot, orange, peach, apple, grape and pineapple, and cherry and strawberry juices and to fruit nectars from Spain and Italy, and the ITX was detected in the range of 0.05-0.78 microg/L.


DNase II is a member of the phospholipase D superfamily.
DNase II is an endodeoxyribonuclease involved in apoptosis and essential for the mammalian development. Despite the understanding of biochemical properties of this enzyme, its structure and relationships to other protein families remain unknown. Using protein fold-recognition we found that DNase II exhibits a catalytic domain common to the phospholipase D superfamily. Our model explains the available experimental data and provides the first structural platform for sequence-function analyses of this important nuclease.


Autophagy promotes cell motility by driving focal adhesion turnover.
In eukaryotic cells, cell migration is a dynamic and complex process that involves finely tuned orchestration of a multitude of proteins including, for example, those involved in focal adhesions (FAs). Cell migration plays an indispensable role in particular stages of development and its proper regulation is crucial in various biological processes, from wound healing to the immune response. FAs are transmembrane protein complexes that traverse cytoskeletal infrastructures all the way to the extracellular matrix, producing traction at the leading edge of the cell, thus allowing for motility. The assembly of FAs has been extensively studied, whereas disassembly remains poorly understood. Here, we highlight 2 recent studies (see the corresponding puncta in the previous and current issues of the journal) that demonstrate a requirement for macroautophagy/autophagy in FA disassembly. These studies also provide a deeper understanding of how autophagy can contribute to cell migration among multiple cell types.


[Development of diagnostically and therapeutically useful human antibody medicines by phage display system].
Phage display has been utilized for making recombinant antibody fragments (Fab or single chain Fv) of human, mouse, or other origins. After construction of an antibody combinatorial library, antigen-specific recombinant antibody fragments can be easily isolated by biopanning of the phage library displaying antibody fragment fused with viral coat protein III against antigen proteins, antigen-expressing live cells, or fixed cells. Using this technique, a variety of human recombinant antibody fragments can be retrieved from bone marrow cells, lymph node cells, or peripheral blood cells of patients with infectious diseases, autoimmune diseases, and cancer. To develop diagnostically and therapeutically useful human antibody medicines, we should first select recombinant antibody fragments not only with antigen-binding activity but also with bioactivity such as virus or toxin neutralization, or tumor-specific cytotoxicity. To achieve this goal, several steps in antibody phage display may be improved: 1) a larger library should be constructed for possible isolation of minor populations present in the repertoire; 2) the biopanning procedure should be improved for isolation of antibody fragments reactive with immunologically minor epitopes; 3) the screening procedure should be based on the measurement of the bioactivity as well as the antigen-binding activity; 4) if necessary, the affinity and specificity of selected antibody fragments should be improved. In this review, I discuss how to isolate clinically useful recombinant antibody fragments efficiently using a phage display system introducing our achievements.


Olfactory regulation of mosquito-host interactions.
Mosquitoes that act as disease vectors rely upon olfactory cues to direct several important behaviors that are fundamentally involved in establishing their overall vectorial capacity. Of these, the propensity to select humans for blood feeding is arguably the most important of these olfactory driven behaviors in so far as it significantly contributes to the ability of these mosquitoes to transmit pathogens that cause diseases such as dengue, yellow fever and most significantly human malaria. Here, we review significant advances in behavioral, physiological and molecular investigations into mosquito host preference, with a particular emphasis on studies that have emerged in the post-genomic era that seek to combine these approaches.


Evaluation of the morphologic characteristics and prevalence of canine urocystoliths from a regional urolith center.
To determine whether morphology of single-mineral urocystoliths and age, sex, or breed data could be applied to facilitate radiographic and clinical urocystolith mineral type prediction, respectively, in dogs. Database of 2,041 dogs with pure mineral composition urocystoliths. All uroliths were characterized according to geologic descriptive terminology and by breed, sex, and age of dog at time of sample submission. Summary statistics were used to compare features with specific mineral types. Observed trends were analyzed for statistical relevance between observed and expected frequencies for age, sex, color, size, shape, and surface, using the null hypothesis that differences by urocystolith mineral type did not exist. On the basis of expected breed occurrence derived by equations, the null hypothesis that urocystolith occurrence paralleled canine breed popularity was tested. Urocystoliths > 10 mm in any dimension were > 92% likely to be magnesium ammonium phosphate hexahydrate (MAP). Smooth, blunt-edged or faceted, and pyramidal urocystoliths were usually MAP. Jackstone shapes were almost always silica. Botryoidal (grape-like clusters) urocystoliths were likely to be oxalates. Breeds with high relative likelihood of urocystoliths included: English Bulldog, Pekingese, Pug, Welsh Corgi, and West Highland White Terrier. Breeds with low relative likelihood of urocystolith production included: German Shepherd Dog, Shar-Pei, and German Shorthaired Pointer. About 94% of urocystoliths produced in females or spayed females were MAP, whereas males and neutered males produced a greater assortment. For pure mineral composition urocystoliths, trends in mineral type among breeds and between sexes can be exploited clinically in the diagnosis and management of urolith-related disease. Size and shape, used in conjunction with age, breed, and sex, can facilitate pure urocystolith mineral type prediction.


Self-Reported Gastrointestinal Symptoms in Type 2 Diabetes Improve With an Intensive Lifestyle Intervention: Results From the Action for Health in Diabetes (Look AHEAD) Clinical Trial.
In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.


The potential elimination of Plasmodium vivax malaria by relapse treatment: insights from a transmission model and surveillance data from NW India.
With over a hundred million annual infections and rising morbidity and mortality, Plasmodium vivax malaria remains largely a neglected disease. In particular, the dependence of this malaria species on relapses and the potential significance of the dormant stage as a therapeutic target, are poorly understood. To quantify relapse parameters and assess the population-wide consequences of anti-relapse treatment, we formulated a transmission model for P. vivax suitable for parameter inference with a recently developed statistical method based on routine surveillance data. A low-endemic region in NW India, whose strong seasonality demarcates the transmission season, provides an opportunity to apply this modeling approach. Our model gives maximum likelihood estimates of 7.1 months for the mean latency and 31% for the relapse rate, in close agreement with regression estimates and clinical evaluation studies in the area. With a baseline of prevailing treatment practices, the model predicts that an effective anti-relapse treatment of 65% of those infected would result in elimination within a decade, and that periodic mass treatment would dramatically reduce the burden of the disease in a few years. The striking dependence of P. vivax on relapses for survival reinforces the urgency to develop more effective anti-relapse treatments to replace Primaquine (PQ), the only available drug for the last fifty years. Our methods can provide alternative and simple means to estimate latency times and relapse frequency using routine epidemiological data, and to evaluate the population-wide impact of relapse treatment in areas similar to our study area.


