Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.
Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.


Oligomerized grape seed proanthocyanidins ameliorates isoproterenol-induced cardiac remodeling in rats: role of oxidative stress.
The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics, cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1 (ASK1) and nuclear factor-κB (NF-κB) cascades in isoproterenol (Iso)-induced cardiac remodelling (CR) rat model were investigated, in addition, the serum SOD activities and MDA content were assayed. Rats were treated with Iso to induce CR and were given distilled water or GSP for 1 week. Control rats received vehicle instead of Iso. Administration of GSP markedly alleviated the elevation of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in the heart, and improved the haemodynamic index. Meanwhile, treatment with GSP significantly ameliorated oxidative stress by improving SOD activities and decreasing MDA formation. Moreover, GSP apparently inhibited the expression ASK1, NF-κB and its targeted gene - COX-2. These findings suggest that administration of GSP has the potential to attenuate Iso-induced CR by repressing oxidative stress and inhibiting the activation of the cellular signaling cascades involving the ASK1 and NF-κB pathways, at least in part, providing a molecular mechanism for the cardioprotective effect of GSP.


Metabolic syndrome in patients with peripheral arterial disease.
The prevalence of metabolic syndrome (MS) in patients with peripheral arterial disease (PAD) and coronary or cerebrovascular disease is increasing, but it is not known whether this association also exists in patients with isolated PAD. The aim of the current study was to assess the prevalence of MS in patients with PAD who had no coronary or cerebrovascular disease, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals in patients with PAD and with and without MS. Multicenter, cross-sectional study of 3.934 patients aged ≥ 45 years with isolated PAD who were treated in primary care and specialized outpatient clinics during 2009. A diagnosis of PAD was reached for ankle brachial indices <0.9, a previous history of amputation or revascularization. In the overall population, the mean age was 67.6 years, 73.8% were males and 63% had MS (95% CI 61.5-64.3%). Patients with MS had a higher prevalence of cardiovascular risk factors and comorbidities, more severe PAD and higher prescription rate of evidence-based cardiovascular therapies. After adjusting for risk factors and comorbidity, there was a more frequent use of renin-angiotensin system blockers, beta-blockers, diuretics and statins among the patients with MS. A lower percentage of patients with MS achieved the therapeutic goals for blood pressure (22% vs. 41.5%, p<0.001). Similarly, a lower percentage of patients with diabetes achieved the glycated hemoglobin goals (44% vs. 53.1%, p<0.001), with no differences in LDL-cholesterol levels (29.8% vs. 39.1%, p=0.265). Patients with PAD have a high prevalence of MS. Patients with MS do not attain therapeutic goals as frequently as those without, despite taking more cardiovascular drugs.


Small nucleolar RNA host gene 8: A rising star in the targets for cancer therapy.
Long non-coding RNAs (lncRNAs) are a group of transcripts that have been considered essential participants in cancer pathogenesis and progression over the past few decades. Small nucleolar RNA host gene 8 (SNHG8) is a newly discovered lncRNA that belongs to the SNHG family, a group of transcripts that can be processed into small nucleolar RNAs and exert important biological functions. As an oncogenic factor, SNHG8 is upregulated in multiple cancer types. Herein, we summarize the biological role of SNHG8 in different cancer types and the underlying mechanisms related to the interaction between SNHG8 and microRNAs, mRNAs, and proteins. In addition, this study emphasizes the clinical value of SNHG8 in cancer, hoping to provide new insights into cancer diagnosis, prognosis, and treatment.


Avulsion fracture of the medial collateral ligament association with Segond fracture.
The Segond fracture is a tibial avulsion injury of the insertion of the middle third of the lateral capsular ligament that is typically associated with anterior cruciate ligament and meniscal tears. The classically assigned mechanism of injury is a combination of internal rotation and varus stress. We report two cases of Segond fractures that presented with a variant pattern including osseous avulsion injuries of the medial collateral ligament at the femoral origin, anterior cruciate ligament tear, and pivot shift-type osseous contusion pattern, suggesting an alternative mechanism of injury that includes dominant valgus stress and external rotation components. Awareness of this pattern may aid radiologists, surgeons, and sport medicine physicians in the accurate diagnosis of this injury complex and initiation of appropriate treatment in a timely fashion.


Avoidance, biomass and survival response of soil dwelling (endogeic) earthworms to OECD artificial soil: potential implications for earthworm ecotoxicology.
Soil dwelling earthworms are now adopted more widely in ecotoxicology, so it is vital to establish if standardised test parameters remain applicable. The main aim of this study was to determine the influence of OECD artificial soil on selected soil-dwelling, endogeic earthworm species. In an initial experiment, biomass change in mature Allolobophora chlorotica was recorded in Standard OECD Artificial Soil (AS) and also in Kettering Loam (KL). In a second experiment, avoidance behaviour was recorded in a linear gradient with varying proportions of AS and KL (100% AS, 75% AS + 25% KL, 50% KS + 50% KL, 25% AS + 75% KL, 100% KL) with either A. chlorotica or Octolasion cyaneum. Results showed a significant decrease in A. chlorotica biomass in AS relative to KL, and in the linear gradient, both earthworm species preferentially occupied sections containing higher proportions of KL over AS. Soil texture and specifically % composition and particle size of sand are proposed as key factors that influenced observed results. This research suggests that more suitable substrates are required for ecotoxicology tests with soil dwelling earthworms.


Tuberculosis incidence and mortality in aboriginal areas of Taiwan, 1997-2001.
People living in aboriginal areas of Taiwan are known to be at especially high risk of developing tuberculosis (TB). This study investigated the incidence and mortality of TB in aboriginal areas of Taiwan. The TB death statistics and notification data from the National TB Register and Department of Health in 1997-2001 were analyzed. From 1997 to 2001, people living in aboriginal areas bore a disproportionate burden of TB disease in Taiwan, with mortality rates 5.5-6.5 times and incidence rates 3.6-5.2 times higher than those of people living in non-aboriginal areas. Among patients with TB living in aboriginal areas, 381 died, accounting for 5.1% of the 7480 TB deaths in Taiwan. A large proportion of the patients with TB who died were older than 65 years, in both aboriginal (40.2%) and non-aboriginal (78.5%) areas; however, the age of TB patients who died in non-aboriginal areas was significantly older (p < 0.001). TB patients living in the aboriginal areas accounted for 3.6% (2618/71,447) of the total number of reported TB patients in Taiwan, and 32.7% were in the age range from 24-45 years. In contrast, TB patients living in non-aboriginal areas were typically older, with only 20.1% in the 24-45 age range (p < 0.001) and 44.4% older than 65 years (p < 0.001). In terms of incidence and mortality rates, men predominated in both groups; however, this pattern was less prominent in aboriginal areas than in non-aboriginal areas. The mortality rates and incidence of TB in aboriginal areas are much higher than those in non-aboriginal areas in Taiwan. Concentration of resources and programs to control TB in aboriginal areas may represent the most effective use of resources for fighting TB.


Linear magnetoresistance due to multiple-electron scattering by low-mobility islands in an inhomogeneous conductor.
Linear transverse magnetoresistance is commonly observed in many material systems including semimetals, narrow band-gap semiconductors, multi-layer graphene and topological insulators. It can originate in an inhomogeneous conductor from distortions in the current paths induced by macroscopic spatial fluctuations in the carrier mobility and it has been explained using a phenomenological semiclassical random resistor network model. However, the link between the linear magnetoresistance and the microscopic nature of the electron dynamics remains unknown. Here we demonstrate how the linear magnetoresistance arises from the stochastic behaviour of the electronic cycloidal trajectories around low-mobility islands in high-mobility inhomogeneous conductors and that this process is only weakly affected by the applied electric field strength. Also, we establish a quantitative link between the island morphology and the strength of linear magnetoresistance of relevance for future applications.


Experimental and Theoretical Study of Evaporation of a Volatile Liquid Lens on an Immiscible Liquid Surface.
The evaporation of a hexane lens on a distilled water surface was experimentally and theoretically studied. The formation of the hexane lens was recorded by a high-speed camera from the side to observe the variations of the contact diameters and contact angles. The experimental results showed that the shape variation of the hexane lens experienced the spreading stage and the evaporation stage. The spreading stage lasted for about 6% of the lens lifetime. For most time of the evaporation stage, the square of the lens contact radius decreased linearly with time, while the contact angle remained almost unchanged. During the final rapid evaporation stage (about 2% of the lens lifetime), the shape of the hexane lens changed and the lens shrank rapidly until it disappeared. A theoretical model based on diffusion-controlled evaporation under the constant contact angle mode was developed to describe the evaporation of the hexane lens on the water surface. In terms of geometry, the model assumes that a lens is composed of upper and lower spherical caps, and the apparent contact angle is defined based on the intersection of the two caps. The results calculated using the model were found to be in good agreement with the experimental data. Finally, the effects of initial lens volume, water temperature, and water surface deformation on lens evaporation were discussed through calculations. The results showed that increase in the water temperature and deformation of the water surface accelerated the evaporation process.


Ablative laser resurfacing: high-energy pulsed carbon dioxide and erbium:yttrium-aluminum-garnet.
The development of the short-pulsed high-energy carbon dioxide laser in the mid 1990's led to the emergence of laser skin resurfacing. Used in the continuous mode, the CO(2) laser can cut and coagulate simultaneously. Used in the pulsed mode, the CO(2) laser is a powerful tool for epidermal ablation in many different contexts both therapeutic and cosmetic. Both the CO(2) and Erbium YAG lasers emit light in the infrared spectrum. Energy is preferentially absorbed by intracellular water creating rapid heating and vaporization of tissue. Because of the wavelength of the Er:YAG laser (2940 nm) more closely approximates the absorption peak of water (3000 nm) the target chromophore than the CO(2) laser (10,600 nm) nearly all of the energy is absorbed in the epidermis and papillary dermis yielding superficial ablation and less underlying thermal damage. The advantages, disadvantages, and applications of each type of laser resurfacing will be discussed. Despite proven efficacy, the public acceptance of laser resurfacing has declined with the emergence of new laser systems that cause dermal remodeling without ablating the overlying epidermis dramatically reducing recovery time. In the absence of blinded comparison studies, it remains unclear whether the clinical results of the newer 'nonablative' laser systems compare with their ablative predecessors.


