Nedaplatin salvage chemotherapy for cervical cancer.
This systematic analysis was conducted to evaluate the efficacy and safety of nedaplatin based salvage chemotherapy for treatment of patients with advanced cervical cancer. Clinical studies evaluating the efficacy and safety of nedaplatin based regimens on response and safety for patients with cervical cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. For nedaplatin based regimens, 5 clinical studies including 264 patients with advanced cervical cancer were considered eligible for inclusion. The analysis showed that, in all patients, pooled RR was 74.6% (197/264). Major adverse effects were leukopenia, thrombocytopenia and nausea/vomiting. No treatment related death occurred with nedaplatin based treatment. This systematic analysis suggests that nedaplatin based regimens are associated with good activity with acceptable tolerability in treating patients with advanced cervical cancer.


Utility of virtual monoenergetic images derived from a dual-layer detector-based spectral CT in the assessment of aortic anatomy and pathology: A retrospective case control study.
To evaluate the ability of the retrospectively generated virtual monoenergetic images (VMIs) from a dual-layer detector-based spectral computed tomography (SDCT) to augment aortic enhancement for the evaluation of aortic anatomy and pathology. 98 patients with suboptimal aortic enhancement (≤200 HU) were retrospectively identified from SDCT scans. VMI from 40 to 80 keV were generated. Attenuation, noise, SNR, and CNR were measured at seven levels in the aorta. Image quality was graded on a 5-point scale, 5 being the best. From the VMI, an ideal set was chosen with mean vascular attenuation above 200 HU while maintaining diagnostic quality. Image parameters and quality of this ideal-set were compared to the standard 120-kVp images. The mean attenuation of all seven measured anatomical regions was 156.6 ± 61.7 HU in the 120-kVp images. Attenuation of the VMI from 40 to 70 keV were higher than the 120-kVp image, measuring 439.2 ± 215.3 HU, 298.5 ± 140.6 HU, 213.4 ± 94.3 HU, and 164.7 ± 90.2 HU, for 40 keV, 50 keV, 60 keV, and 70 keV, respectively (p value <0.01 for 40, 50, 60 keV; 0.07 for 70 keV). SNR and CNR showed similar trends. The 50 keV VMI had the best image quality (4.48 ± 0.84 vs. 2.24 ± 0.92 on 120-kVp images, p < 0.001). Attenuation, CNR, and SNR increased by 90.6%, 85.0%, and 108.1% at 50 keV compared to 120-kVp. A contrast-enhanced CT study can be optimized for the assessment of the aorta by using low-energy VMI obtained using SDCT. At the optimal monoenergetic level, attenuation, SNR, CNR and image quality were significantly higher than that of conventional polyenergetic images.


Adherence to antimalarials and glucocorticoids treatment and its association with self-reported disease activity in systemic lupus erythematosus patients.
We aimed to investigate the rate of non-adherence to antimalarials and glucocorticoids (GCs) and to analyze their potential relationships with sociodemographic characteristics, disease activity and accumulate damage in a cohort of Systemic lupus erythematosus (SLE) patients. A cross-sectional study was conducted among 670 patients. The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) and the Lupus Damage Index Questionnaire (LDIQ) were used to assess disease activity and accumulated damage. The prevalence of non-adherence to antimalarials and GCs were 10.67% and 39.61%. 86.9% of participants indicated that the reason for stopping therapy was the presence of side effects. SLE patients with non-adherence to antimalarials and GCs had significantly higher scores in disease severity (SLAQ) compared to adherence patients (5.03 (2.12) vs 4.39 (2.61); p = .004 and (4.75 (2.29) vs 4.05 (2.78); p ≤ .001). Adherence to the treatment indicated in SLE differs from drug to drug. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.


The source of progesterone in preimplantation rabbit blastocysts.
In vitro and in vivo synthesis of progesterone, sequestration of progesterone from the surrounding medium, and its subsequent conversion to metabolites was investigated in 146 hr post coitus preimplantation rabbit blastocysts. No significant conversion of 3H-pregnenolone to 3H-progesterone was observed throughout the 8 hr incubation. Progesterone content in blastocysts and culture medium did not change during the course of an 8 hr incubation. This suggests that the failure to detect incorporation of label into progesterone was not due to the presence of a large endogenous pool of pregnenolone. Significant uptake (p less than 0.05) of 3H-progesterone from the incubation medium was observed as was significant conversion of the 3H-progesterone to unidentified metabolites. Therefore it would appear that the preimplantation rabbit blastocyst is not capable of de novo synthesis of progesterone from pregnenolone prior to implantation but sequesters progesterone from the surrounding medium and converts it to progesterone metabolites.


Evidence for high risk of cerebral hemorrhage in chronic dialysis patients.
One-half of the total deaths in chronic dialysis patients are due to cardiovascular disease; however, the precise incidence and relative risk of those compared to normals are not known. Therefore, we sought to determine the annual incidence of cardiovascular disease and relative risk of those on chronic dialysis to the general population. Both the general population (1.2 million, Census 1990) and chronic dialysis patients (N = 1,609) in Okinawa, Japan were studied prospectively from April, 1988, to March, 1991. Diagnosis of stroke was made by symptoms and brain CT scan, and acute myocardial infarction was done by changes in electrocardiogram and serum enzymes. The relative risk (observed/expected ratio) was calculated by using the standardized morbidity rate obtained in both sexes and age-class every 10 years in the general population. Forty-one stroke (8 cerebral infarction, 31 cerebral hemorrhage, and 2 subarachnoid hemorrhage) and four acute myocardial infarction cases were registered during the study period in chronic dialysis patients. The incidence per 1,000 person-year was 11.5 in stroke, 2.2 in cerebral infarction, 8.7 in cerebral hemorrhage, 0.6 in subarachnoid hemorrhage, and 1.1 in acute myocardial infarction. The relative risk compared to normals was 5.2 in stroke, 2.0 in cerebral infarction, 10.7 in cerebral hemorrhage, 4.0 in subarachnoid hemorrhage, and 2.1 in acute myocardial infarction. Cerebral hemorrhage occurred at 10 years younger than that of the general population (P < 0.001) and was associated with high prevalence of hypertension and low levels of serum albumin and cholesterol. Our results confirm the importance of blood pressure control and nutritional status in chronic dialysis patients.


Defining a rational back-up policy for emergency departments.
All emergency departments face the possibility of having insufficient personnel to provide adequate care for patients. Such occasions may present an emergency department with several severely injured patients or merely an unusually large number of that emergency department's usual patient profile. When such staffing inadequacies occur, emergency department directors must respond with additional personnel. Since there is no national standard for back-up policies for emergency departments, emergency medicine has a responsibility to examine this question in order to arrive at some possible solutions. In addition, emergency department directors have an obligation to consider their particular staffing and usage patterns in order to try to devise the most efficient back-up policy prior to need. Finally, assessment of the success with which such back-up policies are used is discussed.


GMMchi: gene expression clustering using Gaussian mixture modeling.
Cancer evolution consists of a stepwise acquisition of genetic and epigenetic changes, which alter the gene expression profiles of cells in a particular tissue and result in phenotypic alterations acted upon by natural selection. The recurrent appearance of specific genetic lesions across individual cancers and cancer types suggests the existence of certain "driver mutations," which likely make up the major contribution to tumors' selective advantages over surrounding normal tissue and as such are responsible for the most consequential aspects of the cancer cells' gene expression patterns and phenotypes. We hypothesize that such mutations are likely to cluster with specific dichotomous shifts in the expression of the genes they most closely control, and propose GMMchi, a Python package that leverages Gaussian Mixture Modeling to detect and characterize bimodal gene expression patterns across cancer samples, as a tool to analyze such correlations using 2 × 2 contingency table statistics. Using well-defined simulated data, we were able to confirm the robust performance of GMMchi, reaching 85% accuracy with a sample size of n = 90. We were also able to demonstrate a few examples of the application of GMMchi with respect to its capacity to characterize background florescent signals in microarray data, filter out uninformative background probe sets, as well as uncover novel genetic interrelationships and tumor characteristics. Our approach to analysing gene expression analysis in cancers provides an additional lens to supplement traditional continuous-valued statistical analysis by maximizing the information that can be gathered from bulk gene expression data. We confirm that GMMchi robustly and reliably extracts bimodal patterns from both colorectal cancer (CRC) cell line-derived microarray and tumor-derived RNA-Seq data and verify previously reported gene expression correlates of some well-characterized CRC phenotypes. The Python package GMMchi and our cell line microarray data used in this paper is available for downloading on GitHub at https://github.com/jeffliu6068/GMMchi .


