Microplastics in aquaculture systems: Occurrence, ecological threats and control strategies.
With the intensification of microplastic pollution globally, aquaculture environments also face risks of microplastic contamination through various pathways such as plastic fishing gear. Compared to wild aquatic products, cultured aquatic products are more susceptible to microplastic exposure through fishing tackle, thus assessing the impacts of microplastics on farmed species and human health. However, current research on microplastic pollution and its ecological effects in aquaculture environments still remains insufficient. This article comprehensively summarizes the pollution characteristics and interrelationships of microplastics in aquaculture environments. We analyzed the influence of microplastics on the sustainable development of the aquaculture industry. Then, the potential hazards of microplastics on pond ecosystems and consumer health were elucidated. The strategies for removing microplastics in aquaculture environments are also discussed. Finally, an outlook on the current challenge and the promising opportunities in this area was proposed. This review aims to evaluate the value of assessing microplastic pollution in aquaculture environments and provide guidance for the sustainable development of the aquaculture industry.


The interplay between ASMase signaling pathway and NLRP3 in the epithelial to mesenchymal transition of HBE cells induced by silica.
Epithelial-mesenchymal transition (EMT) is an important part of pulmonary fibrosis. Our earlier study illustrated that the acid sphingomyelinase (ASMase) pathway plays significant role in silica (SiO2 )-induced transformation of lung fibroblasts into myofibroblasts. The metabolite of ASMase, ceramide (Cer), activates the inflammatory response by activating Nod-like receptor protein 3 (NLRP3) in macrophages, and NLRP3 is also involved in the EMT process. However, whether ASMase and NLRP3 are involved in regulating SiO2 -induced EMT has not been confirmed. In this study, an in vitro model of EMT in human bronchial epithelial (HBE) cells was established by SiO2 dust staining to investigate the role of ASMase and NLRP3 in EMT and to provide new clues for the molecular mechanism of silicosis. HBE cells were stained with 100 μg/ml SiO2 dust for 72 h to establish the EMT model. The ASMase inhibitor desipramine decreased the level of S1P and the expression of α-smooth muscle actin (α-SMA) and NLRP3 in SiO2 dust-stained HBE cells, whereas the expression of E-cadherin (E-cad) increased. The NLRP3 inhibitor MCC950 inhibited the secretion of interleukin-1β (IL-1β) and decreased the expression of NLRP3, Caspase-1, and α-SMA in SiO2 dust-stained HBE cells, whereas E-cad expression increased and ASMase activity and S1P levels decreased. It was concluded that SiO2 dust increases the release of the inflammatory factor and induces EMT in HBE cells. Inhibition of ASMase activity or NLRP3 expression reduced the SiO2 dust-induced cell inflammatory response and slowed the occurrence of EMT in HBE cells. Therefore, NLRP3 and ASMase may interact in SiO2 dust-induced EMT in HBE cells.


Pregnancy with retained intrauterine device: national-level assessment of characteristics and outcomes.
Although intrauterine devices provide effective contraceptive protection, unintentional pregnancy can occur. Previous studies have shown that a retained intrauterine device during pregnancy is associated with adverse pregnancy outcomes but there is a paucity of nationwide data and analysis. This study aimed to describe characteristics and outcomes of pregnancies with a retained intrauterine device. This serial cross-sectional study used data from the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population comprised 18,067,310 hospital deliveries for national estimates from January 2016 to December 2020. The exposure was retained intrauterine device status, identified by the World Health Organization's International Classification of Diseases, Tenth Revision, code O26.3. The co-primary outcome measures were incidence rate, clinical and pregnancy characteristics, and delivery outcome of patients with a retained intrauterine device. To assess the pregnancy characteristics and delivery outcomes, an inverse probability of treatment weighting cohort was created to mitigate the prepregnant confounders for a retain intrauterine device. A retained intrauterine device was reported in 1 in 8307 hospital deliveries (12.0 per 100,000). In a multivariable analysis, Hispanic individuals, grand multiparity, obesity, alcohol use, and a previous uterine scar were patient characteristics associated with a retained intrauterine device (all P<.05). Current pregnancy characteristics associated with a retained intrauterine device included preterm premature rupture of membrane (9.2% vs 2.7%; adjusted odds ratio, 3.15; 95% confidence interval, 2.41-4.12), fetal malpresentation (10.9% vs 7.2%; adjusted odds ratio, 1.47; 95% confidence interval, 1.15-1.88), fetal anomaly (2.2% vs 1.1%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.85), intrauterine fetal demise (2.6% vs 0.8%; adjusted odds ratio, 2.21; 95% confidence interval, 1.37-3.57), placenta malformation (1.8% vs 0.8%; adjusted odds ratio, 2.12; 95% confidence interval, 1.20-3.76), placenta abruption (4.7% vs 1.1%; adjusted odds ratio, 3.24; 95% confidence interval, 2.25-4.66), and placenta accreta spectrum (0.7% vs 0.1%; adjusted odds ratio, 4.82; 95% confidence interval, 1.99-11.65). Delivery characteristics associated with a retained intrauterine device included previable loss at <22 weeks' gestation (3.4% vs 0.3%; adjusted odds ratio, 5.49; 95% confidence interval, 3.30-9.15) and periviable delivery at 22 to 25 weeks' gestation (3.1% vs 0.5%; adjusted odds ratio, 2.81; 95% confidence interval, 1.63-4.86). Patients in the retained intrauterine device group were more likely to have a diagnosis of retained placenta at delivery (2.5% vs 0.4%; adjusted odds ratio, 4.45; 95% confidence interval, 2.70-7.36) and to undergo manual placental removal (3.2% vs 0.6%; adjusted odds ratio, 4.81; 95% confidence interval, 3.11-7.44). This nationwide analysis confirmed that pregnancy with a retained intrauterine device is uncommon, but these pregnancies may be associated with high-risk pregnancy characteristics and outcomes.


Topography of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy: results of a combined molecular and histopathologic mapping study.
To determine the anatomic extent of pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients at the time of radical prostatectomy (RP), knowledge about the topography of lymph node (LN) metastases is required. Because small-volume LN metastases may be missed by standard histopathologic examination, we performed an anatomic mapping study combining molecular and histopathologic LN examination in PCa patients treated with RP and extended PLND (ePLND). A total of 52 patients with intermediate- (n=15) and high-risk (n=37) PCa underwent RP and ePLND without neoadjuvant treatment. ePLND included dissection of the obturator fossa and the external, internal, and common iliac vessels. LNs ≥3 mm in diameter were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for prostate-specific antigen (PSA) expression and by standard histopathology. Topography of positive LNs was determined descriptively. Of 1469 dissected LNs (median: 27 LNs per patient), 1186 LNs were ≥3 mm. Molecular LN analysis was positive in 127 LNs of 27 patients (52%) including 32 LNs of 12 patients (23%) with histopathologic positive LNs. Molecular examination was negative in 3 of 35 histopathologic positive LNs (9%). Combining both molecular and histopathologic findings, positive LNs were located in the standard PLND field defined by obturator fossa and external iliac vessels in 71%, along the internal iliac vessels in 16%, and along the common iliac vessels in 13%. Of LN-positive patients, 63% had LN metastases outside the standard PLND field. The internal iliac field was involved in 48% and the common iliac field in 37% of node-positive patients. Notably, internal and common iliac vessels were the only positive regions in 7% and 11% of node-positive patients, respectively. A limitation is the small number of patients included. These findings underline the enhanced sensitivity of qRT-PCR in comparison with standard histopathology for detection of small-volume LN metastases in PCa patients. Our results support an ePLND including the common iliac vessels, at least up to the ureteral crossing, to optimise nodal staging and to remove LNs potentially harbouring metastases.


[MRI for myocarditis].
Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation.


The early development of the human subcommissural organ.
The human subcommissural organ appears in the second month of intrauterine life, in a 27 mm embryo, later than the posterior commissure and concurrently with the pineal gland.


Atenolol and metoprolol: comparison of effects on blood pressure and serum lipoproteins, and side effects.
Several beta-blockers increase VLDL-TG and decrease HDL-cholesterol concentrations. The underlying mechanism is not yet clear. Some studies have suggested that the effect is less pronounced during treatment with selective beta-blockers. The effects of 2 such drugs, metoprolol 200 mg/day and atenolol 50 mg/day, have been compared in 50 hypertensive patients (WHO Stage I-II), mean age 47 years. Serum lipoproteins were determined in 20 patients before treatment and after treatment with either drug for 3 months. Both drugs were equally effective in reducing blood pressure. After atenolol the initial VLDL-cholesterol concentration of 1.04 mmol/l had not changed, but it rose to 1.29 mmol/l after metoprolol (p less than 0.05). The HDL-cholesterol concentration 1.42 mmol/l did not fall during atenolol treatment, but during metoprolol there was a small reduction to 1.31 mmol/l (p less than 0.05). Hyperlipoproteinaemia is common in hypertensive patients, 40% of the present group had hypertriglyceridaemia and 25% had hypercholesterolaemia. Thus, atenolol 50 mg was found not to affect lipoproteins, whereas metoprolol 200 mg increased the VLDL concentration in 75% of the patients.


Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients.
Although the induction of anaesthesia with remifentanil often causes bradycardia, the relationship between the effect-site concentration (Ce) of remifentanil and instantaneous heart rate (HR) has remained unclear. The present study examined the relationship between instantaneous HR and remifentanil Ce at the induction of anaesthesia with and without propofol hypnosis, to facilitate safe management of anaesthesia induction with remifentanil. Instantaneous HR was calculated every 5 s using an electrocardiographic real-time analysis system (MemCalc/Makin2; GMS, Tokyo, Japan). At the beginning of anaesthesia induction, continuous infusion of remifentanil (1 μg min-1 kg-1) preceded hypnosis with propofol in 13 patients [non-hypnosis group; mean age, 67.8 (17.5) years], while propofol bolus (30-50 mg) was injected together with continuous remifentanil medication in 18 patients [hypnosis group; mean age, 62.9 (16.5) years]. Remifentanil Ce was estimated every 5 s using the three-compartment model proposed by Minto et al. and the relationship between estimated remifentanil Ce and instantaneous HR was examined. In the hypnosis group, HR was significantly lower than basal HR when remifentanil Ce was increased to 3.5 ng ml-1 (p < 0.05), whereas no significant HR reduction was found in the non-hypnosis group until remifentanil Ce reached >5 ng ml-1 (p < 0.05). The induction of anaesthesia using remifentanil with propofol hypnotics significantly reduces HR even in a low remifentanil Ce insufficient to suppress the cardiovascular response at tracheal intubation. Preparations to treat bradycardia are recommended for the safe management of anaesthesia induction when remifentanil is combined with hypnotics.