Gastrointestinal Hemorrhage From Esophageal Dissecans Superficialis After the Initiation of a Tyrosine Kinase Inhibitor.
Esophagitis dissecans superficialis (EDS) is described as the peeling of squamous mucosa of the esophagus with regurgitation of esophageal casts. It is a rare endoscopic finding associated with chemical irritants, autoimmune disorders, or medications. Most patients are asymptomatic but clinical manifestations can include dysphagia, heartburn, bleeding, or vomiting. In this report, we present a case of a 70-year-old man with a previous history of small cell lung and hepatocellular carcinoma for which he had undergone chemoradiation and immunotherapy. He had presented with upper gastrointestinal hemorrhage manifested as coffee ground emesis. Endoscopic findings were consistent with EDS. No recurrence of his gastrointestinal hemorrhage was observed after acid-suppressive therapy. With our case report, we aim to increase awareness for EDS as a differential diagnosis for gastrointestinal hemorrhage.


Lack of fluconazole effects on human chemosensation.
Drug effects on the function of smell and taste are occasionally mentioned in prescription information however, most originate from anecdotal reports without even distinguishing between gustatory or olfactory deteriorations. This includes the antifungal fluconazole. In a randomized, placebo-controlled, double-blind, two-way crossover study, 12 healthy men and 9 healthy women (age 26.8 ± 3.7 years) took oral doses of 400 mg fluconazole or placebo once daily for 8 days. Gustatory and olfactory functions were tested before and after the treatment using clinically validated tests ("Taste Strips" and "Sniffin' Sticks", respectively). Baseline taste scores of 12.3 ± 2.2 and 12.5 ± 1.7 for the fluconazole and placebo conditions, respectively, corresponded to normative values. Similarly, baseline (pretreatment) composite olfactory TDI scores (odor "€œthreshold discrimination identification"€) of 35.0 ± 3.2 and 35.7 ± 4.3 for men and 34.8 ± 4.2 and 35.5 ± 2.8 for women during the fluconazole or placebo conditions, respectively, corresponded to normative values. Neither gustation nor olfaction was significantly affected by the fluconazole treatment. The present study provided a negative result regarding fluconazole effects contrasting, for example, with those of sildenafil in a comparatively powered study [1]. Up to the tested dose of 400 mg/d, fluconazole does not have general and reproducible effects on taste and smell in healthy humans. However, it was unlikely to detect rare disturbances with the present study cohort size, and, therefore, rare fluconazole side effects on human chemosensation, as occasionally reported, remain a possibility.


[Polish stomatological bibliography--an attempt of elaboration in the central medical library].
Piloting computer printout of the polish stomatological bibliography for the years of 1982, 1983 based on the data from polish medical literature collected in the Central Medical Library has been discussed. Opinions of users have been quoted. You were informed about Central Medical Library possibilities to prepare and issue bibliography.


MRI Based Validation of Abdominal Adipose Tissue Measurements From DXA in Postmenopausal Women.
Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We sought to validate VAT and SAT area (cm2) from historical DXA scans against MRI. Participants (n = 69) from the Women's Health Initiative (WHI) completed a 3 T MRI scan and a whole body DXA scan (Hologic QDR2000 or QDR4500; 2004-2005). A subset of 43 participants were scanned on both DXA devices. DXA-derived VAT and SAT at the 4th lumbar vertebrae (5 cm wide) were analyzed using APEX software (v4.0, Hologic, Inc., Marlborough, MA). MRI VAT and SAT areas for the corresponding DXA region of interest were quantified using sliceOmatic software (v5.0, Tomovision, Magog, Canada). Pearson correlations between MRI and DXA-derived VAT and SAT were computed, and a Bland-Altman analysis was performed. Participants were primarily non-Hispanic white (86%) with a mean age of 70.51 ± 5.79 years and a mean BMI of 27.33 ± 5.40 kg/m2. Correlations between MRI and DXA measured VAT and SAT were 0.90 and 0.92, respectively (p ≤ 0.001). Bland-Altman plots showed that DXA-VAT slightly overestimated VAT on the QDR4500 (-3.31 cm2); this bias was greater in the smaller subset measured on the older DXA model (QDR2000; -30.71 cm2). The overestimation of DXA-SAT was large (-85.16 to -118.66 cm2), but differences were relatively uniform for the QDR4500. New software applied to historic Hologic DXA scans provide estimates of VAT and SAT that are well-correlated with criterion MRI among postmenopausal women.


Recreational drugs: relationship to AIDS.
Current data suggest that a transmissible agent causes AIDS, but undefined cofactors may also play a role. This paper reviews published data on the relationship between recreational drugs and immune alterations, with particular emphasis on nitrite inhalant (NI) use by homosexual men. In our original cohort of 15 homosexual men, helper:suppressor (H:S) T-cell ratios are stable, but persistently lower in the NI users. A recent analysis of 245 homosexual men shows that NI use is associated with low H:S ratios in homosexual men in Washington, D.C., but not in New York. Although NI use could increase the risk of AIDS by direct or indirect effects, it could also be a surrogate for a lifestyle practice that predisposes homosexual men to the putative AIDS agent. The current evidence concerning use of NI and the risk of AIDS is inconclusive, as is true for two other recreational drugs, heroin and cocaine. Future studies may not be able to dissect the complex interrelationships of drug use and other variables until precise laboratory tests are available for defining exposure to the putative AIDS agent and suspect cofactors.


The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility complex and to the T cell receptor loci.
Most of the gammadelta T cells in the intestinal epithelium of normal mice use the Vgamma1 or the Vgamma7 gene segments. However, the relative proportions of gammadelta intraepithelial lymphocytes expressing either the Vgamma1 or the Vgamma7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gammadelta T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vgamma1, Vgamma4, Vgamma7, and Vdelta4 to examine the TCR repertoire of intraepithelial gammadelta lymphocytes in a set of (C57BL/6 x DBA/2) recombinant inbred strains. Our results show that the representation of different Vgamma and Vdelta gene products among gammadelta intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRgamma, TCRdelta, and major histocompatibility complex loci.


