Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for Feat Against Arthritis Inflammation.
Diclofenac and curcumin is anticipated to have synergistic action. Hence, topical route of administration can be used in minimizing the issues with oral administration of both drugs. This research aims at formulation of controlled release dosage form containing curcumin microspheres and diclofenac diethylamine and then incorporating it into gel formulation for treatment of inflammation associated with rheumatoid arthritis. Curcumin microspheres were prepared, optimized and assayed. Gel containing microspheres was formulated and evaluated for physicochemical parameters like spreadability and viscosity. In vitro and ex vivo diffusion studies were carried out followed by evaluation of efficacy. Efficacy of the developed formulation was evaluated for anti-inflammatory activity. Particle size, Zeta potential, pH, spreadability and viscosity of optimized Batch F1 was found to be in range 0.5 µm - 5 µm,-27.9 mV, 6.2, 105 g cm/s and 7500 cps respectively. In vitro diffusion of developed gel of diclofenac diethylamine and curcumin was found to be 92.16 ± 0.0040 % in 3 h and 92.54 ± 0.0036 % in 12 h as compared to 79.57 ± 0.004 % diffusion in 2 h for marketed gel, thus showing controlled delivery of curcumin. Decreased inflammation in formulation treated group by 72.53% and 50.75% in marketed treated group was seen. Thus the formulation developed showed prolonged activity as well as better anti-inflammatory activity.


Imaging characteristics and associations of left atrioventricular valve atresia and patent aortic root with isometric atrial appendages on multidetector CT.
The present study sought to study the imaging associations of left atrioventricular valve (mitral) atresia and patent aortic root in patients with isomerism of atrial appendages as detected on multidetector computed tomography (CT) angiography MATERIALS AND METHODS: The CT angiography studies performed at a tertiary medical center from January 2014 to December 2021 were retrospectively evaluated to identify patients with left atrioventricular valve atresia and patent aortic root with isometric atrial chambers. The morphology of the atrial appendage and extent of pectinate muscles was used to identify the type of isomeric atrial chambers. A comprehensive assessment of discordant arrangement of organs and the variations in venoatrial connections was done. Left atrioventricular valve atresia in the presence of patent aortic root and isomeric atrial appendages was identified in eight patients (four males). The mean age at diagnosis was 7 years. Right isomerism of the atrial appendages was seen in five patients while three patients had left isomerism. Disharmonious patterns of abdominal visceral arrangement were seen in two patients. Atrial and ventricular septal defects were seen in all patients. The most common pattern of ventricular arterial connection was DORV (double outlet right ventricle) (n = 4). While five patients had normally related great arteries, three had aorta anterior to the pulmonary trunk. Right ventricular outflow obstruction was seen in seven patients. Right aortic arch with mirror image branching was seen in four patients. Coronary artery anomalies were seen in four patients. The presence of left atrioventricular valve atresia and patent aortic root with isomeric atrial appendages is a rare congenital anomaly frequently associated with anomalous systemic and pulmonary drainage, conotruncal anomalies, and right ventricular outflow obstruction. Hence, comprehensive CT-based evaluation is indispensable in providing detailed anatomy and aids in presurgical planning.


Opioid Use Disorder and Assessment of Patient Interactions Among Family Medicine Residents, Medical Students, and Physician Assistant Students.
In light of the opioid overdose epidemic in the US and the necessity of developing training to conduct difficult conversations around opioid dependence, three case-based videos were created to demonstrate providers using motivational interviewing (MI) with patients who have opioid use disorder (OUD). These vignettes displayed a primary care provider interacting with a patient seeking opioids. Learners-including third-year medical and physician assistant (PA) students, and family medicine residents-viewed three videos set in a family medicine clinic and assessed clinician use of MI when interacting with patients with OUD. The patients were at different levels of acknowledging their need to change their opioid use behaviors and/or pursue treatment. Learners rated each video with an MI rating scale, and a facilitator debriefed strengths, weaknesses, and omissions regarding MI. Medical and PA students, and resident family physicians provided 572 ratings. Analysis of variance of mean percent incorrect was lower in residents than in all groups combined, but failed to reach statistical significance (47% + 12.0 vs 53% + 15.0, p = .43). These case-based videos with MI ratings afforded students and residents the opportunity to assess clinician use of MI techniques with patients with OUD. The MI rating scale had clinical significance (residents scored +5 points and had more training) despite lacking statistical significance. These scenarios allowed learners to recognize how to use MI when having a difficult conversation with patients who misuse opioids. We envision individual use or use for group discussion.