Measurement of the e;{+}e;{-}-->bb[over ] Cross Section between sqrt[s]=10.54 and 11.20 GeV.
We report e;{+}e;{-}-->bb[over ] cross section measurements by the BABAR experiment performed during an energy scan in the range of 10.54 to 11.20 GeV at the SLAC PEP-II e;{+}e;{-} collider. A total relative error of about 5% is reached in more than 300 center-of-mass energy steps, separated by about 5 MeV. These measurements can be used to derive precise information on the parameters of the Upsilon(10860) and Upsilon(11020) resonances. In particular we show that their widths may be smaller than previously measured.


Evaluation of novel fusion proteins derived from extracellular matrix binding domains of LigB as vaccine candidates against leptospirosis in a hamster model.
Leptospira binds to host extracellular matrix (ECM) through surface exposed outer membrane proteins called adhesin in order to initiate infection. Of various adhesins present on the surface of the spirochete, Leptospira-immunoglobulin like proteins (Lig proteins) and LipL32 are most abundant, widely distributed among pathogenic serovars and well characterized. Various fragments of Lig proteins (Ligcon4, Ligcon4-7.5, LigBcen2) and C-terminus fragment of LipL32 all of that bind to host ECM were fused, expressed and purified in soluble form as fusion proteins. Four week hamsters were immunized subcutaneously with various fusion proteins emulsified in EMULSIGEN-D adjuvant and subsequently boosted at 3 weeks. The protective efficacy of these novel fusion proteins was evaluated against subsequent challenge with highly virulent L. interrogans serovar Pomona (MLD50-100). Our results indicate that fusion protein based vaccine induced significant protection against acute infection with respect to PBS-adjuvant vaccinated controls as revealed by enhanced survival and reduced pulmonary hemorrhage. Moreover, the protection mediated by these novel proteins was higher than that of conserved region of Lig protein (Ligcon, established protective antigen) and correlated to the level of antibodies. LipL32 failed to impart significant protection, however fusing its immunogenic C-terminus domain to Lig fragments slightly delayed the morbidity of the infected animals. Our results demonstrate that this novel strategy could be promising in developing effective subunit vaccine to combat this zoonotic infection.


Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum.
The cholesterol side-chain cleavage enzyme catalyzes the conversion of cholesterol to pregnanalone in the first step of steroidogenic pathways. Defective enzyme activity leads to the deficiency of all steroid hormones, including progesterone, which is essential to sustain term pregnancy. We report a homozygous point mutation in the CYP11A1 gene in a 46, XY phenotypic female born at term to healthy heterozygous parents, presenting relatively late at the age of 1 yr 9 months with life-threatening adrenal insufficiency and complete sex reversal. She was found to have complete agenesis of corpus callosum. The mutation resulted in a single amino acid substitution: valine for alanine at position 359. The functional analysis of the mutant enzyme revealed markedly reduced enzyme activity, but about 11% residual activity was demonstrated. We explained the completion of pregnancy to term and the late presentation by a possible difference in the mutant enzyme activity in vivo and in vitro or by the residual mutant activity, which would have been enough to maintain pregnancy and viability of the patient. The clinical findings of nearly undetectable levels of steroid hormones at presentation are explained by the total disruption of steroidogenic cells later on, with recurrent ACTH stimulation leading to intramitochondrial cholesterol accumulation and cell death (a two-hit mechanism). This report of a homozygous mutation in CYP11A1 gene in a child with agenesis of corpus callosum shows that homozygous mutations in CYP11A1 gene can be compatible with term pregnancy and delayed presentation.


Differential phosphopeptide expression in a benign breast tissue, and triple-negative primary and metastatic breast cancer tissues from the same African-American woman by LC-LTQ/FT-ICR mass spectrometry.
African-American women have a higher risk for developing triple-negative breast cancer (TNBC). Lacking the expression of receptors for estrogen and progesterone, and without human epidermal growth factor 2 receptor gene amplification, TNBC is a very aggressive type of breast cancer with a high likelihood of metastasis and recurrence. Specific therapeutic targets for this aggressive disease remain to be identified. Phosphorylation, a post-translational modification that adds one or more phosphate groups to a protein, plays a key role in the activation and deactivation of a protein's cellular function. Here, we report the first systematic phosphoproteomic analysis of a benign breast tissue, a primary breast cancer tissue, and a metastatic breast cancer tissue from the same African-American woman. Differential phosphoprotein levels were measured with reversed-phase nano-liquid chromatography coupled to a hybrid linear quadrupole ion trap/Fourier transform ion cyclotron resonance mass spectrometer (LC-LTQ/FT-ICR MS). Five proteins were found to be highly phosphorylated in the metastatic site whereas six proteins were highly phosphorylated in the cancer site of the TNBC patient. Identified phosphoproteins are known to be involved in breast cancer signal transduction pathways and these results may identify new diagnostic and therapeutic targets for TNBC.


Comparison of checking behavior in adults with or without checking symptom of obsessive-compulsive disorder using a novel computer-based measure.
Easy to administer behavioral measures of checking are needed to improve the assessment of this hallmark feature of OCD. We recently developed a new computer-based behavioral assessment of OCD in a previous study. As a follow-up experiment for this method, the goal of this study was to examine whether the new computer-based behavioral assessment would be capable of differentiating behaviors in adults with OCD characterized by checking behavior from those without checking behavior. We compared 22 OCD patients with compulsive checking behaviors (OCD checkers), 17 OCD controls without checking behavior (OCD controls), and 31 healthy controls (HCs) on a novel computer-based behavioral measure of checking behavior. Despite similar levels of successfully completed tasks, OCD checkers demonstrated longer duration of checking behaviors than OCD controls or HCs. Interestingly, no differences were found between OCD controls and HCs in any of the dependent variables. Our new behavioral measure offers a novel, objective, and ecologically valid measure of checking behaviors in a sample of adults with OCD.


Routine Preoperative Nutritional Screening in All Primary Total Joint Arthroplasty Patients Has Little Utility.
Nutritional optimization before total joint arthroplasty (TJA) may improve patient outcomes and decrease costs. However, the utility of serologic laboratory markers, including albumin, transferrin, and total lymphocyte count (TLC), as primary indicators of nutrition is unclear. We analyzed the prevalence of abnormal nutritional values before TJA and identified factors associated with them. We retrospectively reviewed 819 primary cases of TJA performed at 1 institution from January to December 2018. Patient demographic characteristics were assessed for associations with abnormal preoperative nutritional values (albumin <3.5 g/dL, transferrin <200 mg/dL, and TLC <1.5 cells/μL3). Associations of comorbidities, American Society of Anesthesiologists Physical Status classification, and age-adjusted Charlson Comorbidity Index (CCI) with abnormal values were assessed with logistic regression. Values were abnormal for albumin in 21 cases (2.6%), transferrin in 26 cases (5.6%), and TLC in 185 cases (25%). Thirteen cases (1.7%) had abnormal values for 2 markers. Age was associated with abnormal albumin and TLC, and race with abnormal transferrin. Congestive heart failure, chronic kidney disease, pancreatic insufficiency, gastroesophageal reflux disease, osteoporosis, dementia, and CCI were associated with abnormal albumin; Parkinson disease and American Society of Anesthesiologists Physical Status with abnormal transferrin; and dementia, body mass index, cancer history, and CCI with abnormal TLC. We report low prevalence of and a low concordance rate among abnormal nutritional values before primary TJA. Our results suggest that routine testing of all healthy patients is not warranted before TJA.


[Therapy of inoperable bronchial carcinoma].
The results of a prospective randomized study on carcinoma of the bronchus are reported. In a total of 56 patients polychemotherapy, high-dosage vitamin-A treatment, Endoxan and immunotherapy, as well as the application of proteolytic enzymes in altogether 5 combinations of therapy were tested.


Mapping soil pollution by using drone image recognition and machine learning at an arsenic-contaminated agricultural field.
Mapping soil contamination enables the delineation of areas where protection measures are needed. Traditional soil sampling on a grid pattern followed by chemical analysis and geostatistical interpolation methods (GIMs), such as Kriging interpolation, can be costly, slow and not well-suited to highly heterogeneous soil environments. Here we propose a novel method to map soil contamination by combining high-resolution aerial imaging (HRAI) with machine learning algorithms. To support model establishment and validation, 1068 soil samples were collected from an arsenic (As) contaminated area in Zhongxiang, Hubei province, China. The average arsenic concentration was 39.88 mg/kg (SD = 213.70 mg/kg), with individual sample points determined as low risk (66.9%), medium risk (29.4%), or high risk (3.7%), respectively. Then, identified features were extracted from a HRAI image of the study area. Four machine learning algorithms were developed to predict As risk levels, including (i) support vector machine (SVM), (ii) multi-layer perceptron (MLP), (iii) random forest (RF), and (iii) extreme random forest (ERF). Among these, we found that the ERF algorithm performed best overall and that its prediction performance was generally better than that of traditional Kriging interpolation. The accuracy of ERF in test area 1 reached 0.87, performing better than RF (0.81), MLP (0.78) and SVM (0.77). The F1-score of ERF for discerning high-risk points in test area 1 was as high as 0.8. The complexity of the distribution of points with different risk levels was a decisive factor in model prediction ability. Identified features in the study area associated with fertilizer factories had the most important contribution to the ERF model. This study demonstrates that HRAI combined with machine learning has good potential to predict As soil risk levels.