Elbow Torque Is Reduced in Asymptomatic College Pitchers With Elbow Laxity: A Dynamic Ultrasound Study.
To determine the relation between medial elbow torque, as measured by wearable sensor technology, and adaptations of the medial elbow structures on dynamic ultrasound imaging in asymptomatic collegiate pitchers. Thirty-four pitchers from National Collegiate Athletic Association Division II universities were eligible for preseason testing. The exclusion criteria included age younger than 18 years, history of surgery, non-pitcher, or current restrictions. Pitchers were fitted with a wearable sensor sleeve that recorded elbow torque, arm slot, arm speed, and arm rotation. Pitchers threw 5 fastballs in a standardized manner off the mound at game-speed effort. They also underwent dynamic ultrasound imaging of the elbow by a musculoskeletal sonographer, with standardized valgus loading. Images were deidentified, and measurements of the ulnar collateral ligament (UCL) and ulnohumeral joint space (UHJS), to assess elbow laxity, were performed by a musculoskeletal radiologist. The final analysis included 28 pitchers with an average age of 20.1 years (standard deviation, 1.3 years; range, 18-23 years) and playing experience of 15.3 years (standard deviation, 1.8 years; range, 11-19 years). The dominant UCL thickness (P < .001), loaded UHJS (P = .039), and delta UHJS (P < .001) were significantly greater than the nondominant measurements. An inverse correlation was found between loaded UHJS and medial elbow torque (r = -0.4, P < .001). Additionally, every 1-mm increase in UHJS significantly reduced medial elbow torque by 2.27 Nm (P = .032) and arm slot by 8.8° (P = .019) and increased arm rotation by 5.3° (P = .043). Pitchers with a loaded UHJS of 4.4 mm or greater and delta UHJS of 1.25 mm or greater had significantly reduced medial elbow torque (P < .001). Pitchers with a UCL thickness of 1.65 mm or greater had significantly increased medial elbow torque (47.4 Nm vs 44.8 Nm, P = .006). Pitchers with increased dynamic elbow laxity were found to experience reduced medial elbow torque while pitching. Additionally, pitchers with greater UCL thickness on ultrasound were found to experience increased medial elbow torque while pitching. This study's findings suggest a relation between anatomic adaptations found on ultrasound of the pitching elbow and medial elbow torque. Level II, prospective cohort study.


Age-related changes in sleep-dependent novel word consolidation.
Learning new words is a vital, life-long process that benefits from memory consolidation during sleep in young adults. In aging populations, promoting vocabulary learning is an attractive strategy to improve quality of life and workplace longevity by improving the integration of new technology and the associated terminology. Decreases in sleep quality and quantity with aging may diminish sleep-dependent memory consolidation for word learning. Alternatively, given that older adults outperform young adults on vocabulary-based tasks, and that strength of memory encoding (how well older adults learn) predicts sleep-dependent memory consolidation, word learning may uniquely benefit from sleep in older adults. We assessed age-related changes in memory for novel English word-definition pairs recalled following intervals spent asleep and awake. While sleep was shown to fully preserve memory for word/definition pairs in young adults (N = 53, asleep = 32, awake = 21, 18-30 years), older adults (N = 45, asleep = 21, awake = 24, 58-75 years) forgot items equally over wake and sleep intervals but preserved the accuracy of typed responses better following sleep. However, this was modulated by the strength of encoded memories: the proportion of high strength items consolidated increased for older adults following sleep compared to wake. Older adults consolidated a lower proportion of medium strength items across both sleep and wake intervals compared to young adults. Our results contribute to growing evidence that encoding strength is crucially important to understand the expression of sleep-dependent benefits in older adults and assert the need for sufficiently sensitive performance metrics in aging research.


Using virtual reality simulation for training practical skills in musculoskeletal wrist X-ray - A pilot study.
Using virtual reality (VR), students of radiography can practice acquisition and positioning of musculoskeletal radiographs and get immediate feedback on their performance within the simulator. The purpose of this study was to assess usability of a newly developed VR simulator and to explore self-perceived clinical readiness (SPCR) of radiography students before and after training acquisition of wrist radiographs in the VR simulator. A prospective methodology was applied where the students (n = 10) estimated their own SPCR in regard to acquisition of wrist radiographs pre- and post-VR training. A questionnaire on usability, realism, and educational value of the simulator was answered post-VR training. Usability and SPCR scores were calculated. The student's paired t-test was applied to explore the impact of VR training on SPCR. The students (90%) reported that the simulator was realistic and they thought that it could contribute to learning. The pre- and post-SPCR scores were 75 (95% confidence interval [CI]: 54-96) and 77 (95% CI: 59-95), respectively. There was no significant difference (P = 0.4574) between the pre- and post-SPCR scores. Results indicated that the concept of training acquisition and positioning of wrist radiographs in a VR simulator is feasible with positive feedback from the students. The SPCR scores improved slightly, although not statistically significant, after completion of the training session.


Tejas functions as a core component in nuage assembly and precursor processing in Drosophila piRNA biogenesis.
PIWI-interacting RNAs (piRNAs), which protect genome from the attack by transposons, are produced and amplified in membraneless granules called nuage. In Drosophila, PIWI family proteins, Tudor-domain-containing (Tdrd) proteins, and RNA helicases are assembled and form nuage to ensure piRNA production. However, the molecular functions of the Tdrd protein Tejas (Tej) in piRNA biogenesis remain unknown. Here, we conduct a detailed analysis of the subcellular localization of fluorescently tagged nuage proteins and behavior of piRNA precursors. Our results demonstrate that Tej functions as a core component that recruits Vasa (Vas) and Spindle-E (Spn-E) into nuage granules through distinct motifs, thereby assembling nuage and engaging precursors for further processing. Our study also reveals that the low-complexity region of Tej regulates the mobility of Vas. Based on these results, we propose that Tej plays a pivotal role in piRNA precursor processing by assembling Vas and Spn-E into nuage and modulating the mobility of nuage components.


Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica.
To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. In vitro DPPH radical scavenging activity and lipoxygenase (LOX) inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively. Methanolic extract (MEMI), successive water extract (SWMI) and ethyl acetate fraction (EMEMI), n-butanol fraction (BMEMI) and water soluble fraction (WMEMI) of methanolic extract were evaluated along with respective reference standards. In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC(50) values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC(50) value of 1.88 and found to be more potent compared to all the extracts and fractions. In in vitro LOX inhibition assay, the MEMI, EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC(50) values of 96.71, 63.21 and 107.44 μg/mL respectively. While, reference drug Indomethacin also offered significant inhibition against LOX enzyme activity with IC(50) of 57.75. Furthermore, MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity. These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions.


Cellular enzymatic activities in the articular cartilage of osteoarthritic and osteoporotic hip joints of humans: a quantitative cytochemical study.
Quantitative cytochemical methods were applied to measure the activity of several oxidative enzymes in human articular cartilage of the femoral head obtained from osteoarthritic patients (OA) and from patients with fractured femoral neck (OP) due to primary osteoporosis. In both conditions, lactate dehydrogenase (LDH) was found to be the most active one followed by two additional cytosolic enzymes: glyceraldehyde 3-phosphate dehydrogenase (GAPD) and glucose 6-phosphate dehydrogenase (G6PD). On the other hand, the activity of mitochondrial enzymes such as succinate dehydrogenase (SDH) and beta-hydroxyacyl dehydrogenase (HOAD), appeared much lower in degree. Except for HOAD, all the other enzymes exhibited a high degree of activity along the inner zone in the cartilage, i.e., zone 3b, indicative of an apparently more active metabolism in the osteochondral junction. G6PD activity was significantly higher (p less than 0.01) in OP than in OA patients. By contrast, SDH appeared more active in specimens obtained from OA patients. The remaining enzymes showed no appreciable activity differences between cartilages of OP and OA patients. These findings suggest that oxidative enzyme activity in chondrocytes involved in osteoarthritis does not differ substantially from that in cartilage of OP patients.


Assessing the progression of gastric cancer via profiling of histamine, histidine, and bile acids in gastric juice using LC-MS/MS.
Bile acid (BA) imbalance may be directly associated with gastric cancer and indirectly influence stomach carcinogenesis via overexpression of histidine decarboxylase (HDC), which converts histidine (His) into histamine (HIST). Moreover, the progression of gastric cancer, could change the gut microbiome, including bacteria spp. that produce secondary BAs. Gastric juice has various metabolites that could indicate gastric cancer-related stomach conditions. Therefore, profiling of HIST, His, and BAs in gastric juice is crucial for understanding the etiological mechanisms of gastric cancer. We used a profiling method to simultaneously determine targeted metabolites in gastric juice using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We successfully analyzed 70 human gastric juice samples from patients with chronic superficial gastritis (CSG, n = 20), intestinal metaplasia (IM, n = 12), and gastric cancer (n = 38). Furthermore, we investigated the relevance between BA metabolism and gastric cancer. There were statistical differences in the metabolism of cholic acid (CA) into deoxycholic acid (DCA) based on the progression of CSG into IM and gastric cancer. Hence, the progression of gastric cancer might be related to the alterations in gut microbiome composition. We provide insight into the etiological mechanisms of the progression of gastric cancer and biomarkers to diagnose and treat gastric cancer.


Nephrectomy for renal cell carcinoma with metastases.
The percentage of patients with renal cell carcinoma who also have identifiable metastases when first seen is increasing. In the past metastases were considered justification for excluding nephrectomy in the management of the patient. However, numerous opportunities for therapy which are abetted by removal of the primary tumor are presented. It is concluded, depending on several variables, that the advantages of nephrectomy usually justify the procedure.


Information processing in children with minor neurological dysfunction: behavioural and neurophysiological indices.
Minor neurological dysfunction (MND) refers to deviant function of the central nervous system in the absence of localizable neurological disorders. Children with no signs (n = 28) and with varying grades of MND (n = 48), classified according to failure on circumscript neurological subsystems, were administered selective and sustained attention tasks at the age of twelve. During the execution of one of the tasks, electrocortical activity of the brain was recorded at the Fz, Cz, Pz and Oz scalp locations. Of main interest were behavioural and electrophysiological indices of deficits in attentional control. With respect to the latter category, the investigation was focused on differences in event-related potential amplitudes reflecting subprocesses of cognitive processing (processing negativity, P300). Following a linear stage model of information processing, it was found that children who failed on three or more neurological subsystems (in particular on fine manipulation and coordination), exhibited deficits in the encoding, search and decision stages of processing. Furthermore, the children with MND showed a reduced positive parietal shift on target presentation. Under complex task conditions, children without MND showed a decrease in P300 amplitude which reflects the impact of processing negativity as a result of increased task demands; this effect was absent in children with MND. These electrocortical differences suggest imbalances in the external and internal neural regulation of the flow of information in the brain.