Distribution of weight, stature, and growth status in children and adolescents with spinal muscular atrophy: An observational retrospective study in the United States.
Data regarding weight, height/length, and growth status of patients with spinal muscular atrophy (SMA) who have received only supportive care are limited. This cross-sectional study describes these measurements in patients with Type 1 and Types 2/3 SMA and compares them with reference values from typically developing children. Retrospective baseline data from three sites in the Pediatric Neuromuscular Clinical Research Network (Boston, New York, Philadelphia) were used. Descriptive statistics for weight, height/length, body mass index-for-age, as well as weight-for-length and absolute and relative deviations from reference values (ie, 50th percentile from World Health Organization/Centers for Disease Control growth charts) were calculated. Furthermore, growth status was reported. A total of 91 genetically confirmed patients with SMA receiving optimal supportive care and without any disease-modifying treatment were stratified into Types 1 (n = 28) and 2/3 SMA (n = 63). Patients with Type 1 SMA weighed significantly less (median = -7.5%) compared with reference values and patients with Types 2/3 SMA were significantly shorter (mean = -3.0%) compared with reference values. The median weight was considerably below the 50th percentile in both groups of patients, even if they received a high standard of care and proactive feeding support. More research is needed to understand which factors influence growth longitudinally, and how to accurately capture growth in patients with SMA. Further research should investigate the best time to provide feeding support to avoid underweight, especially in patients with Type 1, and how to avoid the risk of overfeeding, especially in patients with Types 2/3 SMA.


Diverse biological responses to different cardiotonic steroids.
Cardiotonic steroids (CS) such as ouabain, digoxin and bufalin, are steroidal drugs prepared from the seeds and dried leaves of the genus Digitalis, and the skin and parotid gland of amphibians, are used as a cardiac stimulant. Steroids similar or identical to the cardiotonic steroids were identified in human tissues. The available literature unequivocally supports the notion that these endogenous CS function as hormones in mammals. Recent studies show that although similar in structure, the different CS exhibit diverse biological responses. This was shown at the molecular, cellular, tissue and whole animal levels. This review summarizes these diversities, raises a possible explanation for their presence and discusses their implication on the physiological role of the different steroids.


Distinct patterns of gene expression in the medial preoptic area are related to gregarious singing behavior in European starlings (Sturnus vulgaris).
Song performed in flocks by European starlings (Sturnus vulgaris), referred to here as gregarious song, is a non-sexual, social behavior performed by adult birds. Gregarious song is thought to be an intrinsically reinforced behavior facilitated by a low-stress, positive affective state that increases social cohesion within a flock. The medial preoptic area (mPOA) is a region known to have a role in the production of gregarious song. However, the neurochemical systems that potentially act within this region to regulate song remain largely unexplored. In this study, we used RNA sequencing to characterize patterns of gene expression in the mPOA of male and female starlings singing gregarious song to identify possibly novel neurotransmitter, neuromodulator, and hormonal pathways that may be involved in the production of gregarious song. Differential gene expression analysis and rank rank hypergeometric analysis indicated that dopaminergic, cholinergic, and GABAergic systems were associated with the production of gregarious song, with multiple receptor genes (e.g., DRD2, DRD5, CHRM4, GABRD) upregulated in the mPOA of starlings who sang at high rates. Additionally, co-expression network analyses identified co-expressing gene clusters of glutamate signaling-related genes associated with song. One of these clusters contained five glutamate receptor genes and two glutamate scaffolding genes and was significantly enriched for genetic pathways involved in neurodevelopmental disorders associated with social deficits in humans. Two of these genes, GRIN1 and SHANK2, were positively correlated with performance of gregarious song. This work provides new insights into the role of the mPOA in non-sexual, gregarious song in starlings and highlights candidate genes that may play a role in gregarious social interactions across vertebrates. The provided data will also allow other researchers to compare across species to identify conserved systems that regulate social behavior.


A simple cytologic method for predicting the malignant potential of intraocular melanoma.
The malignant potential of 100 intraocular uveal melanomas was assessed by determining the mean of the ten largest nucleoli (MTLN). On a single standard microslide from each tumor, the maximum diameter of the ten largest nucleoli was measured using a manually operated micrometer. For comparison, three additional histopathologic parameters were determined for each case: Standard deviation of nucleolar area (SDNA), Callender cell type (CT), and largest tumor dimension (LTD). Of these four parameters, MTLN and SDNA were most highly correlated with death from ocular tumor. Furthermore, repeat measurement of all 100 cases revealed a level of reproducibility for MTLN similar to that for SDNA. Of greatest importance, the micrometer technique employed in this study has substantial cost and labor advantage over the computer-controlled system required to measure SDNA.


The rationale for deltanoids in therapy for myeloid leukemia: role of KSR-MAPK-C/EBP pathway.
The evidence for the promising potential for derivatives of Vitamin D (deltanoids) in the treatment of myeloid leukemias is increasing, but currently is not matched by the understanding of the precise mechanisms by which these anti-neoplastic effects are achieved. Unlike solid tumors in which growth retardation by deltanoids appears to result from inhibition of cell proliferation and the promotion of cell death by apoptosis, control of myeloid leukemia proliferation by deltanoids results from the induction of differentiation of the immature myelo-monocytic cells towards functional monocytic cells. We present here the accumulating evidence that a pathway that is initiated by deltanoid activation of Vitamin D receptor (VDR) and leads to monocytic differentiation of human myeloblastic HL60 cells, includes the MEK-ERK and JNK mitogen-activated protein kinases (MAPKs), their positive and negative regulators and a downstream effector C/EBPbeta. As in other cells, the abundance of VDR protein increases shortly after an exposure of HL60 cells to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2) D(3)). Other early events include a parallel upregulation of kinase suppressor of Ras (KSR-1) and the activation of the ERK MAPK pathway and data suggest that KSR-1 acts to amplify the signal provided by low concentrations of 1alpha,25(OH)(2) D(3). Maintenance of monocytic differentiation may be enhanced by JNK, but diminished by p38, MAPK signaling. Downstream, one of the targets of these pathways is C/EBPbeta, which can directly interact with the promoter for CD14, a gene characteristically expressed in monocytes. Importantly, in freshly obtained acute myeloid leukemia (AML)-M2 cells exposed to PRI-2191, a novel deltanoid with a modified side chain, upregulation of C/EBPbeta paralleled the induction of monocytic differentiation. These data provide a basis for the hypothesis that deltanoid-induced upregulation of C/EBPbeta bypasses the block to granulocytic differentiation in myeloid leukemia cells by redirecting the cells to monocytic differentiation.


Tantali fibromyalgic supplicium: Is there any relief with the antidepressant employment? A systematic review.
Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.


Toxic reaction of a 3-year-old boy due to Hornet multiple stings in Kerman-Iran province: A case report.
A three-year-old boy was attacked by a group of hornets and the head, arms, back and buttocks of the child were targeted to various stings. The child was first taken to a rural clinic and then to a hospital in Baft city. At arrival to rural clinic, the child was conscious and approximately 30 hyperpigmented, painful and itchy papular lesions was seen on his body. Head and neck weren't erythematous and edematous. However gradually, the face, lips, eyelids, and neck became swollen. The child became restless and itchy in the sting sites. Stress induced hyperglycemia occurred. Despite supportive treatments, the clinical conditions get worse and progressed. He referred to the pediatric ward of Afzalipour hospital in Kerman and admitted to intensive care unit (ICU). The child was ill and oliguric. The treatment was started including: hydration with normal saline and diuretic agent (furosemide), insulin, corticosteroid, dopamine and calcium. But a systemic toxic reaction occurred during the hospitalization. Hemolysis, hematuria, anemia, thrombocytopenia and rhabdomyolysis, myoglobinuria, acute renal failure, hepatic injury, epistaxis and respiratory distress was happened. In order to urine alkalinization, sodium bicarbonate was added to his treatments. Also, plasmapheresis was performed. Then according to acute tubular necrosis (ATN) (due to intravascular hemolysis and rhabdomyolysis), pleural effusion and respiratory distress, intermittent hemodialysis was started one day in between. After five intermittent hemodialysis sessions and nineteen days after hospitalization, the patient was discharged in relatively good general condition.


Scabies presenting as a necrotizing vasculitis in the presence of lupus anticoagulant.
A 75-year-old man presented with a progressive eruption of 6 weeks' duration. Purpura and focal areas of cutaneous infarction were present on the legs. There were scabies burrows on the wrists and hands, and a mite was extracted. Histology of a skin biopsy showed a necrotizing leucocytoclastic vasculitis. Circulating lupus anticoagulant was detected. Treatment consisted of topical 5% permethrin cream and systemic steroids.


Association between sex-specific serum uric acid and non-alcoholic fatty liver disease in Chinese adults: a large population-based study.
The aim of this study was to examine the association between sex-specific serum uric acid (sUA) levels and NAFLD in a large population-based study.A total of 60,455 subjects from 2 separate medical centers were included. Sex-specific sUA quartiles (Q1-Q4) were defined: ≤330, 331-380, 381-435, and ≥436 μmol/L for male; ≤230, 231-270, 271-310, and ≥311 μmol/L for female. The odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of sUA, using the Q1 as reference.After adjusting for known confounding variables in this study, the ORs for NAFLD in the cross-sectional population were 1.211 (95% CI 1.109-1.322), 1.519 (95% CI 1.395-1.654), 1.903 (95% CI 1.748-2.072) for Q2, Q3, and Q4, respectively. In the longitudinal population, compared with the reference group, those in Q2, Q3, and Q4 had HRs of 1.127 (95% CI 0.956-1.330), 1.380 (95% CI 1.157-1.644), 1.589 (95% CI 1.310-1.927) for NAFLD, respectively. Analysis for the sex-specific subgroup showed the adjusted ORs for Q4 versus Q1 were 2.898 (95% CI 2.36-3.588) in female and 1.887 (95% CI 1.718-2.072) in male in the cross-sectional population. In the longitudinal population, the HRs for the Q4 were 2.355 (95% CI 1.702-3.259) in female and 1.249 (95% CI 0.975-1.601) in male, compared with Q1.We report that a sex-specific sUA level is independently associated with NAFLD. The association between sUA and NAFLD was significantly greater in females than in males.