Mathematical modeling of the ethanol fermentation of cashew apple juice by a flocculent yeast: the effect of initial substrate concentration and temperature.
In this work, the effect of initial sugar concentration and temperature on the production of ethanol by Saccharomyces cerevisiae CCA008, a flocculent yeast, using cashew apple juice in a 1L-bioreactor was studied. The experimental results were used to develop a kinetic model relating biomass, ethanol production and total reducing sugar consumption. Monod, Andrews, Levenspiel and Ghose and Tyagi models were investigated to represent the specific growth rate without inhibition, with inhibition by substrate and with inhibition by product, respectively. Model validation was performed using a new set of experimental data obtained at 34 °C and using 100 g L-1 of initial substrate concentration. The model proposed by Ghose and Tyagi was able to accurately describe the dynamics of ethanol production by S. cerevisiae CCA008 growing on cashew apple juice, containing an initial reducing sugar concentration ranging from 70 to 170 g L-1 and temperature, from 26 to 42 °C. The model optimization was also accomplished based on the following parameters: percentage volume of ethanol per volume of solution (%V ethanol/V solution), efficiency and reaction productivity. The optimal operational conditions were determined using response surface graphs constructed with simulated data, reaching an efficiency and a productivity of 93.5% and 5.45 g L-1 h-1, respectively.


Does endoscopic release of the first extensor compartment have benefits over open release in de Quervain's disease?
Superficial radial nerve injury, incomplete release of the first extensor compartment, palmar subluxation of the tendons and painful scar are the main reasons for persistent pain and dysfunction after open release. We therefore asked whether the endoscopic release of the first extensor compartment is advantageous over the open release in terms of subjective pain and disability, complication and aesthetic appearance. Fifty wrists treated with either open release (26 wrists) or endoscopic release (24 wrists) of the first extensor compartment in case of de Quervain's disease were included. All patients were evaluated at a minimum of 1-year follow-up using visual analogue scale (VAS) pain ratings and the Disabilities of Arm, Shoulder and Hand (DASH) score. The average operating time of endoscopic release was 4 min longer than that of open release. The mean VAS pain score was improved from an initial 6.4 to 0.5 in the open release group and from 6.7 to 0.1 in the endoscopic release group. The mean DASH score was improved from 60.1 to 6.8 in the open release group and from 64.4 to 1.5 in the endoscopic release group. No clinically significant difference was found between the two groups regarding subjective VAS pain and DASH scores at the last follow-up. In the open release group, superficial radial nerve injuries (five wrists), significant scar tenderness (three) and unsightly scar (six) were identified. Endoscopic release of the extensor compartment seems to be an effective and safe procedure in patients with de Quervain's disease who are unresponsive to non-operative treatments, despite a little increase in operation time.


Comparison of the biomechanical profile of the intact ulnar collateral ligament with the modified Jobe and the Docking reconstructed elbow: an in vitro study.
The modified Jobe and Docking techniques are commonly used to reconstruct the elbow's ulnar collateral ligament. Valgus laxity and kinematic coupling after these reconstructive procedures are similar to those of the native ulnar collateral ligament. Controlled laboratory study. Testing was conducted on 10 pairs of cadaver elbows using a 4 degrees of freedom loading system. Subfailure valgus loads were applied to the native elbows at different flexion angles; motion and ligament elongation were measured. The elbows were then loaded to failure in valgus at 90 degrees of flexion. The reconstructive techniques were then applied and testing was repeated. Only the resting length of the anterior portion of the ulnar collateral ligament anterior bundle remained isometric throughout range of motion. Valgus laxity was nearly equal for the native and reconstructed ligaments at flexion angles of 90 degrees or higher. However, both reconstructions provided less valgus stability than the native ulnar collateral ligament at low flexion angles. Kinematic coupling decreased with increased flexion for both native and reconstructed ligaments. The modified Jobe and Docking techniques reconstruct restraint of the native ulnar collateral ligament to valgus laxity and kinematic coupling at 90 degrees of flexion and higher angles where peak valgus torque is experienced in the throwing elbow. Both reconstructions provide valgus stability comparable to that of the native ulnar collateral ligament at 90 degrees and higher, helping to explain their success in treating throwing athletes. Both reconstructions provide less valgus stability than the native ulnar collateral ligament at low flexion angles, suggesting that patients undergoing ulnar collateral ligament reconstruction should be cautioned against activities that provide valgus stress at low elbow flexion angles, such as side-arm throwing. This study suggests caution against overtightening the reconstructions at the common 30 degrees of flexion.


Triplet births in the United States. An epidemic of high-risk pregnancies.
To more precisely understand the changes in triplet births in recent years. Analysis of recent government and medical publications pertaining to triplets. Triplet births are at much greater risk than singletons of poor birth outcomes. More than 9 of 10 triplet births are born preterm (< 37 completed weeks of gestation) as compared with < 1 of 10 singleton infants. The average weight of a triplet newborn (1,698 g) is one-half that of a singleton newborn (3,358 g). The infant death rate for triplet and other higher-order multiple births is 12 times higher than that for singletons (93.7 as compared with 7.8 infant deaths per 1,000 live births). Based on their frequency of preterm birth, low birth weight and infant death rate, it is appropriate to characterize all triplet pregnancies as high risk.


NAMPT levels are inversely related to nitric oxide formation and positively related to soluble fms-like tyrosine kinase-1 levels in preeclampsia.
NAMPT is a biomarker for endothelial dysfunction, but its relationship with nitrite (marker of NO formation) and soluble fms-like tyrosine kinase-1 (sFLT-1) has not been previously evaluated in preeclampsia. Therefore, we measured plasma NAMPT and sFLT-1 levels using enzyme immunoassays and plasma nitrite concentrations using an ozone-based chemiluminescence assay. NAMPT was positively correlated to nitrite (r = 0.217; P = 0.034) and inversely related to sFLT-1 (r = -0.340; P = 0.029) in healthy pregnant women, but inversely related to nitrite (r = -0.259; P = 0.035) and positively correlated to sFLT-1 (r = 0.326; P = 0.007) in preeclamptic patients, suggesting that NAMPT inhibits NO formation and interacts with the antiangiogenic factor sFLT-1 in preeclampsia.


Mesenchymal Stem Cell Marker Expression in Gastric Cancer Stroma.
Spindle-shaped stromal cells of tumors are derived from various cellular origins, including mesenchymal stem cells (MSCs). MSCs express CD73, CD90 and CD105 antigens. Herein, the aim was to investigate the association between the expression of specific MSC markers in gastric cancer stromal cells and the clinicopathological features of the disease. The expression of CD73, CD90 and CD105 in spindle-shaped cancer stromal cells was studied by immunohistochemistry in tissue arrays containing 546 gastric cancer cases. Univariate and multivariate analyses were performed to evaluate the association of MSC marker expression with clinicopathological variables. Spindle-shaped cancer stromal cells expressing the MSC markers CD73, CD90 or CD105 were associated with larger tumor size, advanced cancer, venous infiltration, lymphatic infiltration, and lymph node metastasis. Statistical analysis demonstrated that the presence of CD105-positive spindle cells was an independent prognostic factor of advanced cancer, lymph node metastasis and EBV infection in multivariate analysis. Spindle-shaped gastric cancer stromal cells expressing CD73, CD90 or CD105 are involved in disease progression, and among them, CD105-positive cells are strongly associated with poor prognosis.


The need for intra aortic balloon pump support following open heart surgery: risk analysis and outcome.
The early and intermediate outcome of patients requiring intraaortic balloon pump (IABP) was studied in a cohort of 2697 adult cardiac surgical patients. 136 patients requiring IABP (5.04%) support analysed over a 4 year period. Prospective data collection, obtained. The overall operative mortality was 35.3%. The "operation specific" mortality was higher on the Valve population.The mortality (%) as per time of balloon insertion was: Preoperative 18.2, Intraoperative 33.3, postoperative 58.3 (p < 0.05).The incremental risk factors for death were: Female gender (Odds Ratio (OR) = 3.87 with Confidence Intervals (CI) = 1.3-11.6), Smoking (OR = 4.88, CI = 1.23- 19.37), Preoperative Creatinine>120 (OR = 3.3, CI = 1.14-9.7), Cross Clamp time>80 min (OR = 4.16, CI = 1.73-9.98) and IABP insertion postoperatively (OR = 19.19, CI = 3.16-116.47).The incremental risk factors for the development of complications were: Poor EF (OR = 3.16, CI = 0.87-11.52), Euroscore >7 (OR = 2.99, CI = 1.14-7.88), history of PVD (OR = 4.99, CI = 1.32-18.86).The 5 years survival was 79.2% for the CABG population and 71.5% for the valve group. (Hazard ratio = 1.78, CI = 0.92-3.46). IABP represents a safe option of supporting the failing heart. The need for IABP especially in a high risk Valve population is associated with early unfavourable outcome, however the positive mid term results further justify its use.


A real world analysis of COVID-19 impact on hospitalizations in older adults with chronic conditions from an Italian region.
Healthcare delivery reorganization during the COVID-19 emergency may have had a significant impact on access to care for older adults with chronic conditions. We investigated such impact among all adults with chronic conditions aged ≥ 65 years, identified through the electronic health databases of two local health agencies-ATS Brianza and ATS Bergamo-from the Lombardy region, Italy. We considered hospitalizations for 2020 compared to the average 2017-2019 and quantified differences using rate ratios (RRs). Overall, in 2017-2019 there were a mean of 374,855 older adults with ≥ 1 chronic condition per year in the two ATS and 405,371 in 2020. Hospitalizations significantly decreased from 84,624 (225.8/1000) in 2017-2019 to 78,345 (193.3/1000) in 2020 (RR 0.86). Declines were reported in individuals with many chronic conditions and for most Major Diagnostic Categories, except for diseases of the respiratory system. The strongest reductions were observed in hospitalizations for individuals with active tumours, particularly for surgical ones. Hospitalization rates increased in individuals with diabetes, likely due to COVID-19-related diseases. Although determinants of the decrease in demand and supply for care among chronic older adults are to be further explored, this raises awareness on their impacts on chronic patients' health in the medium and long run.