The effect of prolonged standing on touch sensitivity threshold of the foot: a pilot study.
To determine the effect of prolonged standing on touch sensitivity of the foot. An observational study with replications. University laboratory. Ten healthy college students (5 men and 5 women), with a mean ± SD age of 23.5 ± 4.1 years and body mass of 67.4 ± 12.6 kg. Semmes-Weinstein monofilament tests were administered to 12 locations on the dorsal and plantar surfaces of the foot before and after 4 hours of standing. These locations were formed into several groupings (toes, metatarsal heads, midfoot, heel, all plantar sites, all dorsal sites), and paired t-tests were used to test for significant changes in sensitivity threshold after standing. The difference between sensitivity thresholds measured before and after standing for different locations on the foot. The average of all sensitivity thresholds on the plantar surface of the foot decreased (indicating increased sensitivity) from 0.56 to 0.36 g (P < .01) after 4 hours of prolonged standing. This change in threshold equated to a difference of 1 Semmes-Weinstein monofilament level. Changes in the sensitivity threshold of the dorsal aspect of the foot were not significant. Analysis of the results suggests that the plantar foot has greater sensitivity to touch after prolonged standing. These findings may be useful for identifying potential unintended bias in clinical touch sensitivity testing. Future research is necessary to understand the underlying mechanisms for this sensitivity change and to determine the onset and recovery times for sensitivity changes.


The relationship of counselor and peer alliance to drug use and HIV risk behaviors in a six-month methadone detoxification program.
The purpose of this study was to examine the relationship of treatment outcomes in opioid detoxification to levels of counselor and peer alliance. Forty-one subjects were recruited from a larger, 180-day study of psychosocial treatment. Beginning at day 90, subjects completed monthly measures of alliance. Outcome measures included treatment retention, drug use and self-reported HIV risk. Measures of alliance were found to be internally consistent and moderately stable over time. During the final 30 days of the methadone taper, higher levels of both types of alliance were associated with less use of illicit opioids. Alliance with counselor was associated with less frequent needle sharing. For subjects who could be located for 30-day follow-up, greater alliance with peers was associated with more frequent HIV (sexual) risk behaviors. Results suggest that treatment outcome may be improved through approaches that address a patient's alliance with both counselor and peers.


Leakage of intraluminal low molecular weight polyethylene glycol as a marker of small bowel transplant rejection.
To facilitate early detection of small bowel allograft rejection, we correlated transluminal leakage of low molecular weight polyethylene glycol (PEG) with the development of allograft rejection. Vascularized allogeneic and syngeneic jejunal transplants were performed in rats, without immunosuppression. A control group underwent creation of jejunal Thiry-Vella fistulas of similar length. Jejunal segments were perfused with a physiologic solution containing [3H]-PEG-900. At the end of an equilibrium period, an urinary bladder aspirate was collected and [3H]-PEG-900 measured by scintillation counting. Results are expressed as disintegrations per minute per 100 microL urine. Histologic examinations were performed at all experimental time points. Two days following transplantation, urinary PEG levels were elevated in both allogeneic and syngeneic groups (3943 +/- 935 and 4007 +/- 1164, respectively). Four days after the transplant, syngeneic urine PEG levels decreased to 581 +/- 159, and were not significantly different (P greater than .05) from Thiry-Vella controls (635 +/- 145). Syngeneic levels remained at this low level for the rest of the experiment. The allogeneic group continued to show significantly higher levels (P less than .05) compared with syngeneic and Thiry-Vella groups from day 4 until the end of the experiment. These elevated levels most likely represented the development of rejection, preceding the first significant histologic signs of rejection, which were found at six days post-transplant. Detection of transluminal leakage of low molecular weight PEG may be a useful adjunct in monitoring for small bowel transplant rejection.


Determinants of induction of ventricular tachycardia in nonsustained ventricular tachycardia after myocardial infarction and the usefulness of the signal-averaged electrocardiogram.
Assessment of the implications of clinical and noninvasive variables, including the results of signal-averaged electrocardiography, was performed > or = 3 weeks after myocardial infarction in 57 patients with nonsustained ventricular tachycardia (VT) who underwent programmed ventricular stimulation to guide antiarrhythmic therapy. The clinical and noninvasive parameters assessed included ages, left ventricular ejection fractions, sites of infarction, presence of akinetic or dyskinetic left ventricular segments, history of syncope, history of coronary artery bypass surgery, and presence or absence of late potentials from signal-averaged electrocardiography. Other than the presence of late potentials, no clinical or noninvasive parameters identified such persons with a significantly higher likelihood of inducible VT. When assessed as positive if 1 or more variables were abnormal, 16 of 16 (100%) patients with versus 17 of 41 without inducible VT had late potentials (p < 0.002). With more stringent criteria required (defined as prolongation of the QRS vector complex duration and low root-mean-square voltage of the terminal 40 ms of the vector complex) 8 of 16 patients (50%) with and 4 of 41 (10%) without inducible VT had late potentials recorded (p < 0.002). Thus, the signal-averaged electrocardiogram may enable identification of persons with nonsustained VT after myocardial infarction who are most likely to have VT induced at programmed ventricular stimulation.


Cardiac risk factors and the use of triptans: a survey study.
To describe current practice in triptan use. Triptans are effective migraine treatments that cause chest symptoms in some patients. True cardiac ischemia is rare. Design.-Headache specialists and family practitioners completed questionnaires regarding the times when triptans are contraindicated, obtaining electrocardiograms (ECGs), and giving the first dose in the office. Sixty-five headache specialists and 67 family practitioners responded. Headache specialists saw an average of 36.3 patients with headache per week. Family practitioners saw an average of 7.2. Family practitioners and headache specialists had similar opinions regarding the age at which triptans were contraindicated with various numbers of risk factors. Sixty-one percent of headache specialists and 50% of family practitioners would not use a triptan at any age for patients with more than three risk factors (P = NS). Ten percent of headache specialists obtained an ECG for all patients being prescribed triptans, while no family practitioners did (P =. 008). Ten percent of both family practitioners and headache specialists never obtained an ECG, even with multiple cardiac risk factors. Headache specialists obtained ECGs more often than family practitioners (P <.002 for one to three risk factors). Family practitioners were more likely to give the first dose of the triptan in the office regardless of cardiovascular risk (58% versus 20%, P <. 001). Forty-five percent of headache specialists and 2% of family practitioners never gave the first dose in the office (P <.001). Family practitioners gave the first dose in the office more readily than headache specialists in patients with no risk factors (P =.001), but not for one or more risk factors. No consensus exists among family practitioners or headache specialists about when to avoid using a triptan due to excessive cardiac risk factors, when to obtain an ECG prior to using a triptan, and when to give the first dose of a triptan in the office. Headache specialists are more likely to obtain ECGs, whereas family practitioners are more likely to give the first dose of a triptan in the office.


Analysis of the inotropic mechanism of enoximone in guinea pig ventricular muscle.
Force and action potentials were recorded in guinea pig papillary muscles. The peak force was 131.8 +/- 3.3% of control at 2 microM and 144.4 +/- 2.0% at 4 microM enoximone. Enoximone (2 microM) increased the rate of rise of force (131.0 +/- 4.9%) and time from peak to half-relaxation (106 +/- 1.1%). The time to peak twitch force shortened (96.7 +/- 0.6%). The action potential duration decreased at 2 microM (96.4 +/- 1.2%) and 4 microM (92.8 +/- 1.4%) enoximone. The action potential amplitude was 106.7 +/- 0.8% in 2 microM and 112.6 +/- 0.6% in 4 microM enoximone. The peak twitch force in response to a test stimulus given after varied intervals (i.e., mechanical restitution) was increased at all test intervals, whereas the time to full restitution was not affected at any concentration. The force in response to the preceding test interval (postextrasystolic potentiation) was also increased. Maximum potentiation was 11.9 +/- 3.0 mN/mm2 in controls, 15.9 +/- 3.3 mN/mm2 in 2 microM enoximone, and 17.02 +/- 3.2 mN/mm2 in 4 microM enoximone. During the decay of postextrasystolic potentiation, there was a linear relationship between the peak force of the postpotentiated contraction and peak force of the potentiated contraction. The slope of the line increased from 0.34 to 0.43 (n = 12, p less than 0.001) by enoximone (2 microM). The results suggest that enoximone exerts its positive inotropic effect by (a) increasing calcium inflow during the action potential and/or (b) reducing calcium outflow, thereby increasing the recirculation of activator calcium.


Greedy Autoaugment for classification of mycobacterium tuberculosis image via generalized deep CNN using mixed pooling based on minimum square rough entropy.
Although tuberculosis (TB) is a disease whose cause, epidemiology and treatment are well known, some infected patients in many parts of the world are still not diagnosed by current methods, leading to further transmission in society. Creating an accurate image-based processing system for screening patients can help in the early diagnosis of this disease. We provided a dataset containing1078 confirmed negative and 469 positive Mycobacterium tuberculosis instances. An effective method using an improved and generalized convolutional neural network (CNN) was proposed for classifying TB bacteria in microscopic images. In the preprocessing phase, the insignificant parts of microscopic images are excluded with an efficient algorithm based on the square rough entropy (SRE) thresholding. Top 10 policies of data augmentation were selected with the proposed model based on the Greedy AutoAugment algorithm to resolve the overfitting problem. In order to improve the generalization of CNN, mixed pooling was used instead of baseline one. The results showed that employing generalized pooling, batch normalization, Dropout, and PReLU have improved the classification of Mycobacterium tuberculosis images. The output of classifiers such as Naïve Bayes-LBP, KNN-LBP, GBT-LBP, Naïve Bayes-HOG, KNN-HOG, SVM-HOG, GBT-HOG indicated that proposed CNN has the best results with an accuracy of 93.4%. The improvements of CNN based on the proposed model can yield promising results for diagnosing TB.