Phagosome maturation in macrophages: Eat, digest, adapt, and repeat.
Phagocytosis is a dynamic process that requires an intricate interplay between phagocytic receptors, membrane lipids, and numerous signalling proteins and their effectors, to coordinate the engulfment of a bound particle. These particles are diverse in their physico-chemical properties such as size and shape and include bacteria, fungi, apoptotic cells, living tumour cells, and abiotic particles. Once engulfed, these particles are enclosed within a phagosome, which undergoes a striking transformation referred to as phagosome maturation, which will ultimately lead to the processing and degradation of the enclosed particulate. In this review, we focus on recent advancements in phagosome maturation in macrophages, highlighting new discoveries and emerging themes. Such advancements include identification of new GTPases and their effectors and the intricate spatio-temporal dynamics of phosphoinositides in governing phagosome maturation. We then explore phagosome fission and recycling, the emerging role of membrane contact sites, and delve into mechanisms of phagosome resolution to recycle and reform lysosomes. We further illustrate how phagosome maturation is context-dependent, subject to the type of particle, phagocytic receptors, the phagocytes and their state of activation during phagocytosis. Lastly, we discuss how phagosomes serve as signalling platforms to help phagocytes adapt to their environmental conditions. Overall, this review aims to cover recent findings, identify emerging themes, and highlight current challenges and directions to improve our understanding of phagosome maturation in macrophages.


Complete sternal cleft associated with right clavicular, manubrial, and thyroid hypoplasia, pectus deformity, and spinal anomalies.
Sternal cleft anomalies are rare. Associated anomalies include pentalogy of Cantrell and posterior fossa abnormalities, hemangiomas, arteriopathy, cardiac anomalies, eye abnormalities, and sternal defects syndrome. There is only a single report of complete sternal cleft, pectus excavatum, and right clavicular hypoplasia in an adult. Thyroid hemiagenesis is also very rare. To our knowledge, this is the first case of complete sternal cleft, pectus deformity, and right clavicular hypoplasia in a child and the first case with right thyroid hemiagenesis.


The partial purification and properties of a human erythrocyte 4-nitroacetophenone reductase.
1. A soluble enzyme which catalyses the NADPH-dependent reduction of 4-nitroacetophenone to 4-nitrophenylmethylcarbinol has been partially purified from human erythrocytes. 2.inter-individual or intra-individual differences in the enzymic activity were small except for very low activity observed in one subject with glucose 6-phosphate dehydrogenase deficiency resulting in decreased levels of NADPH. 3. The enzyme was inactivated above 50 degrees or on storage at 4 degrees for longer than 24 h. The pH optimum was between 7-0-8-0. 4. the enzyme has been differentiated from NADPH-methaemoglobin reductase, NADPH-cytochrome c reductase, glutathione reductase, alpha,beta-unsaturated ketone reductase and aromatic alpha-keto acid reductase activities, but similarities exist between this enzyme and a rabbit kidney cortex aromatic aldehyde/ketone reductase.


A diffusional kurtosis imaging study of idiopathic generalized epilepsy with unilateral interictal epileptiform discharges in children.
To investigate brain abnormalities in children with a clinical diagnosis of idiopathic generalized epilepsy (IGE) and unilateral interictal epileptiform discharges (IED) demonstrated on electroencephalography (EEG) by diffusional kurtosis imaging (DKI). DKI images were obtained from 18 patients (n=9 each in the left and right hemispheres). Fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) maps were estimated through voxel-based analyses, and compared with 18 normal controls matched for age and sex. In the left side group, the significant differences of FA were in the left fusiform gyrus and occipital lobe of the white matter (WM). The significant differences of MD were in the left pons. The significant differences of MK were in the anterior cingulate gyrus, limbic lobe, gray matter (GM) and WM of the right cerebrum. In the right side group, the significant differences of FA were in the WM of the left cerebrum. MD identified differences in the frontal, temporal, occipital, and parietal lobes of both hemispheres, especially in the limbic system, fusiform gyrus, uncus, and parahippocampal gyrus. The significant differences of MK were in the GM of the right cerebrum, particularly in the rolandic operculum and frontal lobe. DKI is sensitive for the detection of diffusion abnormalities in both WM and GM of IGE in children. Secondary brain abnormalities may exist in regions outside the unilateral epileptogenic zone through the limbic epileptic network, and can be detected by DKI indices FA, MD and MK.


The impact of hepatitis B virus infection status on the prevalence of nonalcoholic fatty liver disease: A population-based study.
We aimed to explore the impact of hepatitis B virus (HBV) infection on the prevalence of nonalcoholic fatty liver disease (NAFLD) based on clinical big data. Data were collected from the health examination center of the First Affiliated Hospital of Fujian Medical University. Univariate and multivariate analysis were applied to investigate the relationship between HBV and NAFLD. A total of 14 452 patients were included, with an average age of 43.84 ± 13.03 years. Cases of HBV current infection, past infection, and noninfection were 21 102 110 (14.6%), 90 039 003 (62.3%), and 33 393 339 (23.1%), respectively. The prevalence of NAFLD was significantly lower in the current infection group (29.9%) than in the past infection group (35.8%) and noninfection group (31.9%) (P < .001). After adjusting for age, the prevalence of NAFLD in the current infection group remained the lowest across all of the age groups. Multivariate analysis showed that current infection was at a lower risk of NAFLD (odds ratio [OR] = 0.717, 95% CI: 0.608-0.846), whereas past infection had no effect on NAFLD. Current HBV infection may lower the risk of NAFLD. This effect becomes insignificant when the patient is no longer infected.


New Chemical Constituents from the Bark of Dendropanax morbifera Leveille and their Evaluation of Antioxidant Activities.
Four new constituents, as cis-6-oxogeran-4-enyl-10-oxy-O-β-arabinopyranosyl-4'-O-β-arabinopyranosyl-2''-octadec-9''',12''',15'''-trienoate (1), geran-3(10)-enyl-1-oxy-O-β-arabinopyranosyl-4'-O-β-arabinopyranosyl-2''-octadec-9''',12''',15'''-trienoate (2), geranilan-8-oxy-O-α-d-xylopyranosyl-2'-n-octadec-9'',12'',15''-trienoate (3), 1-cyclohex-2', 5'-dienyl 1-cyclohexylethanol-O-β-d-xylopyranoside (4), along with six known constituents, guaiacol-O-β-d-arabinopyaranoside (5), n-tetradecanyl oleate (6), oleyl-O-β-d-xyloside (7), n-octadec-9,12-dienoyl-O-β-d-arabinopyranoside (8), linolenyl-O-β-d-arabinofuranoside (9) andglyceryl-1,3-dipalmito-2-olein (10), were isolated and identified from the Dendropanax morbifera bark. The new structures were established by one-and two-dimensional NMR (and in combination with IR, FAB-MSand HR-ESI-FTMS. The comparative evaluation of antioxidant potential by phosphomolybdenum, DPPH, FRAP and the NO assay of four different compounds (1-4), we have found that the compounds 1 and 2 have power as a natural antioxidant, whereas the compound 3 and 4 exhibited mild activity in comparison to compounds 1 and 2.


Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.
Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing. A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diagnostic and relapsed samples from patients with relapsed/refractory pediatric solid tumors. The mean coverage for all samples was 930.6× (SD = 213.8). Among the 381 genes, 173 single nucleotide variations (SNVs)/insertion-deletions (InDels), 100 copy number alterations, and 1 structural variation were detected. A total of 72.6% of SNVs in primary tumors were also found in recurrent lesions, and 27.2% of SNVs in recurrent tumors had newly occurred. Among SNVs/InDels detected only in recurrent lesions, 71% had a low variant allele fraction (<10%). Patients were classified into three categories based on the mutation patterns after cancer treatment. A significant association between the major mutation patterns and clinical outcome was observed. Patients whose relapsed tumor had fewer mutations than the diagnostic sample tended to be older, had longer progression-free survival, and achieved complete remission after relapse. Contrastingly, patients whose genetic profile only had concordant mutations without any change had the worst outcome. We characterized genomic changes in recurrent pediatric solid tumors. These findings could help to understand the biology of relapsed childhood cancer and to develop personalized treatment based on their genetic profile.


The GARD™skin assay: Investigation of the applicability domain for metals.
New approach methodologies (NAMs) for hazard identification of skin sensitizing chemicals were adopted as test guidelines by the OECD during the last decade. These alternatives to animal models align to individual key events (KE) in the adverse outcome pathway (AOP) for skin sensitization for which the molecular initiating event (MIE) is covalent binding to proteins. As it currently stands, the AOP does not include mechanistic events of sensitization by metals, and limited information is available on whether NAMs accurately predict the sensitization potential of such molecules, which have been proposed to act via alternative mechanisms to organic chemicals. Methods for assessing the sensitization potential of metals would be valuable tools to support risk management within, e.g., occupational settings during production of new metal salts or within the medical device industry to evaluate leachables from metal alloys. This paper describes a systematic evaluation of the applicability domain of the GARD™skin assay for the assessment of metals. Hazard classifications were supplemented with an extended analysis of gene expression profiles induced by metal sensitizers to compare the induction of toxicity pathways between metals and organic sensitizers. Based on the results of this study, the accuracy, sensitivity, and specificity of GARD™skin for the prediction of skin sensitizing hazard were 92% (12/13), 100% (7/7), and 83% (5/6), respectively. Thus, the performance of GARD™skin for the assessment of metals was found to be similar to that observed for conventional organic substances, providing support for inclusion of metals within the applicability domain of the test method.