Association of periodontitis with preterm birth and low birth weight: a comprehensive review.
It is estimated that six million perinatal deaths occur every year worldwide, with premature birth being the main cause. Scientific evidence has shown that there is an association between periodontal health during pregnancy and adverse outcomes of labor, although interventional studies based on the treatment of periodontitis have failed to document an impact on reducing the incidence of preterm birth (PB) or low birth weight (LBW). Two pathogenic mechanisms have been proposed to explain this association. The direct pathway is based on the presence of gram-negative anaerobic bacteremia originating in the gingival biofilm, whereas the indirect pathway involves the production of pro-inflammatory markers which enter the bloodstream from the gingival submucosa. The result is the same: the development of an immune inflammatory response and/or the local suppression of growth factors in the fetal-placental unit, which in turn triggers labor. In the present review, we describe current concepts pertinent to PB and LBW, chronic and aggressive periodontitis, and the most frequent aspects of periodontal pathology during pregnancy. We evaluate the scientific evidence available to date, and offer a detailed description of the two pathways proposed to explain the association of maternal periodontitis with preterm and LBW delivery.


Electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometric analysis of extrapolysaccharides of Escherichia coli.
Conventional studies of extracellular polymeric substances (EPS) typically require elaborate separation procedures or complicated sample pretreatment processes such as purification by dialysis and lyophilization. The objective of this study is to demonstrate the use of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) as powerful techniques for direct analysis of EPS secreted by E. coli. We have compared the extraction efficiency of two widely used extraction methods including physical extraction (room-temperature centrifugation and high-speed centrifugation) and chemical extraction using EDTA and formaldehyde. We specify the most favorable extraction method and the analyte to extractant concentration with respect to mass spectrometric analysis of EPS, based on the results obtained from ESI-MS and MALDI-MS analysis. Chemical extraction methods were found to be more efficient than physical extraction methods. Of the chemical extractants, EDTA was found more effective compared to formaldehyde and gave more EPS peaks during ESI- and MALDI-MS analysis. We report the classification of E. coli EPS into loosely bound, bound and tightly bound EPS based on a simple modification of an existing methodology. Our studies showed that ESI-MS was very effective for <300 Da EPS studies and MALDI-MS more suitable for rapid analysis of EPS above mass range 400 Da. This is a preliminary study reporting for the first time the feasibility of ESI-MS and MALDI-MS techniques for the analysis of bacterial EPS without prior complicated purification and separation methodologies.


Effects of dexamethasone on human synovial fibroblast-like cells, from osteoarthritic joints, in culture.
The effect of Dexamethasone (DEX) on cell division and macromolecular synthesis was investigated in a line (McCoy cells, A 9) of synovial fibroblast-like cells derived from human osteoarthritic joints. DEX markedly reduced the proliferation of McCoy cells in a time and dose-dependent manner. The maximal inhibition (45%) was found at 500 nM DEX 24 h after incubation and was accompanied by the appearance of giant macrophage-like cells. After DEX treatment cells showed increased content of DNA, proteins and RNA together with the reduction of [3H]-thymidine incorporation into the TCA-precipitable fraction.


High-resolution gas chromatography/mass spectrometric analysis of tobacco and marijuana sterols.
Components of the sterol fraction of tobacco and marijauna were resolved as trimethylsilyl derivatives by gas chromatography with glass capillary columns. Ten phytosterols in tobacco and five in marijuana were identified by comparisons of their retention with authentic compounds on three different stationary phases and through mass-spectral data.


A rarely seen case among retroperitoneal mass lesions: paraganglioma.
Pheochromocytomas are rarely seen cathecolamine-secreting neuroendocrine tumors. Diagnosis, treatment, and prognosis of this rarely seen condition have been discussed. In this study, a retroperitoneal paraganglioma with a diameter of 27 mm was detected in a 29-years old nephrectomized male patient. In our case, in reevaluations performed after definitive establishment of the diagnosis, any abnormal radiological signs suggesting a metastatic lesion were not detected. During the postoperative period the patient was referred to the clinics of endocrinology, and oncology for medical follow-up. In the differential diagnosis of retroperitoneal mass lesions, pheochromocytoma/paraganglioma should not be forgotten. Besides, for malignant tumors chemoradiotherapy, and for benign functional tumors medical treatment should be applied.


Computerized Tomography-Based Morphometric Analysis of Cervical Spinal Canal in Central Indian Population.
Objective Normal cervical spine canal morphometry is critical for understanding the pathology of certain diseases and for proper preoperative planning. Computerized tomography (CT) scan can replace older conventional radiography techniques by providing more accurate morphometric measurements. This study was aimed to find out various dimensions of the cervical spinal canal of central Indian population. Materials and Methods A prospective study was conducted including 100 consecutive cervical spine CT scan of asymptomatic adult subjects. The anteroposterior sagittal canal diameter (SCD), transverse canal diameter (TCD), canal surface area (CSA), and Pavlov-Torg Ratio (PTR) from C2 to C7 were calculated. Statistical Analysis Data were entered in Microsoft Excel Sheet 2007 and statistical analysis was performed by IBM SPSS statistics 2.0 version. p -Value < 0.05 was considered as significant. Results Age ranged from 18 years to 77 years with mean age 39.5 years. There was no significant difference in all the dimensions (SCD, TCD, CSA) in male and female except at C2 level, where SCD, TCD, and CSA were significant larger in male. The mean SCD, TCD, and CSA is largest at C2 level (14.4 ± 1.63 mm, 21.57 ± 1.59 mm, and 156.20 ± 24.98 mm 2 , respectively) and smallest at C4 level (12.77 ± 1.48 mm, 20.37 ± 1.72 mm, and 130.42 ± 21.20 mm 2 ). PTR showed very little variation. Conclusion Normal values of cervical spinal canal could serve as a future reference. CT scan provides more accurate measurement. More studies are needed as there could be variations in dimensions in different regions in India.


