Microsatellite analysis of fecal DNA for colorectal cancer detection.
The advent of noninvasive methods of testing for colorectal cancer that have a high level of specificity and sensitivity is eagerly awaited. Thirty patients with sporadic colorectal cancer and 11 patients with hereditary nonpolyposis colon cancer (HNPCC) enrolled in this study. We analyzed the loss of heterozygosity (LOH) in matched genomic DNA extracted from blood and surgical specimens (tumor and tumor-free colonic mucosa), and the corresponding oral rinse and stool specimens using seven microsatellite loci (APC, p53, DCC, hMLH1, D9S162, D9S171, and IFNA). To reduce the normal colonocyte DNA contamination of the stool samples, we compared three different methods for fecal genomic DNA extraction. As normal controls, we analyzed the LOH using the oral rinse and stool samples from 15 individuals without cancer. The LOH determined from the oral rinse and the stool samples matched those determined from the blood and the neoplastic tissue. All patients with HNPCC had microsatellite alterations at hMLH-1 in tumor DNA and corresponding fecal DNA. There were significant differences in the frequency of p53-LOH and D9S171-LOH between the group with sporadic disease and those with HNSCC (P = 0.0031 and 0.0294, respectively). Two cases with D9S162-LOH were detected in individuals without cancer. For the patients with sporadic disease, using p53 and adenomatous polyposis coli (APC), the sensitivity of the fecal DNA analysis was 96.7% (95% CI, 83-100) with a specificity of 100%. We demonstrate that LOH analysis using oral rinse and stool samples may be a suitable screening tool for colorectal cancer.


Arsenic and other elements in drinking water and dietary components from the middle Gangetic plain of Bihar, India: Health risk index.
This study investigates the level of contamination and health risk assessment for arsenic (As) and other elements in drinking water, vegetables and other food components in two blocks (Mohiuddinagar and Mohanpur) from the Samastipur district, Bihar, India. Groundwater (80%) samples exceeded the World Health Organization (WHO) guideline value (10μg/L) of As while Mn exceeded the previous WHO limit of 400μg/L in 28% samples. The estimated daily intake of As, Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn from drinking water and food components were 169, 19, 26, 882, 4645, 14582, 474, 1449 and 12,955μg, respectively (estimated exposure 3.70, 0.41, 0.57, 19.61, 103.22, 324.05, 10.53, 32.21 and 287.90μg per kg bw, respectively). Twelve of 15 cooked rice contained high As concentration compared to uncooked rice. Water contributes (67%) considerable As to daily exposure followed by rice and vegetables. Whereas food is the major contributor of other elements to the dietary exposure. Correlation and principal component analysis (PCA) indicated natural source for As but for other elements, presence of diffused anthropogenic activities were responsible. The chronic daily intake (CDI) and health risk index (HRI) were also estimated from the generated data. The HRI were >1 for As in drinking water, vegetables and rice, for Mn in drinking water, vegetables, rice and wheat, for Pb in rice and wheat indicated the potential health risk to the local population. An assessment of As and other elements of other food components should be conducted to understand the actual health hazards caused by ingestion of food in people residing in the middle Gangetic plain.


Placebo-controlled randomised trial with liraglutide on magnetic resonance endpoints in individuals with type 2 diabetes: a pre-specified secondary study on ectopic fat accumulation.
The aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus. This study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m2) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported. The trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect -4.5 [95% CI -6.4, -2.6] kg). HbA1c declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol [8.4 ± 1.1% to 7.3 ± 1.2%]; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol [8.2 ± 1.0% to 7.5 ± 0.7%]; estimated treatment effect -2.9 [95% CI -8.1, 2.3] mmol/mol or -0.3 [95% CI -0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm2 to 203 ± 88 cm2; placebo 204 ± 63 cm2 to 200 ± 55 cm2; estimated treatment effect -7 [95% CI -24, 10] cm2), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm2 to 339 ± 131 cm2; placebo 329 ± 107 cm2 to 333 ± 125 cm2; estimated treatment effect -29 [95% CI -51, -8] cm2). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm2 to 9.1 ± 4.7 cm2; placebo 9.6 ± 4.1 cm2 to 9.6 ± 4.6 cm2; estimated treatment effect 0.2 [95% CI -1.5, 1.8] cm2). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect -2.1 [95% CI -5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of -0.1 (95% CI -0.4, 0.2)%. There were no adjudicated serious adverse events. Compared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study. ClinicalTrials.gov NCT01761318. This study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).


Structural Competency in Health Care.
The pandemics of COVID-19, systemic racism, and accelerating climate crises that have unfolded over the last 2 years highlight how social structures bear significant and disparate effects on individual health. The framework of structural competency offers a new way to understand and respond to health inequities in clinical care and health services delivery. Clinicians can work toward achieving structural competency at the individual, interpersonal, clinic, and community levels using the interventions described in the article.


Oxanthrone esters from the roots of Cassia kleinii.
From the roots of Cassia kleinii two new oxanthrone esters, kleinioxanthrone-3 and kleinioxanthrone-4 have been isolated. Their structures were established as 1,8-dihydroxy-3-methyl-9(10H)-anthracenone-10-oxyhexadecanoate 3 and 2,6,7-trihydroxy-1,8-dimethoxy-3-methyl-9(10H)-anthracenone-10-oxydecanoate 4 respectively based on degradative and spectroscopic evidence.


Characteristics of articulatory gestures in stuttered speech: A case study using real-time magnetic resonance imaging.
Most of the previous articulatory studies of stuttering have focussed on the fluent speech of people who stutter. However, to better understand what causes the actual moments of stuttering, it is necessary to probe articulatory behaviors during stuttered speech. We examined the supralaryngeal articulatory characteristics of stuttered speech using real-time structural magnetic resonance imaging (RT-MRI). We investigated how articulatory gestures differ across stuttered and fluent speech of the same speaker. Vocal tract movements of an adult man who stutters during a pseudoword reading task were recorded using RT-MRI. Four regions of interest (ROIs) were defined on RT-MRI image sequences around the lips, tongue tip, tongue body, and velum. The variation of pixel intensity in each ROI over time provided an estimate of the movement of these four articulators. All disfluencies occurred on syllable-initial consonants. Three articulatory patterns were identified. Pattern 1 showed smooth gestural formation and release like fluent speech. Patterns 2 and 3 showed delayed release of gestures due to articulator fixation or oscillation respectively. Block and prolongation corresponded to either pattern 1 or 2. Repetition corresponded to pattern 3 or a mix of patterns. Gestures for disfluent consonants typically exhibited a greater constriction than fluent gestures, which was rarely corrected during disfluencies. Gestures for the upcoming vowel were initiated and executed during these consonant disfluencies, achieving a tongue body position similar to the fluent counterpart. Different perceptual types of disfluencies did not necessarily result from distinct articulatory patterns, highlighting the importance of collecting articulatory data of stuttering. Disfluencies on syllable-initial consonants were related to the delayed release and the overshoot of consonant gestures, rather than the delayed initiation of vowel gestures. This suggests that stuttering does not arise from problems with planning the vowel gestures, but rather with releasing the overly constricted consonant gestures.


Case report: binding of a clinically relevant human leukocyte antigen-DQα-specific antibody in a kidney graft recipient is inhibited by donor-type human leukocyte antigen-DQβ chain.
In this case report, we have found what may be an immunization with donor-specific human leukocyte antigen (HLA)-DQα in combination with recipient-specific HLA-DQβ. A renal allograft recipient who did not comply with immunosuppressive therapy during pregnancy had graft failure 23 months posttransplantation with biopsy-proven humoral and cellular rejection. Sera were tested in a Luminex-based single-antigen bead assay. We compared Luminex reactivity with the degree of eplet mismatching between the recipient's own HLA-DQ chains and the HLA-DQ chains bound to the Luminex beads. Eplet calculations were done with the HLAMatchmaker. HLA-DQ similarities were compared further by dissimilarity scoring in HistoCheck. We observed that Luminex beads with donor-type HLA-DQα and HLA-DQβ bound less antibody than beads with donor-type HLA-DQα combined with recipient HLA-DQβ. In HLAMatchmaker, we identified all eplet mismatches between donor and recipient HLA-DQ. Next, we counted how many of these eplets were represented on the various Luminex beads. We found that antibody binding to the bead increased with the number of such mismatches for HLA-DQα. Surprisingly, antibody binding decreased as the number of eplet mismatches for HLA-DQβ increased, from a mean fluorescence intensity (MFI) value of 18,800 for no mismatched eplets to approximately 10,000 for 12 mismatched eplets. These findings were confirmed by comparing antibody binding with the structural dissimilarity score between the recipient HLA-DQ type and the HLA-DQ bound to the Luminex beads. In this patient, clinically relevant antibodies bound strongly to donor-like HLA-DQα chains when combined with recipient-like HLA-DQβ. HLA-DQβ chains more similar to those of the donor reduced the binding of donor- specific HLA-DQα antibody.


Targeted reaching with monocular depth information and haptic feedback: Comparing between monocular patients and normally sighted observers.
Monocular blindness impairs visual depth perception, yet patients seldom report difficulties in targeted actions like reaching, walking, or driving. We hypothesized that by utilizing monocular depth information and calibrating actions with haptic feedback, monocular patients can perceive egocentric distance and perform targeted actions. We compared targeted reaching in monocular patients, monocular-viewing, and binocular-viewing normal controls. Sixty observers reached either a far or a near target, calibrating reaches to the near target with accurate or false feedback while leaving reaches to the far target uncalibrated. Reaching accuracy and precision were analyzed. Results indicated no difference in reaching accuracy between monocular patients and normal controls; all groups initially underestimated distances before until calibration. Monocular patients responded to calibration sensitively, achieving accuracy in calibrated reaches and generalizing this effect to uncalibrated distances. Thus, with monocular depth information and haptic feedback, monocular patients could perceive distance and accomplish targeted reaching.