Waist-to-calf circumstance ratio is an independent predictor of hepatic steatosis and fibrosis in patients with type 2 diabetes.
Although a combination of central obesity and decreased skeletal muscle mass has been associated with various cardiometabolic disorders, its influence on the presence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D) is unclear. We investigated whether waist-to-calf circumference ratio (WCR) predicts NAFLD or hepatic fibrosis in T2D. Patients with T2D (n = 5507) were enrolled in this study. Hepatic steatosis was diagnosed using abdominal ultrasound and predicting score. NAFLD was defined as 'hepatic steatosis absent other causes of chronic liver disease,' such as virus or alcoholism. Degree of hepatic fibrosis was calculated using non-invasive serum biomarker-based models. Insulin resistance was assessed by short insulin tolerance test. The prevalence of NAFLD and obesity (BMI ≥ 25 kg/m2 , Asian definition) were 46.4% and 38.9%, respectively. NAFLD prevalence was higher with increasing WCR tertiles: lowest tertile (36% in men, 28% in women) versus highest tertile (53.8% in men, 58.2% in women, both P < 0.001 after stratification by insulin resistance status. Increasing WCR tertiles were independently associated with presence of NAFLD: odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.22-1.68 and OR = 1.56, 95% CI = 1.31-1.86, in the middle and highest tertiles, respectively. Furthermore, patients with NAFLD and the highest WCR tertile had significant fibrosis (OR = 8.62, 95% CI = 1.39-53.36, P = 0.021). Also, WCR was correlated with risk of sarcopenia (OR = 3.18, 95% CI = 2.50-4.05, P < 0.001, highest tertile). Higher WCR is associated with increased risk of NAFLD and hepatic fibrosis independent of insulin resistance. This suggests that WCR may be a useful index to predict high risk of hepatic steatosis in T2D.


Awake Craniotomy Language Mapping in Children With Drug-Resistant Epilepsy due to Focal Cortical Dysplasia.
Language mapping during awake craniotomy can allow for precise resection of epileptogenic lesions, while reducing the risk of damage to eloquent cortex. There are few reports in the literature of language mapping during awake craniotomy in children with epilepsy. Some centers may avoid awake craniotomy in the pediatric age group due to concerns that children are unable to cooperate with such procedures. We reviewed pediatric patients from our center with drug-resistant focal epilepsy who underwent language mapping during awake craniotomy and subsequent resection of the epileptogenic lesion. Two patients were identified, both female, aged 17 years and 11 years at the time of surgery. Both patients had frequent and disabling focal seizures despite trials of multiple antiseizure medications. Both patients had resection of their epileptogenic lesions with the aid of intraoperative language mapping; in both cases pathology was consistent with focal cortical dysplasia. Both patients had transient language difficulties in the immediate postoperative period but no deficits at six-month follow-up. Both patients are now seizure-free. Awake craniotomy should be considered in pediatric patients with drug-resistant epilepsy in whom the suspected epileptogenic lesion is in close proximity to cortical language areas.


The role of red cell membrane in the regulation of glycolysis and the 2,3-bisphosphoglycerate-cycle.
Pyruvate and K-ferricyanide stimulation of net ATP and 2,3-bisphosphoglycerate synthesis is very probably due to enhancement of glyceraldehyde 3-phosphate dehydrogenase activity. Significant peculiarities in the K-ferricyanide effect and its depression by non-penetrating-SH inhibitors at low concentrations were noted and suggested that membrane-bound enzymes play a substantial part in the synthesis of ATP and 2,3-bisphosphoglycerate. Experiments with isolated ghosts showed their ATP-and 2,3-bis-phosphogylcerate-building capacity. Pulse-labeling with 32P-Pi and determination of specific radioactive in intracellular inorganic phosphate and ATP-gamma-P demonstrated that the ferricyanide-stimulated compartment utilizes only intracellular inorganic phosphate for ATP (and 2,3-bisphosphoglycerate) synthesis, and does so only when extracellular inorganic phosphate is present.


Compartmentalization of the DNA damage response: Mechanisms and functions.
Cells have evolved an arsenal of molecular mechanisms to respond to continuous alterations in the primary structure of DNA. At the cellular level, DNA damage response proteins accumulate at sites of DNA damage and organize into nuclear foci. As recounted by Errol Friedberg, pioneering work on DNA repair in the 1930 s was stimulated by collaborations between physicists and geneticists. In recent years, the introduction of ideas from physics on self-organizing compartments has taken the field of cell biology by storm. Percolation and phase separation theories are increasingly used to model the self-assembly of compartments, called biomolecular condensates, that selectively concentrate molecules without a surrounding membrane. In this review, we discuss these concepts in the context of the DNA damage response. We discuss how studies of DNA repair foci as condensates can link molecular mechanisms with cell physiological functions, provide new insights into regulatory mechanisms, and open new perspectives for targeting DNA damage responses for therapeutic purposes.


Corrigendum to "Multiband rabi antenna using nest microstrip add-drop filter (NMADF) for relativistic sensing applications" [Heliyon 9(2) (February 2023) e13611].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13611.].


Evidence of a regulatory role of the level of poly (ADP-ribose) in chromosomal proteins in metallothionein gene expression by glucocorticoids but not by heavy metals.
The induction capacity of dexamethasone, a synthetic glucocorticoid, for the synthesis of metallothionein was about the same as that of 3-aminobenzamide, which is an inhibitor of ADP-ribosylation of chromosomal proteins, in cultured mouse mammary tumor cells. Both inductions of metallothionein were temporally correlated with a decrease in the amount of endogenous poly (ADP-ribose) on nonhistone high-mobility-group 14 and 17 proteins. In contrast, the extent of cadmium-induced metallothionein synthesis was 2-3-times that of dexamethasone or 3-aminobenzamide. However, cadmium had essentially no effect on de-ADP-ribosylation of these proteins.


Dowling-Degos disease with reticulate acropigmentation of Kitamura: Extended spectrum of a single entity.
Dowling-Degos disease (DDD) and reticulate acropigmentation of Kitamura (RAK) are rare genodermatoses inherited as an autosomal dominant trait with variable penetrance. They are considered to be part of a spectrum of reticulate pigmentary dermatoses, characterized by the presence of hyperpigmented macules coalescing in a reticular fashion. The authors describe a 28-year-old male patient having hyperpigmented macules on the axillae, neck and face, reticulate acropigmentation of dorsum of the hands, forearms and feet, palmar pitting, and comedo-like lesions over back. The patient showed the unique clinical as well as histopathological overlap of both the rare diseases (DDD and RAK), substantiating the hypothesis that they represent two different features of a single entity with variable phenotypic expression.


Potential of olive oil tourism in promoting local quality food products: A case study of the region of Extremadura, Spain.
This work aims to highlight tourism based on gastronomy, heritage and olive oil-related activities. These activities enhance the knowledge about the product itself and its links with culture and local traditions. Olive oil tourism is based on a typical gastronomic product of internationally recognised quality. This type of tourism boosts sustainable destinations capable of introducing and promoting the consumption of local products. In addition, it favours the implementation of different activities in rural settings, such as routes through the olive groves, gastronomic markets, educational initiatives, historical events, etc. This study analyses the development of olive oil tourism in the district of La Serena in Extremadura (Spain). The study involved 208 tourists that were asked about their experience on oil tourism during their trip. The results emphasize the great potential of development that olive oil tourism can achieve in rural settings as sustainable destinations. From the results obtained, managers of rural settings with a great olive oil tradition can base their tourism strategies on the gastronomic and cultural context of this local product.


Predictors of Postoperative Complications in Patients Who Undergo Radical Nephrectomy and IVC Thrombectomy: A Large Contemporary Tertiary Center Analysis.
In an analysis of a large single-institution experience in the surgical management of renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus, the authors present the effect of RCC characteristics on survival, and aim to identify potential preoperative variables predictive of intraoperative complexity with regard to estimated blood loss, transfusion volume, surgical time, length of stay, and postoperative complication rates. Age, American Society of Anesthesiologists score, Charlson Comorbidity Index, preoperative calcium, preoperative creatinine, and IVC wall invasion were significantly related to complication rates. Preoperative laboratory values are commonly used as markers of health and potential disease burden, however, their effect on perioperative complexity has not previously been assessed. The authors aimed to evaluate the effect of renal cell carcinoma and inferior vena cava (IVC) thrombus characteristics on cancer-specific survival (CSS), and identify potential preoperative variables predictive of intraoperative complexity. In a retrospective chart review we identified 144 patients who underwent nephrectomy and IVC thrombectomy. Univariate and multivariate analyses were used to assess the effect of disease characteristics on CSS and postoperative complications. Linear regression analysis was used to determine the association between preoperative laboratory values and intraoperative complexity characterized by estimated blood loss (EBL), transfusion volume (TV), operative time, and length of hospital stay (LOS). Analysis of intraoperative complexity revealed a significant correlation between preoperative creatinine (Cr) and EBL (P = .022), TV (P = .041), and LOS (P = .005), and preoperative hemoglobin (Hgb) was associated with increased EBL (P < .001) and TV (P < .001). Multivariate analyses showed a significant relationship between overall complication rates and preoperative calcium (Ca; P = .012), American Society of Anesthesiologists (ASA) score (P = .003), and IVC wall invasion (P = .005), and a significant association between major complications and preoperative Ca (P = .011), preoperative Cr (P = .041), age (P = .050), and Charlson Comorbidity Index (CCI; P = .002). With regard to intraoperative complexity and postoperative complications, preoperative Cr and Hgb were significantly associated with increased EBL, TV, and LOS, and ASA score, preoperative Ca, preoperative Cr, IVC wall invasion, age, and CCI were found to have significant relationships with complication rates.