A novel sugar analog enhances sialic acid production and biotherapeutic sialylation in CHO cells.
A desirable feature of many therapeutic glycoprotein production processes is to maximize the final sialic acid content. In this study, the effect of applying a novel chemical analog of the sialic acid precursor N-acetylmannosamine (ManNAc) on the sialic acid content of cellular proteins and a model recombinant glycoprotein, erythropoietin (EPO), was investigated in CHO-K1 cells. By introducing the 1,3,4-O-Bu3 ManNAc analog at 200-300 µM into cell culture media, the intracellular sialic acid content of EPO-expressing cells increased ∼8-fold over untreated controls while the level of cellular sialylated glycoconjugates increased significantly as well. For example, addition of 200-300 µM 1,3,4-O-Bu3 ManNAc resulted in >40% increase in final sialic acid content of recombinant EPO, while natural ManNAc at ∼100 times higher concentration of 20 mM produced a less profound change in EPO sialylation. Collectively, these results indicate that butyrate-derivatization of ManNAc improves the capacity of cells to incorporate exogenous ManNAc into the sialic acid biosynthetic pathway and thereby increase sialylation of recombinant EPO and other glycoproteins. This study establishes 1,3,4-O-Bu3 ManNAc as a novel chemical supplement to improve glycoprotein quality and sialylation levels at concentrations orders of magnitude lower than alternative approaches. Biotechnol. Bioeng. 2017;114: 1899-1902. © 2017 Wiley Periodicals, Inc.


Management of pain in leukemic children using the WHO analgesic ladder.
To ascertain the effectiveness of WHO analgesic ladder in pain management in children with leukemia. Children with leukemia who were referred to a pain and palliative care clinic attached to the Department of Pediatrics of a medical teaching hospital during a period of 6 months were included in the study. Thirty nine (39) children, who constituted 64% of children on treatment for leukemia, required referral to pain and palliative care services during the study period. Of these 92% had Acute Lymphocytic Leukemia (ALL) and 8% had Acute Non Lymphocytic Leukemia (ANLL). 95% of children had nociceptive pain and 5% had neuropathic pain. Step - 1 analgesia was effective in 12 (31%) children and 21 (54%) could be managed with Step - 2 analgesia. Step - 3 analgesia was required in only 6 (15%) children. Step 3 analgesia was required in children with neuropathic pain and bone pain. WHO analgesic ladder is effective in managing pain in children with leukemia. Majority of cases of cancer pain in children could be managed by the treating physician using non-opioids, weak opioids and adjuvants as per the WHO guidelines. Children with bone pain and neuropathic pain may require referral to specialist services and use of strong opioids like morphine. The study emphasizes the need for establishing specialist pain management services in all centres where children with cancer are treated.


Phase separations in aerosol OT reverse micellar solutions in dodecane: a curious case of polar domain composition driven transition from lower consolute temperature (LCT) to upper consolute temperature (UCT) regime.
AOT-based microemulsions have been studied quite extensively on account of their numerous industrial applications and their existence as simple ternary phases. Properties of these microemulsions with higher alkanes as the oil continuous phase are governed by the presence of a strong inter micellar attractive interaction. In water in oil (w/o) microemulsions the inter micellar attraction strengthens with increase in temperature and leads to the observation of critical behavior on approaching the lower consolute temperature (LCT). In this manuscript we show that the phase behavior of AOT-based reverse micellar solutions in dodecane transforms dramatically when the polar domain is changed from water to formamide (FA) and even to aqueous solution of urea and NaCl. In all these cases the temperatures dependence of the microemulsion properties undergo complete reversal, which brings about a transition in their phase separation characteristics from lower consolute temperature (LCT) to upper consolute temperature (UCT) regime. Such systematic transformation in the phase behavior as a function of polar domain composition, which has been explained based on the influence of the polar domain on the properties of the interfacial AOT layer, is first of its kind in any reverse micellar system.


Novel Use of an Accelerometer to Assess Load Asymmetry Over Time After Hip Resurfacing Arthroplasty.
There is limited knowledge regarding usage of wearable technology to guide return to sport after hip resurfacing arthroplasty (HRA). This study evaluated the use of accelerometers to identify when symmetry is restored between operative and nonoperative limbs. A total of 26 primary HRA patients performed 5 validated physical tests before, 3 and 6 months after HRA: broad jump, double-leg vertical jump (DLVJ), hop test, lateral single-leg jump (LSLJ), and vertical single-leg jump. Impact load and average intensity data (g-force units) were collected using accelerometers. Strength data (pounds [lbs.]) for internal and external rotation were collected with a dynamometer. Univariate and correlation analyses analyzed interlimb asymmetries. At preoperation, there were significant impact load asymmetries for DLVJ (P = .008), hop test (P = .021), and LSLJ (P = .003) and intensity asymmetry for DLVJ (P = .010) and LSLJ (P = .003). At 3 months, there was impact load asymmetry for DLVJ (P = .005) and LSLJ (P = .005) and intensity asymmetry for broad jump (P = .020), hop test (P = .042), and LSLJ (P = .005). There were significant strength asymmetries at preoperation and 3 months postoperation for internal (P = .013) and external rotation (P = .037). All significant asymmetries indicated the nonoperative leg had greater output. No significant asymmetries were found for any exercises at 6 months postoperation. An increase in Harris Hip Score was significantly associated with a decrease in impact asymmetry (rs = -0.269, P = .006). Impact loads and strength reach interlimb symmetry at 6 months post-HRA. Wearable accelerometers provide useful metrics to distinguish limb asymmetries for recovery monitoring.


Sequence selective coordination of Mg2+(aq) to DNA.
Thermodynamic parameters for magnesium binding to a series of DNA molecules of defined sequence have been evaluated by 25Mg NMR spectroscopy. These results demonstrate that G/C-DNA binds Mg2+(aq) up to 40 to 100-fold more strongly than A/T-DNA, i.e., coordination of Mg2+(aq) to G/C-DNA is ca. 2.1-2.7 kcal (mole Mg2+)-1 more stable relative to A/T-DNA. Activation free energies [delta G* approximately (12.7-13.3) x 10(3) kcal] and exchange rates [k(ex) approximately (0.5-3.0) x 10(3)s-1] were estimated by variable temperature experiments. The low value of the quadrupole coupling constants (chi B = 0.2-0.6 MHz) is indicative of outer-sphere coordination by Mg(H2O)6(2+).


Need for certification of household water treatment products: examples from Haiti.
To evaluate four household water treatment (HWT) products currently seeking approval for distribution in Haiti, through the application of a recently-developed national HWT product certification process. Four chemical treatment products were evaluated against the certification process validation stage by verifying international product certifications confirming treatment efficacy and reviewing laboratory efficacy data against WHO HWT microbiological performance targets; and against the approval stage by confirming product composition, evaluating treated water chemical content against national and international drinking water quality guidelines and reviewing packaging for dosing ability and usage directions in Creole. None of the four evaluated products fulfilled validation or approval stage requirements. None was certified by an international agency as efficacious for drinking water treatment, and none had data demonstrating its ability to meet WHO HWT performance targets. All product sample compositions differed from labelled composition by >20%, and no packaging included complete usage directions in Creole. Product manufacturers provided information that was inapplicable, did not demonstrate product efficacy, and was insufficient to ensure safe product use. Capacity building is needed with country regulatory agencies to objectively evaluate HWT products. Products should be internationally assessed against WHO performance targets and also locally approved, considering language, culture and usability, to ensure effective HWT.


Effectiveness of Surgical and Postsurgical Interventions for Carpal Tunnel Syndrome-A Systematic Review.
To present an evidence-based overview of the effectiveness of surgical and postsurgical interventions for carpal tunnel syndrome (CTS). The Cochrane Library, PubMed, EMBASE, CINAHL, and PEDro were searched for relevant systematic reviews and randomized controlled trials (RCTs) up to April 8, 2016. Two reviewers independently applied the inclusion criteria to select potential studies. Two reviewers independently extracted the data and assessed the methodologic quality. A best-evidence synthesis was performed to summarize the results. Four systematic reviews and 33 RCTs were included. Surgery versus nonsurgical interventions, timing of surgery, and various surgical techniques and postoperative interventions were studied. Corticosteroid injection was more effective than surgery (strong evidence, short-term). Surgery was more effective than splinting or anti-inflammatory drugs plus hand therapy (moderate evidence, midterm and long-term). Manual therapy was more effective than surgical treatment (moderate evidence, short-term and midterm). Within surgery, corticosteroid irrigation of the median nerve before skin closure as additive to CTS release or the direct vision plus tunneling technique was more effective than standard open CTS release (moderate evidence, short-term). Furthermore, short was more effective than long bulky dressings, and a sensory retraining program was more effective than no program after surgery (moderate evidence, short-term). For all other interventions only conflicting, limited, or no evidence was found. Surgical treatment seems to be more effective than splinting or anti-inflammatory drugs plus hand therapy in the short-term, midterm, and/or long-term to treat CTS. However there is strong evidence that a local corticosteroid injection is more effective than surgery in the short-term, and moderate evidence that manual therapy is more effective than surgery in the short-term and midterm. There is no unequivocal evidence that suggests one surgical treatment is more effective than the other. Postsurgical, a short- (2-3 days) favored a long-duration (9-14 days) bulky dressing and a sensory retraining program seems to be more effective than no program in short-term. More research regarding the optimal timing of surgery for CTS is needed.


AOSD endotypes based on immune cell profiles: patient stratification with hierarchical clustering analysis.
This study aimed to analyse the immune cell profiles of adult-onset Still's disease (AOSD) and to stratify disease-associated endotypes. We included 95 cases of treatment-naïve patients with AOSD and 66 cases of healthy controls. Patients with AOSD were classified via an unbiased hierarchical cluster analysis based on circulating immune cells. Their clinical and laboratory characteristics, treatment management, systemic scores and outcomes were then analysed. The proportions of neutrophils and CD8+ T cells were significantly higher while monocytes and natural killer and CD4+ T cells were decreased in patients with AOSD (all P < 0.005). Unbiased hierarchical cluster analysis classified 95 AOSD into three endotype-based groups: group 1 had the highest percentage of neutrophils (neu-dominant group), group 2 had the highest percentage of monocytes (mono-dominant group) and group 3 had the highest percentage of CD8+ T cells (CD8-dominant group). Patients in group 3 had the highest systemic score at diagnosis and were more likely to have pulmonary infiltrates, pericarditis, splenomegaly and poorer treatment responses. A correlation study revealed that the CD4 to CD8 ratio was negatively correlated with the systemic score and positively correlated with treatment response in patients with AOSD (P = 0.001 and P = 0.0091). During the 24.6 (15.2) months of follow-up, the highest total number of disease flares occurred in group 3 (P < 0.0001). Hierarchical cluster analysis of peripheral immune cells classified AOSD into three disease-related endotypes. Group 3 showed higher systemic score and poorer treatment responses.