Factors Influencing Sedentary Behaviour in Older Adults: An Ecological Approach.
Sedentary behaviour is negatively associated with several health outcomes and is particularly problematic among older adults. Knowledge translation tools and public health promotion strategies are needed; however, little evidence is available to inform framing of such tools or development of intervention programs. The aim of the present study was to use data on the perceptions of sedentary time and the programs or supports older adults identify as important for reducing their sedentary time, to inform knowledge translation strategies targeting this population. Focus groups were conducted with four groups of older adults (n = 26) at local seniors' centres (Ontario, Canada). Participants were 74 ± 8.5 years old and were engaging in both sedentary and physical activities in a social environment. Using the Ecological Model for sedentary time in adults, we categorized data into leisure time, household, transport and occupation domains. Intrinsic and extrinsic factors that worked to either discourage or promote sedentary behaviour were identified. Drawing on both groupings of data, results were synthesized to inform public health strategies on appropriate messaging and better uptake of programming and guidelines. For example, successful programs developed on the topic will need to include a social component and a mentally stimulating component, as these were identified as critical for enjoyment and motivation. It was clear from this analysis that sedentary time reduction strategies will need to consider the different domains in which older adults accumulate sedentary time.


What Makes You Go Faster?: The Effect of Reward on Speeded Action under Risk.
Evaluating the potential reward and risk associated with a choice of action plays an important role in everyday decision making. However, the details behind how reward and risk affect the decisions for actions remain unclear. The present study investigates the influence of reward and risk on a decision to make a speeded motor response. One hundred and ten college students performed a Speed-Rewarded Go-NoGo task during which they were rewarded proportionally based on the speed and accuracy of their response. On each trial, the magnitude of potential reward and the probability of a forthcoming Go signal (Go-probability) were presented prior to the Go or NoGo signal. Personality traits, such as risk taking and impulsive tendencies, were measured to determine their contribution in explaining individual differences in task performance. The results showed that larger amount of rewards can motivate people to respond faster, and this effect was modulated by the assessed risk, suggesting that decisions for actions are based on a systematic trade-off between rewards and risks. Moreover, when the assessed risk was high, individuals with greater risk taking and impulsive tendencies did not adequately adjust their behavior across different reward levels. These findings shed light on the mechanistic understanding of the effect of reward and risk on decisions for a speeded action.


Audit of diabetic ketoacidosis management at a tertiary hospital in Johannesburg, South Africa.
Continuous intravenous infusion (CII) of insulin is the preferred method of treating diabetic ketoacidosis (DKA) worldwide, especially in patients with severe DKA. There is limited evidence evaluating low-dose bolus intravenous (IV) insulin management of DKA out of the intensive care unit (ICU). To conduct an audit of patients admitted with DKA, who were managed with bolus IV insulin at the medical acute-care unit (MACU), Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over a 4-month period to evaluate whether this is an effective treatment modality, as well as assess patient, disease and management characteristics related to the admissions. A prospective cross-sectional cohort study was done, interviewing 69 DKA patients from 1 September to 31 December 2017, and collecting relevant biochemical results from their hospital records. The current management protocol at CHBAH was observed, i.e. insulin therapy administered hourly as 10 IU IV insulin. The time to resolution of DKA, complications and deaths were recorded. Our cohort was predominantly male (60.56%), with an average age of 36 years. All patients were successfully treated with bolus IV insulin, with an average time to resolution of 21 hours. DKA was categorised as mild (19.72%), moderate (50.7%) and severe (29.58). Most patients presented with raised inflammatory markers (64.79%) and some degree of renal impairment (>60%). Complications occurred in 9 patients (12.68%); 7 of these were related to factors precipitating the DKA admission. No deaths occurred. The only factor predicting a longer time to resolution was severity, with an odds ratio of 4.89 (confidence interval 1.04 -22.84; p=0.044). Outcomes are favourable, with bolus IV insulin being used as the treatment modality in patients with mild, moderate and severe DKA at CHBAH. Further studies are needed to corroborate these results in other centres.


Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain-floor.
Connexins (cx) constitute a family of transmembrane proteins that form gap junction channels allowing metabolic and electrical coupling of cellular networks. Initial studies on the expression of cx in the developing brain have suggested that cx may undergo dynamic changes and may possibly be implicated in synchronizing development and differentiation of neural progenitor cells and young neurons. We have investigated expression of cx26, cx32, cx43, and cx45 in the midbrain floor, where nigrostriatal dopaminergic neurons originate and differentiate. This neuron population is of major importance in regulating motor-functions. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed low levels of cx26-mRNA in the midbrain floor at E12, which gradually increased during pre- and postnatal development, reaching a maximum in the adult. Cx32-mRNA-levels reached a first peak at E16, and showed highest levels in adulthood. Cx43 was highly expressed at E12, decreased until E18, and subsequently increased again until adulthood. Cx45 mRNA was prominent at all developmental ages, but slightly decreased after the first postnatal week. Double-labeling for the dopaminergic neuronal marker tyrosine hydroxylase (TH), and cx-immunoreactivities (ir) evaluated by quantitative confocal laser microscopy revealed both distinct and similar developmental patterns for the individual cx investigated. Cx26 was highest at E14, decreased towards birth, and subsequently increased again reaching about 50% of the E14 level in the adult. Cx32-ir peaked at E16 and dropped to low levels after birth. Cx43-ir was highest at E12, decreased sharply at E14, reached its lowest levels at birth, but modestly increased again afterwards. Cx45-ir showed a biphasic pattern, with two prominent peaks at E12 and E18, followed by a massive postnatal decrease. Taken together, our results reveal that expression and ir of cx in the midbrain floor and dopaminergic neurons, respectively, follow cx-type specific patterns that temporally coincide with important steps of midbrain morphogenesis, as e.g. progenitor cell formation and migration (E12), early differentiation (E14-16), target encounter (E16-18) and postnatal functional maturation of the nigrostriatal system.


Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.
Metabolic disorders represent a major therapeutic challenge to public health worldwide due to their dramatically increasing prevalence. Acupuncture is widely used as adjuvant therapy for multiple metabolic diseases. However, detailed biological interpretation of the acupuncture stimulations is still limited. The gut and the liver are intrinsically connected and related to metabolic function. Microbial metabolites might affect the gut-liver axis through multiple mechanisms. Liver metabolomics and 16S rRNA sequencing were used to explore the specific mechanism of electroacupuncture in treating ZDF rats in this study. Electroacupuncture effectively improved glycolipid metabolism disorders of the ZDF rats. Histopathology confirmed that electroacupuncture improved diffuse hepatic steatosis and hepatocyte vacuolation, and promoted glycogen accumulation in the liver. The treatment significantly improved microbial diversity and richness and upregulated beneficial bacteria that maintain intestinal epithelial homeostasis and decreased bacteria with detrimental metabolic features on host metabolism. Liver metabolomics showed that the main effects of electroacupuncture include reducing the carbon flow and intermediate products in the TCA cycle, regulating the metabolism of various amino acids, and inhibiting hepatic glucose output and de novo lipogenesis. The gut-liver axis correlation analysis showed a strong correlation between the liver metabolites and the gut microbiota, especially allantoin and Adlercreutzia. Electroacupuncture treatment can improve abnormal energy metabolism by reducing oxidative stress, ectopic fat deposition, and altering metabolic fluxes. Our results will help us to further understand the specific mechanism of electroacupuncture in the treatment of metabolic diseases.