[Three examples of IPA implementation in medical-psychological centers].
The Paul-Guiraud Hospital Group has three advanced practice nurses (APNs) specializing in psychiatry and mental health who work in different medical-psychological centers. Supported by the institution, each APN project has been thought out by a multi-professional team within the structures, according to their specific needs.


Methods for correcting inference based on outcomes predicted by machine learning.
Many modern problems in medicine and public health leverage machine-learning methods to predict outcomes based on observable covariates. In a wide array of settings, predicted outcomes are used in subsequent statistical analysis, often without accounting for the distinction between observed and predicted outcomes. We call inference with predicted outcomes postprediction inference. In this paper, we develop methods for correcting statistical inference using outcomes predicted with arbitrarily complicated machine-learning models including random forests and deep neural nets. Rather than trying to derive the correction from first principles for each machine-learning algorithm, we observe that there is typically a low-dimensional and easily modeled representation of the relationship between the observed and predicted outcomes. We build an approach for postprediction inference that naturally fits into the standard machine-learning framework where the data are divided into training, testing, and validation sets. We train the prediction model in the training set, estimate the relationship between the observed and predicted outcomes in the testing set, and use that relationship to correct subsequent inference in the validation set. We show our postprediction inference (postpi) approach can correct bias and improve variance estimation and subsequent statistical inference with predicted outcomes. To show the broad range of applicability of our approach, we show postpi can improve inference in two distinct fields: modeling predicted phenotypes in repurposed gene expression data and modeling predicted causes of death in verbal autopsy data. Our method is available through an open-source R package: https://github.com/leekgroup/postpi.


Enhancement of stents using interference of low-frequency ultrasonic echo signals.
We set out to enhance the imaging of stents used for coronary coarctation surgery without imaging the reticulation of the stent. Because the stent is a reticulated structure, there is a relation between ultrasound wavelength and the interstice reticulation that produces the echo. First we performed computer simulation by ultrasound frequency of transmitted signals to analyze this relation. Then, instead of controlling the transmitted wave, we processed the returned signals through a band-pass filter because of the difficulty of controlling the transmitted waves of diagnostic ultrasound equipment. Following this, we conducted experiments on an agar gel phantom containing a stent to verify the effectiveness of this method. The simulation confirmed that the stent was apparent when the ultrasonic wavelength equaled the product of an integer and twice the interval of the reticulation of the stent. Application of a band-pass filter of 0.8 to 1.5 MHz to the waveform returned from the agar gel phantom containing the stent. The effectiveness of this method in depicting the stent was confirmed.


Prostate Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography in the Evaluation of Initial Response in Candidates Who Underwent Salvage Radiation Therapy after Radical Prostatectomy for Prostate Cancer.
We assessed predictors of short-term oncologic outcomes of patients who underwent salvage radiation therapy for biochemical recurrence after robot-assisted laparoscopic radical prostatectomy without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography. We retrospectively analyzed 194 patients with biochemical recurrence after robot-assisted laparoscopic radical prostatectomy who underwent prostate specific membrane antigen positron emission tomography/computerized tomography prior to salvage radiation therapy. Patients with lymph node or distant metastases on restaging imaging or at the time of extended pelvic lymph node dissection during robot-assisted laparoscopic radical prostatectomy were excluded, as were patients who received androgen deprivation therapy during or prior to salvage radiation therapy. A multivariable logistic regression analysis was performed to assess predictors of treatment response, defined as prostate specific antigen value ≤0.1 ng/ml after salvage radiation therapy. Overall treatment response after salvage radiation therapy was 75% (146/194 patients). On multivariable analysis, prostate specific antigen value at initiation of salvage radiation therapy (OR 0.42, 95% CI 0.27-0.62, p <0.001), pathological T stage (pT3a vs pT2 OR 0.28, 95% CI 0.11-0.69, p=0.006; pT3b vs pT2 OR 0.26, 95% CI 0.09-0.71, p=0.009) and local recurrent disease on imaging (OR 5.53, 95% CI 1.96-18.52, p=0.003) were predictors of treatment response. Salvage radiation therapy in patients without evidence of metastases on prostate specific membrane antigen positron emission tomography/computerized tomography showed a good overall treatment response of 75%. Higher treatment response rates were observed in patients with lower prostate specific antigen values at initiation of salvage radiation therapy, those with local recurrent disease on imaging and those with lower pathological T stage (pT2 vs pT3a/b).


Male reproductive health disorders among Aboriginal and Torres Strait Islander men: a hidden problem?
To better understand help-seeking behaviours and reproductive health disorders among Aboriginal and Torres Strait Islander men. A cross-sectional mixed-methods study conducted from 1 May 2004 to 30 April 2005 of 293 Aboriginal and Torres Strait Islander men aged 18 years and over from urban, rural and remote communities in the Northern Territory and Queensland. Subscale of the International Index of Erectile Function, self-reported help-seeking behaviours for erectile dysfunction (ED) and prostate disease, thematic analysis of semi-structured interviews and focus groups. The prevalence of moderate-to-severe ED increased across age groups, from about 10% in younger men (under 35 years) to 28% in men aged 55-74 years. Moderate-to-severe ED was strongly associated with reporting a chronic condition (odds ratio [OR], 3.67) and residing in a remote area (OR, 2.94). Aboriginal and Torres Strait Islander men aged 40-59 years showed similar low levels of help-seeking behaviours compared with non-Indigenous men from a comparable population-based study. About half of the men with ED saw a doctor or received treatment for ED in each population. While prostate cancer rates were low in both studies, testing for prostate problems was less frequent in Aboriginal and Torres Strait Islander men (11.4%) than in non-Indigenous men (34.1%, P < 0.001), despite similar levels of concern about prostate cancer. Barriers to help-seeking included shame, culturally inappropriate services and lack of awareness. This study, the first to investigate reproductive health of Aboriginal and Torres Strait Islander men, found low levels of help-seeking behaviours for reproductive health disorders, with implications for missing a predictor of chronic disease and late diagnosis of prostate disease.


Real-world study of ethnic differences in glycaemic control and clinical characteristics among insulin-naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England.
This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England. Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index. In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2 : White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (-0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient-years before the index to 3.37 events per 100 patient-years post index; event numbers were too low to be analysed by subgroup. Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.


Assessment of earthquake-induced landslide inventories and susceptibility maps using slope unit-based logistic regression and geospatial statistics.
Inventories of seismically induced landslides provide essential information about the extent and severity of ground effects after an earthquake. Rigorous assessment of the completeness of a landslide inventory and the quality of a landslide susceptibility map derived from the inventory is of paramount importance for disaster management applications. Methods and materials applied while preparing inventories influence their quality, but the criteria for generating an inventory are not standardized. This study considered five landslide inventories prepared by different authors after the 2015 Gorkha earthquake, to assess their differences, understand the implications of their use in producing landslide susceptibility maps in conjunction with standard landslide predisposing factors and logistic regression. We adopted three assessment criteria: (1) an error index to identify the mutual mismatches between the inventories; (2) statistical analysis, to study the inconsistency in predisposing factors and performance of susceptibility maps; and (3) geospatial analysis, to assess differences between the inventories and the corresponding susceptibility maps. Results show that substantial discrepancies exist among the mapped landslides. Although there is no distinct variation in the significance of landslide causative factors and the performance of susceptibility maps, a hot spot analysis and cluster/outlier analysis of the maps revealed notable differences in spatial patterns. The percentages of landslide-prone hot spots and clustered areas are directly proportional to the size of the landslide inventory. The proposed geospatial approaches provide a new perspective to the investigators for the quantitative analysis of earthquake-triggered landslide inventories and susceptibility maps.


Systematic investigation on the multi-scale mechanisms of bitter peptide self-assembly for flavor modulation.
Suppressing the aversive bitterness of bioactive peptides is an arduous task as it hinders product acceptability. Three acquisition modes (ddMS2, vDIA, and mDIA) of high-resolution mass spectrometry (HRMS) were designed for structure confirmation and accurate quantification of HPFLEWAR, with the mDIA mode chosen as optimum. HRMS and isothermal titration calorimetry was used to elucidate the mechanism that β-lactoglobulin self-assemble to form association complex in 1:1 stoichiometric ratio (ΔG value - 29.36 kJ mol-1), which automatically attracted HPFLEWAR and reduces its distribution in free form, downgraded the level of bitter perception. Proteomics experiments and molecular dynamics simulations was built to discovered that HPFLEWAR bound and stabilized in the negatively charged region of β-lactoglobulin via four hydrogen bonds (Lys69, Ile72, Asp53, and Glu74) and hydrophobic interactions. These findings were considered to give theoretical foundation for strictly controlling the bitter perception of peptides and the possible application of HPFLEWAR as new functional components.


Bone Marrow Stimulation for Osteochondral Lesions of the Tibial Plafond Yields Good Patient-Reported Outcomes in Daily Living but Moderate Outcomes in Sports Activities at 2- to 22-Years Follow-up.
The purpose of this study was to assess the patient-reported outcomes, as well as the revision and complication rates, of patients who underwent arthroscopic bone marrow stimulation (BMS) for an osteochondral lesion of the tibial plafond (OLTP). Patients with an OLTP treated with arthroscopic BMS at a minimum follow-up of 2-years were cross-sectionally included from a historical database. The primary outcome was the Numeric Rating Scale (NRS) during walking. Secondary outcomes included the NRS in rest and during running, and the Foot and Ankle Outcome Score. Additionally, the association of baseline patient and lesion demographics with follow-up patient-reported outcome measures (PROMs) was assessed with the Spearman rank correlation test. A subanalysis was performed for PROMs in patients with or without a coexisting talar (i.e., bipolar) lesion. Finally, the revision surgery (i.e., repeat surgery for the OLTP) and complication rates were assessed. Fifty-one patients were included at a mean 8.8 (standard deviation [SD] = 5.7, range, 2-22) years follow-up. Seventy-three percent of patients had a solitary OLTP, and 27% had a coexisting talar (bipolar) lesion. Males had a significantly higher rate of bipolar lesions compared to females (P ≤ .01), and patients with a bipolar lesion had a significantly larger OLTP lesion diameter (P = .02) and volume (P = .04). At final follow-up, the mean NRS during walking was 1.9 (SD = 2.3) out of 10. Anterior-posterior OLTP size (r = 0.36; P ≤ .01) was significantly associated with a higher NRS pain score during walking, although the presence of bipolar lesions did not result in inferior clinical outcomes. At final follow-up, 6% of patients underwent revision surgery. Minor complications were observed in 12% of patients. Arthroscopic BMS for OLTP results in favorable patient-reported outcomes at mid- to long-term follow-up, although moderate outcomes were observed in sports activities. Lesion size was associated with increased pain scores, although bipolar lesions did not result in inferior patient-reported outcomes. Six percent of patients required revision surgery, and 12% of patients had minor complications after surgery. Level III, retrospective cohort study.


