[Orbital exenteration. A preventable course in tumor treatment?!].
We reviewed the conditions leading to the mutilating procedure of orbital exenteration in 24 patients at our institution between 1980 and 1993. In 17 cases, including 16 of 17 patients with malignant tumours of the eyelid, this operation could potentially have been avoided. Three of these 17 patients first saw a doctor at an extremely advanced and otherwise untreatable stage of the tumour. The other 14 patients had at least one previous treatment attempt. Six patients with basal cell carcinoma had been primarily treated with radiation alone; two of them developed a squamous cell carcinoma subsequently. In six cases primary reconstruction was performed despite incomplete resection. In one patient a meibomian gland carcinoma was misdiagnosed as a chalazion and excised without histological examination. In another case of squamous cell carcinoma a cutaneous incisional biopsy 6 months prior to orbital exenteration revealed a papilloma. These results emphasize the necessity of careful histological examination in the treatment of lid tumours.


Stimulus intensity modulates associative and nonassociative responding in preweanling rats.
The purpose of the present study was to determine whether preweanling rats respond differentially to the intensity and energy source of a stimulus. Previous studies have suggested that infants process compound stimuli based on net stimulus intensity regardless of the energy source of the compound's elements, but more direct tests have been needed of the infant's response to the stimulus attributes of intensity and energy source. This response was tested for auditory and visual stimuli that had been equated (Experiment 1) in terms of perceived intensity (low and high). Intensity level and energy source of the stimuli were varied independently within nonassociative (Experiment 2) and associative (Experiment 3) procedures. The overall results indicate that stimuli of a low-perceived intensity were processed in terms of their intensity, whereas high-intensity stimuli were processed on the basis of energy source. These results are relevant to contemporary issues of cognitive development in humans and animals.


Aspirin "Allergy"-Induced Thrombocytopenia: A Case Report.
Aspirin is clinically widely used to inhibit platelet aggregation after coronary intervention. Herein we describe a case of aspirin-induced thrombocytopenia that may be related to allergy to aspirin. A 47-year-old man developed a delayed hypersensitivity reaction to aspirin, with pruritus, purpura and thrombocytopenia, increased peripheral blood eosinophils and enlarged inguinal lymph node. All the symptoms disappeared in 2 years after stopping aspirin. Aspirin-induced thrombocytopenia related to allergy is rarely reported. Aspirin hypersensitivity should be taken into consideration in case of unexplained thrombocytopenia in patients taking aspirin. Aspirin "allergy"-induced thrombocytopenia may involve both aspirin related IgG and IgE antibodies.


Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity.
Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.


Effect of interleukin-8 receptor B (IL8RB) rs1126579 C>T variation on the risk to cancer.
Chemokines are a type of cytokine that participate in the migration of macrophages and monocytes to inflammatory cells. In particular, CXC chemokines are involved in the development of many cancers. Evidence for the association between interleukin-8 receptor B (IL8RB) rs1126579 C > T variation and cancer risk remains contradictory. Here, we utilized a comprehensive analysis containing odds ratios (ORs), regression, and in silico tools to evaluate the effect of IL8RB polymorphism on cancer risk. We further employed Gene set enrichment analysis combined with ELISA to evaluate the IL8RB expression in patients with prostate cancer (PRAD). A total of 5,187 cancer cases and 6,691 controls were included in the present analysis. Individuals with the TT genotype were associated with an increased risk of cancer compared to those with the TC+CC genotype. In a subgroup analysis by type of cancer, individuals with the TT genotype had a 39% increased risk of urinary cancer compared to those with the CC genotype. A subgroup analysis by ethnicity showed that Asians carrying the TC genotype had a 26% lower risk of cancer than those carrying the CC genotype. We found that the expression of IL8RB was down-regulated in PRAD. Compared to that in PRAD subjects carrying the CC genotype, the expression of IL8RB was decreased in patients with the TT+TC genotype. In conclusion, the IL8RB rs1126579 C > T variation may be associated with cancer risk, especially in Asian populations and patients with PRAD.


Rational design using sequence information only produces a peptide that binds to the intrinsically disordered region of p53.
Intrinsically disordered regions (IDRs) of proteins are involved in many diseases. The rational drug design against disease-mediating proteins is often based on the 3D structure; however, the flexible structure of IDRs hinders the use of such structure-based design methods. Here, we developed a rational design method to obtain a peptide that can bind an IDR using only sequence information based on the statistical contact energy of amino acid pairs. We applied the method to the disordered C-terminal domain of the tumor suppressor p53. Titration experiments revealed that one of the designed peptides, DP6, has a druggable affinity of ~1 μM to the p53 C-terminal domain. NMR spectroscopy and molecular dynamics simulation revealed that DP6 selectively binds to the vicinity of the target sequence in the C-terminal domain of p53. DP6 inhibits the nonspecific DNA binding of a tetrameric form of the p53 C-terminal domain, but does not significantly affect the specific DNA binding of a tetrameric form of the p53 core domain. Single-molecule measurements revealed that DP6 retards the 1D sliding of p53 along DNA, implying modulation of the target searching of p53. Statistical potential-based design may be useful in designing peptides that target IDRs for therapeutic purposes.


Effects of Valproic Acid on Radiation-Induced Chromosomal Aberrations in Human Lymphocytes.
One of the most widely employed histone deacetylases inhibitors in the clinic is the valproic acid (VA), proving to have a good tolerance and low side effects on human health. VA induces changes in chromatin structure making DNA more susceptible to damage induction and influence DNA repair efficiency. VA is also proposed as a radiosensitizing agent. To know if VA is suitable to sensitize human lymphocytes γ-irradiation in vitro, different types of chromosomal aberrations in the lymphocytes, either in the absence or presence of VA, were analyzed. For this purpose, blood samples from four healthy donors were exposed to γ-rays at a dose of 1.5 Gy and then treated with two different doses of VA (0.35 or 0.70 mM). Unstable and stable chromosomal aberrations were analyzed by means of fluorescence in situ hybridization. Human lymphocytes treated with VA alone did not show any increase in the frequency of chromosomal aberrations. However, a moderate degree of sensitization was observed, through the increase of chromosomal aberrations, when 0.35 mM VA was employed after γ-irradiation, whereas 0.70 mM VA did not modify chromosomal aberration frequencies. The lower number of chromosomal aberrations obtained when VA was employed at higher dose after γ-irradiation, could be related to the induction of a cell cycle arrest, a fact that should be taken into consideration when VA is employed in combination with physical or chemical agents.


Beliefs and Behavior of Saudi Women in the University of Tabuk Toward Breast Self Examination Practice
Background: Breast cancer is one of the most frequent types of malignancy worldwide, Breast Self Exam (BSE) is considered as a simple method to screen and detect breast cancer, then early beginning of treatment and enhancing survival rates. Aim: To Identify the health beliefs about breast Self-Examination and its relationships with the frequency of BSE among the women in the University of Tabuk at Saudi Arabia. Methods: Descriptive, cross-sectional correlational design was used; Champion Health Beliefs Model (CHBM) was utilized to assess health beliefs among 400 women who answered a self-administered questionnaire. Results: Among the 400 respondents, almost all the sample (382,95.5%) heard about BSE. However, only (7.8%) practiced BSE regularly each month in the past year, and (9%) is intended to perform BSE monthly in future. There was a positive relationship between performing BSE last year and the beliefs of susceptibility and confidence. While, intention to perform BSE in the future was significantly correlated to seriousness and confidence. Perceived barriers were negatively related to BSE performance in last 12 months and in future. Conclusion: Health beliefs affect the behavior of women in practicing BSE. Confidence was related positively to BSE in past year, and future practice, while barriers belief was as the negative factor to perform BSE.


Bacterial communities in an optional lichen symbiosis are determined by substrate, not algal photobionts.
Borderline lichens are simple mutualistic symbioses between fungi and algae, where the fungi form loose mycelia interweaving algal cells, instead of forming a lichen thallus. Schizoxylon albescens shows two nutritional modes: it can either live as a borderline lichen on Populus tremula bark or as a saprotroph on Populus wood. This enables us to investigate the microbiota diversity in simple fungal-algal associations and to study the impact of lichenization on the structure of bacterial communities. We sampled three areas in Sweden covering the distribution of Schizoxylon, and using high-throughput sequencing of the 16S rRNA gene and fluorescence in situ hybridization we characterized the associated microbiota. Bacterial communities in lichenized and saprotrophic Schizoxylon were clearly distinct, but when comparing the microbiota with the respective substrates, only the fruiting bodies show clear differences in composition and abundance from the communities in the substrates. The colonization by either lichenized or saprotrophic mycelia of Schizoxylon did not significantly influence the microbiota in the substrate. This suggests that in a morphologically simple form of lichenization, as represented by the Schizoxylon-Coccomyxa system, algal-fungal interactions do not significantly influence bacterial communities, but a more complex structure of the lichen thallus is likely required for hosting specific microbiota.


Real-Time Visualization of Cysteine Metabolism in Living Cells with Ratiometric Fluorescence Probes.
Sulfite from cysteine metabolism in living cells plays a crucial role in improving the water solubility of metabolic xenobiotics for their easier excretion in urine or bile. However, an imbalance of sulfite in vivo would lead to oxidative stress or age-related diseases, and an effective strategy for real-time imaging of cysteine metabolism in living cells is still lacking due to its low metabolite concentration and rapid reaction kinetics. Herein, a cyanine moiety based ratiometric fluorescence probe was developed for highly selective and sensitive detection of sulfite in aqueous solution and living cells. The free probe exhibited an orange emission color, and the fluorescence color would gradually change to blue once sulfite anions selectively reacted with the unsaturated carbon double bonds in the probe molecule. This ratiometric fluorescence manner endowed the probe excellent sensitivity with a detection limit of 0.78 nM, which was then explored to image the kinetic process of sulfite release in hepatic BRL cells after incubating with an excess amount of cysteine. This strategy opens new opportunities for revealing thiol-containing species metabolism and even quantitatively tracking their distributions in live cells or organelles.