Clinical, endocrine and ultrasonographic features of polycystic ovary syndrome in Thai women.
To study the prevalence, reproductive hormone profiles and ovarian sonographic appearance of Thai women with polycystic ovary syndrome (PCOS). One thousand and ninety-five women were screened for oligomenorrhea/amenorrhea, and the clinical symptoms of hyperandrogenism. Ovarian morphology and volume were assessed by ultrasonography in diagnosed cases. Blood was taken for the measurement of the follicle stimulating hormone, luteinizing hormone, prolactin, testosterone, androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone. The prevalence of PCOS was 5.7%. The mean age of women with PCOS was less than that of non-PCOS cases (27.4 +/- 6.5 and 31.1 +/- 6.4 years, respectively; P < 0.0001). Abnormal uterine bleeding and infertility were the leading presenting symptoms. The mean ovarian volume in women with PCO appearance was 9.22 +/- 4.36 mL compared to 6.53 +/- 3.31 mL in those without this appearance (P = 0.04). Hyperandrogenemia was confirmed in 23 of the 62 cases (37.1%). The prevalence and clinical presentations of Thai women with PCOS were similar to those in other reports. However, hirsutism, elevated testosterone level and acanthosis nigricans were uncommon in our population. Serum androstenedione was a more sensitive indicator of hyperandrogenemia than total testosterone. Further research is needed to clarify whether there is an ethnic difference in endocrine profiles and risks of metabolic syndrome.


Association between biochemical hyperandrogenism parameters and Ferriman-Gallwey score in patients with polycystic ovary syndrome: A systematic review and meta-regression analysis.
A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters (BHPs) and Ferriman-Gallwey (FG) score in patients with polycystic ovary syndrome (PCOS). We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000-2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used. Fifty-five study groups with a total of 6593 PCOS patients were analysed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) (P=.034) and dehydroepiandrosterone sulphate (DHEAS) (P=.012), whereas it showed no association with total testosterone (tT), free testosterone (fT), sex hormone bonding globulin (SHBG) and free androgen index (FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity. This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism.


Lipids of nuclear fractions from neurons and glia of rat neocortex under conditions of artificial hypobiosis.
Lipid contents were studied in tissue and nuclei isolated from neurons and glia of neocortex of rats under conditions of normothermia and in the state of artificial hypobiosis caused by hypothermia-hypoxia-hypercapnia. Compared to the neocortex tissue, both nuclear fractions were fivefold impoverished in phospholipids and cholesterol and strongly enriched with mono- and diglycerides and fatty acids. The nuclear fractions from neurons and glia contained similar amounts of phospholipids, and only the cardiolipin content in the neuronal nuclei was lower than in the glial nuclei. The state of artificial hypobiosis in rats led to an increase in the cholesterol/phospholipids ratio (mol/mol) in the nuclei from the neurons and glia; amounts of cholesterol and sphingomyelin in the nuclei from the glia were increased. The increases in the cholesterol and sphingomyelin contents and in the cholesterol/phospholipids ratio suggest an involvement of lipid-dependent signaling systems of the nuclei in the functional response of mammalian neocortex cells to artificial hypobiosis.


The immune response to a B-cell epitope delivered by Salmonella is enhanced by prior immunological experience.
Attenuated, heterologous strains of Salmonella have shown potential as live, recombinant vaccines against foreign pathogens. Studies in animal models have demonstrated that immunization with these heterologous vaccines is an effective way to induce both cellular and humoral immune responses against Salmonella and the foreign antigen. We studied the consequence of priming mice with Salmonella dublin 3-6 months before intraperitoneal administration with the same strain carrying a model B-cell epitope. Mice primed with the carrier strain demonstrated enhanced serum Ig titres against the foreign antigen. This immune enhancement was observed up to approximately 6 months after priming. These findings suggest that previous immunological experience with Salmonella does not limit the immune response to a foreign antigen carried by the same organism. In fact, prior exposure to Salmonella appears to enhance the response to the foreign antigen.


Novel Hemizygous Missense Variant of Spermine Synthase (SMS) Gene Causes Snyder-Robinson Syndrome in a Four-Year-Old Boy.
Snyder-Robinson syndrome (SRS) is an extremely rare X-linked intellectual disability syndrome (MRXSSR; MIM #309583). The main clinical features of SRS include psychomotor delay, hypotonia, and asthenic-type body habitus - reduced body weight and bone abnormalities (osteoporosis, fractures, kyphoscoliosis). We report a case of SRS with a hemizygous missense variant in the SMS gene,c.334C>G (p.Pro112Ala), in a 4-year-old boy, who initially developed hypotonia, delayed motor skills, and subsequently epilepsy. This variant in SMS was found to be de novo. To the best of our knowledge, this novel SMS gene variant has never been previously reported in disease-related variation databases, such as ClinVar or HGMD.


Bilateral dysplasia epiphysealis hemimelica: report of two cases.
Dysplasia epiphysealis hemimelica is a rare congenital disorder characterised by unilateral bone overgrowth from large joints, mainly the ankle or knee. We present two cases with bilateral lesions; only two similar cases with bilateral involvement have been reported hitherto. The differential diagnosis is considered.


Suicide-related over-the-counter analgesic exposures reported to United States poison control centers, 2000-2018.
To investigate suicide-related over-the-counter (OTC) analgesic medication exposures among individuals ≥6 years old reported to United States (US) poison control centers. Data from the National Poison Data System for the years 2000-2018 were retrospectively analyzed. From 2000 to 2018, US poison control centers recorded 549 807 suicide-related cases involving OTC analgesics, including 327 781 cases (59.6%) admitted to the hospital and 1745 deaths (0.3%). Most cases involved a single substance (67.5%) and occurred among females (72.7%) and individuals 6-19 years old (49.7%). Overall, the rate of exposures increased significantly by 33.5% from 2000 to 2018, primarily driven by the increasing exposure rate among 6- to 19-year-old females. From 2000 to 2018, exposure rates for acetaminophen and ibuprofen increased, while that for acetylsalicylic acid decreased. Additionally, the proportion of cases resulting in a serious medical outcome or healthcare facility admission increased for all types of OTC analgesics. Acetaminophen and acetylsalicylic acid accounted for 48.0% and 18.5% of cases, respectively, and 64.5% and 32.6% of deaths, respectively. Both acetaminophen and acetylsalicylic acid had greater odds of healthcare facility admission (ORs 2.56 and 2.63, respectively) and serious medical outcomes (ORs 2.54 and 4.90, respectively) compared with ibuprofen. The rate of suicide-related OTC analgesic cases is increasing. Acetaminophen and acetylsalicylic acid cases are associated with greater morbidity and mortality. Prevention efforts should include implementing unit-dose packaging requirements and restrictions on package sizes and purchase quantities for acetaminophen and acetylsalicylic acid products to reduce access to large quantities of these analgesics.


Validation of self-reported anthropometrics in the Adventist Health Study 2.
Relying on self-reported anthropometric data is often the only feasible way of studying large populations. In this context, there are no studies assessing the validity of anthropometrics in a mostly vegetarian population. The objective of this study was to evaluate the validity of self-reported anthropometrics in the Adventist Health Study 2 (AHS-2). We selected a representative sample of 911 participants of AHS-2, a cohort of over 96,000 adult Adventists in the USA and Canada. Then we compared their measured weight and height with those self-reported at baseline. We calculated the validity of the anthropometrics as continuous variables, and as categorical variables for the definition of obesity. On average, participants underestimated their weight by 0.20 kg, and overestimated their height by 1.57 cm resulting in underestimation of body mass index (BMI) by 0.61 kg/m(2). The agreement between self-reported and measured BMI (as a continuous variable), as estimated by intraclass correlation coefficient, was 0.97. The sensitivity of self-reported BMI to detect obesity was 0.81, the specificity 0.97, the predictive positive value 0.93, the predictive negative value 0.92, and the Kappa index 0.81. The percentage of absolute agreement for each category of BMI (normoweight, overweight, and obese) was 83.4%. After multivariate analyses, predictors of differences between self-reported and measured BMI were obesity, soy consumption and the type of dietary pattern. Self-reported anthropometric data showed high validity in a representative subsample of the AHS-2 being valid enough to be used in epidemiological studies, although it can lead to some underestimation of obesity.


Draft Genome Sequence of the Plant Growth-Promoting Bacterium Pseudomonas pseudoalcaligenes KB-10.
Pseudomonas pseudoalcaligenes KB-10 can enhance salinity tolerance in coriander plants. We report a draft genome sequence of P. pseudoalcaligenes KB-10, comprising a 5,241,174-bp circular chromosome containing 4,921 genes, with a GC content of 62.97%.


Transient receptor potential vanilloid subtype 1 depletion mediates mechanical allodynia through cellular signal alterations in small-fiber neuropathy.
Transient receptor potential vanilloid subtype 1 (TRPV1) is a polymodal nociceptor that monitors noxious thermal sensations. Few studies have addressed the role of TRPV1 in mechanical allodynia in small-fiber neuropathy (SFN) caused by sensory nerve damage. Accordingly, this article reviews the putative mechanisms of TRPV1 depletion that mediates mechanical allodynia in SFN. The intraepidermal nerve fibers (IENFs) degeneration and sensory neuronal injury are the primary characteristics of SFN. Intraepidermal nerve fibers are mainly C-polymodal nociceptors and Aδ-fibers, which mediated allodynic pain after neuronal sensitization. TRPV1 depletion by highly potent neurotoxins induces the upregulation of activating transcription factor 3 and IENFs degeneration which mimics SFN. TRPV1 is predominately expressed by the peptidergic than nonpeptidergic nociceptors, and these neurochemical discrepancies provided the basis of the distinct pathways of thermal analgesia and mechanical allodynia. The depletion of peptidergic nociceptors and their IENFs cause thermal analgesia and sensitized nonpeptidergic nociceptors respond to mechanical allodynia. These distinct pathways of noxious stimuli suggested determined by the neurochemical-dependent neurotrophin cognate receptors such as TrkA and Ret receptors. The neurogenic inflammation after TRPV1 depletion also sensitized Ret receptors which results in mechanical allodynia. The activation of spinal TRPV1(+) neurons may contribute to mechanical allodynia. Also, an imbalance in adenosinergic analgesic signaling in sensory neurons such as the downregulation of prostatic acid phosphatase and adenosine A1 receptors, which colocalized with TRPV1 as a membrane microdomain also correlated with the development of mechanical allodynia. Collectively, TRPV1 depletion-induced mechanical allodynia involves a complicated cascade of cellular signaling alterations.