Effects of cis-diamminedichloroplatinum (II) upon haemopoietic progenitors and the haemopoietic microenvironment in mice.
We studied the short- and long-term effects of a fractionated injection of cis-diamminedichloroplatinum (II) (CDDP) upon the haemopoietic stroma and the haemopoietic precursor cell compartment of young and adult mice. The integrity of the stromal microenvironment was investigated using three different assays including quantification of (a) the fibroblastoid progenitor cell compartment, (b) the regenerative capacity after subcutaneous implantation of spleen and femur, and (c) the growth of normal bone marrow progenitors in lethally irradiated CDDP-treated mice. CDDP treatment induced a slight anaemia which lasted for the observation period of 1 year, and could not be restored by infusion of normal bone marrow cells. The population size of haemopoietic progenitors was severely decreased immediately after CDDP treatment and the CFU-S recovery in the bone marrow was slow and temporary. Stromal function was significantly decreased and normalization occurred within approximately 40 d, depending on the stromal parameter measured. Subsequently, the regenerative capacity of the stroma showed a second decrease which was still detected at 1 year. This pattern of stromal damage has not been reported for any other cystostatic agent. Since the other two assays did not detect a second decrement in stromal integrity it is implied that the three stromal assays used detect different stromal functions. We conclude that CDDP treatment of both young and adult mice results in severe short-term damage and a late occurring secondary regenerative defect of the haemopoietic organ stroma.


Shoulder hemiarthroplasty for fracture with a conservative rehabilitation regime.
Standard rehabilitation regime following hemiarthroplasty for trauma is early mobilisation to prevent the development of a stiff shoulder. However, an aggressive early rehabilitation may lead to non-union of the greater tuberosity. We hypothesise that a delayed rehabilitation will result in a good union rate without undue risk of shoulder stiffness. Between December 1996 and June 2003, 40 patients with three or four part fracture of proximal humerus with or without dislocation, not amenable to open reduction and internal fixation underwent hemiarthroplasty with reconstruction of tuberosities and a conservative rehabilitation regime at our centre (age range of 39-92 with a mean of 68). Pathologic fractures and non-cooperative and/or demented patients were excluded. Patients were kept in a sling for 4 weeks before physiotherapy was commenced. They were reviewed at an average of 55 months (12-95) for assessment of pain, range of movement, activities of daily living and strength. Radiographs were taken to evaluate the union of the greater tuberosity. One patient lost to follow up. In 12.8% of the patients (mainly elderly, with mean age of 78.8) the greater tuberosity failed to heal. In those with a healed greater tuberosity the average elevation was more than 130 degrees , and the average external rotation was 40 degrees . A total of 51.3% of the patients had excellent results, 33.3% had satisfactory and 15.4% had unsatisfactory results. Postoperative immobilisation did not result in excessive stiffness and excellent functional results were achieved, especially in those younger than 70 years of age. However, tuberosity union could not be guaranteed in very old patients.


Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction.
It is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF). In this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. In the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and ≥5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models. The numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, ≥5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for ≥5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for ≥5 years; Pinteraction = 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for ≥5 years duration. Patients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180).


The spin-state transition of the hemochrome non-equilibrium conformation in partially reduced human methemoglobin. A pulse-radiolysis study of aqueous-methanol solutions of methemoglobin.
The effect of external parameters on the relaxation process of the hemochrome-type non-equilibrium conformation in partially reduced methemoglobin has been investigated. The relaxation of the intermediate ferrous low-spin state to the high-spin equilibrium conformation of hemoglobin appears to be facilitated particularly by protons and phosphate ions. In addition to studying the spin-state transition in aquomethemoglobin we have also studied it in complexes of the heme group in methemoglobin with fluoride, azide and cyanide anions.


Modification of energy-transfer processes in the cyanobacterium, Arthrospira platensis, to adapt to light conditions, probed by time-resolved fluorescence spectroscopy.
In cyanobacteria, the interactions among pigment-protein complexes are modified in response to changes in light conditions. In the present study, we analyzed excitation energy transfer from the phycobilisome and photosystem II to photosystem I in the cyanobacterium Arthrospira (Spirulina) platensis. The cells were grown under lights with different spectral profiles and under different light intensities, and the energy-transfer characteristics were evaluated using steady-state absorption, steady-state fluorescence, and picosecond time-resolved fluorescence spectroscopy techniques. The fluorescence rise and decay curves were analyzed by global analysis to obtain fluorescence decay-associated spectra. The direct energy transfer from the phycobilisome to photosystem I and energy transfer from photosystem II to photosystem I were modified depending on the light quality, light quantity, and cultivation period. However, the total amount of energy transferred to photosystem I remained constant under the different growth conditions. We discuss the differences in energy-transfer processes under different cultivation and light conditions.


Alpha-chymotrypsin-catalyzed peptide synthesis using N-protected D-amino acid carbamoylmethyl esters as acyl donors.
Alpha-chymotrypsin-catalyzed peptide synthesis was carried out between an N-protected D-amino acid ester and an L-amino acid amide (acyl donor, 10 mM; acyl acceptor, 50 mM; enzyme, 2 mg ml(-1); pH 8). By using a highly reactive carbamoylmethyl (Cam) ester as acyl donor, the D-amino acid was incorporated into the N-terminus of the resulting dipeptide amide. N-Protected dipeptide amides bearing D-amino acids such as D-Phe, D-Leu and D-Ala at their N-terminus were synthesized in high yields (up to 80%) in 1-3 h.


Effects of preceding stimulation on brain activation in response to colonic distention in humans.
It has been suggested that the pattern of distension (moderate following mild and vice versa) might influence brain activation and the experience of hypersensitivity, offset analgesia, and anticipation. Nevertheless, how the pattern of stimulation affects sensitization and/or desensitization to visceral stimulation remains unknown. In 45 nonclinical healthy participants (12 women, 33 men; 20-26 years old), brain processing of visceral sensation induced by colonic distension was examined using H2(15)O positron emission tomography. Subjective feelings regarding the stimuli were also measured. The descending colon was stimulated using six patterns of three bag pressures (0, 20, and 40 mm Hg). To evaluate the neural sensitization to visceral stimulation arising from the precedence effect, the effects of a 20- or 40-mm Hg distention after a sham or 20- or 40-mm Hg distension were analyzed using statistical parametric mapping. The level of significance was set at a voxelwise level of p < .0001, with cluster extent sizes of k > 50. The midbrain, insula, and cerebellum, were more strongly activated by a 20-mm Hg distension with a preceding 40-mm Hg distention than by a 20-mm Hg distention without a preceding stimulation (p < .0001). Conversely, a sham stimulation after the experience of an intense stimulation activated the midcingulate cortex, compared with a sham stimulation without the experience of actual visceral stimulation (p < .0001). By directly comparing different patterns of visceral stimuli, preceding visceral stimuli may affect neural sensitization and/or desensitization in humans, including elevated midbrain, insula, and midcingulate cortex.


Relationships between the life values of U.S. college students and their cognitive/affective responses to the threat of nuclear war.
The present study was designed to examine relationships between the life values of 399 U.S. college students and their nuclear war-related thoughts, feelings, and behaviors. The students completed four scales from the Life Values Inventory: (i.e. Conventionally Defined Success [CDS]; Religious Faith and Devotion [RFD]; Activist Pursuit of Social Causes [APSC]; Materialistic Orientation [MO]), the Satisfaction With Life Scale, four scales from the Nuclear War Inventory--Nuclear Distress; Salience; Weapons Opposition; Personal Efficacy--and a single behavioral measure of approach toward information concerning nuclear weapons. Consistent with theory regarding the influence of values and commitments on attitudes and behavior, APSC was found to be positively associated with all five nuclear war measures. Additionally, MO was negatively related to Personal Efficacy and Information Approach, and CDS was positively associated with Nuclear Distress. The only value dimension which covaried significantly with general life satisfaction was RFD. Results are discussed with respect to the recent rise in conservative and materialistically-oriented values among American college students.


Antidiabetic Action of Mcy Protein: Studies on Gene Expression and Competitive Binding to Insulin Receptors.
Mcy protein, isolated from the fruits of Momordica cymbalaria, was shown to have antihyperglycemic, antihyperlipidemic activities along with renal as well as hepatoprotective activities in streptozotocin-induced diabetic rats. Mcy protein was shown to have insulin-like structure and/or function and/or insulin secretagogue activity. Hence, the present study was conducted to elucidate the molecular mechanism whereby Mcy protein elicits its therapeutic role and also to know whether the Mcy protein has any structural and functional similarity with insulin. Results of our experiments revealed that the Mcy protein is insulin-like protein. Furthermore, we assessed the effect of treatment with Mcy protein on the glucose transport (levels of glucose transporter, GLUT-2) and on the levels of key regulators of glucose and lipid metabolisms like hepatic glucokinase (GK) and sterol regulatory element-binding protein-1c (SREBP-1c). Our findings demonstrated that Mcy protein elevated the expressions of GK, SREBP-1c, and GLUT-2 that were decreased in diabetic animals. Insulin-receptor binding studies using rat erythrocytes demonstrated that mean specific binding of insulin with insulin receptors was significantly increased in Mcy-treated diabetic rats when compared to diabetic control rats. Scatchard analyses of insulin binding studies yielded curvilinear plots, and the number of receptor sites per cell was found to be 180 ± 21.1 in Mcy-treated diabetic animals and found to be significantly superior to those of diabetic control animals. Kinetic analyses also revealed an increase in the average receptor affinity of erythrocytes of Mcy-treated rats compared to diabetic control rats suggesting acute alteration in the number and affinity of insulin receptors on the membranes of erythrocytes.