Erythrocyte Li-Na countertransport in hypertension: lack of atrial natriuretic peptide effect.
The rate of erythrocyte Li-Na countertransport and cellular Na+ and K+ contents have been determined in normotensive (NT) and hypertensive (HT, essential hypertension) subjects in the presence and absence of atrial natriuretic peptide (ANP). The rate of Li-Na countertransport was significantly higher in erythrocytes of HT subjects, while the Na+ and K+ contents were not different between the NT and HT groups. We found that ANP (10(-9) and 10(-7) M) had no effect on either the rate of Li-Na countertransport or the cellular Na+ and K+ contents. Since ANP does not influence erythrocyte Na pump and Na-K-Cl cotransport, our results suggest that the Na transport systems of human erythrocytes do not respond to ANP and this lack of response in Li-Na countertransport is independent of the status of hypertension. These findings are consistent with the view that the rate of Li-Na countertransport of erythrocytes may serve as a useful genetic marker for essential hypertension in Chinese. However, the erythrocyte transport systems cannot provide further differentiation utilizing ANP response for essential hypertension.


Extending orbital angular momentum multiplexing to radially high orders for massive mode channels in fiber transmission.
Orbital angular momentum (OAM) beams with different angular indices l have the potential to greatly increase communication capacity. However, the finite aperture of optical systems limits the value of the angular index. In order to fully use the orthogonal mode channels supported in the fiber for high-capacity communications, we propose extending the radial indices p of OAM modes as an additional multiplexing dimension. In this paper, we introduce spatially discrete multiple phase planes to multiplex the angular and radial OAM modes simultaneously. Due to the orthogonal property of the central symmetric OAM modes, a two-dimensional (2D) input Gaussian beams array can be converted to coaxial OAM modes through Cartesian to log-polar coordinate transformation by inverse design. For a proof-of-concept demonstration, a 10-mode multiplexer for high-order radial OAM modes was designed using five phase planes. The fabricated multiplexer generated high-quality multiplexed OAM modes with a loss of less than 5.4 dB. The multiplexed OAM modes were coupled into a specially designed ring-core fiber by mode-field matching, achieving stable mode transmission in 2 km fiber. The approach provides a scalable technology to increase the number of transmission channels and could lead to the practical applications of OAM multiplexing in communication.


Impact of a nutrition consultation on the rate of high output stoma-related readmission: an ambispective cohort study.
The aims of this study were to assess the impact of a follow-up nutrition consultation for ostomy patients on the rate of high output stoma (HOS)-related readmissions, as well as on the detection of poor nutritional status and their management, and to determine the associated economic impact. A single-centre ambispective cohort study was conducted in which all adult patients undergoing intestinal resection and stoma creation were recruited. Two nutrition consultations were established for early follow-up after hospital discharge and patients were prospectively included. Additionally, a retrospective search was carried out to include a control group. In both groups, a 12-month follow-up was conducted to record readmissions associated with high output stoma. A multivariate logistic regression was performed. Statistical significance level was established at p < 0.05. 170 patients were recruited, 85 patients in each cohort. Demographic data and clinical characteristics were recorded. A significant difference was observed in HOS-related readmissions, with readmission rates of 28.6% vs 10.3% in the retrospective and prospective cohort, respectively. At the first follow-up consultation, 50.5% of patients presented some degree of protein-calorie malnutrition. A statistically significant improvement in nutritional status was observed in the second evaluation. The intervention carried out resulted in a total saving of €24,175. Early follow-up of patients after discharge resulted in a significant reduction in the rate of HOS-related readmissions and allowed to identify a high percentage of patients with malnutrition. The cost analysis showed the process to be a cost-effective improvement.


Identification of potential biomarkers of gold nanoparticle toxicity in rat brains.
Gold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity. Male Wister rats weighing 150-200 g were injected with 20 μg/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma amino-butyric acid and interferon-γ. In this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-γ in treated animals. This study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-γ, which may lead to inflammation and DNA damage/cell death.


Development of Loop-Mediated Isothermal Amplification Assays for the Detection of Seedborne Fungal Pathogens Fusarium fujikuroi and Magnaporthe oryzae in Rice Seed.
Bakanae disease (caused by Fusarium fujikuroi) and rice blast (caused by Magnaporthe oryzae) are two of the most important seedborne pathogens of rice. The detection of both pathogens in rice seed is necessary to maintain high quality standards and avoid production losses. Currently, blotter tests are used followed by morphological identification of the developing pathogens to provide an incidence of infection in seed lots. Two loop-mediated isothermal amplification assays were developed with primers designed to target the elongation factor 1-α sequence of F. fujikuroi and the calmodulin sequence of M. oryzae. The specificity, sensitivity, selectivity, repeatability, and reproducibility for each assay was assessed in line with the international validation standard published by the European and Mediterranean Plant Protection Organization (PM7/98). The results showed a limit of detection of 100 to 999 fg of DNA of F. fujikuroi and 10 to 99 pg of M. oryzae DNA. When combined with a commercial DNA extraction kit, the assays were demonstrated to be effective for use in detection of the pathogens in commercial batches of infected rice seed of different cultivars, giving results equivalent to the blotter method, thus demonstrating the reliability of the method for the surveillance of F. fujikuroi and M. oryzae in seed-testing laboratories.


Prevention of Atrial Fibrillation: Putting Proteostasis Derailment Back on Track.
Despite the many attempts to treat atrial fibrillation (AF), the most common cardiac tachyarrhythmia in the Western world, the treatment efficacy of AF is still suboptimal. A plausible reason for the suboptimal efficacy is that the current treatments are not directed at the underlying molecular mechanisms that drive AF. Recent discoveries revealed that the derailment of specific molecular proteostasis pathways drive electrical conduction disorders, contractile dysfunction and AF. The degree of this so-called 'electropathology' corresponds to the response to anti-AF treatment. Hence, to develop effective therapies to prevent AF, understanding the molecular mechanisms is of key importance. In this review, we highlight the key modulators of proteostasis derailment and describe the mechanisms that explain how they affect electrical and contractile function in atrial cardiomyocytes and AF. The key modulators of proteostasis derailment include (1) exhaustion of cardioprotective heat shock proteins (HSPs), (2) excessive endoplasmic reticulum (ER) stress and downstream autophagic protein degradation, (3) histone deacetylase 6 (HDAC6)-induced microtubule disruption, (4) activation of DNA damage-PARP1 activation and NAD+ axis and (5) mitochondrial dysfunction. Furthermore, we discuss druggable targets within these pathways that are involved in the prevention of proteostasis derailment, as well as the targets that aid in the recovery from AF. Finally, we will elaborate on the most favorable druggable targets for (future) testing in patients with AF, as well as drugs with potential benefits for AF recovery.


Fatal Acute Pancreatitis in an Adolescent: A Case Report.
Acute pancreatitis is uncommon in children and adolescents, and when it does occur, it is rarely fatal. The cause of death may be misdiagnosed as a death due to diabetic ketoacidosis or an infectious disease if an autopsy is not performed. Because these deaths are often unexpected and may occur before medical care, the forensic pathologist may be contacted to determine the cause of death. Even deaths that occur after hospitalization may be referred to the medical examiner because of the concern for drug involvement, the unusual age of the decedent, or the decreased availability for a hospital autopsy. We report a fatal case of acute pancreatitis in a 14-year-old adolescent girl who was brought unresponsive to the emergency room of a university hospital and died after unsuccessful resuscitation efforts.


Excimer-laser-assisted angioplasty in chronic femoropopliteal occlusion: the significance of an intimal flap in predicting reocclusion.
Angioplasty assisted by excimer laser was performed on 27 chronic femoropopliteal occlusions, ranging from 2 to 30 cm in length, in 26 patients. Twenty-one (78%) of the procedures were successful initially. Of these, 12 (57% [44% of the total]) remained patent at follow-up 3 months later. In seven of the nine cases of reocclusion observed after 3 months (78%) a large intimal flap resulting from the angioplasty-induced dissection could be identified in the postprocedure angiogram. The authors stress the possible importance of such an intimal flap in limiting the success of laser-assisted angioplasty of long femoropopliteal occlusions.


Plasmonics for Telecommunications Applications.
Plasmonic materials, when properly illuminated with visible or near-infrared wavelengths, exhibit unique and interesting features that can be exploited for tailoring and tuning the light radiation and propagation properties at nanoscale dimensions. A variety of plasmonic heterostructures have been demonstrated for optical-signal filtering, transmission, detection, transportation, and modulation. In this review, state-of-the-art plasmonic structures used for telecommunications applications are summarized. In doing so, we discuss their distinctive roles on multiple approaches including beam steering, guiding, filtering, modulation, switching, and detection, which are all of prime importance for the development of the sixth generation (6G) cellular networks.


[Pregnancy of undetermined location: how to find it?]
Early pregnancy is frequently accompanied by abnormal symptoms such as pelvic pain and metrorrhagia. In these situations, it is quite frequent to be unable to identify the pregnancy and in particular its location, even if the pregnancy test is clearly positive. Many clinical, biological and ultrasound approaches have been proposed to try to predict the location and development of the suspected pregnancy, without the individualization of a truly reliable tool. Currently the HCG dosage at 48 heures-interval remains one of the best tools available, but it is challenged by mathematical models such as the M6 model. The M6 model has shown in our experience a very good predictive value with also an ability to reduce the follow-up of patients with low progressive risk, thus allowing a reduction in costs and anxiety for patients and caregivers.


[Proinflammatory cytokines and tumours necrosis factor level change in bleeding of different genesis].
At investigation of 30 patients with peptic ulcer complicated by gastrointesinal bleeding and 16 injured persons with trauma, covering with blood loss, the disseminated intravascular blood coagulation syndrome revealed in 20 and 37.5% of them accordingly. At both groups revealed the proinflammatory cytokines and tumours necrosis factor-alpha level increased, especially expressed at patients with disseminated intravascular blood coagulation syndrome and trauma with blood loss.