Acute kidney injury as the first sign of spontaneous renal vein thrombosis: report of 2 cases.
Spontaneous renal vein thrombosis (RVT) is very rare in the absence of nephrotic syndrome. It is more common in newborns and infants. RVT should always be included in the differential diagnosis of flank pain and hematuria, and because RVT can induce acute renal injury. A 19-year-old man was admitted to our hospital because he complained of right flank pain and oliguria for 3 days. Another patient, a 24-year-old man, complained of a severe and sudden onset of bilateral flank pain and anuria for a day. They were both healthy before they developed the described symptoms and had different levels of decrease in renal function when they visited the hospital. Color Doppler ultrasonography revealed RVT in both the patients. The patients received therapy, including anticoagulation and thrombolysis, following their diagnoses, and they recovered in a few days.


The value of different 18F-FDG PET/CT baseline parameters in risk stratification of stage I surgical NSCLC patients.
Administration of postoperative chemotherapy to patients with completely resected stage I NSCLC is still a matter of debate. The aim of the present study was to evaluate the value of different baseline 18F-FDG PET parameters in identifying surgical stage I NSCLC patients who are at high risk of recurrence, and thus are indicated for further postoperative treatment. This is a retrospective study, which included 49 patients (28 males, 21 females) with the median age of 69 years (range 28-84), who had pathologically proven stage I NSCLC. All patients underwent 18F-FDG PET/CT at baseline followed by complete surgical resection of the tumor (R0). Baseline SUVmax, MTV and TLG were measured. Patients' follow-up records were retrospectively reviewed, and DFS (disease-free survival) was assessed. For each parameter, the most accurate cut-off value for the prediction of recurrence was calculated using the ROC curve analysis and the Youden index. DFS was evaluated for patients above and below the calculated cut-off value using the Kaplan-Meier method and the difference in survival between the two groups was estimated using the log-rank test. Median observation time of the patients after surgery was 28.7 months (range 3.5-58.8 months). 9 patients developed recurrence. The calculated cut-off values for SUVmax, MTV and TLG were 6, 6.6 and 33.6, respectively. Using these cut-offs, the observed sensitivity for SUVmax, MTV and TLG for prediction of recurrence was 100%, 89% and 89%, respectively, while the observed specificity was 43%, 73% and 65%, respectively. The difference in survival between patients below and above the cut-off value was statistically significant in all three studied parameters. The highest AUC was observed for MTV (AUC = 0.825, p = 0.003), followed by TLG (AUC = 0.789, p = 0.007), and lastly SUVmax (AUC = 0.719, p = 0.041). ROC curve analysis showed that volumetric parameters had better predictive performance than SUVmax as regards recurrence. PET-derived parameters at baseline were predictive of recurrence in stage I surgical NSCLC patients. Moreover, the metabolic volume of the tumor was the most significant parameter for this purpose among the studied indices.


Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain.
The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMRglc and rCMR(O2)) during intravenous administration of fenfluramine, using [15O]water, [18F]FDG and [15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR2(O2), but it failed to affect rCMRglc. The findings indicate that quantitative estimation of rCBF by repeated injection of [15O]water was more sensitive than either rCMRO2 or rCMRglc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.


MDCT angiography with 3D image reconstructions in the evaluation of failing arteriovenous fistulas and grafts in hemodialysis patients.
Arteriovenous fistulas and grafts are the methods of choice for vascular access in renal failure patients in need of hemodialysis. Their major complication, however, is stenosis, which might lead to thrombosis. To demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long-term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts (AVF and AVG). During a 17-month period, 31 patients with dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D image postprocessing. Parameters such as comprehension of the anatomy, quality of contrast enhancement, and pathological vascular changes were measured. DSA was then performed in 24 patients. MDCTA illustrated the anatomy of the AVF/AVG and the entire vascular tree to the heart, in a detailed and comprehensive manner in 93.5% of the evaluated segments, and depicted pathology of AVF/AVG or pathology of the associated vasculature. MDCTA demonstrated a total of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24 patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity of 95%. All 24 patients were treated with percutaneous transluminal angioplasty (PTA) with good technical results. MDCTA with 3D reconstructions of dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable diagnostic method helping customize future intervention.


Conversion of sterols and triterpenes by mycobacteria. I Formation of progesterone and 1-dehydroprogesterone from Mycobacterium aurum, strain A+.
Side-chain degradation of sterols by bacteria is known to proceed via oxidation of a terminal methyl group followed by a succession of beta-oxidative steps. By this pathway, the pregnane backbone is not produced. However, examination of cholesterol degradation products using a strain of Mycobacterium aurum shows that progesterone and 1-dehydroprogesterone are present at low levels. These pregnane derivatives were identified by gas-liquid chromatography combined with mass spectrometry. This indicates that an alternative pathway for sterol side-chain degradation occurs in bacteria, which could be of great interest for the biological production of corticosteroid precursors.


Disorders associated with clinically severe obesity: significant improvement after surgical weight reduction.
Surgical treatment for patients with clinically severe obesity mainly aims to reduce morbidity. Sixty-two patients were examined for disorders associated with morbid obesity before and after surgical weight reduction by vertical banded gastroplasty. All patients were followed-up for 12 to 48 months. At the end of the first postoperative year, 84% of the patients had lost at least 50% of their excess weight. Of the 218 weight-related pathologic conditions existing before the operation, 131 (60%) were completely cured, 50 (23%) showed significant improvement, and only 37 (17%) remained unchanged. The same percentages were obtained for patients followed tip for 24, 36, and 48 postoperative months. Surgical treatment of clinically severe obesity has a significant effect on the health of the patients by eliminating the associated disorders.


Transcatheter stenting of the right ventricular outflow tract augments pulmonary arterial growth in symptomatic infants with right ventricular outflow tract obstruction and hypercyanotic spells.
We retrospectively reviewed all the children with right ventricular outflow tract obstruction, hypoplastic pulmonary annulus, and pulmonary arteries who underwent stenting of the right ventricular outflow tract for hypercyanotic spells at our institution between January, 2008 and December, 2013; nine patients who underwent cardiac catheterisation at a median age of 39 days (range 12-60 days) and weight of 3.6 kg (range 2.6-4.3 kg) were identified. The median number of stents placed was one stent (range 1-4). The median oxygen saturation increased from 60% to 96%. The median right pulmonary artery size increased from 3.3 to 5.5 mm (-2.68 to -0.92 Z-score), and the median left pulmonary artery size increased from 3.4 to 5.5 mm (-1.93 to 0 Z-scores). Among all, one patient developed transient pulmonary haemorrhage, and one patient had pericardial tamponade requiring drainage. Complete repair of tetralogy of Fallot +/- atrioventricular septal defect or double-outlet right ventricle was achieved in all nine patients. Transcatheter stent alleviation of the right ventricular outflow tract obstruction resolves hypercyanotic spells and allows reasonable growth of the pulmonary arteries to facilitate successful surgical repair. This represents a viable alternative to placement of a systemic-to-pulmonary artery shunt, particularly in small neonates.


Antiphospholipid syndrome infectious origin.
Antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against beta 2-glycoprotein-I (beta 2GPI). The factors causing production of anti-beta 2GPI remain unidentified, but an association with infectious agents has been reported. Studies on experimental APS models proved that molecular mimicry between beta 2GPI-related synthetic peptides and structures within bacteria, viruses, tetanus toxoid, and CMV are a cause for experimental APS. Any explanation of how microbial infections might set off APS must take into account the observation that all individuals appear to harbor potentially autoreactive lymphocytes, as well as natural antiphospholipid antibodies, but that these cells or antibodies remain innocuous unless somehow activated. Herein, we discuss the association of antiphospholipid antibodies in the infectious state, molecular mimicry as a proposed cause for development of APS, and the contribution of the database to this topic.


Maturation of the postural control in adolescent girls: A 3-year follow-up study.
Stable posture is a manifestation of the appropriate functioning of the neuromuscular system that is essential for proper motor development and control. Balance and stability of the erect posture are shaped during the entire childhood to culminate in its full efficiency in adolescent subjects. In this 3-year follow-up study, the process of the postural control maturation has been assessed in a group of 18 girls at the transition period between childhood to adolescence. Their balance and postural stability control were assessed using standard static posturography supplemented by two postural stability tests: the rising-on-toes (ROT), and the maximum forward lean (MFL), all performed with (EO) and without vision (EC). Balance control was analyzed with the sway vector (SV) and sway directional indices, whereas the anteroposterior trajectories of the center-of- pressure (COP) during forward-leaning and the raise-on-toes tests were used to determine changes in postural stability control. The study documented that stability control in girls aged 11-13 is shaped according to their own pace of development. Their postural sway was characterized by the lower COP velocity but very sensitive to visual input. The directional sway measures remained at the same level for the entire period of observation. MFL and ROT tests provided similar information on postural stability and its dependence on visual input. These tests allow for more thorough assessment of postural stability to compare with quiet stance testing. Subtle changes in postural control in adolescents could be assessed based on the results of combined static and dynamic tests. In particular, the ROT test can be recommended for the assessment of postural stability.