Polydopamine-based permanent coating capillary electrochromatography for auxin determination.
A novel, simple, and economical method for the preparation of open-tubular capillary column using polydopamine coating was reported for the first time. After the capillary was filled with dopamine solution for 20h, polydopamine was formed and deposited on the inner wall of capillary as permanent coating via the oxidation of dopamine by the oxygen dissolved in the solution. Moreover, the electroosmotic flow of the coated capillaries was measured to be dependent on the repetitive coating times. The performance of the polydopamine-coated capillary electrochromatography was validated by the analysis of four auxins, indole-3-butyric acid (IBA), 2,4-dichlorophenoxyacetic acid (dCPAA), indole-3-acetic acid (IAA), and phenoxyacetic acid (PAA). The precisions (RSD, n=5) were in the range of 1.6-2.4% for migration time, 4.0-6.5% for peak area response, and 3.6-4.7% for peak height response for the four auxins at 1microgmL(-1) level. The detection limits were 0.185, 0.172, 0.177, and 0.259microg/mL for IBA, dCPAA, IAA, and PAA, respectively. The method was successfully used to the determination of IAA in the culture media of IAA-producing bacteria.


A comparison of computerised strain gauge plethysmography with D-dimer testing in screening for deep-vein thrombosis.
There has been a significant increase in the amount of diagnostic testing performed to confirm or refute a diagnosis of deep-vein thrombosis (DVT), often in low-risk patients. D-dimer testing and computer-assisted strain gauge plethysmography (SGP) are rapid, inexpensive methods of excluding DVT and, in combination with a clinical probability score for DVT, both have been used to accurately exclude DVT. D-dimer testing, SGP and a combination of both in excluding DVT were compared in 243 ambulant outpatients who followed a prespecified investigation protocol. The negative-predictive value of D-dimer testing alone was 100%, 93.9% (95% CI 93.6-94.1) and 80% (95% CI 73.7-86.3) in patients with a low, moderate and high pretest probability (PTP) score for DVT respectively. The corresponding results for SGP were 95.6% (95% CI 95.5-95.7), 86.1% (95% CI 85.9-86.4) and 77.8% (95% CI 75.9-79.7) in patients with a low, moderate and high PTP score for DVT respectively. D-dimer testing provided a rapid, cost-effective method for excluding DVT in low-risk ambulant patients, which was superior to SGP. Combined use of the modalities did not improve any aspect of clinical decision making.


Renovascular hypertension treated by renal autotransplantation.
Renal autotransplantation is rarely performed by surgical procedure for the management of renovascular hypertension. We report 2 interesting cases of renovascular hypertension which were treated successfully by renal autotransplantation.


Psychometric properties of the English Food Cravings Questionnaire-Trait-reduced (FCQ-T-r).
Food cravings have been implicated in the development and maintenance of a range of eating- and weight-related pathology. The rapid and accurate assessment of food cravings is thus critical in clinical and research settings. Existing measures of specific food cravings are often not suitable for capturing the multiple facets of the craving experience. A short version of the Food Cravings Questionnaire-Trait (FCQ-T), the most widely used measure of general food cravings, was recently developed in German and shown to be a one-factorial, internally reliable measure. Other recent studies validated an Italian and Spanish version of the FCQ-T-reduced (FCQ-T-r) and successfully replicated its basic psychometrics. This study sought to examine the psychometric properties of the English version of the FCQ-T-r. Undergraduate students (n=610, 51.0% female, 53.9% white/Caucasian) completed a battery of questionnaires containing the FCQ-T-r and measures of specific food cravings, eating style, eating disorder symptoms, weight dissatisfaction, and impulsivity. Even though results of a confirmatory factor analysis suggested poor fit with a one-factorial model, the FCQ-T-r was found to be a one-factorial measure in both principal component and parallel analysis. The FCQ-T-r demonstrated excellent internal consistency reliability (Cronbach's α=.94), and scores were significantly and positively correlated with measures of specific food cravings, restrained eating, eating disorder symptoms, and impulsivity. More work is needed to confirm the factor structure of the English FCQ-T-r, but preliminary findings suggest that it constitutes a valid and reliable alternative to lengthier measures of general food cravings.


Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia.
Local hypoxia may be one of the triggers of embryonic reawakening of the stroma and subsequent hyperplastic growth in the prostate. Using a cell culture model of human prostatic stromal cells, we investigated the effects of hypoxia on activation of hypoxia-inducible factor 1 (HIF 1) and on the production of growth factors. Primary prostatic stromal cells were grown in normal and hypoxic (1% O(2)) atmosphere. Activation of HIF 1 was evaluated after different time intervals by Western blot. Induced secretion of growth factors VEGF, FGF-7, TGF-beta, IL 8, and FGF-2 were analyzed by ELISA. To confirm the in vitro findings we also performed immunohistochemistry of HIF 1alpha as well as pro-collagen I, collagens I, III, and IV in the benign tissue of radical prostatectomy specimens. HIF 1 is activated in a time-dependent manner, already starting 1 hr after exposure of stromal cells to hypoxic conditions. Secretion of VEGF, FGF-7, TGF-beta, FGF-2, and IL 8 is increased under hypoxic in vitro conditions in comparison to normoxia. Levels of TGF-beta, VEGF, and IL 8 were rapidly and statistically significantly increased in the supernatant of hypoxic cells. Consistent with the in vitro findings, immunohistochemistry of HIF 1alpha in (benign prostatic hyperplasia) BPH tissue revealed strong HIF 1alpha nuclear staining in hyperplastic areas. No difference was observed in the collagen pattern between hyperplastic and normal prostate tissue. Prostatic stromal cells respond to hypoxia by upregulation of secretion of several growth factors suggesting that hypoxia can trigger prostatic growth. Therefore, hypoxia might be a key factor contributing to the pathogenesis of BPH.


Fatty acid synthetase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from pigeon liver.
The kinetic mechanism of pigeon liver fatty acid synthetase action has been studied using steady state kinetic analysis. Initial velocity studies are consistent with an earlier suggestion that the enzyme catalyzes this reaction by a seven-site ping-pong mechanism. Although the range of substrate concentrations that could be used was limited by several factors, the initial velocity patterns showing the relationship between the substrates acetyl coenzyme CoA, malonyl-CoA, and NADPH appear to be a series of parallel lines, regardless of which substrate is varied at fixed levels of a second substrate. However, two of the substrates, acetyl-CoA and malonly-CoA, apparently exhibit a competitive substrate inhibition with respect to each other, but NADPH shows no inhibition of any kind. Product inhibition patterns suggest that free CoA is competitive versus acetyl-CoA and malonyl-CoA and is uncompetitive versus NADPH, and that NADP+ is competitive versus NADPH and uncompetitive versus acetyl-CoA or malonyl-CoA. These results are consistent with a seven-site ping-pong mechanism with intermediates covalently bound to 4'-phosphopantetheine (part of acyl carrier protein). Double competitive substrate inhibition by acetyl-CoA and malonyl-CoA is consistent with the rate equation derived for the over-all mechanism. The kinetic mechanism developed from these results is capable of explaining the formation of fatty acids from malonyl-CoA and NADPH alone (Katiyar, S. S., Briedis, A. V., and Porter, J. W. (1974) Arch. Biochem. Biophys. 162, 412-420) and also the formation of triacetic acid lactone from either malonyl-CoA alone or acetyl-CoA plus malonyl-CoA.


Role of the Anterior Cingulate Cortex in the Control of Micturition Reflex in a Rat Model of Parkinson's Disease.
In the current study we examined dynamic changes in neural activity of the anterior cingulate cortex and the midbrain periaqueductal gray during the micturition reflex in a Parkinson's disease model as well as the effects of direct stimulation of the anterior cingulate cortex on the micturition reflex. Electrodes were inserted in the anterior cingulate cortex or the periaqueductal gray. The effects of intravenous administration of the adenosine A2A receptor antagonist ZM24138 on pelvic nerve evoked field potentials were examined. The effect of electrical stimulation of the anterior cingulate cortex was also examined. Rats with Parkinson's disease showed bladder overactivity as evidenced by a significant decrease in the intercontraction interval compared with sham operated rats. Intravenous administration of ZM24138 increased the intercontraction interval in both groups with the inhibitory effects greater in rats with Parkinson's disease. It dose dependently increased the amplitude of evoked potentials in the anterior cingulate cortex of rats with Parkinson's disease but not in sham operated rats. Intravenous administration of ZM24138 decreased evoked potential amplitude in the periaqueductal gray of both groups with the inhibitory effects greater in Parkinson's disease vs sham operated rats. Electrical stimulation of the anterior cingulate cortex significantly increased the intercontraction interval. These results suggest that anterior cingulate cortex neurons have an inhibitory role in bladder control. Neural activity in the anterior cingulate cortex was significantly increased along with suppression of bladder overactivity after ZM241385 administration in the Parkinson's disease model and the stimulation of the anterior cingulate cortex inhibited the micturition reflex. Understanding the roles of the anterior cingulate cortex in the modulation of micturition could provide further insights into the pathophysiology of overactive bladder.


Correction to: Identification of emerging contaminants and their transformation products in a moving bed biofilm reactor (MBBR)-based drinking water treatment plant around River Yamuna in India.
The original version of this article unfortunately contains mistakes introduced during the production phase. Figures 7, 8, and 10 were incorrectly captured.