Effects of pairing health warning labels with energy-dense snack foods on food choice and attitudes: Online experimental study.
There is limited evidence concerning the potential effectiveness of health warning labels (HWLs) using images and text to depict possible negative health consequences of consumption, for reducing selection of energy-dense snack foods. Furthermore, the underlying mechanisms have received little attention; particularly effects on implicit attitudes, which previous work has shown may mediate the effect of aversive images on food choice. To assess the impact of pairing image- and text-based HWLs with energy-dense snack foods on a) the selection of, and b) implicit and explicit attitudes towards, those foods. Online experimental study with a representative UK sample (n = 1185), using a 2(Image/No Image) x 2(Text/No Text) factorial between-subjects design. Participants were randomised to one of four study arms, viewing snack food images paired with either: image-only HWLs, text-only HWLs, image-and-text HWLs, or no HWLs (control). HWLs concerned various negative health consequences of excess energy intake, such as heart disease and type 2 diabetes. The primary outcome was hypothetical food choice (energy-dense snack foods versus fruit), assessed post-intervention. Secondary outcomes were implicit and explicit attitudes. Neither food choice nor explicit attitudes were changed significantly by any type of HWL. Implicit attitudes towards energy-dense snack foods were more negative after exposure to text-only or image-and-text HWLs. Both implicit and explicit attitudes predicted unique variance in food choice. This study suggests that short-term repeated exposure to HWLs paired with energy-dense snack foods may not consistently alter food choices, but can change implicit attitudes associated with food choices. Further laboratory and field studies are needed to more definitively assess the impact of HWLs on food selection and consumption in applied contexts and over time, as well as delineate underlying mechanisms.


Cytochalasin D inhibits basal body migration and ciliary elongation in quail oviduct epithelium.
The effects of cytochalasin D (CD) were studied by scanning (SEM) and transmission (TEM) electron-microscopic examination at different stages of ciliary differentiation in epithelial cells of quail oviduct. Immature quails were prestimulated by estradiol benzoate injections to induce ciliogenesis in the undifferentiated oviduct. After 24 h of CD culture, SEM study revealed inhibition of ciliogenesis and dilation of the apex of non-ciliated cells. TEM study showed that 2 h of CD treatment produced dilation of lateral intercellular spaces, after 6 h of treatment, this resulted in intracellular macrovacuolation. Vacuoles were surrounded by aggregates of dense felt-like material. CD also induced the disappearance of microvilli, and rounding of the apical surface of undifferentiated cells and those blocked in ciliogenesis. Centriologenesis was not inhibited by CD; basal bodies assembled in generative complexes in the supranuclear region after 24 h of treatment. However, the migration of mature basal bodies towards the apical surface was impaired. Instead, they anchored onto the membrane of intracellular vacuoles; growth of cilia was induced in the vacuole lumen. Cilium elongation was disturbed, giving abnormally short cilia with a dilated tip; microtubules failed to organize correctly.


Influence of Prenatal Environment on Androgen Steroid Metabolism In Monozygotic Twins With Birthweight Differences.
Although low birthweight (bw) and unfavorable intrauterine conditions have been associated with metabolic sequelae in later life, little is known about their impact on steroid metabolism. We studied genetically identical twins with intra-twin bw-differences from birth to adolescence to analyze the long-term impact of bw on steroid metabolism. 68 monozygotic twin pairs with a bw-difference of <1 standard deviation score (SDS; concordant; n = 41) and ≥1 SDS (discordant; n = 27) were recruited. At 14.9 years (mean age), morning urine samples were collected and analyzed with gas chromatography-mass-spectrometry. No significant differences were detected in the concordant group. In contrast, in the smaller twins of the discordant group, we found significantly higher concentrations not only of the dehydroepiandrosterone sulfate (DHEAS) metabolite 16α-OH-DHEA (P = 0.001, 656.11 vs 465.82 µg/g creatinine) but also of cumulative dehydroepiandrosterone and downstream metabolites (P = 0.001, 1650.22 vs 1131.92 µg/g creatinine). Relative adrenal (P = 0.002, 0.25 vs 0.18) and overall androgen production (P = 0.001, 0.79 vs 0.65) were significantly higher in the formerly smaller discordant twins. All twin pairs exhibited significant intra-twin correlations for all individual steroid metabolites, sums of metabolites, indicators of androgen production, and enzyme activities. Multiple regression analyses of the smaller twins showed that individual steroid concentrations of the larger co-twin were the strongest influencing factor among nearly all parameters analyzed. In monozygotic twin pairs with greater intra-twin bw-differences (≥1 SDS), we found that bw had a long-lasting impact on steroid metabolism, with significant differences regarding DHEAS metabolites and relative androgen production. However, most parameters showed significant intra-twin correlations, suggesting a consistent interrelationship between prenatal environment, genetic background, and steroid metabolism.


Auditory behavioral thresholds for Japanese macaques using insert earphones.
The goal of this study was to measure behavioral auditory thresholds in four Japanese macaques. Animals were trained using food as a reward in an operant reinforcement paradigm. Stimuli were 1-s sinusoids with 10-ms rise/fall times delivered through insert earphones (Etymotic ER-1) having expandable foam eartips. The animals generally produced threshold contours similar in shape to those reported for other macaques species, except that the low-frequency thresholds may have been slightly higher in the present studies. At middle and high frequencies, thresholds fell at the lower extreme of the range previously reported in other macaque species. The possible difference in low-frequency thresholds may have been a result of either transducer and calibration differences between studies or true species variations, or both. Though somewhat limited at high frequencies, the insert earphones used in these studies offer more reliable calibrations, less susceptibility to changes in positioning with movement of the animal, and greater interaural attenuation.


Prevention of respiratory infections at day care centers: recommendations and systematic review of the evidence.
Attending a day care center is a risk factor for respiratory infections. The objective of this study is to review which nonspecific prevention measures are recommended for day care centers and the evidence of their usefulness in this setting. Recommendations regarding nonspecific prevention at national level were searched using Google and the web sites of the Argentine Society of Pediatrics, the ministries of education and the ministries of health from different countries, both in English and Spanish. Recommendations regarding hand hygiene, clearance of secretions, cleaning the environment and elements, breastfeeding, and exclusion of symptomatic subjects were reviewed. A systematic search of the literature was conducted to find intervention studies at day care centers that evaluated the effectiveness of recommendations, published in Spanish and English. Results and the methodological quality of studies were analyzed. Seven guidelines were found. Hand hygiene and environment cleaning were the only recommendations described in all guidelines. The exclusion of symptomatic subjects is mentioned in all, but criteria are heterogeneous. Clearance of nasal secretions and promotion of breastfeeding are outlined only in a few of the guidelines. Eight intervention studies on hand hygiene, cleaning of the environment, and clearance of secretions were found, whose results were heterogeneous and had major methodological limitations. A timely and adequate hand hygiene and an appropriate cleaning of the environment have been uniformly recommended by different guidelines as non-specific prevention measures against respiratory infections. The evidence on the usefulness of these measures in this setting is limited.


Accurate Determination of the Degree of Deacetylation of Chitosan Using UPLC-MS/MS.
The mole fraction of deacetylated monomeric units in chitosan (CS) molecules is referred to as CS's degree of deacetylation (DD). In this study, 35 characteristic ions of CS were detected using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS). The relative response intensity of 35 characteristic ion pairs using a single charge in nine CS samples with varying DDs was analyzed using 30 analytical methods. There was a good linear relationship between the relative response intensity of the characteristic ion pairs determined using ultrahigh performance (UP) LC-MS/MS and the DD of CS. The UPLC-MS/MS method for determining the DD of CS was unaffected by the sample concentration. The detection instrument has a wide range of application parameters with different voltages, high temperatures, and gas flow conditions. This study established a detection method for the DD of CS with high sensitivity, fast analysis, accuracy, stability, and durability.


Miscanthus biochar value chain - A review.
To complete a loop of the Miscanthus value chain including production, phytomanagement, conversion to energy, and bioproducts, the wastes accumulated from these processes have to be returned to the production cycle to provide sustainable use of the feedstock, to reduce costs, and to ensure a zero-waste approach. This can be achieved by converting Miscanthus feedstock into biogas and biochar using pyrolysis and then returning biochar to the production cycle of Miscanthus crop applications in the phytotechnology of trace elements (TEs)-contaminated/marginal lands. These processes are subjects of the current review, which focused on the peculiarities of biochar received from Miscanthus by pyrolysis, its properties, the impact on soil characteristics, the phytoremediation process, biomass yield, and the abundance of soil biodiversity. Results from the literature indicated that the pH, surface area, and porosity of Miscanthus biochar are important in determining its impact on soil characteristics. It was inferred that the most effective Miscanthus biochar was produced with a pyrolysis temperature of about 600 °C with a residence time from about 30 min to an hour. Another important factor that determined the impact of Miscanthus biochar on soil health is the application rate: with its increase, the effect became more essential, and the recommended rate is between 5% and 10%. The influence of Miscanthus biochar on the TEs phytoremediation parameters is less studied, generally Miscanthus biochar produced at higher temperatures and added with higher application rates is more likely to restrict the mobility and availability of TEs by different plants. However, some published results are contradictory to these conclusions and showed absence of significant difference in TEs reduction during application of different Miscanthus biochar doses. The future experimental studies have to focus on determining the impact of a technological pyrolysis regime on Miscanthus biochar properties on TEs-contaminated or marginal land when biochar will be obtained from contaminated rhizomes and waste after the application of phytotechnology. In addition, studies must explore the influence of this biochar on TEs phytoparameters, enhancements in biomass yield, improvements in soil parameters, and the abundance of soil diversity.