Human Papillomavirus-Related Ovarian Metastasis With Endocervical Adenocarcinoma: Report of 2 Cases and Review of Literature.
Most endocervical adenocarcinomas are associated with human papillomavirus (HPV) infection. Studies suggest that synchronous endocervical and ovarian tumors can contain identical HPV subtypes and that, in this setting, the ovarian tumors likely represent metastases from the endocervical adenocarcinoma rather than 2 independent primaries. However, there are still relatively few reports in the literature. We describe 2 patients with HPV-related endocervical adenocarcinoma or adenocarcinoma in situ who had metastatic ovarian tumors that simulated primary ovarian neoplasms. After total hysterectomy and bilateral salpingo-oophorectomy, patient 1, in her mid-40s, was diagnosed with endocervical adenocarcinoma in situ and patient 2, in her early 50s, was diagnosed with endocervical adenocarcinoma showing early focal stromal invasion. The ovarian tumors in both cases simulated independent borderline mucinous tumors without evidence of surface involvement or spread beyond the ovary. However, in both cases, the cervical and ovarian tumors showed diffuse, strong P16 staining and contained identical high-risk HPV subtypes (subtypes 16 and 18 in patient 1 and subtype 16 in patient 2). Patient 1 was treated with radiation therapy and remains recurrence free 5 years after diagnosis, and patient 2 has recently completed combined modality treatment with radiation therapy and cisplatin chemotherapy and remains recurrence free 10 months after diagnosis. A high index of suspicion and ancillary testing, including P16 immunostaining and molecular genetic testing for HPV, is required to properly diagnose and subclassify HPV-related endocervical adenocarcinoma metastatic to the ovary.


Cognitive analysis of decision support for antibiotic ordering in a neonatal intensive care unit.
Clinical decision support systems (CDSS) are a method used to support prescribing accuracy when deployed within a computerized provider order entry system (CPOE). Divergence from using CDSS is exemplified by high alert override rates. Excessive cognitive load imposed by the CDSS may help to explain such high rates. The aim of this study was to describe the cognitive impact of a CPOE-integrated CDSS by categorizing system use problems according to the type of mental processing required to resolve them. A qualitative, descriptive design was used employing two methods; a cognitive walkthrough and a think-aloud protocol. Data analysis was guided by Norman's Theory of Action and a theory of cognitive distances which is an extension to Norman's theory. The most frequently occurring source of excess cognitive effort was poor information timing. Information presented by the CDSS was often presented after clinicians required the information for decision making. Additional sources of effort included use of language that was not clear to the user, vague icons, and lack of cues to guide users through tasks. Lack of coordination between clinician's task-related thought processes and those presented by a CDSS results in excessive cognitive work required to use the system. This can lead to alert overrides and user errors. Close attention to user's cognitive processes as they carry out clinical tasks prior to CDSS development may provide key information for system design that supports clinical tasks and reduces cognitive effort.


Correlation between osteoporotic vertebral fracture and abdominal trunk muscle strength in middle-aged and older women.
We investigated the correlation between abdominal trunk muscle strength and spinal deformities in middle-aged and older women. The results indicated that abdominal trunk muscle weakness, older age, and low lumbar bone mineral density were significant risk factors associated with the presence of OVFs in the lower thoracic and lumbar spine. We developed an innovative exercise device for the abdominal trunk muscles that also measures muscle strength. We investigated the correlation between the strength and thoracolumbar spinal deformity in middle-aged and older women. This study included 206 consecutive female patients who were 50 years or older and scheduled to undergo surgery for degenerative diseases of the lower extremities. Patients with a history of symptomatic osteoporotic vertebral fractures (OVFs) requiring treatments were excluded. Before surgery, patients underwent physical measurements including abdominal trunk muscle strength using our device, full-spine standing radiography, and bone mineral density measurement of the lumbar spine (L-BMD). According to radiographic findings of the radiogram, patients were divided into four groups: control group (n = 134), listhesis group (n = 29), scoliosis group (n = 19), and fracture group (n = 24). The Tukey-Kramer honestly significant difference test was used to compare all measurements among the four groups. To identify factors associated with the presence of OVFs, a multivariate logistic regression analysis was performed. The average abdominal trunk muscle strength in the fracture group was significantly lower than that of the control group. The multivariate analysis revealed that abdominal trunk muscle weakness, older age, and a low L-BMD were associated with OVF findings. Abdominal trunk muscle weakness in middle-aged and older women was associated with OVF. The strength measurement can be a risk assessment of OVF.