Microsurgical anatomy of the arteries of the pituitary stalk and gland as viewed from above.
The microsurgical anatomy of the arteries of the pituitary stalk and gland as viewed from above was studied in 50 adult cadaveric hemispheres using the operating microscope. There were three types of vessels to the pituitary from above: the superior hypophyseal artery originating from the internal carotid artery, the infundibular artery from the posterior communicating artery, and the prechiasmal artery from the ophthalmic artery. The superior hypophyseal artery originated from the medial to posterior aspect of the internal carotid artery. The average number of vessels of the superior hypophyseal artery was 2.2 per hemisphere, and the diameter was 0.25 mm on average. The majority (76%) of superior hypophyseal arteries arose from the proximal half of the segment between the origins of the ophthalmic and posterior communicating arteries of the internal carotid artery. The infundibular artery originated mainly from the medial side (69%) of the posterior communicating artery. Its diameter was 0.22 mm, and number 0.23 per hemisphere. The number of prechiasmal arteries was 0.06 per hemisphere. As a result, there were on average 2.5 vessels per hemisphere, totally 5 per brain, with the average diameter 0.25 mm, supplying the pituitary stalk and gland from above. The clinical application of these anatomical data to the diagnosis and treatment of suprasellar tumours and carotid-ophthalmic aneurysms is discussed.


The Coprinopsis cinerea septin Cc.Cdc3 is involved in stipe cell elongation.
We have identified and characterized a Coprinopsis cinerea mutant defective in stipe elongation during fruiting body development. In the wild-type, stipe cells elongate at the maturation stage of fruiting, resulting in very slender cells. In the mutant, the stipe cells fail to elongate, but become rather globular at the maturation stage. We found that the mutant phenotype is rescued by a gene encoding a homolog of Saccharomyces cerevisiae CDC3 septin, Cc.Cdc3. The C. cinerea genome includes 6 septin genes, 5 of which, including Cc.cdc3, are highly transcribed during stipe elongation in the wild type. In the mutant, the level of Cc.cdc3 transcription in the stipe cells remains the same as that in the mycelium, and the level of Cc.cdc10 transcription is approximately 100 times lower than that in the wild-type stipe cells. No increase in transcription of Cc.cdc3 in the mutant may be due to the fact that the Cc.cdc3 gene has a 4-base pair insertion in its promoter and/or that the promoter region is methylated in the mutant. Overexpressed EGFP-Cc.Cdc3 fusion protein rescues the stipe elongation in the transformants, localizes to the cell cortex and assembles into abundant thin filaments in the elongating stipe cells. In contrast, in vegetative hyphae, EGFP-Cc.Cdc3 is localized to the hyphal tips of the apical cells of hyphae. Cellular defects in the mutant, combined with the localization of EGFP-Cc.Cdc3, suggest that septin filaments in the cell cortex provide the localized rigidity to the plasma membrane and allow cells to elongate cylindrically.


Influence of wine-related physicochemical factors on the growth and metabolism of non-Saccharomyces and Saccharomyces yeasts in mixed culture.
The influence of two physicochemical factors involved in winemaking, temperature and SO(2), on the kinetics and metabolic behavior of Kloeckera apiculata and Saccharomyces cerevisiae was examined. Highest biomass was reached at 15 and 25 degrees C for K. apiculata and S. cerevisiae, respectively. Pure cultures of K. apiculata died off early with increasing temperature, but in co-culture with S. cerevisiae it showed higher viability and a change in the death curve from exponential to linear. Statistical analysis revealed that metabolite production was significantly different for the three cultures and also at the different fermentation temperatures. Besides, the interaction between culture type and temperature was significant. At temperatures from 15 to 30 degrees C the mixed culture showed similar ethanol and lower acetic acid production compared with a pure culture of K. apiculata. SO(2) addition slightly increased survival of the non-Saccharomyces species in pure and mixed cultures. Statistical evaluation indicated that culture type and SO(2) addition significantly affected metabolite production, but the interaction between culture and SO(2) was not significant. These results contribute to current knowledge of enological factors and their effect on prevalence and fermentative activities of the composite yeast flora and the statistical significance emphasizes the importance of the combined influence of the culture type and physicochemical factors on the production of fermentation metabolites.


Bifunctional Lewis Base Catalyzed Asymmetric N-Allylic Alkylation of 2-Hydroxypyridines.
A chiral Lewis base catalyzed enantioselective N-allylic alkylation of 2-hydroxypyridines and MBH carbonates is documented, affording a convenient access to N-alkylated 2-pyridones with up to 99% ee and 99% yield. Experimental and computational studies have revealed that the strong hydrogen bond interaction between the chiral Lewis base catalyst and 2-hydroxypyridines plays a crucial role in this reaction for the reactivity, chemoselectivity, and enantioselectivity.


Overall survival from breast cancer in women pregnant or lactating at or after diagnosis. Auckland Breast Cancer Study Group.
The effect of concurrent or subsequent pregnancy or lactation has been studied in women with breast cancer to determine if these variables influence prognosis. Information was collected from 382 women potentially capable of bearing children, aged less than 45 years, in the Auckland Breast Cancer Study Group data file, a consecutive series of women diagnosed with breast cancer from 1976 to 1985, with a median follow-up of 10.2 years. The prevalence of both pregnancy at diagnosis and lactation at diagnosis was 2.6%. The incidence of pregnancy subsequent to diagnosis was 3.9%. Women pregnant at the time of breast cancer diagnosis had significantly more advanced disease than non-pregnant patients, and there was a similar trend for women lactating at diagnosis. Overall survival in these women was poor compared with the non-pregnant and non-lactating groups; only 2 of 10 pregnant patients and 0 of 10 lactating patients survived more than 12 years. The adverse outcome for women lactating at diagnosis of their breast cancer persisted despite allowance for nodal status, tumour size and age. However, survival was similar between pregnant and non-pregnant patients when these variables were taken into account. No significant differences in survival were found between those women who had pregnancies subsequent to diagnosis of breast cancer and breast cancer patients who did not become pregnant.


Evaluation of topical therapy with silver-kaolin (Argostop) in an experimental model of burn wound sepsis.
Burn wound therapy with silver-kaolin, a topical agent applied as an aerosol spray, was evaluated in male rats given a 20 per cent total body surface area, full thickness dorsal scald burn. Burn wounds treated with silver-kaolin healed at rates comparable to untreated wounds. No significant differences were noted in the numbers or types of organisms colonizing the wounds of treated and untreated rats at 5, 12 and 19 days post-burn. To evaluate the effectiveness of silver-kaolin in treating burn wound sepsis, rats were inoculated on the wound surface with 2.5 x 10(8) Pseudomonas aeruginosa. This inoculum resulted in 100 per cent mortality in untreated rats. Rats treated with silver-kaolin had a mortality rate of 71 per cent, compared to a 9 per cent mortality rate in rats treated with 1 per cent silver sulphadiazine. When silver-kaolin was applied to the wound prior to bacterial inoculation, the mortality rate was reduced to 6 per cent. When wounds were treated with kaolin alone and then inoculated with bacteria, the mortality rate was 50 per cent, indicating that part of the effectiveness of silver-kaolin appeared to be due to a barrier effect. These results indicate that silver-kaolin may be useful for preventive topical antimicrobial therapy of acute burns or after wound debridement or excision, but is not suitable for therapy of wounds previously colonized by microorganisms.


Solitary mycosis fungoides: a distinct clinicopathologic entity with a good prognosis: a series of 15 cases and literature review.
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), accounting for almost 50% of all primary cutaneous lymphomas. The occurrence of solitary lesions, which are clinically and histopathologically indistinguishable from classic MF has been described. We describe 15 cases of solitary MF and discuss the relationship to classic MF, "reactive" processes and to other, rarer forms of CTCL that may present with solitary lesions. We conducted a retrospective chart review and a PubMed search to identify all reported cases of solitary MF to date, as well as information about other CTCLs presenting as a solitary lesion. Fifteen patients were identified. Follow-up data were available on 10 patients with a median follow-up of 10 months (range, 1 to 48 months). Clinical, pathological, immunocytochemical, and molecular-genetic features were analyzed. Five cases were diagnosed as folliculotropic MF (FMF). Of the 10 cases with follow-up, 2 were treated with topical steroids, 2 were completely excised, 5 received radiotherapy, and 1 received tacrolimus. One hundred twenty-eight cases of solitary MF were identified in the literature and reviewed for commonalities to and differences with our cases and other CTCLs. This study was retrospective; follow-up data were not available in some cases and were only short term in others. Solitary MF appears to have a good prognosis. In lesions that are not completely excised, curative radiotherapy can be used. Long-term follow up is advised.


Foliar-applied silicon and selenium nanoparticles modulated salinity stress through modifying yield, biochemical attribute, and fatty acid profile of Physalis alkekengi L.
Soil salinity is a major environmental problem owing to its negative impact on agricultural productivity and sustainability. Nanoparticles (NPs) have recently been highlighted for their ability to alleviate salinity stress. The current study aimed to alleviate salt stress by using silicon (Si) and selenium (Se) NPs on the growth and physiological attributes of Physalis alkekengi L. Plants were irrigated with saline water at 50, 100, and 200 mM NaCl, and Si NPs (200 mg L-1) and Se NPs (50 mg L-1) were sprayed on leaves three times in a pot experiment in 2022. Leaf chlorophyll (Chl) content, antioxidant capacity, and fatty acid (FA) profile of fruits were measured to find the effects of NPs and salinity in the plants. Salinity at 50 mM did not significantly differ from the control, but at 100-200 mM, salt stress had a substantial impact on the majority of traits. Compared with non-saline conditions, 200 mM NaCl led to decreases in shoot weight (40%), fruit weight (30%), Chl a (30%), Chl b (39%), anthocyanin (31%), ascorbic acid (16%), total phenolic content (TPC, 11%) but increases in total soluble solids (TSS, 79%), titration acidity (TA, 17%), and TSS/TA (52%) in plants without spraying the NPs. However, Si and Se NPs modulated salinity stress by increasing shoot and fruit weight, Chl content, anthocyanin, and TPC, and with decreasing TSS and TSS/TA. Salinity elevated polyunsaturated fatty acids (PUFAs) and lowered monounsaturated fatty acids (MUFAs). According to multivariate analysis, 50 mM and control were found to be in the same cluster, whereas 100 and 200 mM were shown to be in different clusters. Foliar application of Si and Se NPs at 200 and 50 mg L-1, respectively, can be recommended for mitigating salt stress at 100-200 mM NaCl in P. alkekengi L. Plants. Farmers can use the findings to increase the ability of Si and Se NPs to protect plants against salt.