Sclerotherapy for Orbital Lymphangioma - Case Series and Literature Review.
Orbital lymphangioma is a lymphatic system lesion that commonly presents in childhood. Management of these lesions is complex. Sclerotherapy is a therapy used to treat and shrink lesions prior to or as an alternative to surgery. We present three cases of orbital lymphangioma that were treated with sclerotherapy. Case 1: A 6-month-old boy was presented in 2010 with right ptosis and proptosis. Magnetic resonance imaging (MRI) identified a lesion involving the right orbit and face. Case 2: A 3-year-old girl was presented in 2011 with intermittent right periorbital swelling and medial canthal bleeding. MRI identified a soft-tissue lesion in the right orbit, extending into the face. Case 3: A 3-year-old girl was presented in 2012 with vomiting, and painful right proptosis. MRI identified an intra-conal lesion in the right orbit with fluid filled levels. All three patients were treated with sclerotherapy (sodium tetradecylsulfate). Sclerotherapy is a promising treatment for orbital lymphangioma. Its use may prevent the need for, or minimise the amount of surgical management. Several sclerosants are now commonly used to treat these lesions.


Diagnostic performance of breast tumor tissue selection in diffusion weighted imaging: A systematic review and meta-analysis.
Several methods for tumor delineation are used in literature on breast diffusion weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC). However, in the process of reaching consensus on breast DWI scanning protocol, image analysis and interpretation, still no standardized optimal breast tumor tissue selection (BTTS) method exists. Therefore, the purpose of this study is to assess the impact of BTTS methods on ADC in the discrimination of benign from malignant breast lesions in DWI in terms of sensitivity, specificity and area under the curve (AUC). In this systematic review and meta-analysis, adhering to the PRISMA statement, 61 studies, with 65 study subsets, in females with benign or malignant primary breast lesions (6291 lesions) were assessed. Studies on DWI, quantified by ADC, scanned on 1.5 and 3.0 Tesla and using b-values 0/50 and ≥ 800 s/mm2 were included. PubMed and EMBASE were searched for studies up to 23-10-2019 (n = 2897). Data were pooled based on four BTTS methods (by definition of measured region of interest, ROI): BTTS1: whole breast tumor tissue selection, BTTS2: subtracted whole breast tumor tissue selection, BTTS3: circular breast tumor tissue selection and BTTS4: lowest diffusion breast tumor tissue selection. BTTS methods 2 and 3 excluded necrotic, cystic and hemorrhagic areas. Pooled sensitivity, specificity and AUC of the BTTS methods were calculated. Heterogeneity was explored using the inconsistency index (I2) and considering covariables: field strength, lowest b-value, image of BTTS selection, pre-or post-contrast DWI, slice thickness and ADC threshold. Pooled sensitivity, specificity and AUC were: 0.82 (0.72-0.89), 0.79 (0.65-0.89), 0.88 (0.85-0.90) for BTTS1; 0.91 (0.89-0.93), 0.84 (0.80-0.87), 0.94 (0.91-0.96) for BTTS2; 0.89 (0.86-0.92), 0.90 (0.85-0.93), 0.95 (0.93-0.96) for BTTS3 and 0.90 (0.86-0.93), 0.84 (0.81-0.87), 0.86 (0.82-0.88) for BTTS4, respectively. Significant heterogeneity was found between studies (I2 = 95). None of the breast tissue selection (BTTS) methodologies outperformed in differentiating benign from malignant breast lesions. The high heterogeneity of ADC data acquisition demands further standardization, such as DWI acquisition parameters and tumor tissue selection to substantially increase the reliability of DWI of the breast.


Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy.
Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetization-transfer-weighted imaging of the LC. Parameters of "race models" of go- versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer nondecision times, and more lapses of attention. The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioral modeling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioral changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimization of noradrenergic treatment is likely to benefit from stratification according to LC integrity.SIGNIFICANCE STATEMENT Response inhibition deficits contribute to clinical symptoms and poor outcomes in people with Parkinson's disease and progressive supranuclear palsy. We used cognitive modeling of performance of a response inhibition task to identify disease-specific mechanisms of abnormal inhibitory control. Response inhibition in both patient groups was associated with the integrity of the noradrenergic locus coeruleus, which we measured in vivo using ultra-high field MRI. We propose that the imaging biomarker of locus coeruleus integrity provides a trans-diagnostic tool to explain individual differences in response inhibition ability beyond the classic nosological borders and diagnostic criteria. Our data suggest a potential new stratified treatment approach for Parkinson's disease and progressive supranuclear palsy.


Lanthanide-Doped Nanoparticles with Upconversion and Downshifting Near-Infrared Luminescence for Bioimaging.
We designed and synthesized NaYF4:Yb,Tm@LiLuF4:Nd core-shell nanoparticles, which can emit at ∼800 nm under 980 nm excitation and at ∼1060 nm under 808 nm excitation, simultaneously having an upconversion and downshifting mechanism for near-infrared (NIR) emission. After surface modification with sodium citrate, the soluble nanoparticles were used in the in vitro NIR luminescence imaging to compare the penetration depth and the scattering of tissue. Furthermore, to determine the differences between the upconversion and downshifting fluorescence for biological imaging, the soluble nanoparticles also were operated on the aforementioned two modes for in vivo imaging.


Template strand switching by T7 RNA polymerase.
T7 RNA polymerase (RNAP) is able to traverse a variety of discontinuities in the template (T) strand of duplex DNA, including nicks, gaps, and branched junctions in which the 3' end of the T strand is not complementary to the non-template (NT) strand. The products represent a faithful copy of the T strand, with no insertions or deletions. On double-stranded templates having protruding 3' ends the polymerase is able to insert the free 3' end of the NT strand and to utilize this as a new T strand ("turn around transcription"), resulting in the anomalous production of high molecular weight transcripts. The capacity of T7 RNAP to bypass interruptions in the T strand depends upon the stability of the elongation complex. Sequences that are expected to stabilize a local RNA:DNA hybrid (such as the presence of a C6 tract in the T strand) dramatically reduce dissociation of the RNAP while still allowing the enzyme to insert a new 3' end. Similar effects on RNAP release are observed when the enzyme reaches the end of a template (i.e. when synthesizing runoff products), resulting in markedly different yields of RNA product during multiple rounds of transcription.


A Genome Wide Association Study Revealed Key Single Nucleotide Polymorphisms/Genes Associated With Seed Germination in Gossypium hirsutum L.
Fast and uniform seed germination is essential to stabilize crop yields in agricultural production. It is important to understand the genetic basis of seed germination for improving the vigor of crop seeds. However, little is known about the genetic basis of seed vigor in cotton. In this study, we evaluated four seed germination-related traits of a core collection consisting of 419 cotton accessions, and performed a genome-wide association study (GWAS) to explore important loci associated with seed vigor using 3.66 million high-quality single nucleotide polymorphisms (SNPs). The results showed that four traits, including germination potential, germination rate, germination index, and vigor index, exhibited broad variations and high correlations. A total of 92 significantly associated SNPs located within or near 723 genes were identified for these traits, of which 13 SNPs could be detected in multiple traits. Among these candidate genes, 294 genes were expressed at seed germination stage. Further function validation of the two genes of higher expression showed that Gh_A11G0176 encoding Hsp70-Hsp90 organizing protein negatively regulated Arabidopsis seed germination, while Gh_A09G1509 encoding glutathione transferase played a positive role in regulating tobacco seed germination and seedling growth. Furthermore, Gh_A09G1509 might promote seed germination and seedling establishment through regulating glutathione metabolism in the imbibitional seeds. Our findings provide unprecedented information for deciphering the genetic basis of seed germination and performing molecular breeding to improve field emergence through genomic selection in cotton.


Chromosome conformation capture technologies as tools to detect structural variations and their repercussion in chromatin 3D configuration.
3D genome organization regulates gene expression in different physiological and pathological contexts. Characterization of chromatin structure at different scales has provided information about how the genome organizes in the nuclear space, from chromosome territories, compartments of euchromatin and heterochromatin, topologically associated domains to punctual chromatin loops between genomic regulatory elements and gene promoters. In recent years, chromosome conformation capture technologies have also been used to characterize structural variations (SVs) de novo in pathological conditions. The study of SVs in cancer, has brought information about transcriptional misregulation that relates directly to the incidence and prognosis of the disease. For example, gene fusions have been discovered arising from chromosomal translocations that upregulate oncogenes expression, and other types of SVs have been described that alter large genomic regions encompassing many genes. However, studying SVs in 2D cannot capture all their regulatory implications in the genome. Recently, several bioinformatic tools have been developed to identify and classify SVs from chromosome conformation capture data and clarify how they impact chromatin structure in 3D, resulting in transcriptional misregulation. Here, we review recent literature concerning bioinformatic tools to characterize SVs from chromosome conformation capture technologies and exemplify their vast potential to rebuild the 3D landscape of genomes in cancer. The study of SVs from the 3D perspective can produce essential information about drivers, molecular targets, and disease evolution.