Effects of self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane and dopamine on the corrosion behaviors and biocompatibility of a magnesium alloy.
Magnesium based alloys are attracting tremendous interests as the novel biodegradable metallic biomaterials. However, the rapid in vivo degradation and the limited surface biocompatibility restrict their clinical applications. Surface modification represents one of the important approaches to control the corrosion rate of Mg based alloys and to enhance the biocompatibility. In the present study, in order to improve the corrosion resistance and surface biocompatibility, magnesium alloy (AZ31B) was modified by the alkali heating treatment followed by the self-assembly of 3-phosphonopropionic acid, 3-aminopropyltrimethoxysilane (APTMS) and dopamine, respectively. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectra (XPS) indicated that the molecules were successfully immobilized on the magnesium alloy surface by the self-assembly. An excellent hydrophilic surface was obtained after the alkali heating treatment and the water contact angle increased to some degree after the self-assembly of dopamine, APTMS and 3-phosphonopropionic acid, however, the hydrophilicity of the modified samples was better than that of the pristine magnesium substrate. Due to the formation of the passivation layer after the alkali heating treatment, the corrosion resistance of the magnesium alloy was obviously improved. The corrosion rate further decreased to varying degrees after the self-assembly surface modification. The blood compatibility of the pristine magnesium was significantly improved after the surface modification. The hemolysis rate was reduced from 56% of the blank magnesium alloy to 18% of the alkali heating treated sample and the values were further reduced to about 10% of dopamine-modified sample and 7% of APTMS-modified sample. The hemolysis rate was below 5% for the 3-phosphonopropionic acid modified sample. As compared to the pristine magnesium alloy, fewer platelets were attached and activated on the modified surfaces and the activated partial thromboplastin times (APTT) were prolonged to some degree. Furthermore, the modified samples showed good cytocompatibility. Endothelial cells exhibited the improved proliferative profiles in terms of CCK-8 assay as compared to those on the pristine magnesium alloy. The modified samples showed better endothelial cell adhesion and spreading than the pristine magnesium alloy. Taking all these results into consideration, the method of this study can be used to modify the magnesium alloy surface to improve the corrosion resistance and biocompatibility simultaneously.


[Development and Evaluation of the Work-Related Intervention "Perspective Job" for the Oncological Rehabilitation].
The knowledge about contents and arrangement of work-related measures in oncological rehabilitation is limited. The aim of the study was to develop a multimodal work-related module called Perspective Job for the oncological rehabilitation as well as to evaluate the process of development and the module itself. Perspective Job was developed within a rehabilitation team. For an examination of the process of development and of the module expert interviews with clinic employees and group interviews with patients were conducted. Group interviews were conducted before as well as after the implementation of Perspective Job to demonstrate changes in the rehabilitation from the patients point of view. Participants were oncological patients with substantial work-related problems. The module Perspective Job consists of work-related therapies as well as job trainings. The expert interviews illustrates: The process of development is valued as positive and meaningful by the rehabilitation team. Furthermore synergetic effects were used and the exchange of information and the communication within the team were promoted. The interviews with the patient emphasized that most perspective job therapies were classified as work-related and that an individual occupation-oriented care took place. The promoting exchanges of experience between the participants has been positively evaluated. In addition, they seemed to be well-prepared for the return to work. The development of a work-related module in the rehabilitation team is possible. The process was valued by the team members positively and promoted the multiprofessional cooperation. An occupationally oriented arrangement of the rehabilitation was solely perceived by the participants of Perspective Job, which felt better prepared to reintegrate into working life. The results emphasize the importance of teamwork for the development and implementation of work-related therapy modules for the oncological rehabilitation.


Bone changes post-sleeve gastrectomy in relation to body mass and hormonal changes.
To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG). Twenty-four-month longitudinal observational study. Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates. Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load. Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions. Clinical trial registration number: The study is registered in ClinicalTrials.gov (NCT02557438).


Influence of t-butylhydroquinone and beta-naphthoflavone on formation and transport of 4-methylumbelliferone glucuronide in Caco-2/TC-7 cell monolayers.
Human Caco-2 cells have been established as a model system for intestinal biotransformation and permeability. When grown on Transwell polycarbonate filters they develop morphologic and biochemical characteristics of enterocytes with well separated apical and basolateral surfaces. In addition, Caco-2/TC-7 cells have proven to be useful to study regulation of human UDP-glucuronosyltransferases (UGTs) by Ah receptor agonists and antioxidant-type inducers such as beta-naphthoflavone (BNF) and t-butylhydroquinone (TBHQ). In the present investigation, formation and transport of 4-methylumbelliferone glucuronide was studied in intact Caco-2 cell monolayers. The following results were obtained: when loaded with 50-200 microM MUF either apically or basolaterally, MUF-GA was the major metabolite which was mostly released (80%) at the basolateral surface, probably via the multidrug resistance protein isoform MRP3; MUF sulfate formation was low (5 +/-2%). Pretreatment of cells with 80 microM TBHQ or 50 microM BNF for 72 hr before addition of 100 microM MUF enhanced basolateral secretion of MUF-GA 1.4- and 1.7-fold, respectively. However, at >200 microM MUF, MUF-GA secretion and induction was smaller, probably due to inhibition of intracellular UGT activity. MRP3 protein was localized to the basolateral surface of Caco-2 cells but was not induced by TBHQ or BNF. The results suggest that MUF-GA is mostly secreted basolaterally in Caco-2 cell monolayers. Treatment with TBHQ or BNF significantly enhanced MUF-GA formation in the intact cell.


Structure, function and binding selectivity and stereoselectivity of siderophore-iron outer membrane transporters.
To get access to iron, microorganisms produce and release into their environment small organic metal chelators called siderophores. In parallel, they produce siderophore-iron outer membrane transporters (also called TonB-Dependent Transporters or TBDT) embedded in the outer membrane; these proteins actively reabsorb the siderophore loaded with iron from the extracellular medium. This active uptake requires energy in the form of the proton motive force transferred from the inner membrane to the outer membrane transporter via the inner membrane TonB complex. Siderophores produced by microorganisms are structurally very diverse with molecular weights of 150 up to 2000Da. Siderophore-iron uptake from the extracellular medium by TBDTs is a highly selective and sometimes even stereoselective process, with each siderophore having a specific TBDT. Unlike the siderophores, all TBDTs have similar structures and belong to the outer membrane β-barrel protein superfamily. The way in which the siderophore-iron complex passes through the TBDT is still unclear. In some bacteria, TBDTs are also partners of signaling cascades regulating the expression of proteins involved in siderophore biosynthesis and siderophore-iron acquisition.


[The effect of vitamin E on the survival rate and biochemical parameters such as isocitrate dehydrogenase, lactate and selected peptidases and proteases during endotoxic shock in the rat].
Protective effect of the investigated alpha-tocopherol solution regarding survival and changes of several biochemical parameters in rat endotoxin shock could already be demonstrated after application of the solvent (special oil HCO-60) alone. An additional effect of Vitamin E was observed only in DP IV activity and leukocyte counts.


The elementary events of Ca2+ release elicited by membrane depolarization in mammalian muscle.
Cytosolic [Ca(2+)] transients elicited by voltage clamp depolarization were examined by confocal line scanning of rat skeletal muscle fibres. Ca(2+) sparks were observed in the fibres' membrane-permeabilized ends, but not in responses to voltage in the membrane-intact area. Elementary events of the depolarization-evoked response could be separated either at low voltages (near -50 mV) or at -20 mV in partially inactivated cells. These were of lower amplitude, narrower and of much longer duration than sparks, similar to 'lone embers' observed in the permeabilized segments. Their average amplitude was 0.19 and spatial half-width 1.3 microm. Other parameters depended on voltage. At -50 mV average duration was 111 ms and latency 185 ms. At -20 mV duration was 203 ms and latency 24 ms. Ca(2+) release current, calculated on an average of events, was nearly steady at 0.5-0.6 pA. Accordingly, simulations of the fluorescence event elicited by a subresolution source of 0.5 pA open for 100 ms had morphology similar to the experimental average. Because 0.5 pA is approximately the current measured for single RyR channels in physiological conditions, the elementary fluorescence events in rat muscle probably reflect opening of a single RyR channel. A reconstruction of cell-averaged release flux at -20 mV based on the observed distribution of latencies and calculated elementary release had qualitatively correct but slower kinetics than the release flux in prior whole-cell measurements. The qualitative agreement indicates that global Ca(2+) release flux results from summation of these discrete events. The quantitative discrepancies suggest that the partial inactivation strategy may lead to events of greater duration than those occurring physiologically in fully polarized cells.


Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis.
Lung cancer mortality largely results from metastasis. Despite curative surgery many patients with early-stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background, we functionally screened for novel metastasis modulators using a barcoded shRNA library and an orthotopic lung cancer model. We identified aryl hydrocarbon receptor (AHR), a sensor of xenobiotic chemicals and transcription factor, as suppressor of lung cancer metastasis. Knockdown of endogenous AHR induces epithelial-mesenchymal transition signatures, increases invasiveness of lung cancer cells in vitro and metastasis formation in vivo. Low intratumoral AHR expression associates with inferior outcome of patients with resected lung adenocarcinomas. Mechanistically, AHR triggers ATF4 signaling and represses matrix metalloproteinase activity, both counteracting metastatic programs. These findings link the xenobiotic defense system with control of lung cancer progression. AHR-regulated pathways are promising targets for innovative anti-metastatic strategies.


Ultrastructural evidence for adrenergic nerve degeneration in the guinea pig uterus during pregnancy.
In the guinea pig myometrium, the adrenergic nerves selectively demonstrated at the ultrastructural level after treatment with 5-OH-DA, show varying degree of degeneration during pregnancy. The changes are more extensive in a late gestational stage (40-45 days) than in an early one (20-25 days), and are particularly evident in the uterus overlying the conceptus as compared to the regions between the fetuses. Scattered degenerative changes were also observed in myometrial specimens from virgin animals, but probably reflect the normal continuous turnover of axons.