Determining optimal population monitoring for rare butterflies.
Determining population viability of rare insects depends on precise, unbiased estimates of population size and other demographic parameters. We used data on the endangered St. Francis' satyr butterfly (Neonympha mitchellii francisci) to evaluate 2 approaches (mark-recapture and transect counts) for population analysis of rare butterflies. Mark-recapture analysis provided by far the greatest amount of demographic information, including estimates (and standard errors) of population size, detection, survival, and recruitment probabilities. Mark-recapture analysis can also be used to estimate dispersal and temporal variation in rates, although we did not do this here. Models of seasonal flight phenologies derived from transect counts (Insect Count Analyzer) provided an index of population size and estimates of survival and statistical uncertainty. Pollard-Yates population indices derived from transect counts did not provide estimates of demographic parameters. This index may be highly biased if detection and survival probabilities vary spatially and temporally. In terms of statistical performance, mark-recapture and Pollard-Yates indices were least variable. Mark-recapture estimates were less likely to fail than Insect Count Analyzer, but mark-recapture estimates became less precise as sampling intensity decreased. In general, count-based approaches are less costly and less likely to cause harm to rare insects than mark-recapture. The optimal monitoring approach must reconcile these trade-offs. Thus, mark-recapture should be favored when demographic estimates are needed, when financial resources enable frequent sampling, and when marking does not harm the insect populations. The optimal sampling strategy may use 2 sampling methods together in 1 overall sampling plan: limited mark-recapture sampling to estimate survival and detection probabilities and frequent but less expensive transect counts.


Dermoid cyst mimicking hematoma in the posterior fossa.
Intracranial dermoid cysts are usually reported to be associated with long lasting or waxing-waning symptoms. Computer tomography (CT) scans usually depict such neoplasms as well-defined areas of low density. This report is about a case of a dermoid cyst, the acute clinical features and CT hyperdensity of which mimicked a hematoma in the posterior fossa. The association of acute onset with CT hyperdensity makes this case of dermoid cyst very unusual.


Anti-inflammatory effect of sinomenine by inhibition of pro-inflammatory mediators in PMA plus A23187-stimulated HMC-1 Cells.
Sinomenine is an alkaloid compound and a prominent anti-inflammatory agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the mechanism of human mast cell line (HMC)-1-mediated inflammation remained unknown. To provide insight into the biological effects of sinomenine, we examined its influence on the pro-inflammatory cytokine production in HMC-1 cells stimulated by phorbol 12-myristate-13-acetate (PMA) plus A23187 by evaluating the stimulated cells in the presence or absence of sinomenine. In the present study, the pro-inflammatory cytokine production was measured using ELISA, Reverse Transcription-polymerase chain reaction (RT-PCR) and nuclear factor (NF)-kappaB, mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Also, cyclooxygenase (COX)-2 expression was measured through Western blot and RT-PCR analysis. Sinomenine inhibited the pro-inflammatory cytokine production induced by PMA plus A23187 in a dose-dependent manner. Furthermore, sinomenine inhibited the phosphorylations of extracellular signal-regulated kinase (ERK) and p38 MAPKs as well as the translocation of NF-kappaB p65 through reduced IkappaBalpha degradation. In addition, sinomenine suppressed COX-2 protein and mRNA expression dose-dependently. Taken together, the results of this study indicate that the anti-inflammatory effects of sinomenine may occur via the inhibition of pro-inflammatory cytokine and COX-2 production through the inhibition of MAPKs and NF-kappaB pathway activation by PMA plus A23187 stimulation in HMC-1 cells.


Colitis and lower abdominal mass by Actinomyces israelii in a patient with an IUD.
Abdominal actinomycosis is a rare disorder. The diagnosis is frequently missed preoperatively. We describe a patient who had had an intrauterine contraceptive device in situ for 5 years. She presented with a painful pelvicoabdominal mass, located between the uterus and rectum, and a colitis-like disease of the distal colon. Culture of the removed IUD demonstrated Actinomyces. She was intensively treated with intravenously penicillin for six weeks. Following this conservative treatment the abdominal tumor and the colitis-like symptoms totally disappeared. During two years follow-up she is free of symptoms and no signs of recurrence of the disease have been noticed. The case described here strongly underlines that Actinomyces infection should be born in mind in the differential diagnosis of a young female with an IUD, presenting with colitis, fever and an abdominal mass. Prolonged intravenously administered penicillin is warranted before surgery should be considered.


Depression symptoms in boys with autism spectrum disorder and comparison samples.
This study compares severity of specific depression symptoms in boys with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), or chronic multiple tic disorder (CMTD) and typically developing boys (Controls). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 (CSI-4) and a demographic questionnaire. Mothers' and teachers' ratings generally indicated the most severe symptoms in boys with ASD ± ADHD. Associations of depression with ASD severity and IQ varied considerably for specific symptoms of depression, ASD functional domain, and informant. Findings provide additional support for the differential influence of neurobehavioral syndromes on co-occurring symptom severity and illustrate how more fine-grained analyses of clinical phenotypes may contribute to a better understanding of etiology and current nosology.


Impaired gap junction formation and intercellular calcium signaling in urinary bladder cancer cells can be improved by Gö6976.
Calcium wave propagation and connexin 26, 32 and 43 expression were studied in normal and malignant urothelial cells. Human urothelial cell cultures were established from tissue biopsies obtained from three healthy control persons and compared to human transitional cell carcinoma (TCC) cell line 5637. Fluo-3 was used to study intercellular calcium signaling in urothelial cells. The cells were stimulated mechanically in the presence of inhibitors of gap-junctional or ATP-mediated communication to determine which pathways are operative in intercellular calcium signaling. In addition, Gö6976 was used to determine the effects of PKC alpha and betaI inhibition on intercellular calcium signaling. In normal urothelial cells, the primary pathway for intercellular calcium mediated cell signaling was gap junctional intercellular communication (GJIC), but the paracrine ATP-mediated signaling was also operative. In 5637 TCC cells, GJIC and ATP-mediated signaling routes were altered when compared to normal urothelial cells. More specifically, inhibition of GJIC resulted in a complete block of intercellular calcium signaling, while inhibition of ATP-mediated signaling decreased signal transduction in 5637 TCC cells. The results of the present study also demonstrated that connexin 26 was the most abundant gap junction plaque protein in cultured normal human urothelial cells and that it did not form gap junction plaques in 5637 TCC cell culture. Treatment with Gö6976 induced gap junction plaque formation by connexin 26 in 5637 TCC cells. In addition, the exposure to Gö6976 enhanced intercellular calcium mediated signaling in 5637 TCC cells, but not in normal cells. The results of the present study suggest that gap junctions play a major role in intercellular calcium signaling in urothelial cells. In addition, intercellular calcium signaling is altered in urinary bladder carcinoma cells, and it can be improved by PKC alpha and betaI inhibition. (Supplementary materials are available for this article. Go to the publisher's online edition of Cell Communication and Adhesion for the following free supplemental resources; Movie files of Fig. 2normal Gö6976-, normal Gö6976+, TCC Gö6976-, TCC Gö6976+ and image of Supplementary Figure 1).


Reproducibility of right ventricular function by longitudinal strain and other echocardiographic parameters in the ELSA-Brasil study.
Right ventricular (RV) free wall longitudinal strain (RVFWLS), and four-chamber longitudinal strain (RV4CLS) using speckle tracking echocardiography have demonstrated increased accuracy and discrimination to measure right ventricular function in different clinical conditions. Reproducibility data of these measures are scarce and mainly tested in small or reference populations. The main objective of this study was to investigate their reproducibility, and of other traditional RV parameters, from unselected participants of a large cohort study. RV strain reproducibility was analyzed using echocardiographic images of 50 participants from a randomly selected sample from The ELSA-Brasil Cohort. Images were acquired and analyzed following the study protocols. The mean RVFWLS was - 26.9 ± 2.6% and the mean RV4CLS was - 24.4 ± 1.9%. The intra-observer reproducibility parameters of RVFWLS demonstrated a coefficient of variation (CV) of 5.1% and an intraclass correlation coefficient (ICC [95%CI] 0.78[0.67-0.89]), and for RV4CLS were CV = 5.1% and ICC = 0.78[0.67-0.89]. Reproducibility for RV fractional area change was CV = 12.1%; ICC = 0.66 [0.50-0.81] and for RV basal diameter was CV = 6.3%; ICC = 0.82 [0.73-0.91]. The inter-observer reproducibility for RVFWLS was CV = 8.3%; ICC 0.54[0.34-0.74] and for RV4CLS, CV = 6.3%; ICC = 0.53[0.34-0.73], following the same pattern among conventional RV parameters. We found adequate reproducibility of RV longitudinal strain parameters. This information is relevant for the long-term follow-up of cohort participants and reinforces the utility of RV longitudinal strain as a tool to monitor subclinical changes in RV systolic function.