Comparison of two different methods of preoperative marking for toric intraocular lens implantation: bubble marker versus pendulum marker.
To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex(®)3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform.


Aerobic vs anaerobic exercise training effects on the cardiovascular system.
Physical exercise is one of the most effective methods to help prevent cardiovascular (CV) disease and to promote CV health. Aerobic and anaerobic exercises are two types of exercise that differ based on the intensity, interval and types of muscle fibers incorporated. In this article, we aim to further elaborate on these two categories of physical exercise and to help decipher which provides the most effective means of promoting CV health.


Is planned continuous irrigation indicated for haemorrhage following transurethral resection of the prostate?
A prospective audit was carried out of this unit's policy of non-irrigation following transurethral prostatectomy (TURP). Over an 11-month period 121 TURPs were performed. Only 29 patients required intervention to maintain bladder drainage post-operatively, 23 of these requiring bladder washout alone. In the remaining 6 patients catheter change and continuous irrigation were required. The weight of tissue resected was the only factor investigated which bore a significant relationship to the necessity for further intervention in bladder drainage post-operatively. Despite this, patients requiring continuous irrigation post-operatively could not be easily identified prior to or during surgery.


[A method of analyzing the chromosome localization of repetitive nucleotide sequences by using hybridization in situ].
To increase precision in the quantitative analysis of chromosomal distribution of repeated DNA sequences detected by in situ hybridization, a number of factors important in studies of the molecular basis of chromosome polymorphism should be considered. While analysing results of hybridization, one should only use the number of grains over the sites of their regular localization, instead of those over the whole chromosome. It is also evident that to decrease variability conditioned by differences in the labelling degree of separate cells, the relative numbers of labelled grains over chromosomes should be used in the analysis and not the absolute ones. Data from those cells ought to be only included in the analysis, in which the labelling degree is sufficient to show all localization sites of the repeated sequences studied, i.e. cells should be used with comparatively constant relative numbers of labelled grains over all their regular localization sites.


Structural analysis of the capsid polypeptides of herpes simplex virus types 1 and 2.
Capsids of herpes simplex virus (HSV) types 1 and 2 contain seven polypeptides ranging in molecular weight from 154,000 to 12,000 (termed NC-1 through NC-7 in order of descending molecular weight). Antibodies prepared to HSV-1 capsid polypeptides isolated from sodium dodecyl sulfate-polyacrylamide gels reacted in an immunofluorescence assay against HSV-1-infected KB cells. Three of the antibodies (anti-NC-1, anti-NC-2, and anti-NC-3,4) also reacted with HSV-2-infected cells. Tryptic peptide analysis showed that each of the HSV-1 capsid polypeptides had a unique methionine peptide profile, and none appeared to be derived from the major capsid polypeptide. Comparative peptide analysis of HSV-1 and HSV-2 showed that one polypeptide (NC-7, 12,000 molecular weight) had an identical methionine peptide profile and a very similar arginine peptide profile in both virus types. The arginine peptide profile of NC-7 of HSV-1 was very different from the arginine profile of KB histone H4. Although there were certain intertypic similarities in the methionine peptide profiles of the other capsid components especially in NC-1 (the major capsid protein), there was no case where the tryptic peptides were identical in the two virus types.


[Erythema nodosum and Crohn's disease].
Erythema nodosum was found on 11 out of 106 patients with Crohn's disease (10.4%), being the most common skin complication after the perianal ones. Women were affected more often than men (2.7:1) and most of the patients were above 15 and below 40 years of age. Patients with ileocolic lesions were more often affected than those with lesions confined to the small bowel. No cases of erythema nodosum were found in association with granulomatous colitis, as opposed to other authors experience. The eruption was usually related to the periods of active inflammatory bowel disease but not to the administration of salazopyrine. The morphology and evolution of the lesions was typical of erythema nodosum and joint involvement was almost constant. The differential diagnosis with other nodular eruptions that can occur in association with Crohn's disease are discussed and hypothetical common etiopathogenic factors to both Crohn's disease and erythema nodosum are briefly considered. The relevant literature is reviewed and commented upon.


The Triglyceride-Glucose Index is Associated with Vitamin D Status in Metabolic-Associated Fatty Liver Disease.
Vitamin D deficiency was thought to be associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD). The aim of this study was to investigate the relationship between the triglyceride-glucose (TyG) index, a useful surrogate biomarker of insulin resistance, and vitamin D status in patients with MAFLD. A total of 566 patients with MAFLD were included in this retrospective cross-sectional study. Clinical characteristics were compared between participants with and without vitamin D deficiency. The association between the TyG index and serum 25-hydroxyvitamin D [25(OH)D] levels was determined by Spearman correlation analysis and logistic regression analysis. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficacy of TyG index for vitamin D deficiency in MAFLD patients. The TyG index levels were higher in the vitamin D deficient group than in the non-vitamin D deficient group, and serum 25(OH)D was negatively correlated with the TyG index. The TyG index was an independent risk factor for vitamin D deficiency in patients with MAFLD. The area under the curve (AUC) of the TyG index for the identification of vitamin D deficiency in MAFLD patients was 0.744 (95% CI: 0.701-0.787, p<0.001). The TyG index is negatively associated with vitamin D status in patients with MAFLD. In patients with MAFLD, a higher TyG index may be an indication of a higher prevalence of vitamin D deficiency.


The synthesis and thymidylate synthase inhibitory activity of L-gamma-L-linked dipeptide and L-gamma-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583).
Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.