The comparison of capnography and epigastric auscultation to assess the accuracy of nasogastric tube placement in intensive care unit patients.
Placement of nasogastric (NG) tubes is a common procedure for patients especially in intensive care units (ICUs). Thus, it is important to determine the correct placement of the tube to prevent misplacement in the airways. Accordingly, the aim of this study was to compare the epigastric auscultation and capnography in assessing the accuracy of NG tube insertion in ICU patients. In this descriptive comparative study, 60 patients were selected trough convenience sampling. After insertion of the NG tube in a standard method, the accuracy of placement of the tube with both epigastric auscultation and capnography was investigated. The NG tube insertion accuracy was then confirmed via radiography. Data analysis was performed using statistical software SPSS version 23. The result showed that capnography had a sensitivity, specificity, and accuracy of 100, 92.5, and 95% respectively, but epigastric auscultation had 90, 80, and 83.4% respectively. The Kappa agreement coefficient between two methods was - 0.759. The results revealed that the use of the capnography is preferable over the epigastric auscultation to confirm the correct insertion of the NG tube. It is recommended that more than one method be applied to detect and confirm the correct insertion of the NG tube.


Visual recognition impairment following medial thalamic lesions in monkeys.
Monkeys with surgical lesions which removed the medial portions of the medial and anterior thalamic nuclei were markedly impaired on a test of object recognition. The same animals were able to learn visual pattern discriminations and a spatial delayed response task at a normal rate. These findings indicate that lesions in the medial thalamus produce a selective impairment in visual recognition memory in monkeys and, consequently, may provide an experimental model for human "diencephalic amnesia".


Metal pollution in Spanish terrestrial ecosystems during the twentieth century.
We show here additional biological evidence of the alteration in global biogeochemistry by human activities during the twentieth century. The mineral concentration of herbarium specimens of 24 species of vascular plants and three species of bryophytes collected in North and East regions of Spain have substantially changed throughout the twentieth century. While V, a proxy tracer of oil pollution, exponentially increased in the last decades, other metals such as Cr, Ba, Sr, Al, Fe, Pb, Cd and Ti increased up to 1960-1970 and started to decrease in 1985-1995, when environmental legal regulations started to be effective. Multivariate principal component analysis showed an overall change in plant elemental concentrations throughout the different decades of the century and a clear separation of vascular plants and bryophytes. Likely important consequences for ecosystem structure and functioning and even for human health may be expected from these changes in mineral concentration.


Response of mouse liver coumarin 7-hydroxylase activity to hepatotoxins: dependence on strain and agent and comparison to other monooxygenases.
Acute effects of a single intraperitoneal dose of allyl alcohol (AA, 64 mg/kg), dimethylnitrosamine (DMNA, 30 mg/kg), hexachlorobutadiene (HCBD, 50 mg/kg), carbon tetrachloride (CCl4, 24 mg/kg), cocaine (60 mg/kg) and pyrazole (300 mg/kg) on the hepatic histology and monooxygenases in DBA/2 and C57Bl/6 strains of mice were investigated. All substances caused histologically verified injury to the liver, which varied in appearance and severity depending on the compound and the mouse strain. Responses of P450-catalyzed reactions were highly dependent on the toxin and varied between different monooxygenase (MO) reactions and two mouse strains. In DBA/2 strain, coumarin 7-hydroxylase (COH) activity was increased from 3- to 5-fold by pyrazole, cocaine, HCBD and CCl4. With respect to P450 content and other MO activities, no changes or even decreases were generally observed. Some exceptions to this rule were found: HCBD significantly increased T15 alpha OH, PROD and EROD activities in C57Bl/6 mice, whereas cocaine caused a significant stimulation of T15 alpha OH and PROD in DBA/2 mice, It is concluded that i) different hepatoxins cause different types of liver injury and responses of the monooxygenase complex ("hepatotoxinspecific finger prints"), ii) although DBA/2 and C57Bl/6 mice responded rather similarly to hepatotoxins, also with respect to P450 content and most MO activities, they displayed a profound difference in the behaviour of COH activity, and iii) within the P450 superfamily, the regulation of COH activity seems to be rather unique, also when compared to its structurally close enzyme, testosterone 15 alpha-hydroxylase.


Platelet shape changes and adhesion under high shear flow.
Recent studies have revealed that the platelet adhesive process under flow is tightly regulated by multiple ligand-receptor interactions. However, platelet morphological changes during this process, particularly its physiological relevance, remain unknown under blood flow conditions. Using epifluorescence and scanning electron microscopy, we evaluated the real-time changes in platelet morphology during a platelet adhesive process on a von Willebrand factor-coated surface under physiological high shear flow in a perfusion chamber. Here, we show that dynamic platelet shape changes occurring during distinct phases of the adhesive process are precisely regulated by "inside-out" and "outside-in" integrin signals and are also a key regulatory element in successful platelet thrombogenesis opposing rapid blood flow in vivo.


Caloric Intake From Fast Food Among Children and Adolescents in the United States, 2011-2012.
Consumption of fast food has been linked to weight gain in adults (1). Fast food has also been associated with higher caloric intake and poorer diet quality in children and adolescents (2). From 1994 through 2006, caloric intake from fast food increased from 10% to 13% among children aged 2-18 years (3). This report presents the most recent data on the percentage of calories consumed from fast food among U.S. children by sex, age group, race and Hispanic origin, poverty status, and weight status.


Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study.
Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.


The characteristic of the key aroma-active components in white tea using GC-TOF-MS and GC-olfactometry combined with sensory-directed flavor analysis.
White tea has become more and more popular with consumers due to its health benefits and unique flavor. However, the key aroma-active compounds of white tea during the aging process are still unclear. Thus, the key aroma-active compounds of white tea during the aging process were investigated using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and gas chromatography-olfactometry (GC-O) combined with sensory-directed flavor analysis. A total of 127 volatile compounds were identified from white tea samples with different aging years by GC-TOF-MS. Fifty-eight aroma-active compounds were then determined by GC-O, and 19 of them were further selected as the key aroma-active compounds based on modified frequency (MF) and odor activity value (OAV). Aroma recombination and omission testing confirmed that 1-octen-3-ol, linalool, phenethyl alcohol, geraniol, (E)-β-ionone, α-ionone, hexanal, phenylacetaldehyde, nonanal, (E, Z)-(2,6)-nonadienal, safranal, γ-nonalactone and 2-amylfuran were the common key aroma-active compounds to all samples. Cedrol, linalool oxide II and methyl salicylate were confirmed peculiar in new white tea, while β-damascenone and jasmone were peculiar in aged white tea. This work will offer support for further studies on the material basis of flavor formation of white tea. © 2023 Society of Chemical Industry.


A retrospective study on patients with chronic knee pain treated with ultrasound-guided radiofrequency of the genicular nerves (RECORGEN trial).
Radiofrequency (RF) treatment of the genicular nerves is a promising treatment for chronic osteoarthritic and persistent postsurgical knee pain (PPSP), refractory to conventional medical management. The RECORGEN study is a retrospective single-center cohort study of patients treated with ultrasound-guided conventional RF of the genicular nerves for chronic knee pain in Hospital Oost-Limburg, Genk from September 2017 to June 2020. Subgroup analysis based on etiology of pain (PPSP and degenerative knee pain) was performed in addition to the total study population analysis. Outcome parameters were global perceived effect (GPE), Numeric Rating Scale for pain, consumption of strong opioids, and safety of the treatment at 6 weeks and cross-sectionally at a variable time point. Treatment success was defined as GPE≥50%. Sixty-eight cases were screened of which 59 (46 diagnosed with PPSP and 13 with degenerative knee pain) were included in the study. Treatment success at 6 weeks was achieved in 19 of 59 interventions (32.2%) and was similar in both groups. Seventeen responders were evaluated at follow-up. 45.1% (8/17) continued to have a positive effect at the second time point. The mean duration of effect of the RF treatment was 8.3 months. Safety analysis at 6 weeks and at the second time point showed a good safety profile of the treatment. Conventional RF of the genicular nerves was clinically successful in more than 30% of the study population refractory to conventional medical management. Overall, the treatment was well tolerated. The mean duration of effect was 8.3 months.


The cochlear microphonic potential does not reflect the passive basilar membrane traveling wave.
Understanding the cochlear microphonic potential (CM) can contribute to its clinical usefulness, e.g. in auditory neuropathy where the CM is present, while auditory evoked neural potentials are absent. The space-time pattern of the basilar membrane traveling wave in the cochlea is thought to be responsible for generation of the CM and its pattern along the cochlea. This relationship was studied in two experiments. EXPERIMENT I: The threshold of the CM was measured in animals before and after drilling a hole in the wall of the inner ear vestibule. Such a hole likely reduces the magnitude of the basilar membrane traveling wave. The hole did not cause a change in CM threshold. This is evidence that the passive basilar membrane traveling wave described by von Bekesy in cadavers in response to high intensity stimulation may not be the trigger for cochlear activation and CM generation at low intensities. EXPERIMENT II: A saline filled tube provided fluid coupling between the cochlea of one animal and that of a second through the perforated round windows of their cochleae. In response to sound stimulation of animal 1, CM (and ABR) could be recorded in animal 2, even when animal 1 was no longer living. It is highly unlikely that a basilar membrane traveling wave could have been induced in cochlea 2 in these conditions. It is therefore suggested that at low sound intensities, the initial event activating the cochlea in general and the CM in particular is the fluid pressures (condensations/rarefactions) induced in the cochlear fluids by sound-induced stapes footplate vibrations.