Relationship of serum homocysteine and vitamin D with positive, negative, and extrapyramidal symptoms in schizophrenia: a case-control study in Iran.
Schizophrenia is a devastating condition characterized by frequent recurrences, cognitive decline, and emotional and functional disabilities. This condition includes positive and negative symptoms and cognitive impairments resistant to drug treatment. According to studies, many biomarkers can affect this disorder. However, there is little information about vitamin D and homocysteine levels in patients with disease complications. We aimed to investigate this relationship in schizophrenia. In this case-control study, 33 patients with schizophrenia and 33 healthy individuals were enrolled from Golestan, the north of Iran, in 2021. Blood samples were taken from all participants to assess vitamin D and homocysteine serum levels. In addition, schizophrenic patients completed the Positive And Negative Syndrome Scale (PANSS) and Simpson-Angus Extrapyramidal Side Effects Scale (SAS). Data analysis was performed at a significance level of 0.05 using SPSS 16 software. Of the 66 participants, 66.7% had vitamin D deficiency, and 71.2% had normal homocysteine levels. However, the serum level of vitamin D was lower in schizophrenic patients than in controls (p = 0.035), and serum homocysteine levels were higher in the schizophrenic group than in controls (p < 0.001). Vitamin D levels in patients with schizophrenia were significantly correlated with the overall assessment of extrapyramidal symptoms (r = 0.35, p = 0.04). However, no significant relationship existed between vitamin D and homocysteine levels and PANSS results (p > 0.05). Serum levels of vitamin D and homocysteine were significantly lower and higher in schizophrenic patients than in the control group. Improvement of extrapyramidal symptoms in schizophrenic patients had a direct and significant relationship with serum vitamin D.


Akt-GSK3β-mPTP pathway regulates the mitochondrial dysfunction contributing to odontoblasts apoptosis induced by glucose oxidative stress.
Diabetes Mellitus can cause dental pulp cells apoptosis by oxidative stress, and affect the integrity and function of dental pulp tissue. Mitochondria are the main attack targets of oxidative stress and have a critical role in apoptosis. However, whether mitochondria are involved in dental pulp damage caused by diabetes mellitus remains unclear. This study aimed to investigate the role of mitochondria in the apoptosis of odontoblast-like cell line (mDPC6T) induced by glucose oxidative stress, and to explore its possible mechanism. We established an oxidative stress model in vitro using glucose oxidase/glucose to simulate the pathological state under diabetic conditions. We found that the opening of mitochondrial permeability transition pore (mPTP) contributed to the apoptosis of mDPC6T treated with glucose oxidase, as evidenced by enhanced mitochondrial reactive oxygen species (mtROS) and intracellular Ca2+ disorder, significantly reduced mitochondrial membrane potential (MMP) and ATP production. Antioxidant N-acetylcysteine (NAC) or Cyclosporine A (mPTP inhibitor) blocked the mPTP opening, which significantly attenuated mitochondrial dysfunction and apoptosis induced by glucose oxidative stress. In addition, we found that glucose oxidative stress stimulated mPTP opening may through inhibition of Akt-GSK3β pathway. This study provides a new insight into the mitochondrial mechanism underlying diabetes-associated odontoblast-like cell apoptosis, laying a foundation for the prevention and treatment of diabetes-associated pulp injury.


Industrial-scale composting of swine manure with a novel additive-yellow phosphorus slag: Variation in maturity indicators, compost quality and phosphorus speciation.
Composting experiment of swine manure, adding with yellow phosphorus slag(YPS) at 5% (w/w), was conducted in an industrial-scale reactor covered with semi-permeable membrane. During 27 days of composting, the changes in temperature, compost quality and phosphorus(P) speciation of products were monitored. Results indicated that the temperature of compost pile was sharply increased on day 2, and the thermophilic period lasted for 15 days. The dynamics in germination index(GI), pH, nutrient contents, etc. of products were in line with conventional composting process. For P distribution, the contents of total-P and citric acid extracted-P(CAP) of products were increased during composting, while that of Olsen-P was decreased. HCl extracted inorganic P(HCl-Pi), a slowly release fraction of P, was dominated in the product, which showed an increasing trend during the composting. These results suggest that the industrial-scale composting with novel YPS additive can be accomplished, and its product contains abundant slowly released P.


Temporal trends of stroke in Valle d'Aosta, Italy. Incidence and 30-day fatality rates.
The objective of this study was to evaluate temporal changes of stroke in an Italian community by comparing the present incidence rates with those reported in the same area for 1989. The two studies were conducted by the same research group and met almost all the criteria proposed for an "ideal" stroke incidence study. The annual incidence rate per 1000 inhabitants increased (p < 0.01) by 29%, from 2.23 (95% CL, 1.96-2.50) in 1989 to 2.89 (95% CL, 2.58-3.20) in 1997. No statistically significant change was found when these rates were adjusted to the 1991 Italian population. The overall incidence rate was 2.40 (95% CL, 2.14-2.66) in 1989 and 2.65 (95% CL, 2.39-2.91) in 1997. The thirty-day case fatality rate declined dramatically (p < 0.001) from 31% (95% CL, 26-36) to 20% (95% CL, 16-24) between 1989 and 1997. Ageing of the population and better identification of cases could explain the high incidence rate, whereas the decrease of fatality rate may be due to a general improvement in acute care and inclusion of milder cases.


Early treatment of wounds polluted by sea water.
During construction or training at sea, wounds are commonly seen and irresistibly polluted by sea water. An early and proper treatment of wounds polluted by sea water is very important for wound healing and function recovery of extremities. Some wounds even result in vegetation. In this study, we have reported the treatment results of 132 cases of wounds polluted by sea water admitted from 1985 to 1999.


Real-time monitoring of L-glutamate release from mouse brain slices under ischemia with a glass capillary-based enzyme electrode.
Real-time monitoring of L-glutamate release from various neuronal regions of mouse hippocampal slices under ischemia (a glucose-free hypoxia condition) is described. A glass capillary microelectrode with a tip size of approximately 10 microm containing a very small volume ( approximately 2 microL) of a solution of glutamate oxidase (GluOx) and ascorbate oxidase was used. First, the amperometric response behavior of the electrode at 0 V versus Ag/AgCl was characterized with a standard glutamate solution in terms of continuous measurements, effect of oxygen, viscosity of solution and concentration dependence. The electrode was applied to the real-time monitoring of L-glutamate released from different neuronal regions of acute hippocampal slices submerged in a hypoxia solution. The time-resolved amounts of L-glutamate released at various neuronal regions (CA1, CA3 and DG) of mouse hippocampal slices were quantified and compared with the reported L-glutamate fluxes using difference-image analysis during ischemia.


Mental health diagnoses and early removal of long-acting reversible contraception.
Having a mental health diagnosis is associated with contraceptive non-adherence and user-related contraceptive failures of short-acting methods. There is a lack of research on the relationship between mental health diagnoses and early discontinuation of highly effective long-acting reversible (LARC) methods such as the intrauterine device (IUD) and subdermal implant (SDI). Using a Primary Care and Obstetrics and Gynecology Patient Data Registry, we conducted a cross-sectional analysis of the relationship between any mental health diagnosis (any anxiety disorder or depression) and early LARC removal (<1 year post-insertion) among 385 reproductive-aged (14-50 years) women in 2008-16. Adjusted logistic regression was used to calculate odds ratios and 95% confidence intervals. Almost 10% (n = 37) of the sample had an early LARC removal, of which 62.2% were hormonal IUD and 37.8% were SDI. Women with a mental health diagnosis had a higher prevalence of early LARC removal (13.6% vs. 8.0%, p = =.090). Although non-significant, there was a trend in adjusted analyses indicating twice the odds of early removal for women with a mental health diagnosis versus no diagnosis (OR = =2.04, 95% CI = =0.97-4.27). This study is limited by a small sample size and availability of variables from a reportable medical record database. Pregnancy intentions and side effects of method use could not be accounted for which may have impacted timing of removal. Understanding why women choose early LARC removal can inform counseling to help women make informed choices about their contraceptive method that meets their reproductive needs.


HIV protocol for the pediatric otolaryngology office.
With the increasing awareness and concern over the transmission of human immunodeficiency virus (HIV) to health care providers, the development of a reasonable approach to patient care is necessary with those suspected of or documented as being HIV-positive. Children are all too frequently the innocent victims of this deadly disease and will often require the services of the otolaryngologist for evaluation, diagnosis, and treatment. In order to provide appropriate care for these children and reduce the risk of possible contamination of health care professionals or other patients a protocol was established for the Pediatric Otolaryngology Division of Children's Hospital at Washington University. This protocol is discussed in detail with explanation of rationale and alternatives.


Anthropogenic pressures and life history predict trajectories of seagrass meadow extent at a global scale.
Seagrass meadows are threatened by multiple pressures, jeopardizing the many benefits they provide to humanity and biodiversity, including climate regulation and food provision through fisheries production. Conservation of seagrass requires identification of the main pressures contributing to loss and the regions most at risk of ongoing loss. Here, we model trajectories of seagrass change at the global scale and show they are related to multiple anthropogenic pressures but that trajectories vary widely with seagrass life-history strategies. Rapidly declining trajectories of seagrass meadow extent (>25% loss from 2000 to 2010) were most strongly associated with high pressures from destructive demersal fishing and poor water quality. Conversely, seagrass meadow extent was more likely to be increasing when these two pressures were low. Meadows dominated by seagrasses with persistent life-history strategies tended to have slowly changing or stable trajectories, while those with opportunistic species were more variable, with a higher probability of either rapidly declining or rapidly increasing. Global predictions of regions most at risk for decline show high-risk areas in Europe, North America, Japan, and southeast Asia, including places where comprehensive long-term monitoring data are lacking. Our results highlight where seagrass loss may be occurring unnoticed and where urgent conservation interventions are required to reverse loss and sustain their essential services.