Determining the effectiveness of cognitive behavioral therapy interventions based on the transdiagnostic approach in the treatment of common mental health problems: Presenting an experience from the Islamic Republic of Iran.
There is growing support to develop transdiagnostic approaches that provide new insights into mental health problems and cut across the existing traditional diagnostic boundaries all over the world. The present study was conducted to test the transdiagnostic cognitive behavioral therapy (TCBT) approach in treating patients with common mental health problems and evaluate its effectiveness compared to the current treatment settings of the healthcare system. A randomized controlled trial was conducted in Semnan Province, north of Iran. The study took pace in urban health centers. A sample of 520 Iranian adults, tested as positive on the Kessler Psychological Distress Scale, were enrolled. Participants who received a score above the cut-off point in any of the three mental health disorders (depression, anxiety, or obsessive compulsive disorder [OCD]) based on the locally validated study instrument were randomly allocated to the study. The intervention group received TCBT during eight sessions provided by trained general health service providers without previous mental health training; the standby control group received Mental Health Services as Usual (MHSU). The post-test interviews were conducted using the study instrument after the completion of both group treatments. A total of 459 individuals (87.8% female) ultimately entered the study. The withdrawal rate was 24% (53 participants in the TCBT and 56 in the MHSU). Reduction in depression, anxiety, and OCD symptoms was significant within each group and when comparing TCBT and MHSU (mean difference). This trial recommends that the transdiagnostic CBT approach can be effective in improving common mental health problems and functions among individuals by trained general healthcare providers in the primary healthcare system. The results can be more useful in decision making when defining the process of providing mental healthcare in the National Primary Healthcare System.


The retinoic acid receptor-related orphan nuclear receptor γ1 (RORγ1): a novel player determinant of insulin sensitivity in morbid obesity.
The orphan nuclear receptors (ONRs), retinoic acid receptor-related orphan receptor γ-1 (RORγ1) and peroxisome proliferator-activated receptor γ-2 (PPARγ2), are central mediators controlling adipocyte (AD) differentiation. Through their distinct tissue distribution and specific target gene activation, ONRs control diverse aspects of fatty acid metabolism and insulin sensitivity. Adding further complexity, obesity begets resistance to insulin signals and can ultimately result in diabetes. In this study, we investigate whether there are differences in the RORγ1 and PPARγ2 expression in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbid obesity (MO) individuals either insulin resistant (high-IR MO) or insulin sensitivity (low-IR MO). Our results indicate for the first time in human the RORγ1 mRNA and protein expression levels and activation with coactivator, such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) were higher in the VAT from high-IR MO. In contrast, PPARγ2 expression and activation were higher in the VAT from low-IR MO. In this way, we have also found a positive association between RORγ1 mRNA and protein expression with many components of metabolic syndrome, with a strong dependence of insulin and HOMA(IR) index in VAT, but not in SAT. Our data suggest that RORγ1 may be added to the growing list of nuclear receptors in adipose tissue use to modulate the insulin resistance associated to the obesity. Measurement of RORγ1 and PPARγ2 in adipose tissue might be useful for evaluating the outcomes of various clinical interventions for obesity-related diabetes type II.


Neisseria gonorrhoeae triggers the PGE2/IL-23 pathway and promotes IL-17 production by human memory T cells.
PGE2 is a potent modulator of the T helper (Th)17 immune response that plays a critical role in the host defense against bacterial, fungal and viral infections. We recently showed high serum levels of interleukin (IL)-17 in patients with gonococcal infection and we hypothesized that Neisseria gonorrhoeae could exploit a PGE2 mediated mechanism to promote IL-17 production. Here we show that N. gonorrhoeae induces human dendritic cell (DC) maturation, secretion of prostaglandin E2 and proinflammatory cytokines, including the pro-Th17 cytokine IL-23. Blocking PGE2 endogenous synthesis selectively reduces IL-23 production by DC in response to gonococcal stimulation, confirming recent data on PGE2/IL-23 crosstalk. N. gonorrhoeae stimulated DC induce a robust IL-17 production by memory CD4(+) T cells and this function correlates with PGE2 production. Our findings delineate a previously unknown role for PGE2 in the immune response to N. gonorrhoeae, suggesting its contribute via Th17 cell expansion.


Complete healing of ulceration within a gastric leiomyoma.
A case of an ulcerated, bleeding gastric leiomyoma is presented in which a follow-up UGI examination showed no evidence of residual ulceration within the tumor. Radiologists should be aware that it is occasionally possible to document complete healing of ulceration within a gastric leiomyoma and that conservative medical management may be an alternative when surgical resection cannot be performed.


Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia.
Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound loss of galactose-1-phosphate uridylyltransferase (GALT). CG is detected by newborn screening (NBS) in many countries; however, conclusive diagnosis can be complex due to broad and overlapping ranges of GALT activity. Molecular studies can also be complex due to allelic heterogeneity at the GALT locus. We conducted both biochemical and molecular follow-up studies for an infant flagged by NBS for possible galactosemia. To clarify the diagnosis we also conducted biochemical and RNA studies of lymphoblasts prepared from the child and one parent. We identified a novel noncoding GALT variant, c.377+17C>T, that was homozygous in the child and heterozygous in both parents. The child and both parents also showed diminished GALT activity in red blood cells, and transformed lymphoblasts from the child and one parent further showed diminished GALT activity. However, qRT-PCR studies demonstrated apparently normal GALT mRNA levels in lymphoblasts, and Gal-1P values measured in the child following galactose exposure in infancy and at 1 year were normal. These results highlight the existence of rare but apparently benign variants in GALT and underscore the need for functional studies to distinguish pathogenic from benign variants.


Learning from the early careers of master clinicians.
Master clinicians are recognized as multidimensional experts in clinical medicine. Studying their formative clinical activities could generate insights to guide medical trainees and early career clinicians. To investigate which early career activities were adopted more commonly by master clinicians than their matched peers and to characterize master clinicians' early career activities across institutions and specialties. We surveyed master clinicians at seven medical centres about their early career activities. For master clinicians in the Department of Medicine (DOM), we also surveyed matched internist peers. Of 150 master clinician respondents, 65% were internists (DOM); 35% practiced in other specialties. Compared to their internist peers, there was a trend toward internist master clinicians reading more about their patients' conditions (6.0 vs. 4.8 h per week), reading more case reports (4.0 vs. 2.1 per month), engaging in more frequent teaching duties and devoting less time to research. The early career activities identified in this study can be adopted by clinicians pursuing clinical excellence and promoted by training programs that seek to foster life-long learning.


Onlay frontal cranioplasty using wire reinforced methyl methacrylate.
Methyl methacrylate is a biologically inert alloplastic material that is commonly used to rebuild the calvarial vault. Since methyl methacrylate does not permit tissue incorporation it is susceptible to displacement and/or fracture. In order to increase the tensile strength of methyl methacrylate onlay cranioplasties, we use wire reinforced masonry techniques. A 56-year-old female presents with forehead asymmetry due to displacement and fracture of a silicone alloplastic implant. This patient, treated with onlay wire reinforced methyl methacrylate, demonstrates the utility of this novel technique. Wire is passed through 2-mm outer cortex tunnels like spokes on a wheel, around the perimeter of the defect to form a rebar grid. Methyl methacrylate is poured onto the rebar grid and contoured after it solidifies. Wire reinforced methyl methacrylate is a simple technique to improve the tensile strength of calvarial alloplastic reconstructions.


Inoperable and recurrent carcinoma of the rectum and rectosigmoid. Aspects of radiation treatment and prognosis.
35 patients treated with radiotherapy for recurrent (23) or primarily inoperable (12) rectal or rectosigmoid carcinoma are presented. The radiation treatment was delivered in 28 cases with megavoltage equipment, in two cases with a conventional X-ray unit and in seven cases with intracavitary radium or cathetron applications. 17 of the patients (49%) lived for more than one year. Six patients from the recurrent cases lived (26%) for more than two years, and four patients (17%) survived three years. Relief of symptoms was observed in at least 20 cases. The importance of early diagnosis of recurrent tumor is stressed especially in the follow-up of Dukes' A and B groups.


Association of Caffeine and Hearing Recovery After Acoustic Overstimulation Events in a Guinea Pig Model.
Noise-induced hearing loss is an increasingly worrisome problem. Although caffeine intake is common in people involved in noise-related environments, the effect of caffeine on the recovery of hearing after a temporary threshold shift requires further understanding. To determine whether caffeine impairs hearing recovery in a guinea pig model exposed to acoustic overstimulation. This experiment at the McGill University Auditory Sciences Laboratory used 24 female albino guinea pigs (age, 6 months; weight, 500-600 g) divided randomly into 3 groups of 8 animals each. Group 1 was exposed to caffeine; group 2, acoustic overstimulation events (AOSEs); and group 3, both. Data were collected from July 1, 2013, to March 30, 2014, and analyzed from April 1 to August 1, 2014. Daily caffeine dose for groups 1 and 3 consisted of 25 mg/kg administered intraperitoneally for 15 days. The AOSEs were administered on days 1 and 8 and consisted of 1 hour of 110-dB pure-tone sound. Serial auditory brainstem response (ABR) tests to determine the audiological threshold shift and recovery were obtained at baseline and on days 1 (1 hour after the first AOSE), 4, 8 (before and 1 hour after the second AOSE), 11, and 15. Scanning electron and light microscopy of the cochleas were performed to determine morphologic changes. The day 1 post-AOSE measurement resulted in a similar threshold shift in all animals in groups 2 and 3 at all frequencies tested (8, 16, 20, and 25 kHz). The maximum threshold shift was at 16 kHz, with a mean of 66.12 dB. By day 8, the threshold shift in group 2 recovered completely at all frequencies except 20 kHz, where a mean threshold shift of 20.63 dB of sound pressure level (SPL) was present. Hearing impairment in group 3 persisted in 8-, 16-, and 25-kHz frequencies with thresholds of 21.88, 28.13, and 26.25 dB SPL, respectively (P = .001). After a second AOSE at day 8, similar threshold shift and outcome were recorded on day 15 compared with day 8, with a mean threshold shift at 20 kHz of 29.38 dB SPL in group 2 and mean threshold shifts at 8, 16, 20, and 25 kHz of 29.38, 35.63, 40.63, and 38.75 dB SPL, respectively, in group 3. The difference in ABR threshold recovery was in concordance with scanning electronic and light microscopy findings for each group. A daily dose of caffeine was found to impair the recovery of hearing after an AOSE.