Can an extracorporeal glenoid aiming device be used to optimize the position of the glenoid component in total shoulder arthroplasty?
Successful total shoulder arthroplasty (TSA) requires a correct position of the glenoid component. This study compares the accuracy of the positioning with a new developed glenoid aiming device and virtual three-dimensional computed tomography (3D-CT) scan positioning. On 39 scapulas from cadavers, a K-wire (KDev) was positioned using the glenoid aiming device. It consists of glenoid components connected to the aiming device, which cover 150° of the inferior glenoid circle, has a fixed version and inclination and is available with several different radii. The aiming device is stabilized at the most medial scapular point. The K-wire is drilled from the center of the glenoid component to this most medial point. All scapulas were also scanned with CT and 3D reconstructed. A virtual K-wire (Kct) was positioned in the center of the glenoid and in the scapular plane. Several parameters were compared. Radius of the chosen glenoid component (rDev) and the virtual radius of the glenoid circle (rCT), spinal scapular length with the device (SSLdev) and virtual (SSLct), version and inclination between KDev and Kct, difference between entry point and exit point ("Matsen"-point). Mean rDev: 14 mm ± 1.7 mm and mean rCT: 13.5 mm ± 1.6 mm. There was no significant difference between SSLdev (110.6 mm ± 7.5 mm) and SSLct (108 mm ± 7.5 mm). The version of KDev and Kct was -2.53° and -2.17° and the inclination 111.29° and 111.66°, respectively. The distance between the "Matsen-point" device and CT was 1.8 mm. This glenoid aiming device can position the K-wire on the glenoid with great accuracy and can, therefore, be helpful to position the glenoid component in TSA. The level of evidence: II.


The renal clearance and infusion clearance of inulin are similar, but not identical.
Thirty-eight simultaneous renal (R-Cin) and infusion (INF-Cin) clearances of inulin were done. The equilibration period preceding the clearance studies was of at least two hours duration. The R-Cin on each subject was based on two clearance periods during which the plasma inulin concentration ([P(in)]) varied by 1.0 mg/dl or less and the rate of inulin excretion by less than 10%. There was excellent correlation between the R-Cin and the INF-Cin (r = 0.976), but the INF-Cin consistently exceeded the R-Cin (mean difference = 13.8 +/- 8.8 ml/min/1.73 m2, t = 9.7163 and P = < 0.001). Complete equilibration of inulin in body fluids has been assumed when [P(in)] levels were relatively constant (variation < 10%). However, complete equilibration of inulin would not be present, even with relatively constant P(in) levels, if the rate of infusion of inulin were equal to the rate of excretion plus the rate of penetration of inulin into less permeable components of the extracellular fluid compartment (that is, dense connective tissue solids). Estimation of glomerular filtration rate using the INF-Cin requires complete equilibration of inulin in body fluids, a process probably requiring 12 to 15 hours or longer.


Altered metabolite levels and correlations in patients with colorectal cancer and polyps detected using seemingly unrelated regression analysis.
Metabolomics technologies enable the identification of putative biomarkers for numerous diseases; however, the influence of confounding factors on metabolite levels poses a major challenge in moving forward with such metabolites for pre-clinical or clinical applications. To address this challenge, we analyzed metabolomics data from a colorectal cancer (CRC) study, and used seemingly unrelated regression (SUR) to account for the effects of confounding factors including gender, BMI, age, alcohol use, and smoking. A SUR model based on 113 serum metabolites quantified using targeted mass spectrometry, identified 20 metabolites that differentiated CRC patients (n = 36), patients with polyp (n = 39), and healthy subjects (n = 83). Models built using different groups of biologically related metabolites achieved improved differentiation and were significant for 26 out of 29 groups. Furthermore, the networks of correlated metabolites constructed for all groups of metabolites using the ParCorA algorithm, before or after application of the SUR model, showed significant alterations for CRC and polyp patients relative to healthy controls. The results showed that demographic covariates, such as gender, BMI, BMI2, and smoking status, exhibit significant confounding effects on metabolite levels, which can be modeled effectively. These results not only provide new insights into addressing the major issue of confounding effects in metabolomics analysis, but also shed light on issues related to establishing reliable biomarkers and the biological connections between them in a complex disease.


High yield exogenous protein HPL production in the Bombyx mori silk gland provides novel insight into recombinant expression systems.
The silk gland of Bombyx mori (BmSG) has gained significant attention by dint of superior synthesis and secretion of proteins. However, the application of BmSG bioreactor is still a controversial issue because of low yields of recombinant proteins. Here, a 3057 bp full-length coding sequence of Hpl was designed and transformed into the silkworm genome, and then the mutant (Hpl/Hpl) with specific expression of Hpl in posterior BmSG (BmPSG) was obtained. In the mutants, the transcription level of Fib-L and P25, and corresponding encoding proteins, did not decrease. However, the mRNA level of Fib-H was reduced by 71.1%, and Fib-H protein in the secreted fibroin was decreased from 91.86% to 71.01%. The mRNA level of Hpl was 0.73% and 0.74% of Fib-H and Fib-L, respectively, while HPL protein accounted for 18.85% of fibroin and 15.46% of the total amount of secreted silk protein. The exogenous protein was therefore very efficiently translated and secreted. Further analysis of differentially expressed gene (DEG) was carried out in the BmPSG cells and 891 DEGs were detected, of which 208 genes were related to protein metabolism. Reduced expression of endogenous silk proteins in the BmPSG could effectively improve the production efficiency of recombinant exogenous proteins.


Environmentally-specified patterns of movement coordination in normal and split-brain subjects.
Rhythmic movement patterns between the hands in response to environmental signals are studied in normal (musicians and nonmusicians) and split-brain subjects. Only two phase-locked states - in-phase and anti-phase - are shown to be stable for all subjects. Split-brain subjects show an even greater attraction to these patterns, thus providing no support for the notion that reduced cortical interaction between the hemispheres allows for independent visuomotor control of the hands in such tasks. Moreover, differences in trajectories produced by normal individuals and those without an intact corpus callosum are remarkable. The resultant patterns of coordination afford 1) a generalization of previous results on intrisincally generated rhythmic behavior to environmentally-specified movement patterns; and 2) a discussion of neural mechanisms underlying stable phase relations.


Knowledge, Attitudes, and Perceptions Towards Hand Hygiene of Optometry Students Pre- and Peri-COVID-19 at a Tertiary Institution in Johannesburg, South Africa.
Limited research has been completed relating to the knowledge, attitudes and practices (KAP) towards hand hygiene in optometry. The necessity of identifying possible gaps in the cycle of the optometric examination that may have an impact on standard hygiene practices is essential, especially seen in the context of the COVID-19 pandemic. The purpose of the study was to determine if optometry students' KAP towards hand hygiene changed pre- and peri-COVID-19 to minimize the risk of possible infection it may have for their patients, family, and themselves. A cross-sectional purposeful sample study was completed among optometry students at a training institution in Johannesburg, South Africa, pre- (2019) and peri-COVID-19 (2022). The WHO hand hygiene knowledge and perception questionnaires for health care workers were adapted and used in the current study. Statistical analyses were performed to test for significant changes between the two groups. There was a significant change (p < 0.01) in the use of alcohol-based hand rub (ABHR) in 2022 (87.2%) compared to 2019 (46.5%), although only 41% of students peri-COVID-19 (2022), were aware that a minimum of 20 seconds is required to effectively clean hands. Students, both pre-COVID-19 (63.8%) and peri-COVID-19 (81.8%) perceived performing a hand hygiene regime during an optometric examination to be problematic. A significant peri-COVID-19 (2022) change in perception (p < 0.01) regarding the importance of completing required hand hygiene practices in front of a patient during examination was seen. The COVID-19 pandemic provided a unique opportunity to research a possible change in KAP towards hand hygiene practices in optometry students that have not been investigated before. Students were more aware of the impact of hand hygiene practices and the perception thereof, especially by patients and fellow students during the peri-COVID-19 (2022) period. An important finding was the difficulty that students experienced to perform a hand hygiene regime during an optometric examination.


A model of IP3 receptor with a luminal calcium binding site: stochastic simulations and analysis.
We have constructed a stochastic model of the inositol 1,4,5-trisphosphate receptor-Ca2+ channel that is based on quantitative measurements of the channel's properties. It displays the observed dependence of the open probability of the channel with cytosolic [Ca2+] and [IP3] and gives values for the dwell times that agree with the observations. The model includes an explicit dependence of channel gating with luminal calcium. This not only explains several observations reported in the literature, but also provides a possible explanation of why the open probabilities and shapes of the bell-shaped curves reported in [Nature 351 (1991) 751] and in [Proc. Natl. Acad. Sci. U.S.A. 269 (1998) 7238] are so different.


Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran.
Medicinal plants are an important element of medical system. These resources are usually regarded as part of cultural traditional knowledge. We present for the first time the results of an ethnobotanical survey in Kohghiluyeh va Boyer Ahmad province of Iran, conducted between 2008 and 2010. This information could be the basis of an evidence based investigation to discover new drugs. Ethnobotanical data were analyzed by use-reports in addition important indices like relative frequency of citation (RFC) and cultural importance index (CI) were calculated. Totally 23 informants were interviewed. Our study reports 138 traditionally used plant species, belonging to 52 plant families from this province. Asteraceae and Lamiaceae are the dominant locally used families. The highest number of species and application were reported for digestive system disorder, metabolic disorder and respiratory system, respectively. The part of the plant most frequently used was the aerial part (31.9%), leaves (14.8%) and fruits (11.7%). The plants are used both for medicinal and non-medicinal purposes. Daphne mucronata Royle. and Teucrium polium L. have the largest value of relative frequency of citation and cultural importance index, respectively. Kohghiluyeh va Boyer Ahmad has good ethnobotanical potential for medicinal plants. This study is the first contribution to the ethnobotany of this region. We have gathered from this province some considerable knowledge about local medicinal plants for treating common health problem that is ready to be further investigated in the laboratory.