Evaluation of the Effect of Intravitreal Dexamethasone (Ozurdex®) Implant on Intraocular Pressure in Vitrectomized and Non-Vitrectomized Eyes with Macular Edema.
This study aimed to retrospectively evaluate the intraocular pressure (IOP) change in vitrectomized and non-vitrectomized patients receiving 0.7 mg intravitreal dexamethasone implant to treat macular edema due to different indications. The patients' diagnoses, IOP values before receiving the intravitreal dexamethasone implant and in follow-up examinations at 1-3 days, 1 month, 2 months, 3 months, 6 months, 9 months, and 12 months after implantation, pachymetry values, medications used, and history of vitrectomy surgery were recorded. A total of 134 eyes of 112 patients between 46 and 85 years of age who received intravitreal dexamethasone implants were evaluated. Seventeen eyes (12.7%) were vitrectomized and 117 (87.3%) were not vitrectomized. In non-vitrectomized eyes, the mean IOP was 14.01±2.36 mmHg before and 14.8±2.96 at 1-3 days, 16.71±3.97 at 1 month, 17.88±5.27 at 2 months, 15.54±3.35 at 3 months, 15.1±3.24 at 6 months, and 14.61±3.71 mmHg at 12 months after receiving the first dose. In this group, the increases in mean IOP at 1-3 days, 1 month, 2 months, and 3 months were significant compared to the mean IOP before the first dose (p<0.05). In vitrectomized eyes, only the increase in mean IOP at 6 months was significant compared to the mean IOP before the first dose (p<0.05). Twenty-three of the 134 eyes (17.2%) were prescribed 1-3 medications due to IOP elevation (one drug for 73.9%, two drugs for 17.4%, and three drugs for 8.7% of these eyes). The IOP increase that occurs as a side effect of intravitreal dexamethasone administration is generally mild and temporary in both vitrectomized and non-vitrectomized eyes, regardless of indication. There was no cumulative effect in patients who received two or three doses.


Two-dimensional growth of crystalline nanofiber fabricated from Gemini-type amphiphilic diamide derivative inducing the thixotropic property.
The formation of a nanofiber morphology at the mesoscopic scale and the molecular-level packing of a gemini-type amphiphilic diamide derivative with two hydrocarbons were investigated from two perspectives. First, it was confirmed that a diamide derivative with two hydrocarbons forms crystalline nanofibers even in a monomolecular layer. The height, thickness, and lattice spacing of the two-dimensional orthorhombic system of this crystalline nanofiber in the monolayer of a diamide derivative with two hydrocarbons are 5, 30, and 0.4nm, respectively. Next, it was determined that the fibrous growth of the diamide derivative with two hydrocarbons, which contributes to the thixotropic ability, can be achieved by the addition of a quaternary ammonium cation with long chains, modified with montmorillonite. Here, the interlayer spacing was about 3.8nm for the organo-modified montmorillonite and was consistent with the layer spacing of the diamide derivative having two hydrocarbons. The surface pressure-area isotherms of the mixed monolayers suggest that there is miscibility between these materials. From "the affinity due to the van der Waals interaction between the terminal groups of the alkyl chains" and the "similarity of layer spacing," epitaxial growth is expected.


Improved neonatal heart preservation with an intracellular cardioplegia and storage solution.
The optimal conditions for preservation of the neonatal heart for transplantation remain uncertain. An isolated, working neonatal piglet heart model was used to compare a standard extracellular-like cardioplegic solution followed by storage at 4 degrees C in normal saline for 12 hr (n = 8) to cardioplegia and storage at 4 degrees C for 24 hr in an intracellular-like solution (n = 7). Seven of eight hearts in the 12-hr Extracellular Group failed to regain function, with a maximum stroke work index (SWI), developed at a left ventricular end-diastolic pressure (LVEDP) of 9 mm Hg of 0.91 +/- 0.30 x 10(3) erg/g (mean +/- standard error of the mean), 7.1% of nonpreserved control hearts. In contrast, all hearts arrested and stored for 24 hr in the intracellular solution regained function with a maximum SWI, again at a LVEDP of 9 mm Hg of 9.51 +/- 1.98 X 10(3) erg/g, 73.7% of control (P less than 0.05). Ultrastructural changes seen by electron microscopy paralleled the functional results. We conclude that an intracellular arrest and storage solution may be superior to conventional solutions for extended preservation of the neonatal heart.


Standalone Totally Thoracoscopic Left Appendage Clipping: Safe, Simple, Standardized.
Totally thoracoscopic standalone left atrial appendage exclusion has become a valid treatment option for stroke prevention in patients with a contraindication to anticoagulants. As with most other video-assisted surgeries, this procedure requires appropriate patient and port positioning to obtain the most advantageous working angles and standard thoracoscopic skills. Furthermore it is mandatory to have a closure device specifically designed for the appendage to guarantee efficacy and safety and to optimize surgical placement that allows the best clinical outcomes. Here we describe the surgical technique of a unilateral left-sided thoracoscopic approach for surgical exclusion of the appendage on the beating heart.


Response of normal canine ureter to photodynamic therapy using a cylindrical fiber.
Photodynamic therapy (PDT) was performed utilizing a cylindrical optical fiber to determine feasibility of distal ureteral treatment on 10 study and two control NIH foxhounds. The study animals were administered three mg./kg. dihematoporphyrin ether (Photofrin II) intravenously followed 48 hours later by open cystotomy. One ureter was irradiated with 42 joules of 630 nm. light delivered by a 660 micron diameter optical fiber modified for cylindrical light distribution. Intravenous urography was performed both at three days and six weeks post PDT. Hydroureteronephrosis was revealed in one treated ureter and one untreated ureter. Mild dilatation of the ureter was noted by urography in another treated ureter and in one ureter that did not undergo light irradiation; no distal obstruction was revealed in either case by proximal infusion of saline or by histopathology. Nine of the 10 treated ureters were found to have either no abnormal pathology or only minimal lymphocytic infiltration. In this study, the normal ureter was shown to tolerate photodynamic therapy at energy densities equivalent to those used to effect tumor regression and the feasibility of using a cylindrical optical fiber for treatment of ureteral malignancies was confirmed.


Amantadine sulphate in treating Parkinson's disease: clinical effects, psychometric tests and serum concentrations.
Intravenous administration of amantadine has been shown to be a quick-acting and highly effective method of treating patients with Parkinson's disease. The duration of this therapeutic effect during long-term oral treatment has, however, remained controversial. Therefore, the effect of intravenous treatment was compared with long-term oral treatment over a period of 6 months. Clinical scores and psychometrically determined dexterity improved significantly during 10-day infusion therapy (200 mg amantadine sulphate/day). This improvement was successfully maintained by oral treatment (600 mg/day). A decrease in effectiveness was not observed. Reaction times were within the normal range for the age group involved and did not change significantly during the course of the study. Amantadine serum concentration during the infusion period ranged between 500 and 1000 micrograms/l and produced values nearly half as high as those obtained during oral treatment (600 mg/day). There was a constant relationship (quotient: 1.3) between serum and cerebrospinal fluid concentration. Considerable inter-individual variations were noted. A significant inter-individual correlation between serum concentration and clinical and psychological improvement was not discernible.


Quantification of oral epithelial hyperplasia in rats after topical application of the carcinogen 4-nitroquinoline 1-oxide.
Hyperplasia of the palatal epithelium was quantified in two groups of rats exposed thrice weekly to the carcinogen 4NQO for 2 weeks and 2 months, respectively. The lengths and areas of the epithelial layers were measured with a computerized line-following device. In the group treated for 2 weeks the maximum area of the nuclear layer was nearly three times and the maximum length of the epithelial/connective tissue interface almost twice the normal at the end of the carcinogen application period. The maximum area of the cornified layer was three times and the maximum lengths of the epithelial surface and the keratin/nuclear layer interface almost one and a half times the normal 1 week after painting with 4NQO. Thereafter the lengths and areas decreased gradually in both experimental groups. The area of the cornified layer and the length of the epithelial/connective tissue interface in the group treated for 2 months were significantly larger than those in animals treated for 2 weeks. These variables may be two of several indicators of prognostic significance in the assessment of dose-related premalignant epithelial hyperplasia.


Significance of adverse outcome pathways in biomarker-based environmental risk assessment in aquatic organisms.
In environmental risk assessments (ERA), biomarkers have been widely used as an early warning signal of environmental contamination. However, biomarker responses have limitation due to its low relevance to adverse outcomes (e.g., fluctuations in community structure, decreases in population size, and other similar ecobiologically relevant indicators of community structure and function). To mitigate these limitations, the concept of adverse outcome pathways (AOPs) was developed. An AOP is an analytical, sequentially progressive pathway that links a molecular initiating event (MIE) to an adverse outcome. Recently, AOPs have been recognized as a potential informational tool by which the implications of molecular biomarkers in ERA can be better understood. To demonstrate the utility of AOPs in biomarker-based ERA, here we discuss a series of three different biological repercussions caused by exposure to benzo(a)pyrene (BaP), silver nanoparticles (AgNPs), and selenium (Se). Using mainly aquatic invertebrates and selected vertebrates as model species, we focus on the development of the AOP concept. Aquatic organisms are suitable bioindicator species whose entire lifespans can be observed over a short period; moreover, these species can be studied on the molecular and population levels. Also, interspecific differences between aquatic organisms are important to consider in an AOP framework, since these differences are an integral part of the natural environment. The development of an environmental pollutant-mediated AOP may enable a better understanding of the effects of environmental pollutants in different scenarios in the diverse community of an ecosystem.


Antimicrobial, antioxidant activities, and total phenolic contents of Pycnanthus angolensis Sap and Cryptolepis sanguinolenta root extracts.
The death of many people in tropical countries can be attributed to microbial infection, probably, because synthetic antibiotics are failing in the treatment of most microbial infections, attributed to the ability of the microorganisms to mutate and adapt to harsh conditions. This study evaluated, in vitro, the antimicrobial activities, antioxidant potentials, and the total phenolic as well as phytochemical contents of aqueous and ethanol extracts of the root of Cryptolepis sanguinolenta (Lindl.) and the crude sap of Pycnanthus angolensis (Welw) using selected standard bacteria strains (Staphylococcus aureus (ATCC 25,923), Staphylococcus saprophyticus (ATCC 15,305), Escherichia coli (ATCC 25,922), Salmonella typhi (ATCC 19,430), Pseudomonas aeruginosa (ATCC 27,853), and Proteus mirabilis (ATCC 49,565). The modified agar well diffusion method was used to evaluate the antimicrobial activities of the plant extracts. Chloramphenicol and tetracycline were used as positive controls. The extracts were screened for specific phytochemicals with total phenolic contents were determined using Folin Ciocalteu reagent test. The phytoconstituents observed were alkaloids, cardiac glycosides, and saponins in both Cryptolepis sanguinolenta and Pycnanthus angolensis. For the antimicrobial activities, all the test bacteria were susceptible to the crude sap of Pycnanthus angolensis except Proteus mirabilis. In the case of the Cryptolepis sanguinolenta, only S. aureus was susceptible to both aqueous and ethanol extracts. The total phenolic content, expressed in g/100 g GAE, recorded values of 55.427 ± 4.248 for the crude sap of Pycnanthus angolensis, and 11.642 ± 4.248 and 26.888 ± 4.248 for the aqueous and ethanol extracts of Cryptolepis sanguinolenta, respectively. It is concluded that Cryptolepis sanguinolenta and Pycnanthus angolensis are excellent candidates for further development of antimicrobial agents in the fight against microbial infections given the pressing need for novel efficacious agents.