Sarcophytrols G - L, Novel Minor Metabolic Components from South China Sea Soft Coral Sarcophyton trocheliophorum Marenzeller.
Minor metabolic components, six new cembranoids sarcophytrols G - L (1 - 6) along with two known related analogues 7 and 8, were isolated from the South China Sea soft coral Sarcophyton trocheliophorum. Their structures were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, and ESI-MS) as well as comparison with literature data. As part of our ongoing research project for discovering bioactive substances from Chinese marine invertebrates, compounds 1 - 8 were tested for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of Type-II diabetes and obesity. However, none of them exhibited potent PTP1B inhibitory activities.


The level of aryl acylamidase activity displayed by human butyrylcholinesterase depends on its molecular distribution.
Butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) display both esterase and aryl acylamidase (AAA) activities. Their AAA activity can be measured using o-nitroacetanilide (ONA). In human samples depleted of acetylcholinesterase, we noticed that the ratio of amidase to esterase activities varied depending on the source, despite both activities being due to BuChE. Searching for an explanation, we compared the activities of BuChE molecular forms in samples of human colon, kidney and serum, and observed that BuChE monomers (G(1)) hydrolyzed o-nitroacetanilide much faster than tetramers (G(4)). This fact suggested that association might cause differences in the AAA site between single and polymerized subunits. This and other post-translational modifications in BuChE subunits probably determine their level of AAA activity. The higher amidase activity of monomers could justify the presence of single BuChE subunits in cells as a way to preserve the AAA activity of BuChE, which could be lost by oligomerization.


Heck coupling of haloaromatics with octavinylsilsesquioxane: solution processable nanocomposites for application in electroluminescent devices.
A new solution processable nanocomposite material has been prepared via the Heck coupling of octavinylsilsesquioxane with a selected bromoaromatic hole transport compound. Resultant electroluminescent devices show an 18% improvement in external quantum efficiencies over their small molecule analogues.


A novel, environmentally friendly dual-signal water toxicity biosensor developed through the continuous release of Fe3.
In this work, a novel, environmentally friendly and simple electrochemical/colorimetric water toxicity biosensor was rationally developed by the continuous release of Fe3+ in a medium. The bioluminescent bacterium Vibrio Fischeri (V. fischeri) was used for the first time as a model bacterium to assess water toxicity for a mediated electrochemical biosensor. The green substance composited by Prussian blue (PB) and yellow K3[Fe(CN)6] was used as the indicator of the colorimetric biosensor. To obtain an ideal electrochemical/colorimetric performance, analytical conditions of the bioassay including NaCl concentration, temperature, concentrations of cells and K3[Fe(CN)6], and incubation time were optimized to 0.5%, 22 oC, 4 (OD600), 10 mM, and 15 min, respectively. The IC50 values of Zn2+, Hg2+, Cd2+ and 3,5-dichlorophenol (3,5-DCP) obtained by electrochemical method were 4.7, 5.0, 17.6 and 10.6 mg/L, respectively. The limits of detection (LODs) of Zn2+, Hg2+, Cd2+ and 3,5-DCP obtained by the naked eye were 6.3, 1.6, 12.5 and 12.5 mg/L, respectively. Two real water samples taken from tap water pipe and the Yitong river were also detected sensitively, and the inhibition ratios obtained were 3.8% and 14.0%, respectively. These results indicate that the V. fischeri-based bioassay is simple, sensitive and inexpensive, which is promising alternative for acute biotoxicity assessment.