Geometric frustration of hard-disk packings on cones.
Conical surfaces pose an interesting challenge to crystal growth: A crystal growing on a cone can wrap around and meet itself at different radii. We use a disk-packing algorithm to investigate how this closure constraint can geometrically frustrate the growth of single crystals on cones with small opening angles. By varying the crystal seed orientation and cone angle, we find that-except at special commensurate cone angles-crystals typically form a seam that runs along the axial direction of the cone, while near the tip, a disordered particle packing forms. We show that the onset of disorder results from a finite-size effect that depends strongly on the circumference and not on the seed orientation or cone angle. This finite-size effect occurs also on cylinders, and we present evidence that on both cylinders and cones, the defect density increases exponentially as circumference decreases. We introduce a simple model for particle attachment at the seam that explains the dependence on the circumference. Our findings suggest that the growth of single crystals can become frustrated even very far from the tip when the cone has a small opening angle. These results may provide insights into the observed geometry of conical crystals in biological and materials applications.


Striatal dopamine turnover and L-dopa treatment after short-term exposure of rats to manganese.
The turnover rate of striatal dopamine (DA) and the effect of L-dopa treatment was investigated in rats after the daily oral administration of MnCl2 . 4H20 for a period of 30 days. The turnover rate of striatal DA, as determined by the administration of alpha-methyl-p-tyrosine, increased significantly in manganese-exposed rats. L-Dopa administration resulted in a significant elevation in the levels of DA and its metabolite, homovanillic acid, in manganese-exposed rats, but these neurochemical changes could not be correlated with the concentration of manganese in the striatum. We therefore advise the L-dopa therapy should not be tried in early manganese intoxication, as it may aggravate manic symptoms due to marked increase in brain DA.


HOXB5 expression in oral squamous cell carcinoma.
Human HOX genes encode transcription factors that act as master regulators of embryonic development. They are important in several processes such as cellular morphogenesis and differentiation. The HOXB5 gene in particular has been reported in some types of neoplasm, but not in oral cancer. The present study investigated the expression of HOXB5 in oral squamous cell carcinoma (SCC) and in non-tumoral adjacent tissues, focusing on verifying its possible role as a broad tumor-associated gene and its association with histopathological and clinical (TNM) characteristics. RT-PCR was performed to amplify HOXB5 mRNA in 15 OSCCs and adjacent non-tumoral epithelium. A possible association with TNM and histopathologic data was verified by the chi-square and post-hoc t-test. HOXB5 was amplified in 60% non-tumoral epithelium and in 93.3% carcinomas. No statistically significant differences were found regarding the HOXB5 mRNA expression and TNM or histological grade. HOXB5 is expressed in OSCCs and its role in cancer progression should be further investigated.


New technologies in cancer. Protein microarrays for biomarker discovery.
The emergence of proteomic techniques and methodological approaches to study disease has kindled the quest for new biomarkers. Thus, the use of protein microarrays has surged as a powerful tool for large-scale testing of biological samples. In this mini-review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers.


The impact of MYC gene amplification on the clinicopathological features and prognosis of radiation-associated angiosarcomas of the breast.
Radiation-associated angiosarcomas (RT-ASs) of the breast are rare tumours with a poor prognosis. MYC gene amplification is considered to be the hallmark of RT-AS, and is sometimes used as a diagnostic tool to distinguish it from other radiation-associated vascular lesions. However, a small subset of RT-ASs lacks MYC amplification, and this may be associated with better outcome. Loss of trimethylation at lysine 27 of histone 3 (H3K27me3) expression by immunohistochemistry (IHC) has been recently postulated as an additional diagnostic marker for RT-AS. The aims of this study were to evaluate the impact of MYC amplification as detected by fluorescence in-situ hybridisation and/or next-generation sequencing on clinicopathological features and outcome in a large cohort of RT-ASs, compare outcome with those of radiation-associated sarcomas (RT-Ss) of the breast other than angiosarcoma, and evaluate expression of H3K27me3 IHC in these groups. Eighty-one RT-ASs were identified, including 73 that were MYC-amplified and 8 (10%) that were MYC-non-amplified. MYC-amplified RT-ASs were diagnosed in older patients (median age, 69 years versus 61 years). The 5-year disease-specific survival and 5-year overall survival rates were 56% and 47%, respectively. Older age, larger tumour size, positive margin and MYC amplification were associated with worse prognosis. None of the RT-ASs showed complete loss of H3K27me3 IHC expression. All 18 RT-Ss were MYC-non-amplified, and complete loss of H3K27me3 expression was seen in 2 cases. We found no difference in prognosis between RT-AS and RT-S. RT-AS of the breast is associated with a poor prognosis. Older age at diagnosis, larger tumour size, positive margin at excision and MYC amplification are associated with worse prognosis.


Advances in treatment of biliary atresia.
During 29 years from 1953 through 1981, 224 patients with congenital biliary atresia were treated and 200 of them underwent corrective operation at the Second Department of Surgery, Tohoku University Hospital. With the advance of surgical techniques and early diagnosis of biliary atresia, the rate of jaundice disappearance improved from the initial 15 per cent to the recent 69 per cent. Important factors contributing to the improvement of operative results included (1) an early operation, preferably within 60 days after birth, (2) a precise dissection and adequate transection of the porta hepatis, (3) prevention of post-operative cholangitis and (4) reoperation if indicated. Delayed operation and occurrence of post-operative cholangitis affected not only immediate but also long term operative results. Although, nearly all the patients with biliary atresia had portal hypertension at the time of surgery, the portal vein pressure decreased after successful operation, mainly due to improvement in portal venous circulation of the liver. It is considered from recent operative results that more than 80 per cent of patients with biliary atresia can be cured when an adequate corrective operation is carried out before 60 days of age and post-operative cholangitis is prevented.


Enzymatic methylation of cytosine in DNA is prevented by adjacent O6-methylguanine residues.
The effect of O6-alkylation of guanine residues on the enzymic methylation of cytosine has been studied using synthetic oligonucleotides in which all guanines in cytosine-guanine sequences at potentially methylatable sites are replaced by O6-methylguanine. In contrast with the unmodified forms, which showed high acceptance activity for methyl-3H-labeled groups from S-adenosyl-L-[methyl-3H]methionine in the presence of DNA methylase, the modified oligonucleotides were not substrates for the enzyme either in the single-stranded or annealed forms. In view of the importance of cytosine methylation in the down-regulation of certain genes, the potential to affect gene expression by this mechanism may be a contributory factor in the toxic and carcinogenic effects of chemical methylating agents.


Plasma soluble leptin receptor levels are associated with pancreatic β-cell dysfunction in patients with type 2 diabetes.
A soluble form of the leptin receptor (soluble Ob-R) in the circulation regulates leptin's bioactivity, and is inversely associated with body adiposity and circulating leptin levels. However, no study has examined the clinical impact of soluble Ob-R on glucose metabolism in diabetes. The present study aimed to investigate the association of plasma soluble Ob-R levels with insulin resistance and pancreatic β-cell function in patients with type 2 diabetes. A total of 289 Japanese patients with type 2 diabetes were included in the present study. Fasting plasma soluble Ob-R levels and plasma leptin levels were measured by enzyme-linked immunosorbent assay. Insulin resistance and pancreatic β-cell function were estimated by homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and fasting C-peptide index. The median plasma soluble Ob-R level and plasma leptin level were 3.4 ng/mL and 23.6 ng/mL, respectively. Plasma soluble Ob-R levels were negatively correlated with homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the C-peptide index, whereas plasma leptin levels were positively correlated with each index in univariate analyses. Multivariate analyses including plasma soluble Ob-R levels, plasma leptin levels and use of sulfonylureas, along with age, sex, body mass index and other covariates, showed that soluble Ob-R levels were independently and negatively associated with homeostasis model assessment of β-cell function and the C-peptide index, but not significantly associated with homeostasis model assessment of insulin resistance. Plasma soluble Ob-R levels are independently associated with pancreatic β-cell function, but not with insulin resistance, in patients with type 2 diabetes. The present study implicates the role of soluble Ob-R in pancreatic β-cell dysfunction in type 2 diabetes.


Hidden Markov model-based heartbeat detector using electrocardiogram and arterial pressure signals.
The automatic detection of a heartbeat is commonly performed by detecting the QRS complex in the electrocardiogram (ECG), however, various noise sources and missing data can jeopardize the reliability of the ECG. Therefore, there is a growing interest in combining the information from many physiological signals to accurately detect heartbeats. To this end, hidden Markov models (HMMs) are used in this work to jointly exploit the information from ECG, arterial blood pressure (ABP) and pulmonary arterial pressure (PAP) signals in order to conceive a heartbeat detector. After preprocessing the physiological signals, a sliding window is used to extract an observation sequence to be passed through two HMMs (previously trained on a training dataset) in order to obtain the log-likelihoods of observation and signals a detection if the difference of log-likelihoods exceeds an adaptive threshold. Several HMM-based heartbeat detectors were conceived to exploit the information from the ECG, ABP and PAP signals from the MIT-BIH Arrhythmia, PhysioNet Computing in Cardiology Challenge 2014, and MGH/MF Waveform databases. A grid search methodology was used to optimize the duration of the observation sequence and a multiplicative factor to form the adaptive threshold. Using the optimal parameters found on a training database through 10-fold cross-validation, sensitivity and positive predictivity above 99% were obtained on the MIT-BIH Arrhythmia and PhysioNet Computing in Cardiology Challenge 2014 databases, while they are above 95% in the MGH/MF waveform database using ECG and ABP signals. Our detector approach showed detection performances comparable with the literature in the three databases. The online version contains supplementary material available at 10.1007/s13534-021-00192-x.