Radiographic Parameters in Cervical Myelopathy: Review of Current Literature.
This was a narrative review. Provide a comprehensive review of radiographic alignment parameters and their effect on procedure selection, surgical decision-making, and clinical outcomes for the treatment of cervical spondylotic myelopathy (CSM). The use of radiographic parameters to predict prognosis and surgical outcomes in patients with CSM is an evolving field given the complex presentation of patients with this condition. A literature search was conducted using PubMed for surgical treatment of CSM, with an emphasis on cervical radiographic parameters and clinical outcomes. The principal goals of spine surgery can be broken down into decompression, stabilization, and restoration of alignment. The principle of restoring balance takes careful preoperative planning and attention to radiographic parameters including cervical lordosis, C2-C7 sagittal vertical axis, neck tilt, thoracic inlet angle, T1 slope, K-line, and modified K-line. Surgical interventions for CSM include anterior cervical discectomy and fusion, posterior cervical fusion, or laminoplasty and careful consideration of radiographic measures guide surgical decision-making is essential to ensure optimal outcomes. Utilization of key radiographic parameters in surgical planning and decision-making allows surgeons to optimize clinical outcomes for CSM. Level V.


Hospital-onset IgA vasculitis triggered by infectious endocarditis.
This is a case of IgA vasculitis developed in the hospital during treatment of infective endocarditis. When purpura appears in a patient under IE treatment, we should consider IgA vasculitis as a differential diagnosis and check renal function.


The use of sugar-coated beads to study phagocytosis in normal and dystrophic retina.
In this study, a technique is described for coupling the sugars to carboxylated latex beads for use in phagocytic studies of dystrophic and normal retinal pigment epithelium. The presence and distribution of the sugars, mannose and fucose, on the bead surfaces are visualized by transmission electron microscopy using the lectin-Ferritin conjugates. Concanavalin A-Ferritin (Con A-Fe) and Ulex-europeus-Ferritin (Ulex-Fe), respectively. Both lectin-Ferritin conjugates label the surfaces of the sugar coated beads. Control experiments to determine the extent of nonspecific lectin-Ferritin binding using Con A-Fe with fucose-coated beads, Ulex-Fe with mannose-coated beads, or beads without coupling reagent show little to no labeling. Lectin-Ferritin conjugates are also incubated with the appropriate sugar-coated beads and their competing sugars and little to no labeling is observed. Our data shows that when sugar-coated beads are presented to retinal pigment epithelial explants, differences in phagocytic uptake are observed. Uncoated beads are avidly taken up by normal and dystrophic tissue, but fucose-coated beads are not taken up by either. Twice as many mannose beads are phagocytized by the normal as compared to dystrophic tissue. It remains to be established whether these differences in bead uptake indicate a difference in ligand-receptor interactions between normal and dystrophic retinal pigment epithelium.


Neurological condition at birth in relation to the electroencephalogram (EEG) and visual evoked potential (VEP) at the age of 5.
The correlation between the neonatal neurological condition (Prechtl) and VEP and EEG parameters at the age of 5 have been investigated in 87 normal children. It was found that the more optimal the neurological condition at birth, the shorter the VEP peak latencies (especially of the late components) at the age of 5. Only few and weak correlations between the neonatal condition and EEG at the age of 5 were found. The VEP appears to be a more sensitive detector for late sequelae of supposed perinatal neurological problems than EEG. VEP changes can be explained by "inattention' or "distraction'. Another factor may be delayed maturation.


Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug; (-)-C75 has antitumor activity.
C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identifying it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential different biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that (-)-C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.


Recombinant expression and molecular engineering of the keratinase from Brevibacillus parabrevis for dehairing performance.
Keratinase is capable of distinctive degradation of keratin, which provides an eco-friendly approach for keratin waste management towards sustainable development. In this study, the recombinant keratinase (KERBP) from Brevibacillus parabrevis was successfully expressed in Escherichia coli. The purified KERBP had the specific activity of 6005.3 U/mg. It showed remarkable tolerance to various surfactants and also no collagenolytic activity. However, the moderate thermal stability limited its further application. Thus, protein engineering was further adopted to improve its stability. The variants of T218S, S236C and N181D were constructed by site-directed mutagenesis and combinatorial mutagenesis. Compared with the wild type, the t1/2 at 60 °C for the variants T218S, S236C and N181D were 3.05-, 1.18- and 1-fold increase, respectively. Moreover, the double variants N181D-T218S and N181D-S236C significantly improved thermostability with 5.1 and 2.9 °C increase of T50, and prolonging t1/2 at 60 °C with 4.09 and 1.54-fold, respectively. And the catalytic efficiency of the T218S and N181D-T218S variants was also significantly improved. Furthermore, the keratinase displayed favorable ability to dehair wool from skin within 7 h, which showed potential in leather dehairing. Our work contributes to a further insight into the thermostability of keratinase and offers a promising alternative for industrial leather application.


MAFLD and risk of CKD.
Whereas nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and extra-hepatic diseases is not known. The aim of this cross-sectional study was to compare the prevalence of chronic kidney disease (CKD) in patients with either MAFLD or NAFLD, and then to examine the association between the presence and severity of MAFLD and CKD and abnormal albuminuria. A total of 12,571 individuals with complete biochemical and liver ultrasonography data from the Third National Health and Nutrition Examination Survey (1988-1994) were included in the analysis. Multivariable logistic regression analyses were performed to test the independence of associations between MAFLD or MAFLD severity as the key exposures and CKD (defined as either CKD stage ≥1 or stage ≥3) or abnormal albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol) as the outcomes. The prevalence of MAFLD and NAFLD was 30.2% (n = 3794) and 36.2% (n = 4552), respectively. MAFLD individuals had a lower eGFR (74.96 ± 18.21 vs. 76.46 ± 18.24 ml/min/1.73 m2, P < 0.001) and a greater prevalence of CKD (29.60% vs. 26.56%, P < 0.05) than NAFLD individuals. Similarly, there was a higher prevalence CKD in MAFLD than in non-metabolic dysfunction-associated NAFLD (P < 0.05). Notably, after adjustment for sex, age, ethnicity, alcohol intake and diabetes, the severity of MAFLD (i.e. NAFLD fibrosis score ≥ 0.676) was associated with 1.34-fold higher risk of prevalent CKD (P < 0.05). MAFLD identifies patients with CKD better than NAFLD. MAFLD and MAFLD with increased liver fibrosis score are strongly and independently associated with CKD and abnormal albuminuria.


Low-Rank Approximation via Generalized Reweighted Iterative Nuclear and Frobenius Norms.
The low-rank approximation problem has recently attracted wide concern due to its excellent performance in real-world applications such as image restoration, traffic monitoring, and face recognition. Compared with the classic nuclear norm, the Schatten-p norm is stated to be a closer approximation to restrain the singular values for practical applications in the real world. However, Schatten-p norm minimization is a challenging non-convex, non-smooth, and non-Lipschitz problem. In this paper, inspired by the reweighted ℓ1 and ℓ2 norm for compressive sensing, the generalized iterative reweighted nuclear norm (GIRNN) and the generalized iterative reweighted Frobenius norm (GIRFN) algorithms are proposed to approximate Schatten-p norm minimization. By involving the proposed algorithms, the problem becomes more tractable and the closed solutions are derived from the iteratively reweighted subproblems. In addition, we prove that both proposed algorithms converge at a linear rate to a bounded optimum. Numerical experiments for the practical matrix completion (MC), robust principal component analysis (RPCA), and image decomposition problems are illustrated to validate the superior performance of both algorithms over some common state-of-the-art methods.


Molecular Genetic Etiology and Revisiting the Middle Ear Surgery Outcomes of Branchio-Oto-Renal Syndrome: Experience in a Tertiary Referral Center.
To explore the phenotypes and genotypes of patients with branchio-oto-renal (BOR) and branchio-otic (BO) syndrome, and to analyze the middle ear surgery outcomes qualitatively and quantitatively, proposing a factor usefully prognostic of surgical outcomes. Retrospective cohort study. Tertiary referral center. Eighteen patients with BOR/BO syndrome in 12 unrelated Korean families. Middle ear surgery, including either stapes surgery or ossicular reconstruction. Clinical phenotypes, genotypes, and middle ear surgery outcomes. Eight probands (66.7%) were confirmed genetically; the condition segregated as a dominant or de novo trait. Six EYA1 heterozygous variants were identified by exome sequencing and multiplex ligation-dependent probe amplification. All variants were pathogenic or likely pathogenic based on the ACMG/AMP guidelines. Two novel EYA1 frameshift variants (p.His373Phefs*4 and p.Gln543Asnfs*90) truncating a highly conserved C-terminal Eya domain were identified, expanding the genotypic spectrum of EYA1 in BOR/BO syndrome. Remarkably, middle ear surgery was individualized to ensure optimal audiological outcomes and afforded significant audiological improvements, especially in BOR/BO patients without enlarged vestibular aqueducts (EVAs). A significant difference in air-bone gap closure after middle ear surgery was noted between the two groups even after adjusting for confounders: -20.5 dB in ears without EVAs (improvement) but 0.8 dB in ears with EVAs (no change or deterioration). Furthermore, the success rate was significantly associated with the absence of EVA. The results of this study were against the notion that middle ear surgery is always contraindicated in patients with BOR/BO syndrome, and an EVA could be a negative prognostic indicator of middle ear surgery in BOR/BO patients. This may aid to determine the strategy of audiological rehabilitation in patients with BOR/BO syndrome.