A three-dimensional study of organelle interrelationships in regenerating rat liver. 4. Multivesicular bodies.
Double-membraned plasma-membrane-loops are formed from the plasma membrane and released into the cytoplasm. The vesiculation of mainly their inner membrane may transform them into MVB. The so-formed internal vesicles contain cytosol. In many MVB the surface of all their internal vesicles to gether corresponds well with the surface of their bordering membrane. This correlation may be the result of a dynamic equilibrium whereby degradation (and partial recyclage) of internal vesicles is compensated for by the formation of new internal vesicles. When this equilibrium becomes disturbed, MVB may show much less internal vesicles. Such 'depleted' MVB are often producing peribiliary vesicles and may themselves transform into lacunate emptying into the bile canaliculi.


Pattern-constrained multiple polypeptide sequence alignment.
Multiple sequence alignment (MSA) is one of the fundamental research topics in computational biology. The alignments help us to find functional assignment, evolutionary history and conserved region. Previous methods use a substitution matrix and do not incorporate knowledge of the sequences being aligned. Therefore, they do not assure the alignment of similar structures and common patterns in the sequences. We have been investigating into the solution to the problem in multiple and making use of knowledge of the sequences being aligned, including patterns in the Prosite databank, Blocks+, eBlocks databases, as well as motif and structural information. A pattern-constrained algorithm has been developed. Experiments with protein sequences have shown more accurate alignments with incorporation of the domain knowledge available in the sequences.


Aquatic polymer-based edible films of fish gelatin crosslinked with alginate dialdehyde having enhanced physicochemical properties.
Fish-derived gelatin (FG), a raw material for edible films, has recently been spotlighted as an alternative source of mammalian gelatin. However, its low stability under moisture conditions and weak mechanical properties limit its application. In this study, a water-stable and mechanically robust FG film was prepared using alginate dialdehyde (ADA) as an eco-friendly crosslinking agent. The crosslinking process of FG with ADA was easily recognized by the change in the color of the FG/ADA composite film, and the browning index of the FG/ADA film could be correlated well with the actual crosslinking degree. The mechanical strength and Young's modulus of the FG/ADA composite film increased significantly with an increase in the content of the ADA crosslinker. In the case of FG/ADA10, the tensile strength and Young's modulus increased by 400 and 600 %, respectively, compared to those of FG. Remarkably, the FG-ADA crosslinking process greatly decreased the vulnerability of FG in moisture environments. Consequently, the FG/ADA10 film remained stable for 30 days under wet environment. In addition, the FG-ADA crosslinking process could enhance the antioxidative capacity of the FG/ADA edible film. According to this study, FG/ADA composite films fabricated in an effective manner using polymers derived from aquatic species like gelatin from fish and ADA from algae could have practical applications in the edible film-based packaging industry.


PPARGC1A gene polymorphism is associated with exercise-induced fat loss.
Obesity is a widespread problem within modern society, serving to increase the risk of cardiovascular, metabolic, and neurodegenerative disorders. Peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator 1 α (PGC1α) play a key role in the regulation of cellular energy metabolism and is implicated in the pathology of these diseases. This study examined the association between polymorphisms of the PPARG and PPARGC1A genes and individual variability in weight loss in response to physical activity intervention. 39 obese Ukrainian women (44.4 ± 7.5 years, BMI > 30.0 kg/m2) undertook a 3-month fitness program whilst following a hypocaloric diet (~ 1500 cal). Anthropometric and biochemical measurements took place before and after the program. Single nucleotide polymorphisms within or near PPARG (n = 94) and PPARGC1A (n = 138) were identified and expression of PPARG mRNA was measured via reverse transcription and amplification. The association between DNA polymorphisms and exercise-induced weight loss, initial body mass, biochemistry and PPARG expression was determined using one-way analysis of variance (ANOVA). The present intervention induced significant fat loss in all participants (total fat: 40.3 ± 5.3 vs 36.4 ± 5.7%; P < 0.00001). Only one polymorphism (rs17650401 C/T) within the PPARGC1A gene was found to be associated with fat loss efficiency after correction for multiple testing, with T allele carriers showing the greatest reduction in body fat percentage (2.5-fold; P = 0.00013) compared to non-carriers. PPARGC1A (rs17650401) is associated with fat loss efficiency of the fitness program in obese women. Further studies are warranted to test whether this variation is associated with fat oxidation.