Jejunoileal bypass reversal: effect on renal function, metabolic parameters and stone formation.
While the effect of jejunoileal bypass (JIB) reversal has been well studied regarding hepatic function, there is little information regarding the effect of reversal on renal function and even less data regarding the metabolic urinary stone environment. We evaluated the results of JIB reversal on renal function, the urinary stone milieu and the clinical development of recurrent calculi in affected patients. From 1995 to 2003, 4 female patients with a mean age of 48.2 years underwent JIB reversal primarily for refractory stone disease. The clinical and metabolic courses prior to and following bypass reversal were reviewed specifically to evaluate renal function, serum and urinary metabolic stone profiles, and clinical stone formation. At initial presentation following JIB all 4 patients had significantly increased 24-hour urinary oxalate (range 80 to 160 mg, mean 112.5, normal less than 50) and significantly low 24-hour urinary citrate (range 5 to 62 mg, mean 21.5, normal greater than 320). Following reversal 24-hour urinary oxalate normalized to between 31 and 36 mg (mean 33.75). However, 24-hour urinary citrate continued to be low (range 215 to 248 mg, mean 226.5). After JIB reversal all 4 patients continued to have new stones until the commencement of urinary alkalization, following which only 1 had 1 calculus, which occurred 47 months after reversal. After JIB mean serum creatinine was 1.48 mg/dl (range 0.8 to 1.9) and mean urinary creatinine excretion was 0.91 mg per hour (range 0.69 to 1.15). After JIB reversal mean serum creatinine was 1.28 mg/dl (range 0.6 to 2.0) and mean urinary creatinine excretion was 1.0 mg per hour (range 0.85 to 1.10). JIB reversal normalizes 24-hour urinary oxalate. While urinary citrate improves, it continues to be low and such patients are at high risk for recurrent stone formation. However, in this setting appropriate replacement therapy has a significant and positive impact on that propensity.


An effective electron donor to cytochrome oxidase. Purification, identification, and kinetic characterization of a contaminant of ruthenium red, hexaamineruthenium II/III.
When the calcium-transport inhibitor, ruthenium red, is chromatographed on a cation exchange resin, it yields a number of colored fractions and a colorless component that absorbs in the ultraviolet. The electron transfer activity previously ascribed to ruthenium red (Schwerzmann, K., Gazzotti, P., and Carafoli, E. (1976) Biochem. Biophys. Res. Commun. 69, 812) fractionates exclusively with the UV-absorbing material. On the basis of spectral, physical, and activity studies, we have identified this compound as Ru(NH3)62+/3+. It is shown that Ru(NH3)62+/3+ is an efficient electron donor directly to cytochrome oxidase, without mediation by cytochrome c. The steady state kinetics of electron transfer from Ru(NH3)62+ to purified oxidase resembles that of cytochrome c, showing a biphasic pattern but higher apparent Km values (Km1 = 8 microM, Km2 = 88 microM). Under conditions that favor tight binding to the oxidase, cytochrome c acts as a competitive inhibitor of Ru(NH3)62+, indicating that the two electron donors interact with cytochrome oxidase at the same site(s). The efficiency of Ru(NH3)62+ as an electron mediator to cytochrome aa3 and the similarity of its kinetic behavior to that of cytochrome c, make it a potentially valuable tool for investigating the mechanism of energy conservation in the terminal segment of the mitochondrial respiratory chain.


A pilot study of an automated personal identification process: Applying machine learning to panoramic radiographs.
This study aimed to assess the usefulness of machine learning and automation techniques to match pairs of panoramic radiographs for personal identification. Two hundred panoramic radiographs from 100 patients (50 males and 50 females) were randomly selected from a private radiological service database. Initially, 14 linear and angular measurements of the radiographs were made by an expert. Eight ratio indices derived from the original measurements were applied to a statistical algorithm to match radiographs from the same patients, simulating a semi-automated personal identification process. Subsequently, measurements were automatically generated using a deep neural network for image recognition, simulating a fully automated personal identification process. Approximately 85% of the radiographs were correctly matched by the automated personal identification process. In a limited number of cases, the image recognition algorithm identified 2 potential matches for the same individual. No statistically significant differences were found between measurements performed by the expert on panoramic radiographs from the same patients. Personal identification might be performed with the aid of image recognition algorithms and machine learning techniques. This approach will likely facilitate the complex task of personal identification by performing an initial screening of radiographs and matching ante-mortem and post-mortem images from the same individuals.


Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium.
Hemoglobin (Hb) is the most abundant protein in whole blood. This fact implies that the oxygen binding and releasing function of Hb is the most vital for sustaining life. All Hb is compartmentalized in red blood cells (RBCs) with corpuscular Hb concentration of about 35 g/dL, covered with a thin biomembrane. In spite of its abundance, Hb sometimes shows toxicity once it is leaked from RBCs. The shielding effect of the RBC membrane is physiologically important. Based on this structural importance, we have studied artificial red cells (Hb vesicles, HbV) as artificial oxygen carriers, which encapsulate a purified and concentrated Hb solution in phospholipid vesicles, mimicking the cellular structure of RBCs. Our academic research consortium has clarified the safety and efficacy of this HbV, aiming at clinical applications. Because of some superior characteristics to those of RBCs, HbV has the potential for use not only as a transfusion alternative but also for oxygen and carbon monoxide therapeutics, perfusate for transplant organs, and photosensitizer. In this review paper, such potential applications are summarized.


O knowledge, where art thou? Evidence and suspected appendicitis.
Much effort goes into developing and publishing guidelines which physicians fail to implement. We feel that major discrepancies still exist between theory and reality and that the translational approach to this aspect of medical care has not yet established itself. We therefore decided to investigate in an exemplary audit how liberally inappropriate imaging is used in our emergency department (ED) to rule out acute appendicitis. Our electronic medical record ED database 'Qualicare' (http://www.qualidoc.ch) was searched using the 'appendicitis' sub data base. The frequency and accuracy of abdominal imaging was determined in patients with clinically suspected appendicitis on admission over a 5-year period at a university hospital emergency unit. In total, 272 (41.2%) of the 577 patients were male and 305 (46.3%) were female. The attending physicians ordered abdominal X-rays in 133 patients, abdominal ultrasounds in 319, and abdominal computerized tomography (CT) scans in 93 patients. 125 patients underwent more than one imaging procedure. In all, 85/125 patients received a combination of X-rays, ultrasound and CT scanning! Physicians are often insecure about indications for surgery and therefore order useless imaging procedures. The reliability of such procedures in excluding acute appendicitis is limited, which was confirmed by our results. Although evidence-based medicine guidelines exist, they are neglected for many reasons. Future academic efforts should therefore focus more on knowledge translation and the implementation of existing knowledge by heightening awareness, rather than on simply creating new guidelines.


PGC-Enriched miRNAs Control Germ Cell Development.
Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs (mRNAs) involved in the growth and development of a variety of cells, including primordial germ cells (PGCs) which play an essential role in germ cell development. However, the target mRNAs and the regulatory networks influenced by miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC development through targeting mRNAs involved in various cellular pathways. We reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b, -18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis. This integrative study utilizing mRNA microarray analysis and miRNA target prediction demonstrates the regulatory networks through which these miRNAs regulate their potential target genes during PGC development. The elucidated networks of miRNAs disclose a coordinated molecular mechanism by which these miRNAs regulate distinct cellular pathways in PGCs that determine germ cell development.


Lipid storage myopathy in familial hyperlipoproteinemia.
We studied a 23-year-old man with lipid storage myopathy. Five members of his family had hyperlipoproteinemia, and his consanguineous parents had elevated serum creatine kinase levels, although only the father showed clinical evidence of myopathy. The patient's intramuscular carnitine content was slightly reduced, but the reduction was not significant compared with the average value for reported cases with carnitine deficiency. Urinary excretion of carnitine showed good responses to starvation, long-chain fatty acid loading, and corticotropin administration. Therefore, his carnitine metabolism was normal. Administration of corticotropin or carnitine did not bring about any improvement of the symptoms. A connection between lipid storage myopathy and hyperlipoproteinemia was suggested.


Work-related injuries among Iowa farm operators: an analysis of the Iowa Farm Family Health and Hazard Surveillance Project.
In 1994, the Iowa Farm Family Health and Hazard Surveillance Project carried out a two-stage, stratified, cluster survey of Iowa farms using a mail survey. With data from this representative sample of Iowa farmers, we examined the associations between farm-work-related injuries and possible risk factors for 390 principal farm operators. Forty (10.3%) of these operators reported being injured while doing farm work. We developed a logistic regression to assess associations between potential risk factors and injury. We found three factors significantly associated with injury: younger age (odds ratio [OR] = 3.1, confidence interval [CI] = 1.1-9.3), having an impairment or health problem that limits work (OR = 2.4, CI = 1.5-3.8), and hand or arm exposure to acids or alkalis (OR = 2.6, CI = 1.1-5.9). In the univariate analysis, safety training did not seem to protect farmers from injuries.


The sequelae of surgical exposure of unerupted teeth.
The late effects of surgical exposure of unerupted teeth were analyzed. Of 121 teeth, 62 had only the crowns exposed; additional traction was applied to 31 teeth and 28 were repositioned. Postoperative observation time ranged from eight months to 13 years. One hundred and eleven teeth assumed their position in the arch and were deemed successfully treated; ten teeth failed to erupt. Of the successfully treated teeth, 23% showed biological aberrations such as obliteration of the pulp, dwarfed roots, and denervation. These pathophysiologic changes, alone or in combination, were commensurate with the amount of trauma inflicted on the teeth. Teeth that wer repositioned showed the most change, whereas teeth that only had crowns exposed showed the least change.


Cosmological tests of general relativity with future tomographic surveys.
Future weak lensing surveys will map the evolution of matter perturbations and gravitational potentials, yielding a new test of general relativity on cosmic scales. They will probe the relations between matter overdensities, local curvature, and the Newtonian potential. These relations can be modified in alternative gravity theories or by the effects of massive neutrinos or exotic dark energy fluids. We introduce two functions of time and scale which account for any such modifications in the linear regime. We use a principal component analysis to find the eigenmodes of these functions that cosmological data will constrain. The number of constrained modes gives a model-independent forecast of how many parameters describing deviations from general relativity could be constrained, along with w(z). The modes' scale and time dependence tell us which theoretical models will be better tested.