Ultrasound-assisted enzymatic hydrolysis for iodinated amino acid extraction from edible seaweed before reversed-phase high performance liquid chromatography-inductively coupled plasma-mass spectrometry.
The combination of reverse phase high performance liquid chromatography (RP-HPLC) with inductively coupled plasma mass spectrometry (ICP-MS) was used for the determination of monoiodotyrosine (MIT) and diiodotyrosine (DIT) in edible seaweed. A sample pre-treatment based on ultrasound assisted enzymatic hydrolysis was optimized for the extraction of these iodinated amino acids. Pancreatin was selected as the most adequate type of enzyme, and parameters affecting the extraction efficiency (pH, temperature, mass of enzyme and extraction time) were evaluated by univariate approaches. In addition, extractable inorganic iodine (iodide) was also quantified by anion exchange high performance liquid chromatography (AE-HPLC) coupled with ICP-MS. The proposed procedure offered limits of detection of 1.1 and 4.3ngg(-1) for MIT and DIT, respectively. Total iodine contents in seaweed, as well as total iodine in enzymatic digests were measured by ICP-MS after microwave assisted alkaline digestion with tetramethylamonium hydroxide (TMAH) for total iodine assessment, and also by treating the pancreatin extracts (extractable total iodine assessment). The optimized procedure was successfully applied to five different types of edible seaweed. The highest total iodine content, and also the highest iodide levels, was found in the brown seaweed Kombu (6646±45μgg(-1)). Regarding iodinated amino acids, Nori (a red seaweed) was by far the one with the highest amount of both species (42±3 and 0.41±0.024μgg(-1) for MIT and DIT, respectively). In general, MIT concentrations were much higher than the amounts of DIT, which suggests that iodine from iodinated proteins in seaweed is most likely bound in the form of MIT residues.


Environmental sustainability assessment due to stone quarrying and crushing activities in Jaflong, Sylhet.
Quarrying and crushing activities constitute a major threat to the environment and occupational health of the workers in Jaflong, Sylhet. This study aims to determine the environmental sustainability of stone quarrying and crushing activities considering four dominant environmental components, viz. physicochemical parameters of water, PM2.5 and PM10, sound, and land use land cover (LULC). Water quality was measured in a seasonal variation, and air and sound data were collected in an 8-h period of every weekday of 2 months while LULC data were also collected from 1999 to 2019 with 5 years of interval. Water quality index (WQI) and cluster analysis were applied to classify the pollution sources while inverse distance weighting (IDW) and weighted overlay were used to show the vulnerable zone. All the parameters were considered with the established limit of WHO. WQI detects that the sampling stations located near the quarrying site were responsible for the deterioration of the water quality. Cluster analysis identified that the S8 and S10 sites were heavily susceptible to air and sound pollution. IDW and WO ranked the south-western lower stream and tribal village located at the north-western side as moderately to highly polluted. Correlation analysis illustrated that the values of air and sound parameters were concentrated above the permissible limit. Besides, LULC change revealed the significant lowering trend of vegetation and water bodies whereas it shows the upward trend of barren land and settlement. Finally, the extensive quarrying and crushing activities without any safety measure lead to breaking the environmental sustainability as well as workers and nearby dwellers were exposed to several respiratory diseases.


Effects of Leisure-Time Physical Activity on Vertebral Dimensions in the Northern Finland Birth Cohort 1966.
Vertebral fractures are a common burden amongst elderly and late middle aged people. Vertebral cross-sectional area (CSA) is a major determinant of vertebral strength and thus associated with vertebral fracture risk. Previous studies suggest that physical activity affects vertebral CSA. We aimed to investigate the relationship between leisure-time physical activity (LTPA) from adolescence to middle age and vertebral dimensions in adulthood. We utilized the Northern Finland Birth Cohort 1966, of which 1188 subjects had records of LTPA at 14, 31 and 46 years, and had undergone lumbar magnetic resonance imaging (MRI) at the mean age of 47 years. Using MRI data, we measured eight dimensions of the L4 vertebra. Socioeconomic status, smoking habits, height and weight were also recorded at 14, 31 and 46 years. We obtained lifetime LTPA (14-46 years of age) trajectories using latent class analysis, which resulted in three categories (active, moderately active, inactive) in both genders. Linear regression analysis was used to analyze the association between LTPA and vertebral CSA with adjustments for vertebral height, BMI, socioeconomic status and smoking. High lifetime LTPA was associated with larger vertebral CSA in women but not men. Further research is needed to investigate the factors behind the observed gender-related differences.


Prospective analyses of alertness, sleep, and fitness to drive one year after de novo multiple sclerosis diagnosis.
The prevalence and functional burden of the chronic demyelinating disease multiple sclerosis (MS) are well documented; however, little is known about the initial clinical course of alertness, sleep, cognitive, and psychological symptoms. This exploratory, prospective, longitudinal study multidimensionally investigated the development and progression of alertness, sleep, fitness to drive, and psychological symptoms in the first year after de novo MS diagnosis. Twenty-five people with MS (pwMS) were assessed cognitively, psychologically, and using polysomnography soon after diagnosis and one year later, with outcomes compared to matched healthy controls. In the early stage of the disease, psychological symptoms of pwMS were comparable with those of controls, and patient conditions did not deteriorate within the first disease year. A small percentage of pwMS experienced increased levels of anxiety and depression after diagnosis. Alertness, sustained attention, and fitness to drive were comparable between both groups, and fatigue levels remained low over the course of the year. This study highlights patient experiences within the initial clinical course of MS in a small group of patients. Further research is needed to understand the progression of symptoms and impairments in MS over a longer period and in different stages of the disease.


The impact of FNAC in the management of salivary gland lesions: Institutional experiences leading to a risk-based classification scheme.
Fine-needle aspiration cytology (FNAC) has proven its value as an essential step in the diagnosis of salivary gland lesions. Although the majority of salivary gland lesions, especially those that are common and benign, can be diagnosed with ease on FNAC, limited cellularity and morphologic lesion heterogeneity can pose diagnostic challenges and lead to false-positive and false-negative diagnoses. This study presents the institutional experience of FNAC of salivary gland lesions from 2 academic centers. A retrospective analysis was conducted on 1729 salivary gland FNAC specimens that were diagnosed over an 8-year period from January 2008 to March 2015. All samples were processed either with liquid-based cytology alone or in combination with air-dried, Diff-Quik-stained or alcohol-fixed, Papanicolaou-stained smears. Surgical excision was performed in 709 of 1749 FNACs (41%) that were diagnosed as nondiagnostic/inadequate (n = 29), benign (n = 111), neoplasm (n = 453), atypical (n = 15), suspicious for malignancy (n = 28), and malignant (n = 73). The overall concordance between cytologic and histologic diagnoses was 92.2%, with 91.8% concordance in the benign category and 89.5% concordance in cases diagnosed as suspicious for malignancy and malignant. The most frequent benign and malignant lesions were pleomorphic adenoma and squamous cell carcinoma, respectively. There were 46 false-negative and 13 false-positive results, leading to an overall specificity of 97.6% and diagnostic accuracy of 91.3%. FNAC is a reliable diagnostic modality for the diagnosis and management of salivary gland lesions based on its high specificity and diagnostic accuracy. Cancer Cytopathol 2016;124:388-96. © 2016 American Cancer Society.


Effect of antiretroviral combination therapies including efavirenz in heavily pretreated HIV-infected children.
In this retrospective study the effect of antiretroviral combination regimens including the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) on viral load (VL) and CD4-cell count in heavily pretreated HIV-infected children was investigated. The data of 15 children (< 16 years) were evaluated during a treatment period of at least 52 weeks. Patients received a median of 4 prior antiretroviral regimens and were changed to combinations with EFV because of renewed increasing VL. Viral load (Amplicor, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks. The median reduction of the viral load for the total study population was 1.9 log10 (0.8 - 4.7), 2.3 log(10) (0.5 - 4.7) and 2.6 log(10) (0-4.7) after 12, 24 and 52 weeks, respectively. After 24 weeks 7/15 children and after 52 weeks 9/15 patients had reductions of the VL below the detection limit. The median increase of CD4-cells in the study population during the treatment period were 104 cells/microl (189-969), 220 cells/microl (170-831) and 321 cells/ml (162-574) after 12, 24 and 52 weeks, respectively. In children with intensive prior antiretroviral therapy and multiple therapeutic failures with PI-containing regimens, combination therapy including EFV resulted in an excellent antiretroviral efficacy. After 52 weeks 9/15 patients had persistent reductions of the VL below 50 copies/ml, although none of these children reached this level of viral suppression during their multiple prior protease inhibitor-containing regimens.


Cytomegalovirus pneumonitis complicated by a central peribronchial pattern of organising pneumonia.
We present five cases of cytomegalovirus (CMV) pneumonitis occurring in patients after recent T cell deplete allogeneic stem cell transplantation (AlloHSCT). These cases were complicated by an organising pneumonia (during the recovery period) with a predominantly central peribronchial pattern. All patients presented with evidence of active CMV pneumonitis which was treated successfully with anti-viral therapy but was followed by persistent severe dyspnoea, cough and hypoxia. High resolution computed tomography (HRCT) imaging showed widespread central peribronchial consolidation with traction bronchiectasis. There was a marked clinical and physiological improvement after treatment with systemic corticosteroids. However, in all patients the lung function remained abnormal and in some cases imaging revealed a fibrosing lung disease. These cases represent a previously undescribed central peribronchial pattern of organising pneumonia complicating CMV pneumonitis that can result in chronic lung damage.