Increased proinsulin levels as an early indicator of B-cell dysfunction in non-diabetic twins of type 1 (insulin-dependent) diabetic patients.
Glucose tolerance and insulin secretion were studied in two groups of non-diabetic identical twins of recently-diagnosed Type 1 (insulin-dependent) diabetic patients: (1) a group of 5 twins with islet cell antibodies, and (2) a group of 6 twins without. Despite similar fasting glucose, insulin and C-peptide concentrations both groups of twins had significantly higher fasting proinsulin concentrations than the control group (p less than 0.05). The twins with complement-fixing islet cell antibodies had reduced glucose tolerance and clearance, whilst the twins without islet cell antibodies did not. Neither group of twins showed any abnormality in insulin, C-peptide or proinsulin response to oral or intravenous glucose. We conclude that increased fasting proinsulin levels precede abnormalities of insulin secretion, and are an early indication of minor B-cell damage in these twins irrespective of their risk of developing diabetes.


Median arcuate ligament syndrome: A case report of a rare disease.
Median arcuate ligament syndrome (MALS) is a rare condition caused by the compression of the celiac trunk by the median arcuate ligament, which may trigger a typical symptom triad: postprandial abdominal pain, weight loss, nausea and vomiting. A 58-year-old male was admitted to the emergency department due to abdominal pain, vomiting, fever and diarrhea. On admission, the patient was tachycardic, had abdominal distension, no peritoneal irritation signs, and a serum lactate level of 5 mmol/L. The computed tomography (CT) scan showed gastric and intestinal pneumatosis associated with pneumoportia. Conservative treatment with intravenous fluids, antibiotics and low molecular weight heparin, was initiated. The reassessment CT scan showed resolution of the gastric and intestinal pneumatosis and a severe stenosis of the initial portion of the celiac trunk with associated angulation. After recovery from the acute episode, an abdominal duplex ultrasound and an aortoiliac arteriography in forced inspiration and expiration was performed, corroborating the diagnosis of MALS. A laparoscopic decompression of the celiac trunk was performed. Symptoms of MALS closely mimic other abdominal disorders, and it should be considered in the differential diagnosis. Currently, there are no international guidelines on MALS diagnostic criteria. Treatment is focused on decompression of the median arcuate ligament constriction of the celiac artery, with or without celiac lymph node removal. MALS diagnostic and therapeutic approach must be patient focused. Laparoscopic decompression is an effective treatment and can provide immediate symptomatic relief, associated with the benefits of the less invasive nature of the procedure.


Subtle introduction of membrane polarization-catalyzed H2O dissociation actuates highly efficient electrocoagulation for hardness ion removal.
Electrocoagulation represents a promising process for hardness removal from cooling water. Nevertheless, the slow hydrolysis reaction severely restricted the floc formation, inhibiting the hardness co-precipitation and simultaneously causing secondary pollution from dissolved Al3+. Inspired by the detrimental membrane fouling phenomenon in conventional electrodialysis, we reported a rational strategy to substantially enhance the hardness removal efficiency in electrocoagulation by introducing a special membrane polarization-catalyzed H2O dissociation herein. Leveraging the electron transfer between functional groups (-SO3- and -N(CH3)3+) of ion exchange membrane (IEM) and surface-adsorbed H2O under the electric field-induced ion depletion scenario, H2O dissociation could be effectively catalyzed, with this catalytic activity more intensive in -SO3- than in -N(CH3)3+. Such a special H2O dissociation beneficially created a widely distributed and well-simulated alkalinity zone around the anodic region of IEM, which promoted the conversion of dissolved Al3+ to floc Al, thereby enhancing floc formation and circumventing secondary pollution. All these features enabled the resulting membrane-enhanced electrocoagulation (MEEC) to achieve a super-prominent hardness removal rate of 318.9 g h-1 m-2 with an ultra-low specific energy consumption of 3.8 kWh kg-1 CaCO3, considerably outperforming those of other conventional hardness removal processes reported to date. Additionally, in conjunction with a facile air-scoured washing method, MEEC exhibited excellent stability and universal applicability in various reaction conditions.