Action of harmaline and diazepam on the cerebellar content of cyclic GMP and on the activities of two endogenous inhibitors of protein kinase.
The rat cerebellum contains a significant amount of cGMP-dependent protein kinase, cAMP-dependent and cyclic nucleotide-independent protein kinase, and a large concentration of protein kinase inhibitors. These inhibitors are thermostable proteins which can be separated by gel chromatography into two molecular forms: the type 1 and type 2 inhibitors of protein kinase (14). The type 1 inhibitor blocks the rat cerebellar cAMP-dependent protein kinase activity while the type 2 inhibitor blocks the cGMP-dependent protein kinase, the cAMP-dependent protein kinase, and the cyclic nucleotide-independent protein kinases. The activity of the type 2 inhibitor increased or decreased in opposite direction to changes of cerebellar cGMP content generated by injection of 10 mg/kg harmaline 2.5 mg diazepam. No changes of type 1 inhibitor were observed under these conditions. The drug-induced shift of type 2 inhibitor of protein kinase was not mediated by changes in protein synthesis because it persisted after pretreatment with cycloheximide. These results are compatible with the hypothesis that cGMP modulates phosphorylation in cerebellum by changing the relationship between cGMP-dependent protein kinase and type 2 inhibitor content.


Gastroesophageal reflux during gastrostomy feeding.
Aspiration pneumonia is one of the most serious complications of gastrostomy tube feeding, with a reported incidence of 10%-20% in nursing home patients. The aims of this prospective study were to examine lower esophageal sphincter (LES) pressure before and after placement of gastrostomy tubes and to examine the effects of rapid intragastric bolus and slow, continuous feeding on LES pressure. Ten subjects were enrolled in the study. Basal LES pressure was measured before and after placement of gastrostomy tubes. Thereafter, LES pressure was measured for 15 minutes during rapid intragastric infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous infusion of the enteral feeding formula at 80 mL/h. Scintigrams evaluating gastroesophageal reflux were obtained during each method of feeding. Placement of gastrostomy tubes had no effect on basal LES pressure. Rapid intragastric bolus infusion led to a reduction in LES pressure to incompetent levels at 2.1 +/- 2.0 mm Hg (P < 0.001). Free gastroesophageal reflux to the sternal notch was shown by scintigraphy. Slow, continuous gastrostomy feedings did not alter LES pressure (P > 0.05) or show free gastroesophageal reflux by scintigraphy. Gastroesophageal reflux and aspiration in patients fed via the gastrostomy tube may be caused by LES relaxation secondary to gastric distention caused by distention of the stomach.


Claudin expression and tight junction protein localization in the lining epithelium of the keratocystic odontogenic tumors, dentigerous cysts, and radicular cysts.
The aim of this study was to evaluate the expression and localization of tight junction proteins (TJPs) or claudins in the keratocystic odontogenic tumor (KCOT) and to correlate with its biological behavior. Five claudins (-1, -3, -4, -5, and 7) were examined immunohistochemically in 25 KCOTs and compared with 10 dentigerous cysts (DCs) and 10 radicular cysts (RCs). Marked claudin-3 loss of expression in KCOT basal layer (n=24/25; 96%) compared with DCs (n=1/10; 10%) and RCs (n=5/10; 50%) (P<.05) suggests that claudin-3 downregulation may indicate altered or loss of basal cell polarity and impaired barrier function of KCOT lining epithelium and this might contribute indirectly to its biological behavior. In contrast, claudins-1, -4, -5, and -7 distribution patterns were less distinctive in all three entities, suggesting that these TJP molecules probably play limited roles in influencing their different growth potentials. Present findings suggest that differential claudin expressions in the lining epithelium of KCOTs, DCs, and RCs probably reflect their neoplastic or nonneoplastic nature.


Hepatic pathology in patients after Fontan operation: A computed tomography imaging study.
Hepatic dysfunction is an important long-term complication in Fontan patients. The purpose of this study was to evaluate the hepatic computed tomography (CT) findings after Fontan surgery and identify their association with clinical parameters. This study recruited 43 patients (23 male and 20 female patients aged 15.3 ± 6.8 years), who underwent Fontan surgery. Medical records were reviewed to collect their age, sex, congenital heart disease type, date of Fontan surgery, laboratory data, and hepatic CT findings. The relationship between hepatic findings and clinical parameters was analyzed. The follow-up duration was 6.8 ± 4.1 years. Abnormal hepatic parenchymal enhancement was observed in 77% of the patients, with mild degree in 18, moderate degree in 10, and severe degree in 5 patients. According to the univariate analysis, risk factors for hepatic parenchymal enhancement were follow-up duration (odds ratio [OR]: 1.354 [95% confidence interval (CI): 1.024-2.078]; p = 0.042), hypoplastic left heart syndrome (HLHS) (OR: 3.262 [95% CI: 1.145-5.628]; p = 0.002), mean pulmonary artery pressure (OR: 1.598 [95% CI: 1.089-2.132]; p = 0.026), pulmonary vascular resistance index (OR: 1.263 [95% CI: 1.068-1.245]; p = 0.032), and brain natriuretic peptide (OR: 1.956 [95% CI: 1.085-2.673]; p = 0.045). According to the multivariate analysis, only HLHS (OR: 3.856 [95% CI: 1.389-5.863]; p = 0.001), mean pulmonary artery pressure (OR: 1.846 [95% CI: 1.362-2.549]; p = 0.015), and pulmonary vascular resistance index (OR: 1.185 [95% CI: 1.042-1.736]; p = 0.047) were significant risk factors for abnormal parenchymal enhancement. Abnormal hepatic parenchymal enhancement detected through CT is common in Fontan patients. Regular liver function test in conjunction with imaging studies may be considered when following up Fontan patients.


Spatiotemporal characteristics of acid refluxate and relationship to symptoms in premature and term infants with chronic lung disease.
The prevalence of gastroesophageal reflux (GER) is high among infants with chronic lung disease (CLD), and the associated pathogenic mechanisms are not clear. The relationship of symptoms to the extent or duration of acid reflux events (AREs) is not well known in preterm or term infants. Our aim was to evaluate the relationship between spatial (height) and temporal (duration) characteristics of AREs (pH <4.0) with symptoms in CLD. We tested the hypothesis that in infants with CLD, AREs into the pharynx are associated with increased symptom occurrence and delayed clearance. Nine infants born at 29.8 +/- 5.5 wk gestation (mean +/- SD, range 24.7-39.0 wk) with CLD were evaluated for GER at 49.7 +/- 8.0 wk postmenstrual age (mean +/- SD, range 39.9-67.4 wk). Esophageal manometry was first performed to determine the nares-lower esophageal sphincter (LES) distance. A pH-impedance probe was placed at 87% of the nares-LES distance, and a recording was performed for about 24 h at cribside. Symptoms (respiratory, sensory, and movement) were documented by nurses that were blinded to the pH-impedance recordings. A symptom was considered associated with an ARE if it occurred 2 min before, during, or 2 min after the ARE. The proximal extent and associated clearance mechanisms were correlated with symptom sensitivity index (SSI = number of AREs with symptoms/total AREs *100). Multiple logistic regression methods, analysis of variance (ANOVA) models, and chi(2) tests were performed. Data are described as median, mean +/- SD, or %. A total of 511 AREs, based on pH-Impedance methods, were analyzed from 203 h of recordings in the nine infants. The distal esophagus was the maximal height reached in 80% of AREs (P < 0.001, compared to other esophageal segments). Overall 33% of the AREs were associated with symptoms, and an SSI of 77% was noted with high AREs into the pharynx. The average acid clearance time was prolonged with symptomatic AREs versus nonsymptomatic AREs by 3.5-fold (P < 0.001). The occurrence and frequency of symptoms with AREs depend on the most proximal extent of the ARE and the acid clearance time.


A modeling framework for characterizing near-road air pollutant concentration at community scales.
In this study, we combine information from transportation network, traffic emissions, and dispersion model to develop a framework to inform exposure estimates for traffic-related air pollutants (TRAPs) with a high spatial resolution. A Research LINE source dispersion model (R-LINE) is used to model multiple TRAPs from roadways at Census-block level for two U.S. regions. We used a novel Space/Time Ordinary Kriging (STOK) approach that uses data from monitoring networks to provide urban background concentrations. To reduce the computational burden, we developed and applied the METeorologically-weighted Averaging for Risk and Exposure (METARE) approach with R-LINE, where a set of selected meteorological data and annual average daily traffic (AADT) are used to obtain annual averages. Compared with explicit modeling, using METARE reduces CPU-time by 88-fold (46.8h versus 32min), while still retaining accuracy of exposure estimates. We show two examples in the Piedmont region in North Carolina (~105,000 receptors) and Portland, Maine (~7000 receptors) to characterize near-road air quality. Concentrations for NOx, PM2.5, and benzene in Portland drop by over 40% within 200m away from the roadway. The concentration drop in North Carolina is less than that in Portland, as previously shown in an observation-based study, showing the robustness of our approach. Heavy-duty diesel vehicles (HDDV) contribute over 55% of NOx and PM2.5 near interstate highways, while light-duty gasoline vehicles (LDGV) contribute over 50% of benzene to urban areas where multiple roadways intersect. Normalized mean error (NME) between explicit modeling and METARE in Portland ranges from 12.6 to 14.5% and normalized mean bias (NMB) ranges from -12.9 to -11.2%. When considering a static emission rate (i.e. the emission does not have temporal variability), both NME and NMB improved (10.5% and -9.5%). Modeled concentrations in Detroit, Michigan at an array of near-road monitors are within a factor of 2 of observed values for CO but not NOx.