The influence of ADHD-hyperactivity/impulsivity symptoms on the development of oppositional defiant disorder symptoms in a 2-year longitudinal study.
The structural relations among ADHD-inattention (IN), ADHD-hyperactivity/impulsivity (H/I), and oppositional defiant disorder (ODD) factors were examined in a 2-year longitudinal study with 752 children. Structural equation procedures showed that higher scores on the H/I factor in Year 1 were associated with higher scores on ODD factor in Years 2 and 3. Higher scores on the H/I factor in Year 2 were also associated with higher scores on ODD factor in Year 3. The ODD factor did not predict the H/I and IN factors in subsequent years. The IN factor did not predict the ODD and H/I factors in subsequent years and the H/I factor did not predict the IN factor. The ability of the H/I factor to predict the subsequent ODD factor occurred even after taking into account the ability of the ODD, H/I, and IN factors to predict themselves across time. These results suggest that the H/I aspect of ADHD influences the development of ODD behavior.


Research Note: Phosphorus digestibility in conventional canola meal determined using different balance assays.
Three experiments were conducted to determine ileal P digestibility and excreta P retention values for canola meal (CM) using 3 different types of balance assays. The first experiment was an ad libitum-fed chick experiment which evaluated the effect of phytase on ileal P digestibility and excreta P retention values. Chicks were fed a P-deficient cornstarch-dextrose-45% CM basal diet (0.13% nonphytate P) as diet 1 or that diet plus 125 or 250 FTU/kg of phytase, respectively, from 8 to 21 D of age. The digestibility/retention of P was 38% and phytase linearly increased both ileal digestibility and excreta retention of P (P < 0.05). The second experiment was a precision-fed chick assay conducted to determine ileal digestibility of P in CM at 21 D. Mean ileal P digestibility was determined to be 47.5% in chicks fed 6 g and 40.0% in chicks fed 9 g of CM and the values were not significantly different. Experiment 3 was an ad libitum-fed chick assay to determine ileal P digestibility and excreta P retention for CM with and without increasing levels of dietary supplemental Ca. The chicks were fed P-deficient - dextrose - CM diets containing increasing levels of 13.5, 27, 40.5, or 54% CM, respectively, with Ca:nonphytate P ratio maintained at 2:1 in diets 1-4 and 6:1 in diets 5-8. Based on regression analysis of ileal digesta or excreta P output on dietary P concentration, digestibility/retention of P in CM was 30%. Ileal P digestibility (and to a lesser extent excreta P retention) at 21 D was reduced by increased Ca:P ratio. The results of this study indicated that the 3 balance assays yielded reasonably consistent values of 30-40% for P digestibility/retention and ileal P digestibility was greatly affected by Ca:P ratio.


An in vitro platform for study of the human gut microbiome under an oxygen gradient.
The complex, dynamic environment of the human lower gastrointestinal tract is colonized by hundreds of bacterial species that impact health and performance. Ex vivo study of the functional interactions between microbial community members in conditions representative of those in the gut is an ongoing challenge. We have developed an in vitro 40-plex platform that provides an oxygen gradient to support simultaneous maintenance of microaerobic and anaerobic microbes from the gut microbiome that can aid in rapid characterization of microbial interactions and direct comparison of individual microbiome samples. In this report, we demonstrate that the platform more closely maintained the microbial diversity and composition of human donor fecal microbiome samples than strict anaerobic conditions. The oxygen gradient established in the platform allowed the stratification and subsequent sampling of diverse microbial subpopulations that colonize microaerobic and anaerobic micro-environments. With the ability to run forty samples in parallel, the platform has the potential to be used as a rapid screening tool to understand how the gut microbiome responds to environmental perturbations such as toxic compound exposure, dietary changes, or pharmaceutical treatments.


Incidence of abnormal mammograms after reduction mammoplasty: implications for oncoplastic closure.
Reduction mammoplasty requires significant tissue dissection, which may impact the interpretation of future mammograms used in breast cancer surveillance. The aim of this study was to define the incidence of abnormal mammography after reduction mammoplasty and to assess the impact of substantial tissue remodeling on interpreting mammography. We conducted a single-center retrospective case-control study examining results of postoperative mammography after reduction mammoplasty over a 5-year period. Between 2001 and 2005, 87 patients underwent breast reduction and had available postoperative mammography. A control group of 30 patients were identified who underwent consultation for breast reduction but did not have surgery. The median time to postoperative mammography was 52 weeks. The incidence of abnormal first postoperative mammogram (Breast Imaging-Reporting and Data System [BIRADS] 0, 3-6) was not significantly different between reduction mammoplasty patients and controls (n = 23, 26% vs 8, 27%, respectively, P = 1.00). Age, postoperative complications, tissue pathology, history of previous breast biopsy, and abnormal preoperative mammography did not significantly predict abnormal postoperative mammogram. Postoperative mammography led to additional imaging in 20 patients (23%) and breast biopsy in 1 patient (1.1%). Despite the substantial tissue mobilization performed during reduction mammoplasty, postoperative screening mammography does not lead to significantly more imaging or diagnostic interventions when compared with nonoperative controls. This small case-control study suggests that oncoplastic closure techniques should not adversely impact subsequent mammography.


Comprehensive diffusion MRI dataset for in vivo human brain microstructure mapping using 300 mT/m gradients.
Strong gradient systems can improve the signal-to-noise ratio of diffusion MRI measurements and enable a wider range of acquisition parameters that are beneficial for microstructural imaging. We present a comprehensive diffusion MRI dataset of 26 healthy participants acquired on the MGH-USC 3 T Connectome scanner equipped with 300 mT/m maximum gradient strength and a custom-built 64-channel head coil. For each participant, the one-hour long acquisition systematically sampled the accessible diffusion measurement space, including two diffusion times (19 and 49 ms), eight gradient strengths linearly spaced between 30 mT/m and 290 mT/m for each diffusion time, and 32 or 64 uniformly distributed directions. The diffusion MRI data were preprocessed to correct for gradient nonlinearity, eddy currents, and susceptibility induced distortions. In addition, scan/rescan data from a subset of seven individuals were also acquired and provided. The MGH Connectome Diffusion Microstructure Dataset (CDMD) may serve as a test bed for the development of new data analysis methods, such as fiber orientation estimation, tractography and microstructural modelling.


Association Between Serum Myostatin Levels, Hospital Mortality, and Muscle Mass and Strength Following ST-Elevation Myocardial Infarction.
This study aimed to evaluate the association between serum myostatin levels, hospital mortality, and muscle mass and strength following ST-segment elevation myocardial infarction (STEMI). This was a prospective observational study. Within 48 hours of admission, bioelectrical impedance and handgrip strength were assessed and blood samples collected for myostatin evaluation. Hospital mortality was recorded. A multiple logistic regression model was also constructed, adjusted by parameters that exhibited significant differences in the univariate analysis, to evaluate the association between myostatin levels and hospital mortality. One hundred and two (102) patients were included: mean age was 60.5±10.6 years, 67.6% were male, and 6.9% died during hospital stay. Univariate analysis showed that patients with lower myostatin levels had higher mortality rates. Serum myostatin levels positively correlated with handgrip strength (r=0.355; p<0.001) and appendicular skeletal muscle mass index (r=0.268; p=0.007). Receiver operating characteristic (ROC) curve analysis revealed that lower myostatin levels were associated with hospital mortality at the <2.20 ng/mL cut-off. Multiple logistic regression showed that higher serum myostatin levels were associated with reduced hospital mortality when adjusted by β blocker use (OR, 0.228; 95% CI, 0.054-0.974; p=0.046). Serum myostatin concentrations positively correlated with muscle mass and strength in STEMI patients. Further assessment of serum myostatin association with mortality should be conducted using a larger sample and assessing the additive value to the Global Registry of Acute Coronary Events (GRACE) or thrombolysis in myocardial infarction (TIMI) risk scores.


"It's Important to hear a Human Voice," Jews under COVID-19: An Oral History Project.
This article presents research notes on an oral history project on the impact of coronavirus disease 2019 (COVID-19) on Jews over the age of 65 years. During the first stage of the project, we conducted nearly 80 interviews in eight cities worldwide: Amsterdam, Berlin, London, Milan, New York, Paris, Rio de Janeiro, and St. Petersburg, and in Israel. The interviews were conducted in the spring of 2020 and reflect the atmosphere and perception of interviewees at the end of the first lockdown. Based on an analysis of the interviews, the findings are divided into three spheres: (1) the personal experience during the pandemic, including personal difficulties and the impact of the lockdown on family and social contacts; (2) Jewish communal life, manifested in changed functions and emergence of new needs, as well as religious rituals during the pandemic; and (3) perceived relations between the Jewish community and wider society, including relations with state authorities and civil society, attitudes of and towards official media, and the possible impact of COVID-19 on antisemitism. Together, these spheres shed light on how elderly Jews experience their current situation under COVID-19-as individuals and as part of a community. COVID-19 taught interviewees to reappraise what was important to them. They felt their family relations became stronger under the pandemic, and that their Jewish community was more meaningful than they had thought. They understood that online communication will continue to be present in all three spheres, but concluded that human contact cannot be substituted by technical devices.


Central visual field changes associated with acquired pits of the optic nerve.
With the increased use of a hand-held indirect lens and slit-lamp biomicroscopy for stereoscopic viewing of the optic nerve, the authors believe that an acquired pit of the optic nerve is more common than was recognized previously. This increased recognition has led to the awareness that the central visual field was affected frequently in the presence of such an acquired pit. The authors retrieved the charts of a series of 97 patients who had an acquired pit of the optic nerve during an 18-month period and retrospectively reviewed the automated visual fields associated with these pits using the Humphrey Visual Field Analyzer Programs 30-2 and 10-2 and looked for involvement of the central visual field. In 81.7% of the acquired pits of the optic nerves, one of the central-most test points (3 degrees from fixation) in the appropriate hemifield on the 30-2 format was depressed severely by Statpac II (P < 0.5). The authors therefore restudied as many patients as possible using the 10-2 format to determine the extent of central visual field involvement in the presence of an acquired optic nerve pit. Among these patients, the 10-2 format demonstrated that the approach of the defect to fixation varied, but was frequently inside 3 degrees, reaching between 1 degrees and 3 degrees from fixation in 96.7% of the eyes with depression of at least one central point on the 30-2 format. It was more likely that an acquired pit located at the inferior pole of the optic nerve would produce a visual field defect within 3 degrees of fixation than such a pit at the superior pole (P = 0.03). The authors showed that the presence of an acquired pit in an optic nerve damaged by glaucoma frequently is associated with a threat to fixation.