Efficient, "On-the-Fly", Born-Oppenheimer and Car-Parrinello-type Dynamics with Coupled Cluster Accuracy through Fragment Based Electronic Structure.
We recently developed two fragment based ab initio molecular dynamics methods, and in this publication we have demonstrated both approaches by constructing efficient classical trajectories in agreement with trajectories obtained from "on-the-fly" CCSD. The dynamics trajectories are obtained using both Born-Oppenheimer and extended Lagrangian (Car-Parrinello-style) options, and hence, here, for the first time, we present Car-Parrinello-like AIMD trajectories that are accurate to the CCSD level of post-Hartree-Fock theory. The specific extended Lagrangian implementation used here is a generalization to atom-centered density matrix propagation (ADMP) that provides post-Hartree-Fock accuracy, and hence the new method is abbreviated as ADMP-pHF; whereas the Born-Oppenheimer version is called frag-BOMD. The fragmentation methodology is based on a set-theoretic, inclusion-exclusion principle based generalization of the well-known ONIOM method. Thus, the fragmentation scheme contains multiple overlapping "model" systems, and overcounting is compensated through the inclusion-exclusion principle. The energy functional thus obtained is used to construct Born-Oppenheimer forces (frag-BOMD) and is also embedded within an extended Lagrangian (ADMP-pHF). The dynamics is tested by computing structural and vibrational properties for protonated water clusters. The frag-BOMD trajectories yield structural and vibrational properties in excellent agreement with full CCSD-based "on-the-fly" BOMD trajectories, at a small fraction of the cost. The asymptotic (large system) computational scaling of both frag-BOMD and ADMP-pHF is inferred as [Formula: see text], for on-the-fly CCSD accuracy. The extended Lagrangian implementation, ADMP-pHF, also provides structural features in excellent agreement with full "on-the-fly" CCSD calculations, but the dynamical frequencies are slightly red-shifted. Furthermore, we study the behavior of ADMP-pHF as a function of the electronic inertia tensor and find a monotonic improvement in the red-shift as we reduce the electronic inertia. In all cases a uniform spectral scaling factor, that in our preliminary studies appears to be independent of system and independent of level of theory (same scaling factor for both MP2 and CCSD implementations ADMP-pHF and for ADMP DFT), improves on agreement between ADMP-pHF and full CCSD calculations. Hence, we believe both frag-BOMD and ADMP-pHF will find significant utility in modeling complex systems. The computational power of frag-BOMD and ADMP-pHF is demonstrated through preliminary studies on a much larger protonated 21-water cluster, for which AIMD trajectories with "on-the-fly" CCSD are not feasible.


Innovative PhD-DNP Faculty Collaboration to Advance Baccalaureate Student Population Health Competencies.
Entry-level nurses require health promotion, chronic disease self-management, care coordination, data utilization, and evidence translation competencies to address complex population health needs. An innovative PhD-DNP faculty collaboration implemented a descriptive survey design to evaluate simulation-based strategies using an unfolding chronically ill adult case to address population health. Results showed the PhD-DNP faculty team was effective in developing clinically meaningful learning experiences to assist baccalaureate students to develop population health competencies. This project provides strong evidence supporting the value and positive impact of engaging faculty from research and practice for future educational research.


Cardiac myosin-binding protein-C phosphorylation and cardiac function.
The role of cardiac myosin binding protein-C (cMyBP-C) phosphorylation in cardiac physiology or pathophysiology is unclear. To investigate the status of cMyBP-C phosphorylation in vivo, we determined its phosphorylation state in stressed and unstressed mouse hearts. cMyBP-C phosphorylation is significantly decreased during the development of heart failure or pathologic hypertrophy. We then generated transgenic (TG) mice in which the phosphorylation sites of cMyBP-C were changed to nonphosphorylatable alanines (MyBP-C(AllP-)). A TG line showing &40% replacement with MyBP-C(AllP-) showed no changes in morbidity or mortality but displayed depressed cardiac contractility, altered sarcomeric structure and upregulation of transcripts associated with a hypertrophic response. To explore the effect of complete replacement of endogenous cMyBP-C with MyBP-C(AllP-), the mice were bred into the MyBP-C(t/t) background, in which less than 10% of normal levels of a truncated MyBP-C are present. Although MyBP-C(AllP-) was incorporated into the sarcomere and expressed at normal levels, the mutant protein could not rescue the MyBP-C(t/t) phenotype. The mice developed significant cardiac hypertrophy with myofibrillar disarray and fibrosis, similar to what was observed in the MyBP-C(t/t) animals. In contrast, when the MyBP-C(t/t) mice were bred to a TG line expressing normal MyBP-C (MyBP-CWT), the MyBP-C(t/t) phenotype was rescued. These data suggest that cMyBP-C phosphorylation is essential for normal cardiac function.


The role of the distal nephron mechanisms in the concentration of contrast medium in the urine.
The concentrating mechanisms affecting contrast medium in the distal nephron have been studied using three contrast media of differing osmolality (monomer, dimer and non-ionic compounds) in antidiuretic dogs with three different basal solute excretion rates. Evidence has been obtained that, under conditions of contrast medium osmotic diuresis, the loop of Henle generates more free water. If the free water generated in response to the contrast medium solute load is reabsorbed in the collecting ducts, this can in part mask the different proximal tubular effects of contrast media of different osmolality. However, as basal solute excretion increases, the compensatory mechanism is overwhelmed and urine osmolality falls exponentially. At the higher basal solute excretion rates, different osmolar loads of contrast medium no longer produce different urine osmolalities and different urine contrast medium concentrations. It is therefore considered unlikely that contrast media of reduced osmolality will produce significant increases in urine contrast medium concentration under the conditions of solute diuresis which occur in renal failure.


Can Flexible Instruments Create Adequate Femoral Tunnel Lengths at 90° of Knee Flexion in Anterior Cruciate Ligament Reconstruction?
This study aims to study femoral tunnel lengths drilled with a flexible reamer and the distance to important lateral structures obtained by flexing the knee at various angles and by drilling the guide pins arthroscopically to resemble clinical practice. The purpose of this cadaveric study was twofold: 1. to determine whether femoral tunnel lengths of greater than 20 mm can be created with a flexible reamer system at 90 ° of knee flexion and 2. to determine whether the lateral structures of the knee are safe with this technique. Ten fresh cadaveric knees were utilized. The intra-osseous length can be measured with a specially de - signed flexible guide pin. Flexible pins were inserted with the knee at 70°, 90°, and 120° of flexion. The intra-osseous length was measured with the measuring device. Each speci - men was dissected around the lateral aspect of the knee to identify the critical structures, the common peroneal nerve, and the LCL. The distance from the guide pins to the com - mon peroneal nerve and femoral attachment of the LCL were measured with a standard flexible paper ruler to the nearest millimeter. There is a trend for progressively increasing mean intra-osseous length associated with increased flexion of the knee. The mean intra-osseous length for 70° flexion was 25.2 mm (20 mm to 32 mm), which was statistically significant when compared to mean intra-osseous lengths of 32.1 mm (22 mm to 45 mm) and 38.0 mm (34 mm to 45 mm) in the 90° and 120° flexion groups, respectively (p < 0.05). There were no significant differences among the groups with respect to distance to the LCL. There is a trend toward longer distances to the common peroneal nerve with increased flexion. There was a statistically significant dif - ference when comparing 120° versus 70° (p < 0.05). This study that shows that adequate femoral tunnel lengths can be safely created without knee hyperflex - ion using flexible instruments via an anteromedial portal.