An anomalous effect of the intermediate products of riboflavine photolysis on the intestinal absorption of poorly absorbed water-solbule drug in rats.
The influence of the intermediate products of riboflavine photolysis on the absorption of poorly absorbed water-soluble drugs from the rat small intestine has been examined using an in situ recirculation technique. The absorption of phenol red, bromphenol blue (BPB) and their biliary excretion, and lactose isonicotinoyl-hydrazone (lactose-INH) and its plasma concentration were increased in experiments made in the presence of light in contrast to other made in the dark. The absorption of both phenol red and lactose-INH were concentration-dependent. On the other hand, a saturation phenomenon was demonstrated when the concentration of phenol red was kept constant while that of the water-soluble compound flavine mononucleotide (FMN) was changed. The results which were obtained from pretreatment experiments suggest an alteration in the permeability of the intestinal membrane. No enhancement effect could be demonstrated for lumichrome in the presence of absence of light.


Trends in Hospital-to-Hospital Transfers for Aneurysmal Subarachnoid Hemorrhage: A Single-Institution Experience from 2006 to 2017.
Despite evidence to support that aneurysmal subarachnoid hemorrhage (aSAH) is best treated at high-volume centers, it is unknown whether clinical practice reflects these findings. We analyzed patients transferred to our high-volume center for aSAH between 2006 and 2017. Data collection included number of transfers, demographic data, Hunt and Hess score, Fisher score, comorbid conditions, length of stay (LOS), discharge disposition, in-hospital mortality rates, insurance status, and hospital charges. Comparisons were made across 3 time periods (2006-2009, 2010-2013, and 2014-2017) and included subgroup analyses by treatment modality (endovascular vs. microsurgical). aSAH transfers declined from 213 in 2006-2009 to 160 in 2014-2017. While there was no change in presenting Hunt and Hess scores, the percentage of modified Fisher scores of 4 increased from 2006-2009 to 2014-2017. Transferred patients had a greater comorbidity index and decreased predicted 10-year survival. Despite this, the average LOS decreased. In-hospital mortality decreased from 2006-2009 to 2014-2017, especially in the endovascular cohort. The proportions of patients who were either self-pay or Medicaid did not change. Overall inflation-adjusted hospital charges decreased from $76,975 in 2006-2009 to $59,870 in 2014-2017. Between 2006 and 2017, transfers to our center for aSAH declined. However, transferred patients had greater levels of complexity, more comorbidities, and were at greater risk for vasospasm based on their presenting Fisher score. Nonetheless, average LOS, in-hospital mortality, and cost declined. These changing referral patterns have implications for outcome data, quality reporting, resident education, and developing systems of care to optimize outcomes.


Chronic Cystitis Associated With Keratinizing Squamous Metaplasia Progressing to Squamous Papilloma.
We present a patient with extensive keratinizing squamous metaplasia that progressed to squamous papilloma over the course of follow-up. To our knowledge, this is the first published case of keratinizing squamous metaplasia with melanotic deposits of an unknown material with synchronous development of squamous papilloma.


Violent behavior by girls reporting violent victimization: a prospective study.
To assess the relationships between individual victimization and neighborhood-level violence on subsequent violent perpetration by adolescent girls in a community-based sample. Longitudinal, multilevel analysis of data collected by the Project on Human Development in Chicago Neighborhoods. Three in-home interviews were conducted approximately 24 months apart between November 1995 and January 2002 with youth and their caregivers. Community-level data also were collected in 1995 from a random sample of Chicago residents. Hierarchical regression models and propensity scores were used. Families and neighborhoods in Chicago. Population-based sample of 637 girls, ages 9 to 15 years at baseline, and the neighborhoods in which they resided. This sample is diverse in race/ethnicity, socioeconomic status, family structure, and neighborhood characteristics. Self-reports of violent behavior in the 12 months before the third interview. At baseline, 38% of the girls reported perpetrating at least 1 violent behavior in the prior 12 months, 28% reported past year violent behavior at the first follow-up interview, and 14% reported past year violent behavior at the third interview. The odds of violent behavior were 2.2 times higher among girls who reported prior violent victimization, after prior confounding factors and baseline violent behavior were controlled (95% confidence interval, 1.3- 4.4). Homicides and concentrated poverty in girls' neighborhoods also were associated with aggression by girls. Improving safety in communities and homes may reduce rates of violent perpetration by adolescent girls. Study results suggest that, to facilitate identification of and healing among adolescent survivors of violence, practitioners should recognize perpetration of violence as potential sequelae of prior violent victimization.