Anterior Cruciate Ligament Return to Play: Where Are We Now?
Anterior cruciate ligament reconstruction (ACLR) is a commonly performed orthopaedic procedure, and it is crucial to assess an athlete's readiness to safely return to sports following ACLR to minimize the risk of reinjury. Despite this, determining optimal return to play (RTP) criteria following ACLR that is accurate, accessible, and reproducible remains challenging. This review aims to discuss commonly employed RTP criteria domains, including functional assessments, patient-reported outcomes, and psychological tests, as well as emerging technologies such as magnetic resonance imaging (MRI) that may play a role as a gold standard in RTP assessment. The findings of this review suggest RTP decision making after ACL surgery is nuanced and traditionally used objective measures do not perfectly predict RTS rates or clinical outcomes. In the future, a standardized MRI screening tool could help predict reinjury. The role of functional and psychological patient-reported outcome measures needs to defined, and objective criteria should be rigorously evaluated for whether they accurately screen an athlete's physical readiness and should be expanded to include more sport-specific movement analysis.


Notalgia paresthetica associated with cervical spinal stenosis and cervicothoracic disk disease at C4 through C7.
Notalgia paresthetica (NP) is a common refractory, sensory, neuropathic syndrome with the hallmark symptom of localized pruritus of the unilateral infrascapular back. It generally is a chronic noncurable condition with periodic remissions and exacerbations. While the dermatologic syndrome may be multifactorial in etiology, a possible association with underlying cervical spine disease should be evaluated for proper treatment. Collaborative multispecialty evaluation by dermatology, radiology, orthopedic surgery, and neurology may be indicated for primary management of this condition. First-line therapy for NP with associated cervical disease may include nondermatologic noninvasive treatments such as spinal manipulation, physical therapy, massage, cervical traction, cervical muscle strengthening, and oral nonsteroidal anti-inflammatory drugs and muscle relaxants. Notalgia paresthetica may in fact be a cutaneous sign of an underlying degenerative cervical spine disease. We report a case of a patient with cervical spinal stenosis that corresponded directly with the clinical findings of NP.


On the inactivity of thiol-subtilisin. The role of the intramolecular electric field.
Based on computed proton affinities for several model systems, the energetics of proton transfer and the acidity of the catalytic triads Cys-His-Asn (papain). Cys-His-Asp (thiol-subtilisin) and Ser-His-Asp (subtilisin) are discussed. It is shown that in papain the ion-pair Cys--HisH+ exists owing to the intramolecular electric field, and that a similar situation is found in thiol-subtilisin. but not in subtilisin. Assuming similar reaction mechanisms for papain and thiol-subtilisin - i.e. proton transfer from HisH+ to the NH group of the scissile peptide bond - the inactivity of thil-subtilisin towards proteins is explained by the much greater basicity of His in the complex His-Asp- than in His-Asn. In order for this explanation to be consistent, it is tentatively concluded that the catalytic mechanism of the serine proteases is different from that of the cystein proteases, and involves direct transfer of the serine proton to the leaving group in the acylation step.


Assessment of Initial Guesses for Self-Consistent Field Calculations. Superposition of Atomic Potentials: Simple yet Efficient.
Electronic structure calculations, such as in the Hartree-Fock or Kohn-Sham density functional approach, require an initial guess for the molecular orbitals. The quality of the initial guess has a significant impact on the speed of convergence of the self-consistent field (SCF) procedure. Popular choices for the initial guess include the one-electron guess from the core Hamiltonian, the extended Hückel method, and the superposition of atomic densities (SAD). Here, we discuss alternative guesses obtained from the superposition of atomic potentials (SAP), which is easily implementable even in real-space calculations. We also discuss a variant of SAD which produces guess orbitals by purification of the density matrix that could also be used in real-space calculations, as well as a parameter-free variant of the extended Hückel method, which resembles the SAP method and is easy to implement on top of existing SAD infrastructure. The performance of the core Hamiltonian, the SAD, and the SAP guesses as well as the extended Hückel variant is assessed in nonrelativistic calculations on a data set of 259 molecules ranging from the first to the fourth periods by projecting the guess orbitals onto precomputed, converged SCF solutions in single- to triple-ζ basis sets. It is shown that the proposed SAP guess is the best guess on average. The extended Hückel guess offers a good alternative, with less scatter in accuracy.


Venous thromboembolism does not share familial susceptibility with retinal vascular occlusion or glaucoma: a nationwide family study.
Inherited hypercoagulable states (i.e. thrombophilia) have been suggested to be involved in retinal vascular occlusion but results are divergent. Vascular micronutrition and ischemia have been hypothesised to be involved in the pathogenesis of glaucoma. This nationwide study determines the importance of family history of venous thromboembolism (VTE) as a risk factor for retinal vein occlusion (RVO), retinal artery occlusion (RAO), primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). A total of 6,007,042 Swedish individuals were studied. Data from the Swedish Multigeneration Register for subjects aged 0-78 years old for the period 1997-2010 were linked to the Swedish Hospital Discharge Register and the Hospital Outpatient Register. Main exposure measure was family history of VTE in first-degree relatives (parents and/or siblings). Main outcomes were hazard ratios (HRs) for RVO, RAO, POAG, and PACG. During follow-up 9036 individuals developed RVO, 2137 individuals developed RAO, 29,176 individuals developed POAG and 1498 individuals developed PACG. There was no association between family history of VTE and risk of RVO (HR = 1.04, 95 % CI 0.98-1.10), RAO (HR = 1.00, 95 % CI 0.89-1.13), POAG (HR = 0.96, 95 % CI 0.93-0.99), and PACG (HR = 0.92, 95 % CI 0.80-1.06) in the crude age and sex adjusted model. The results were similar in the fully adjusted model: RVO (HR = 1.04, 95 % CI 0.99-1.11), RAO (HR = 1.01, 95 % CI 0.89-1.13), POAG (HR = 0.97, 95 % CI 0.94-1.00), and PACG (HR = 0.91, 95 % CI 0.79-1.05). Family history of VTE is not a risk factor for RVO, RAO, POAG and PACG. Thus, it is unlikely that strong and common genetic variants associated with VTE are of importance for these disorders.


Should patients with obesity be more afraid of COVID-19?
COVID-19 crisis has lasted since the late 2019 to the present day. The severity of the disease is positively correlated with several factors, such as age and coexisting diseases. Furthermore, obesity is increasingly considered as a yet another risk factor, particularly, because it has been observed that people suffering from excessive body weight may experience a more severe course of COVID-19 infection. On the basis of current research, in our nonsystematic review, we have investigated the extent to which obesity can affect the SARS-CoV-2 course and identify the potential mechanisms of the disease. We have also described the role of proper nutrition, physical activity and other aspects relevant to the management of obesity.


Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus.
A 17-month-old boy presented with failure to thrive, polyuria, and vomiting. He had been diagnosed clinically with nephrogenic diabetes insipidus and treated by amiloride and hydrochlorothiazide combination without a satisfactory outcome at another center since 1 year of age. The diagnosis was confirmed by genetic analysis (AVPR2mutation), and the treatment was modified to include rofecoxib (a selective cyclooxygenase-2 inhibitor) in addition to hydrochlorothiazide and amiloride. This combination along with a low-salt diet resulted in a dramatic decrease in urinary free-water loss, while no side effect was noted. Because of prohibition of rofecoxib, it had to be substituted first by indomethacin and then by ibuprofen. However, both drugs were ineffective in controlling water diuresis. Thus, we had to replace these drugs by celecoxib (another selective cyclooxygenase-2 inhibitor). We conclude that the combination hydrochlorothiazide/amiloride/cyclooxygenase-2 inhibitor could be successfully used to treat congenital nephrogenic diabetes insipidus.


Phylogenetic evidence for horizontal transfer of an intervening sequence between species in a spirochete genus.
The 23S rRNA genes (rrl genes) of some strains of certain species of the spirochete genus Leptospira carry an intervening sequence (IVS) of 485 to 759 bases flanked by terminal inverted repeat and encoding an open reading frame for a putative protein of over 120 amino acids. The structure and the sporadic distribution of the IVS suggest that it might be a mobile element that can be horizontally transferred within or between species. Phylogenetic hypotheses based on the sequences for six IVS open reading frames from various species were compared with hypotheses constructed by using DNA sequences from the 16S rRNA gene (rrs), which is not closely linked to rrl in this genus. The predicted phylogenies for the IVS and rrs differed in a major respect: one strain that claded with L. weillii in the tree based on the rrs data claded with L. noguchi in the tree based on the IVS data. Neither set of data supported a tree in which this strain was constrained to be in the same clade as was supported by the other set of data. This result indicates a probable horizontal transfer of the IVS from a recent ancestor of L. noguchi to a recent ancestor of one of the L. weillii strains. This observation is the first indication of horizontal transfer of elements encoded on the chromosomes of spirochetes.


On the mechanism of preadipocyte differentiation. Masking of poly(ADP-ribose) synthetase activity during differentiation of 3T3-L1 preadipocytes.
Differentiation of 3T3-L1 preadipocytes, induced by methylisobutylxanthine (MIX), dexamethasone (DEX), and insulin, produces cells with the morphological and biochemical characteristics of adipocytes. Poly(ADP-ribose) synthetase activity in 3T3-L1 cells treated with MIX, DEX, and insulin underwent an abrupt decrease in activity, remained low for several hours, and then increased; this rise was delayed by readdition of MIX, DEX, and insulin. The drop of synthetase activity represents the earliest alteration of a specific enzyme yet detected during the differentiation of 3T3-L1 cells. Nondifferentiating 3T3-C2 control cells do not exhibit changes in poly(ADP-ribose) synthetase activity when treated with MIX, DEX, and insulin. The transient reduction in poly(ADP-ribose) synthetase activity in 3T3-L1 cells occurred prior to the appearance of the adipocyte phenotype induced by the above agents and was not observed when preparations were assayed in the presence of DNase I. It is evident that poly(ADP-ribose) synthetase activity was masked following treatment with MIX, DEX, and insulin since the synthetase is sensitive to agents that affect the physical properties of DNA. This transient reduction in activity may be an early event in differentiation which reflects changes in chromatin structure.