The Impact of the Coronavirus (COVID-19) Infection on the Drug-Metabolizing Enzymes Cytochrome P450s.
Coronaviruses cause disease in human and animals. In 2019 a novel coronavirus was first characterized in Wuhan, China. It causes acute respiratory disease and designated the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19. The COVID-19 spread to all cities of China, and in 2020 to the whole world. Patients with COVID-19 may recover without medical treatment. However, some patients need medical care. The Cytochrome p450s (CYP450s) are large superfamily of enzymes catalyze the metabolism of endogenous substrates and xenobiotics. CYP450s catalyze the biotransformation of 80% of the drug in clinical use. The CYP450 present in liver, lungs, intestine and other tissues. COVID-19 has been reported to decrease the activity of certain isoforms of CYP450s in an isoform specific manner. Furthermore, the COVID-19 infection decreases the liver functions including the drug clearance or detoxification medicated by the CYP450s. The healthcare providers should be aware of this disease-drug interaction when prescribing drugs for treatment of COVID-19 and other comorbidities.


PET/CT imaging artifacts.
The purpose of this paper is to introduce the principles of PET/CT imaging and describe the artifacts associated with it. PET/CT is a new imaging modality that integrates functional (PET) and structural (CT) information into a single scanning session, allowing excellent fusion of the PET and CT images and thus improving lesion localization and interpretation accuracy. Moreover, the CT data can also be used for attenuation correction, ultimately leading to high patient throughput. These combined advantages have rendered PET/CT a preferred imaging modality over dedicated PET. Although PET/CT imaging offers many advantages, this dual-modality imaging also poses some challenges. CT-based attenuation correction can induce artifacts and quantitative errors that can affect the PET emission images. For instance, the use of contrast medium and the presence of metallic implants can be associated with focal radiotracer uptake. Furthermore, the patient's breathing can introduce mismatches between the CT attenuation map and the PET emission data, and the discrepancy between the CT and PET fields of view can lead to truncation artifacts. After reading this article, the technologist should be able to describe the principles of PET/CT imaging, identify at least 3 types of image artifacts, and describe the differences between PET/CT artifacts of different causes: metallic implants, respiratory motion, contrast medium, and truncation.


Examining the Role of Income Inequality and Neighborhood Walkability on Obesity and Physical Activity among Low-Income Hispanic Adults.
Obesity is a major public health issue affecting rising medical costs and contributing to morbidity and premature mortality. We aimed to identify factors that may play a role in obesity and physical activity at the individual and environmental/neighborhood levels. We analyzed data from an adult sample who were parents of students enrolled in a school-based health and wellness program. The sample was restricted to those who were Hispanic and whose children were on free/reduced lunch (n = 377). Dependent variables: body mass index (BMI); neighborhood walkability. Walk Score® was used to assess neighborhood walkability. Overall, 46% of participants were obese and 31% were overweight. The median age of respondents was 34 years, and the majority were female (88%) and married (59%). Participants who resided in a census tract with a higher relative income inequality (high, OR 2.54, 90% CI 1.154-5.601; moderate-high OR 2.527, 90% CI 1.324-4.821) and those who were unmarried (OR 1.807, 90% CI 1.119-2.917) were more likely to be obese versus normal weight. Overweight individuals that resided in areas that were walkable versus car-dependent averaged more days engaging in walking for at least 30-min (p <.05). Identifying individual and neighborhood factors associated with obesity can inform more targeted approaches to combat obesity at multiple ecological levels. The importance of understanding how neighborhood characteristics influence health-related and behavioral outcomes is further reinforced with the current findings. Identifying effective strategies to engage communities and organizations in creating, implementing, adopting, evaluating, and sustaining policy and/or environmental interventions will be needed to combat the obesity epidemic.


Pregnancy-related acute renal failure.
From 1958 to 1987, 81 cases of pregnancy-related acute renal failure (PR-ARF) were observed (9% of the total number of acute renal failure [ARF] needing dialysis). In the three successive ten-year periods (1958-67, 1968-77, 1978-87) the incidence of PR-ARF fell from 43% to 2.8% with respect to the total number of ARF, and from 1/3,000 to 1/15,000 with respect to the total number of pregnancies. Maternal mortality was high (32%), with 5 cases of death in the last ten years. Irreversible renal damage was recorded in 11.6% of PR-ARF, and, in particular, in 26.3% of cases in preeclampsia-eclampsia (PE-E). Worse maternal and renal prognosis occurred in PE-E complicated by abruptio placentae. Neither disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia nor prostacyclin imbalance were significantly related to the severity of renal damage. Heparin therapy did not modify DIC evolution and renal outcome and was aggravated by severe hemorrhagic complications. In conclusion, PR-ARF has become a rare, but still critical occurrence, and the most effective measures would be a program of careful prevention.


Eating speed and the risk of type 2 diabetes: explorations based on real-world evidence.
Metabolic syndrome, especially diabetes, has gained global attention over the past few decades and became one of the major public health concerns. Alongside known and well-established risk factors, eating behaviors, mainly eating speed has shown the potential as one of the novel risk factors that could supplement the development of diabetes. However, there is a paucity in evidence, and only a few studies have addressed this question so far. In this review, with a focus on eating speed and the risk of developing diabetes, authors attempted to shed some light on the high-quality studies that were conducted around the world using real-world data in drawing inferences, which could add-on to the literature and assist public in making informed decisions.