Clinical assessment of the relationship between the third molar and the inferior alveolar canal using panoramic images and computed tomography.
To predict the relationship between lower third molars and the inferior alveolar canal (IAC) from panoramic radiographs, and to establish criteria for using computed tomography (CT). A retrospective cohort study was performed involving 443 patients (695 teeth). Predictor variables were the distance between the third molar and the IAC, and findings according to the Rood's criteria. Outcome variables were the absence of cortication between the third molar and the IAC on the CT image, and injury of the inferior alveolar nerve (IAN). Statistical analysis was performed to assess the relationship between predictor and outcome variables. All patients had preoperative panoramic radiographs, and 71 patients (119 teeth) also had CT images. On CT examination, 48 teeth (40.3%) showed absence of cortication. Injury of the IAN was reported in 7 cases (1.0%), 5 of which exhibited absence of cortication; the remaining 2 did not have CT scans. Five of the 48 cases showing absence of cortication exhibited IAN injury, and none of the cases with cortication exhibited IAN injury. On the panoramic images, the following signs were strongly correlated with absence of cortication: a superimposed relationship between the third molar and the IAC; darkness of the root; and diversion and narrowing of the IAC. Presence of Rood's criteria was a predictor for a contact relationship between the third molar and the IAC, and an indication for CT examination. However, a superimposed relationship and the absence of Rood's criteria did not necessarily signify a separate relationship between third molar and the IAC.


Leucine and isoleucine as in vitro precursors for lipid synthesis by rat aorta.
The in vitro conversion of 14C-labeled leucine, isoleucine, and pyruvate to specific lipids was compared in rat aorta, diaphragm, anf fat pad. Total lipid specific radioactivity from all precursors was greatest in aorta. The ratio of label incorporated into polar lipids vs. neutral lipids by aorta was generally several-fold that incorporated by muscle and fat pad. The labeling of sterols in the aorta from 14C-leucine and pyruvate was equivalent. It is concluded that leucine may be a substantial precursor to polar lipids and to sterols in rat aorta.


Acefylline activates filaggrin deimination by peptidylarginine deiminases in the upper epidermis.
Peptidylarginine deiminases (PADs) catalyze deimination (or citrullination), a calcium-dependent post-translational modification involved in several physiological processes and human diseases, such as rheumatoid arthritis and cancer. Deimination of filaggrin (FLG) by PAD1 and PAD3 during the last steps of keratinocyte differentiation is a crucial event for the epidermis function and homeostasis. This allows the complete degradation of FLG, leading to the production of free amino acids and their derivatives that are essential for epidermal photoprotection and moisturizing of the stratum corneum. To increase the flux of this catabolic pathway, we searched for activators of PADs. A large chemical library was screened first in silico and then by using an automated assay based on an indirect colorimetric measurement of recombinant human PAD activity. Potential activators were then confirmed using a recombinant human FLG as a substrate, and secondly after topical application at the surface of three-dimensional reconstructed human epidermis. The data obtained after the library screening pointed to xanthine derivatives as potential PAD activators. Among seven xanthine derivatives tested at 50-300μM, caffeine, theobromine and acefylline proved to be the most potent enhancers of in vitro deimination of FLG by PAD1 and PAD3. After topical application of a gel formulation containing 3% acefylline at the surface of reconstructed epidermis, immunoblotting analysis showed an increase in the total amount of deiminated proteins, and confocal microscopy showed an enhanced deimination in the stratum corneum. This demonstrated the activation of PADs in living cells. As a PAD activator, acefylline will be useful to study the role of deimination and could be proposed to increase or correct the hydration of the cornified layers of the epidermis.


Photodynamic therapy of the canine prostate: intra-arterial drug delivery.
Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model. To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.


Asthma Network of West Michigan: a model of home-based case management for asthma.
Asthma remains a serious health risk in the United States, particularly among children from low-income families. This article presents an overview of the Asthma Network of West Michigan, the local asthma coalition serving West Michigan, and its intensive home-based case management model for individuals with uncontrolled asthma. The Asthma Network is believed to be the first grassroots asthma coalition in the nation to contract with health plans and obtain reimbursement for these services. The Asthma Network's program has had a positive impact on health care use as well as cost savings, and its model has been replicated in other communities.


Epigenetic phase variation of the pap operon in Escherichia coli.
Expression of the pyelonephritis-associated pilus (pap) operon in Escherichia coli is regulated by a complex epigenetic phase-variation mechanism involving the formation of differential DNA-methylation patterns. This review discusses how DNA-methylation patterns are formed by protein-DNA interactions and how methylation patterns, in turn, control pap gene expression.


Signal detection evidence for limited capacity in visual search.
The nature of capacity limits (if any) in visual search has been a topic of controversy for decades. In 30 years of work, researchers have attempted to distinguish between two broad classes of visual search models. Attention-limited models have proposed two stages of perceptual processing: an unlimited-capacity preattentive stage, and a limited-capacity selective attention stage. Conversely, noise-limited models have proposed a single, unlimited-capacity perceptual processing stage, with decision processes influenced only by stochastic noise. Here, we use signal detection methods to test a strong prediction of attention-limited models. In standard attention-limited models, performance of some searches (feature searches) should only be limited by a preattentive stage. Other search tasks (e.g., spatial configuration search for a "2" among "5"s) should be additionally limited by an attentional bottleneck. We equated average accuracies for a feature and a spatial configuration search over set sizes of 1-8 for briefly presented stimuli. The strong prediction of attention-limited models is that, given overall equivalence in performance, accuracy should be better on the spatial configuration search than on the feature search for set size 1, and worse for set size 8. We confirm this crossover interaction and show that it is problematic for at least one class of one-stage decision models.


Responding to consumer demand: a study of alternative birth centers.
Responding to consumer demands, many hospitals are setting up ABCs for couples who desire a more self-directed, family-centered experience. Such programs require that administrators and staff anticipate potential problems for personnel and clients.


The possible involvement of JNK activation in the spinal dorsal horn in bortezomib-induced allodynia: the role of TNF-α and IL-1β.
Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in BTZ-induced allodynia in rats. Male Sprague-Dawley rats were used as the model animals. The paw withdrawal test, in which mechanical stimuli (von Frey hairs) is applied to the plantar surface of the hindpaw, was used to determine any changes in the paw withdrawal threshold of the treated rats. A PE-10 catheter was placed intrathecally to deliver TNF-α neutralizing antibody, IL-1 receptor antagonist (IL-1ra) or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. The mRNA levels of various cytokines were measured by real-time quantitative PCR. The expression of TNF-α, IL-1β and mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn was measured by western blot analysis and immunohistochemistry. All data were expressed as the mean ± standard error of the mean and analyzed using the SPSS version 13.0 software program. The BTZ treatment induced an upsurge in the mRNA and protein levels of TNF-α in the neurons and IL-1β in the astrocytes in the spinal dorsal horn. It also significantly upregulated the phosphorylation of JNK but not of extracellular signal-regulated kinases (ERK) and p38-MAPK in astrocytes of the spinal dorsal horn. Inhibition of TNF-α or IL-1β ameliorated JNK activation and mechanical allodynia induced by BTZ. Co-administration of thalidomide (TNF-α synthesis inhibitor) and IL-1ra prevented BTZ-induced mechanical allodynia. Our results suggest that the TNF-α or IL-1β/JNK pathway in the spinal dorsal horn may play a critical role in the development of painful peripheral neuropathy induced by BTZ.


[Family-groups in a children-psychiatric-hospital (author's transl)].
The author presents a report of a kind of care for children, suffering from behavior disorders, which consists in structure of a large-family. The first experiences show, that children suffering from minimal brain dysfunction and secondary manifestation of deprivation better grow up in family-groups than in groups of children of the same age.


Attention and cardiac activity: heart rate responses during a variable foreperiod, disjunctive reaction time task.
A variable foreperiod disjunctive reaction time task was used to evaluate the effects of stimulus discriminability on cardiac activity. In two sessions, 20 male undergraduates received easy or difficult auditory discrimination trials in blocked and random series. In the random session only, when the warning stimulus provided information about the difficulty of the subsequent discrimination, difficult trials were associated with greater foreperiod deceleration. Cardiac accelerations also tended to be greater in the foreperiods of difficult trials. There was an effect of both warning and imperative stimuli on the heart rate of the cycle in which the stimuli occurred which depended on the difficulty of the trial. The results are discussed in terms of the psychological significance of the different heart rate responses.


Evaluation of high-intensity therapeutic ultrasound irradiation in the treatment of experimental hepatoma.
A study evaluating the efficacy of high-intensity therapeutic ultrasound (HITU) as a treatment modality in experimental hepatoma is reported. Morris hepatoma (3924) 1 x 10(6) cells were transferred subcutaneously into 40 male ACI rats (weight, 150 to 200 g). Animals were divided into four experimental groups: group 1 (n = 10) consisted of untreated controls; group 2 (n = 10) received intraperitoneal cyclophosphamide 50 mg/kg as a single dose; group 3 (n = 10) underwent HITU only; and group 4 (n = 10) received both chemotherapy (as in group 2) and HITU (as in group 3). HITU was administered with a 5.5-cm diameter 4-MHz quartz transducer creating a continuous wave with 400 W/cm2 focal intensity. The entire tumor was irradiated in 1-mm increments (horizontal and vertical) using treatment cycles of 4 seconds on and 11 seconds off. Total body weight and tumor volume were measured on the day of treatment, and 4 weeks later. At 4 weeks, the animals were killed, the tumor was excised and weighed, and tumor volume was determined. Tumor volume in all treated animals (groups 2, 3 and 4) was significantly smaller than in controls (P less than .001) at 4 weeks, and tumor volume for animals in group 4 was significantly smaller than for those in groups 2 and 3 (P less than .01). These data indicate that HITU significantly reduces tumor size when compared with control rats with Morris hepatoma. A synergistic effect of chemotherapy and HITU was observed and resulted in an enhanced tumor response and reduction of tumor size.(ABSTRACT TRUNCATED AT 250 WORDS)