The association between prior statin use and long-term outcomes after critical care admission.
Statins may have immunomodulatory effects that benefit critically ill patients. Therefore, we retrospectively examined the association between survival and the prescription of statins prior to admission to an intensive care unit (ICU), or high dependency unit (HDU), as a result of major elective surgery or as an emergency with a presumed diagnosis of sepsis. We retrospectively studied critical care patients (ICU or HDU) from a tertiary referral UK teaching hospital. Nottingham University Hospitals have more than 2200 beds, of which 39 are critical care beds. Over a 5-year period (2000-2005), 414 patients were identified with a presumed diagnosis of sepsis, and 672 patients were identified who had planned ICU/HDU admissions following elective major surgery. Patients prescribed statins prior to hospital admission were compared with those who were not. Demographics, medical history, drug history, and Acute Physiology and Chronic Health Evaluation II scores were examined. Univariate and multivariate analyses were applied using the primary end point of survival at 5 years after admission. Patients prescribed statins prior to critical care admission were, on average, older and had higher initial Acute Physiology and Chronic Health Evaluation II scores and more preexisting comorbidities. Statins were almost invariably stopped following admission to critical care. Statin use was not associated with significantly altered survival during hospital admission, or at 5 years, for either patients with sepsis (9% vs 15%, P=.121; 73% vs 84%, P=.503, respectively) or postoperative patients (55% vs 58%, P=.762; 57% vs 63%, P=.390). Prior statin use was not associated with improved outcomes in patients admitted to critical care after elective surgical cases or with a presumed diagnosis of sepsis.


Smoking behavior of males attending the quit tobacco clinics in Bahrain and their knowledge on tobacco smoking health hazards.
One third of Bahraini adult (20-64 years) males and 7.0% of females use some form of tobacco. The corresponding rates for cigarette and waterpipe tobacco smoking (WTS) are 11.0% and 6.0%, respectively. The objective of the study was to determine the knowledge on tobacco smoking and past smoking related behavior of male patients attending the Quit Tobacco Clinics (QTC) in Bahrain. A sample of 339 male clinic attendees was taken proportional to the population distribution in the three QTC at Al Hoora Health Center, Hamad Kanoo Health Center, and Bank of Bahrain and Kuwait Health Center. Data collection was performed until the sample size was completed (September 2015 to December 2016). Knowledge on the health effects of cigarette and WTS was examined based on 10 statements on cigarette and similar ones on WTS. Respondents "agreeing" with the statements were considered knowledgeable and those "disagreeing" or responding "don't know", not knowledgeable. All the "agree" responses for cigarette/WTS were summed across the 10 health effects and average health knowledge scores for cigarette/WTS were computed. Most of the study participants were Bahraini nationals, ever married and educated with at least secondary level. The majority (65.8%) of participants smoked a single type of tobacco product, and the rest, two (28.0%) or three or more (6.2%). Age of starting cigarette and WTS was 16.2 ± 4.0 and 19.3 ± 6.7 years, respectively. The majority (81%) smoked in the presence of other family members and 26.3% in the presence of a child. 76.2% smoked in the presence of others in their cars. 18.9% of the attendees had quit smoking at the time of interview. 81% of the participants knew about the hazards of both cigarette and WTS with a significantly higher (p = 0.0001) mean knowledge score for cigarette (93.3 ± 3.0%) than WTS (85.2 ± 2.1%). The relative lack of knowledge on the hazards of WTS in a sample of Arab country population with an increasing trend of WTS warrants the attention of health policy makers in the country and region.


Lesion miss rates and false-negative rates for 1115 consecutive cases of stereotactically guided needle-localized open breast biopsy with long-term follow-up.
To retrospectively determine the lesion miss rate and false-negative rate of needle-localized open breast biopsy (NLOBB) with stereotactic guidance in a large study population. The ethical review board approved the study; the need for informed consent was waived. A total of 1115 stereotactic NLOBBs performed in 1068 women aged 22-90 years (mean age, 54 years) were tracked to determine outcomes. In cases of malignancy, NLOBB was considered to be diagnostically successful. The mammographic outcomes in all patients with benign results at NLOBB were tracked for at least 2 years. Cases without such mammographic follow-up were cross-referenced with a tumor registry after at least 54 months. The lesion miss rate was based on all malignant lesions and all lesions with long-term mammographic follow-up. Results from all 1115 NLOBBs were used to report the false-negative rate. Of 1115 NLOBBs, 472 (42%) had malignant results. Mammographic follow-up data were available for 535 (83%) of 643 NLOBBs with benign results. Mammographic follow-up revealed 11 lesions that were missed with NLOBB, of which five were malignant and six benign. Thus, the lesion miss rate with NLOBB was 1.1% (11/[472 + 535]). Among the 643 cases, in 108 of them without mammographic follow-up (17%), cross-referencing with a tumor registry did not reveal missed cases of breast carcinoma. The false-negative rate was therefore 1.0% (5/[472 + 5]). On the basis of the results of long-term follow-up, the authors noted a lesion miss rate of 1.1% and a false-negative rate of 1.0%, which indicate that NLOBB with stereotactic guidance is an accurate method for diagnosing breast lesions.


Successful treatment of two cases of acute myocarditis with colchicine.
Colchicine is an FDA-approved medicine that has been used for many years to prevent and treat gout flares as well as familial mediterranean fever. It is also used off-label to treat pericarditis, calcium pyrophosphate illness, and Behçet's syndrome. There are additional studies on the use of colchicine, which is accepted as the standard treatment for pericarditis in adults, post-pericardiotomy syndrome, post-operative and post-ablation atrial fibrillation, coronary artery disorders, prior to percutaneous coronary procedures, and myocarditis. Colchicine appears to be a promising oral cardiovascular treatment targeting the inflammatory axis, owing to its low cost and moderate side-effect profile. Our aim is to emphasise that colchicine treatment, which has a strong and effective anti-inflammatory effect profile, should be kept in mind in addition to conventional treatment in childhood myocarditis.


Fatigue measurement system designed for a chalcogenide-based device using a homemade heater tip.
A fatigue measurement system is designed using a homemade tungsten (W) heater tip. This system is composed of a pulse generator and an atomic force microscope with the W heater tip attached. Also included are a parameter analyzer and control devices. The entire measurement process is controlled by a designed program without communication errors. Additionally, a process to fabricate the sharp W heater tip that applies an electrical pulse and evaluates the electrical properties is introduced. The analysis of the tip, carried out by scanning electron microscopy and electron backscattering diffraction, shows that the tip has great thermomechanical stability. Using this fatigue measurement system, the resistance of the Ge(2)Sb(2)Te(5) (GST) cell was successfully measured as a function of the number of set/reset cycles. The specific area (both program area and failure area) was easily observed. It is expected that the expansion of GST is a source of information regarding the fatigue of a GST cell.


Congenitally corrected transposition of the great arteries: a clinical and surgical study.
From 1967 to 1979, 40 patients with the diagnosis of congenitally corrected transposition of the great arteries (C-TGA) have been followed. Associated cardiac defects were present in all but one patient, most frequently ventricular septal defect (80%), and pulmonary stenosis (70%). Left sided atrio-ventricular valve dysfunction developed in 25%, third degree atrio-ventricular block (at least intermittently) in 33% of the patients. Twenty-eight patients were operated: palliative procedures were done in 6, corrective operations in 22 patients. Ten of the 40 patients have died during a mean observation period of 4 years: 4 early postoperatively, 3 late postoperatively and 3 non-operated patients. Sudden unexplained cardiac arrest has been the most frequent cause of death (2 late postoperative and 2 non-operated patients). The incidence of residual ventricular septal defects and residual pulmonary stenosis after corrective surgery has been relatively high owing to the complex anatomy in these patients. Also reconstruction of the atrio-ventricular valves has been difficult because of severe deformities, particularly of the left side. It is concluded that in C-TGA the pacemaker should be implanted early, at the first sign of AV-conduction disturbance. Since the relief of the pulmonary stenosis is difficult, the operation should be deferred until an adequate-sized conduit can be implanted.


Use of sequence microdivergence in mycobacterial ortholog to analyze contributions of the water-activating loop histidine of Escherichia coli uracil-DNA glycosylase in reactant binding and catalysis.
Uracil-DNA glycosylase (Ung), a DNA repair enzyme, pioneers uracil excision repair pathway. Structural determinations and mutational analyses of the Ung class of proteins have greatly facilitated our understanding of the mechanism of uracil excision from DNA. More recently, a hybrid quantum-mechanical/molecular mechanical analysis revealed that while the histidine (H67 in EcoUng) of the GQDPYH motif (omega loop) in the active site pocket is important in positioning the reactants, it makes an unfavorable energetic contribution (penalty) in achieving the transition state intermediate. Mutational analysis of this histidine is unavailable from any of the Ung class of proteins. A complication in demonstrating negative role of a residue, especially when located within the active site pocket, is that the mutants with enhanced activity are rarely obtained. Interestingly, unlike the most Ung proteins, the H67 equivalent in the omega loop in mycobacterial Ung is represented by P67. Exploiting this natural diversity to maintain structural integrity of the active site, we transplanted an H67P mutation in EcoUng. Uracil inhibition assays and binding of a proteinaceous inhibitor, Ugi (a transition state substrate mimic), with the mutant (H67P) revealed that its active site pocket was not perturbed. The catalytic efficiency (Vmax/Km) of the mutant was similar to that of the wild type Ung. However, the mutant showed increased Km and Vmax. Together with the data from a double mutation H67P/G68T, these observations provide the first biochemical evidence for the proposed diverse roles of H67 in catalysis by Ung.