The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion.
Continuous processing is superseding conventional batch processing as a means of manufacturing within the pharmaceutical research/industry. This paradigm shift has led to the implementation of Process Analytical Technology (PAT) as a semi-automatic, predictive tool offering real-time quality control that can be built into the production line. However, PAT tools have been mainly utilised to monitor a single process (e.g. powder blending, synthesis of biopharmaceuticals and small molecules) rather than a full continuous manufacturing process. In addition, there is a paucity of guidance documents that consider the continuous and dynamic conditions of real-time measurements for validation purposes. In this study, the feasibility of developing and validating a predictive and reliable Raman method based on quality by design (QbD) and PAT frameworks for the real-time quantification of Ramipril (RMP) during hot-melt extrusion (HME) were investigated. Through QbD, a design space elucidating the quality attributes of RMP stability was successfully identified based on offline HPLC measurements. Process temperature and powder feeding rate were the main quality attributes to affect the stability of RMP during HME. The optimum combination of process and formulation variables were extracted from the validated design space and used to extrude RMP at a concentration range of 2.5-12.5 %w/w. Three calibration models were established using PLS regression analysis. The developed PLS calibration models showed excellent linearity (R2 = 0.989, 0.995, 0.992), accuracy (RMSEcv = 0.31, 0.26, 0.30%) and specificity (PC1 = 81, 85, 89%) for models 1, 2 and 3, respectively. Furthermore, the developed QbD-PAT model was able to predict the quantity of RMP at varied process feed rate (10, 35 rpm) operating under long processing time (60 min). The output of this study allows in-process optimisation of formulation and process variables to control the quality and quantity of RMP during HME. Furthermore, it allows the implementation of PAT tools as routine methods of analysis within the laboratory.


The effects of desipramine, fluoxetine, or tianeptine on changes in bulbar BDNF levels induced by chronic social instability stress and inflammation.
Stress is a major predisposing factor in the development of psychiatric disorders and potential source of augmented inflammatory processes in the brain. Increasing body of evidence shows an important role of alterations in the olfactory bulbs (OBs) function in stress-related disorders. The aim of the present study was to investigate the impact of antidepressants on the alterations of brain-derived neurotrophic factor (BDNF) induced by lipopolysaccharide (LPS) in female rats subjected to chronic social instability stress (CSIS). 9 weeks old female rats were subjected to CSIS and injected ip once daily with desipramine (10mg/kg), fluoxetine (5mg/kg), or tianeptine (10mg/kg) for 4 weeks. On the last day of the experiment, rats being at the estrus phase of cycle were injected ip with LPS (1mg/kg) or saline. The BDNF mRNA and protein levels were evaluated in the olfactory bulbs. and the BDNF protein levels were measured in plasma. A single LPS administration in the stressed rats resulted in significant decrease in the bulbar BDNF mRNA, but not in the protein level. Chronic administration of desipramine, fluoxetine, or tianeptine increased the BDNF mRNA expression and protein levels in the LPS-injected stressed rats. There was no effect of the studied antidepressants on the reduction of the plasma BDNF protein level induced by CSIS and LPS. These results suggest that studied antidepressants were effective in inhibiting the impact of LPS on BDNF expression in the stressed rats what may be significant for beneficial action of this drugs.


Theory and practice of combining coagulant fixation and microwave histoprocessing.
The German, F. Blum, introduced formalin as a fixative in 1893. Formalin rapidly became popular for hardening and preserving gross human and animal specimens. As a result, microscopy for diagnostic pathology by combining paraffin embedding and formalin fixation was developed. Alcohol-based fixatives have coagulation of proteins as their main preservative effect. Because there is no cross-linking, immunostaining is not compromised, and DNA and RNA is not damaged. Ethyl alcohol was used by Dutch scientists of the 18th century, but was replaced by the cheaper formalin. Addition of low molecular weight polyethylene glycol (PEG) optimized the coagulant fixative, Kryofix. The polyethylene glycol prevents excessive hardening and enhances the speed of coagulation of proteins. Kryofix was used on a large scale for skin biopsies in Leiden between 1987 and 2001. DNA preservation by the formulated coagulant fixative, BoonFix, is related to the concentration of ethyl alcohol, PEG and acetic acid. BoonFix has been used since 2004 in Leiden for over 40,000 diagnostic skin biopsies and more than 100,000 cervical samples. A literature review and three decades of experience with coagulant, formalin-free fixatives in pathology suggest that when health authorities realize that formalin invalidates expensive tests, it might eventually be eliminated legislatively from diagnostic pathology. Finally, coagulant fixation is optimal for microwave histoprocessing where ethyl alcohol is followed by isopropanol.


[Minimally invasive and organ-saving operations in abdominal trauma].
Results of surgical treatment with modern minimally invasive methods of 968 patients with isolated and combined abdominal trauma were analyzed. These methods permitted to make topic diagnosis earlier and to perform adequate surgery on injured organs in 82.0% patients, including in 34.0% with endoscopic-assisted operations, in 36.0% patients diagnostic laparotomies were avoided. In spleen trauma organ-saving and replacement operations were performed for prophylaxis of postsplenectomy syndrome. Vagodestruction of the stomach and pancreas with electromagnetic waves was successfully used in 32 patients for prophylaxis of traumatic pancreatitis and gastrointestinal ulcers. Minimally invasive technologies and organ-saving operations permitted to reduce intra- and postoperative complications rate from 29.7 to 16.8%, lethality--from 12.3 to 7.4%.


Screening for post-intensive care syndrome: Validation of the Healthy Aging Brain Care Monitor Self-Report Chinese version.
The Healthy Aging Brain Care Monitor Self-Report (HABC-M SR) is a tool to evaluate physical, mental and cognitive impairments. It has been validated in several countries for post-intensive care syndrome (PICS) assessment, but there is no Chinese version yet. The aim of this study is to translate and cross-cultural adapt HABC-M SR, and validate its psychological properties among Chinese ICU survivors. This is a cross-sectional study. the HABC-M SR was translated into Chinese and validated in intensive care unit survivors (n = 145). Measures of internal consistency, construct validity, concurrent validity, and content validity were evaluated. A 19-item Chinese version of HABC-M SR was yielded, with good reliability (Cronbach's α = 0.92) and validity (the variance was 64.4%, overall content validity was 0.91, and correlation coefficients were 0.62-0.90). The 19-item Chinese version HABC-M SR is a reliable and valid tool for PICS assessing and may be regarded as a standard measurement. The Chinese version HABC-M SR may help in selecting PICS high-risk survivors for ICU follow-up interventions. The HABC-M SR can also be regarded as a standard specific PICS measurement, thus promote the comparability between studies and transformation of the clinical evidence.