Fourier transform infrared spectroscopic study of water-in-supercritical CO2 microemulsion as a function of water content.
Fourier transform infrared (FT-IR) spectrum of water-in-supercritical CO(2) microemulsion was measured at 60 degrees C and 30.0 MPa over a wide range of water/CO(2) ratio from 0.0 to 1.2 wt % to study the distribution of water into CO(2), interfacial area around surfactant headgroup, and core water pool. The microemulsion was stabilized by sodium bis(1H,1H,2H, 2H-heptadecafluorodecyl)-2-sulfosuccinate [8FS(EO)(2)] equimolarly mixed with sodium 1-oxo-1-[4-(tridecafluorohexyl)phenyl]-2-hexanesulfonate [FC6HC4] or with poly(ethylene glycol) 2,6,8-trimethyl-4-nonyl ether [TMN-6]. The signal area of the O-H stretching band of water suggested that the number of water molecules in the microemulsion increases linearly with the water/CO(2) ratio, except for a slow initial increase below 0.4 wt % due to a part of water dissolved in CO(2). The amount of water in CO(2) was evaluated by decomposing the bending band of water into two components, one at lower frequency ascribed to water in CO(2) and the other at higher frequency to water in the microemulsion. The decomposition confirmed that CO(2) is saturated with water at the water content of 0.4 wt %. It was also revealed, from the symmetric SO stretching frequency of the surfactant, that the sulfonate headgroup is completely hydrated at the water/CO(2) ratio of 0.4-0.5 wt %. The results demonstrated that water is introduced preferentially into CO(2) and the interfacial area at small water content, and then is loaded into the micelle core after the saturation of CO(2) with water and the full hydration of the surfactant headgroup.


[Value of dual contrast-enhanced ultrasound in the preoperative T staging of rectal carcinoma].
Objective: To explore the value of dual contrast-enhanced ultrasound in preoperative T staging of rectal carcinoma. Methods: Dual contrast-enhanced ultrasound examinations were performed on 72 patients with rectal carcinoma via transrectal infusion and intravenous injection. The accordance of preoperative dual contrast-enhanced ultrasound results and postoperative pathologic results was evaluated retrospectively. Results: The overall accordance rate of preoperative T staging was 73.6% (53/72). And accordance rate was 100.0% (3/3), 100.0% (5/5), 68.4% (13/19), 71.4% (25/35)and 70.0% (7/10) for Tis , T1, T2, T3 and T4, respectively. The consistency was good (κ=0.607, χ(2) =8.363, P<0.01). The accordance rate of middle/lower vs high rectal carcinoma was 68.7% and 85.7%. Conclusion: Dual contrast-enhanced ultrasound can provide reference for preoperative T staging for patients with rectal carcinoma.


Use of distal arteries for microvascular reconstruction in forearm and hand surgery.
Three techniques that use distal arteries for microvascular reconstruction in forearm and hand surgery are described: (1) distal based supply from the deep branch of the radial artery, (2) proximal reversal of the radial artery, and (3) distal based supply from the ulnar artery. Nine cases are described to illustrate the use of these techniques: three vascularized bone grafts, three toe-to-hand transfers, one free cutaneous flap, one brachial artery reconstruction, and one replantation of an amputated palm. The technique offers a number of advantages: (1) it eliminates the need for vein grafts, (2) it requires only a single arterial microvascular anastomosis, (3) it minimizes microvascular size discrepancies, (4) the distal artery can be prepared in the same operative field as the rest of the reconstruction, and (5) the technique enables an undamaged artery to be brought into a zone of trauma and used as a recipient vessel. The technique has the disadvantage that it sacrifices part of the collateral circulation to the hand and it is therefore important to check the blood supply to the hand preoperatively.


Oral Health and Swallowing Problems.
Oral health impacts systemic health. Therefore, oral care is an important consideration in maintaining quality of life (QOL). Previously, maintenance and improvement of oral hygiene was considered essential for achieving oral health. In addition to oral hygiene, oral care in terms of oral function is now considered to maintain QOL. Ingestion of exogenous nutrients via the oral cavity is fundamental to the function of all higher animals, not only human beings. Chewing and swallowing processes are critical for normal food intake, and adequate saliva supply and oral care to allow proper functioning of these processes are indispensable for maintaining QOL. In this review, we will summarize the relationship between chewing and swallowing and effects of saliva secretion on these functions, and discuss methods to maintain ingestion of exogenous nutrients and prevent swallowing problems, especially in elderly people.


A computer modelling study of the uptake, structure and distribution of carbonate defects in hydroxy-apatite.
Computer modelling techniques have been employed to qualitatively and quantitatively investigate the uptake and distribution of carbonate groups in the hydroxyapatite lattice. Two substitutional defects are considered: the type-A defect, where the carbonate group is located in the hydroxy channel, and the type-B defect, where the carbonate group is located at the position of a phosphate group. A combined type A-B defect is also considered and different charge compensations have been taken into account. The lowest energy configuration of the A-type carbonate has the O-C-O axis aligned with the channel in the c-direction of the apatite lattice and the third oxygen atom lying in the a/b plane. The orientation of the carbonate of the B-type defect is strongly affected by the composition of the apatite material, varying from a position (almost) flat in the a/b plane to being orientated with its plane in the b/c plane. However, Ca-O interactions are always maximised and charge compensating ions are located near the carbonate ion. When we make a direct comparison of the energies per substitutional carbonate group, the results of the different defect simulations show that the type-A defect where two hydroxy groups are replaced by one carbonate group is energetically preferred (DeltaH = -404 kJ mol(-1)), followed by the combined A-B defect, where both a phosphate and a hydroxy group are replaced by two carbonate groups (DeltaH = -259 kJ mol(-1)). The type-B defect, where we have replaced a phosphate group by both a carbonate group and another hydroxy group in the same location is energetically neutral (DeltaH = -1 kJ mol(-1)), but when the replacement of the phosphate group by a carbonate is charge compensated by the substitution of a sodium or potassium ion for a calcium ion, the resulting type-B defect is energetically favourable (DeltaH(Na) = -71 kJ mol(-1),DeltaH(K) = -6 kJ mol(-1)) and its formation is also promoted by A-type defects present in the lattice. Our simulations suggest that it is energetically possible for all substitutions to occur, which are calculated as ion-exchange reactions from aqueous solution. Carbonate defects are widely found in biological hydroxy-apatite and our simulations, showing that incorporation of carbonate from solution into the hydroxyapatite lattice is thermodynamically feasible, hence agree with experiment.


Aspiration of the elbow joint for treating radial head fractures.
Radial head fracture is the most common fracture of the elbow. It usually results from a fall onto an outstretched arm. In 1954, Mason classified these fractures into type 1 (undisplaced), type 2 (simple displaced), and type 3 (comminuted fractures). Aspiration of the elbow joint aims to relieve pressure in the elbow joint and has been used as an initial treatment option for radial head fractures. However, it is an invasive technique with the potential for complications such as infection and injury to nerves and vessels. To assess the effects (benefits and harms) of elbow joint aspiration for treating radial head fracture in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (14 April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (14 April 2014), MEDLINE (1946 to April Week 1 2014) and EMBASE (1980 to 2014 Week 15), trial registries, bibliographies and conference proceedings. Randomised and quasi-randomised controlled clinical trials comparing aspiration versus no aspiration for treating radial head fractures in adults. Two review authors independently selected articles, assessed risk of bias and extracted data. Disagreements were resolved by discussion. Where appropriate, we pooled results of comparable studies using fixed-effect meta-analysis. We included two trials that involved 126 participants but provided results for only 108 participants. Most participants were adults, typically over 30 years of age. Both trials were at high risk of selection, performance, detection and reporting bias. Reflecting this high risk of bias, we downgraded the quality of evidence two levels for study limitations and a further level for imprecision. Thus we judged the evidence for all outcomes to be 'very low' quality, meaning that we are very uncertain about these estimates.One trial included participants with Mason type 1, 2 or 3 radial head fractures and also a few cases of traumatic elbow hemarthrosis without fracture. The other trial included participants with Mason type 1 and 2 fractures. All participants were managed non-surgically.Neither trial reported functional outcome based on validated patient-reported outcome measures of function or pain using validated measures such as a visual analogue scale. Very low quality evidence (108 participants, two trials) indicates little difference between aspiration and no aspiration in impaired function (unable to carry heavy loads; discomfort when carrying loads) at 12 months (9/51 in aspiration group versus 7/57 in the no aspiration group; risk ratio 1.43 favouring no aspiration, 95% confidence interval (CI) 0.57 to 3.58). Very low quality evidence (two trials) suggests a beneficial effect of aspiration on pain relief immediately after aspiration. Very low quality evidence (one trial, 28 participants) shows less pain after aspiration at three weeks, but it is unclear whether this applies subsequently. Neither trial reported on adverse events (for example, nerve and vascular injuries; deep or superficial infection) from the procedure, but aspiration was reported as being unsuccessful in three participants (7.9%) in one trial. Very low quality evidence indicates little difference in range of motion (based on elbow extension) between the two groups at six weeks (28 participants, one trial) or 12 months (108 participants, two trials). The report of adverse events was incomplete, but one trial (80 participants) reported the absence of three specific complications: myositis ossificans, joint instability or late displacement of the fracture. There is insufficient evidence to determine the effectiveness of joint aspiration for the initial treatment of radial head fracture in terms of function, pain and range of motion or to determine the safety of the procedure. An examination of current aspiration use, the prospective collection of adverse events and consultation with patients as to their preferences and values would be helpful in guiding decisions about the future design of a multicentre randomised trial aiming to obtain definitive evidence on the use of aspiration for treating radial head fractures.


Contrast mechanism due to interface trapped charges for a buried SiO2 microstructure in scanning electron microscopy.
We clarify the scanning electron microscopic contrast mechanism for imaging a buried SiO(2) trench microstructure with interface trapped charges by simulating both electron scattering and transport. Here, the interface trapped charges make the SiO(2) film more negatively charged and increase excess holes in the space charge distribution of the electron scattering region. The generated positive surface electric field thus redistributes some emitted secondary electrons and results in the dark contrast. This contrast mechanism is validated by comparing with experiments, and it may also provide an interesting approach for imaging and detecting deep interface trapped charges in insulating films.


Hereditary antithrombin III deficiency: biochemical aspects.
Since the description of the first thrombophilic family with congenital AT-III deficiency, increasing numbers of different types of the condition have become evident. Initially the anomaly seemed to be homogeneous and simple: the three main characteristics of AT-III (thrombin inactivating and heparin cofactor activity, antigen concentration) were decreased. This type of AT-III deficiency (type 1) was later divided into type 1a and 1b on the basis of the heparin affinity of the AT-III molecule. The first family with a different qualitative AT-III disorder (type 2) was described by our group in 1974. In the members of this family the AT-III antigen concentration was normal, but the molecule had no functional activity (AT-III Budapest). In the last few years some new variants of type 2 hereditary AT-III disorders have been observed; they are characterized by a loss of one or more functional properties of the AT-III molecule.


Plant sulphate transporters: co-ordination of uptake, intracellular and long-distance transport.
Proton/sulphate co-transport in the plasma membrane of root cells is the first step for the uptake of sulphate from the environment by plants. Further intracellular, cell-to-cell and long-distance transport must fulfil the requirements for sulphate assimilation and source/sink demands within the plant. A gene family of sulphate transporters, which may be subdivided into five groups, has been identified with examples from many different plant species. For at least two groups, proton/sulphate co-transport activity has been confirmed. It appears that each group represents sulphate transporters with distinct kinetic properties, patterns of expression, and cell/tissue specificity related to specific roles in the uptake and allocation of sulphate. High-affinity sulphate uptake and low-affinity vascular transport, as well as vacuolar efflux, are controlled by the nutritional status of the plant. Most notably there is an apparent increase in capacity for cellular sulphate uptake and vacuolar efflux when sulphur supply is limiting. Within the groups, the individual sulphate transporters may be further subdivided by differences in temporal, cellular and tissue expression. Many of the transporters are regulated by the nutritional status of the individual tissues, to optimize sulphate movement within and between sink and source organs.


Genome scan for teratogen-induced clefting susceptibility loci in the mouse: evidence of both allelic and locus heterogeneity distinguishing cleft lip and cleft palate.
Nonsyndromic clefting of the lip and palate in humans has a highly complex etiology, with both multiple genetic loci and exposure to teratogens influencing susceptibility. Previous studies using mouse models have examined only very small portions of the genome. Here we report the findings of a genome-wide search for susceptibility genes for teratogen-induced clefting in the AXB and BXA set of recombinant inbred mouse strains. We compare results obtained using phenytoin (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate). We use a new statistical approach based on logistic regression suitable for these categorical data to identify several chromosomal regions as possible locations of clefting susceptibility loci, and we review candidate genes located within each region. Because cleft lip and cleft palate do not frequently co-aggregate in human families and because these structures arise semi-independently during development, these disorders are usually considered to be distinct in etiology. Our data, however, implicate several of the same chromosomal regions for both forms of clefting when teratogen-induced. Furthermore, different parental strain alleles are usually associated with clefting of the lip versus that of the palate (i.e., allelic heterogeneity). Because several other chromosomal regions are associated with only one form of clefting, locus heterogeneity also appears to be involved. Our findings in this mouse model suggest several priority areas for evaluation in human epidemiological studies.


Infertility status of male individuals with abnormal spermiogram evaluated by cytogenetic analysis and in vitro sperm penetration assay.
The possibility of a link between altered sperm morphology and functional ability, possibly reflected on the genetic level, is still a matter of controversy. 60 infertile males with pathological spermiogram and 14 healthy individuals with confirmed in vivo fertility were selected for our study. Ejaculated sperm was assessed according to the standard criteria set by the World Health Organization, which constituted a basis for subgroup classification. The sperm penetration assay (SPA) using human sperm and hamster oocytes was subsequently performed with concomitant cytogenetic analysis of peripheral blood leukocytes (PBL). More than 55% of infertile males with pathological spermiogram exhibited a decreased ability for penetration of the oocyte (SPAL30%). The lowest penetration ability was observed in the semen of patients with oligoasthenoteratozoospermia (OAT), of whom as many as 75% presented negative SPA values. We noted only 1 case of chromosome aberration (Robertsonian translocation) in the analyzed cohort of infertile patients. Strikingly, in the identified group of infertile patients with chromosome structural polymorphism (acrocentric chromosomes), we revealed a statistically significant decreased rate of sperm - oocyte penetration. A causative link may exist between sperm malfunction and a specific feature of the chromosome variants detected in the blood leukocytes of infertile males with pathological spermiogram.


Disproportionate impact of diabetes in a Puerto Rican community of Chicago.
We assessed the impact of diabetes in a large Puerto Rican community of Chicago by measuring the prevalence of diagnosed diabetes and calculating the diabetes mortality rate. Data were analyzed from a comprehensive health survey conducted in randomly selected households in community areas. Questions on diagnosed diabetes and selected risk factors were asked. In addition, vital records data were analyzed in order to calculate the age-adjusted diabetes mortality rate. When possible, rates were compared to those found in other studies. The diabetes prevalence located in this community (20.8%: 95% CI = 10.1%-38.0%) is the highest ever reported for Puerto Ricans and one of the highest ever reported in the United States for a non-Native American population. For instance, it is twice the prevalence for Puerto Ricans in New York (11.3%) and Puerto Rico (9.3%-9.6%). Diagnosed diabetes was found to be significantly associated with obesity (p = 0.023). The prevalence was particularly high among older people, females, those born in the US, and those with a family history of diabetes. Notably, the diabetes mortality rate (67.6 per 100,000 population) was more than twice the rate for all of Chicago (31.2) and the US (25.4). Understanding why the diabetes prevalence and mortality rates for Puerto Ricans in this community are so much higher than those of other communities is imperative for primary and secondary prevention. Collaboration between researchers, service providers and community members can help address the issues of diabetes education, early screening and diagnosis, and effective treatment needed in this community.


HSP27 Modulates Neuropathic Pain by Inhibiting P2X3 Degradation.
The role of heat shock protein 27 (HSP27), a chaperone, in neuropathic pain after nerve injury has not been systematically surveyed despite its neuroprotective and regeneration-promoting effects. In this study, we found that HSP27 expression in sensory neurons of the dorsal root ganglia (DRG) mediated nerve injury-induced neuropathic pain. Neuropathic pain behaviors were alleviated by silencing HSP27 in the DRG of a rat spinal nerve ligation (SNL) model. Local injection of an HSP27-overexpression construct into the DRG of naïve rats elicited neuropathic pain behaviors. HSP27 interacted with a purinergic receptor, P2X3, and their expression patterns corroborated the induction and reversal of neuropathic pain according to two lines of evidence: colocalization immunohistochemically and immunoprecipitation biochemically. In a cell model cotransfected with HSP27 and P2X3, the degradation rate of P2X3 was reduced in the presence of HSP27. Such an alteration was mediated by reducing P2X3 ubiquitination in SNL rats and was reversed after silencing HSP27 in the DRGs of SNL rats. In summary, the interaction of HSP27 with P2X3 provides a new mechanism of injury-induced neuropathic pain that could serve as an alternative therapeutic target.


The Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ): an instrument to assess outcomes of schizophrenia care.
Advances in treatment technologies and development of evidence-based standards of care demand better methods for routine assessment of outcomes for schizophrenia in systems of care. This article describes the development and psychometrics of a new instrument to assess outcomes of routine care for persons with schizophrenia in service systems. Candidate items for the Schizophrenia Care and Assessment Program Health Questionnaire (SCAP-HQ) were drawn from existing measures. Domains covered include disease outcomes (symptoms, subjective medication effects, substance abuse), functional status, health status, quality of life, and public safety. A sample of 1,584 patients with schizophrenia or schizoaffective disorder who were recruited into a large prospective, naturalistic study on the course of treatment for schizophrenia completed the SCAP-HQ at baseline and 1 year later (n = 434), providing data for factor analysis, assessment of internal consistency, convergent validity, and responsiveness to change. A subsample of 121 patients completed a test-retest protocol. Fifteen scales were derived by factor analysis from 55 outcome items on the SCAP-HQ. These factors covered psychiatric symptoms, life satisfaction, instrumental activities of daily living, health-related disability, subjective medication side effects, vitality, legal problems, social relations, mental health-related disability, suicidality, drug and alcohol use, daily activities, victimization, violence, and employment. For most scales, standard psychometric parameters, including internal consistency and test-retest reliability, convergent validity, and responsiveness to change, were acceptable for application to large sample evaluations of care systems. This new measure represents an advance in the development of outcome measures for schizophrenia for use in large-scale studies of routine care.


Early Diagnosis of Cardiovascular Diseases in Workers: Role of Standard and Advanced Echocardiography.
Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality and consequently early diagnosis is of paramount importance. Working conditions can be regarded as an additional risk factor for CVD. Since different aspects of the job may affect vascular health differently, it is important to consider occupation from multiple perspectives to better assess occupational impacts on health. Standard echocardiography has several targets in the cardiac population, as the assessment of myocardial performance, valvular and/or congenital heart disease, and hemodynamics. Three-dimensional echocardiography gained attention recently as a viable clinical tool in assessing left ventricular (LV) and right ventricular (RV) function, volume, and shape. Two-dimensional (2DSTE) and, more recently, three-dimensional speckle tracking echocardiography (3DSTE) have also emerged as methods for detection of global and regional myocardial dysfunction in various cardiovascular diseases and applied to the diagnosis of subtle LV and RV dysfunction. Although these novel echocardiographic imaging modalities have advanced our understanding of LV and RV mechanics, overlapping patterns often show challenges that limit their clinical utility. This review will describe the current state of standard and advanced echocardiography in early detection (secondary prevention) of CVD and address future directions for this potentially important diagnostic strategy.