Neuroendocrine response to estrogen and brain differentiation in heterosexuals, homosexuals, and transsexuals.
Since 1964, we have found positive estrogen feedback to be a relatively sex-specific reaction of the hypothalamo-hypophyseal system in rats as well as in human beings. It is dependent on the estrogen-convertible androgen level during sexual brain differentiation and also on estrogen priming in adulthood. The lower the estrogen-convertible androgen or primary estrogen level during brain differentiation, the higher the evocability of a positive estrogen action on LH secretion in later life. In clinical studies, we induced a positive estrogen feedback luteinizing hormone secretion in most intact homosexual men, in clear-cut contrast to intact heterosexual or bisexual men. In addition, the evocability of a positive estrogen feedback was also demonstrable in most homosexual male-to-female transsexuals in significant contrast to hetero-or bisexual male-to-female transsexuals. The following relations have been found between sex hormone levels during brain differentiation and sex-specific responses in adulthood: (i) Estrogens, which are mostly converted from androgens, are responsible for the sex-specific organization of gonadotropin secretion and hence the evocability of a positive estrogen feedback in later life; (ii) both estrogens and androgens, occurring during brain differentiation, predetermine sexual orientation, and (iii) androgens, without conversion to estrogens, are responsible for the sex-specific organization of gender role behavior. Furthermore, the organization periods for sex-specific gonadotropin secretion, sexual orientation, and gender role behavior are not identical but overlapping. Thus, combinations as well as dissociations between deviation of the neuroendocrine organization of sex-specific gonadotropin secretion, sexual orientation, and gender role behavior may occur.


Clinical features of familial moyamoya disease.
This study aims to clarify the genetic background of moyamoya disease by comparing clinical features between familial and sporadic cases to reveal the responsible genes for familial moyamoya disease. This study included 155 Japanese patients with moyamoya disease, which included 24 familial cases (10 family pedigrees) and 131 sporadic cases. Clinical features were compared between the familial and sporadic cases. A female preponderance was significantly more prominent in the familial than in the sporadic group (P=0.0421). Mean age at onset was significantly lower in familial than in sporadic cases (P=0.004). In eight parent-offspring pairs, mean age at onset was significantly lower in the second than in the first generation (P<0.0001). These results suggest that familial moyamoya disease is associated with genetic anticipation and female predominance and that a genetic analysis study focused on expanded triplet repeats may clarify the pathogenesis of the disease.


Cost effectiveness of strategies to combat neuropsychiatric conditions in sub-Saharan Africa and South East Asia: mathematical modelling study.
To assess the comparative costs and effects of interventions to combat five neuropsychiatric conditions (schizophrenia, bipolar disorder, depression, epilepsy, and heavy alcohol use). Cost effectiveness analysis based on an epidemiological model. Two epidemiologically defined World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE); and countries in South East Asia with high adult and high child mortality (SearD). Published studies, costing databases. Cost per capita and cost per disability adjusted life year (DALY) averted, expressed in international dollars ($Int) for the year 2005. Across 44 assessed intervention strategies for the five neuropsychiatric conditions, cost effectiveness values differed by as much as two orders of magnitude (from $Int100-250 to $Int10,000-25,000 for a year of healthy life gained). In both sub-regions, inpatient based treatment of schizophrenia with newer antipsychotic drugs was the most costly and least cost effective strategy. The most cost effective strategies in the African sub-region related to population based alcohol control, while in the South East Asian sub-region the most cost effective intervention was drug treatment of epilepsy in primary care. The cumulative cost per capita of the most cost effective set of interventions covering all five conditions was estimated at $Int4.90-5.70. This package comprises interventions for epilepsy (older first line antiepileptic drugs); depression (generically produced newer antidepressants and psychosocial treatment); bipolar disorder (mood stabiliser drug lithium); schizophrenia (neuroleptic antipsychotic drugs and psychosocial treatment); and heavy alcohol use (increased taxation and its enforcement, reduced access, and, in the African sub-region, advertising bans and brief advice to heavy drinkers in primary care). Reallocation of resources to cost effective intervention strategies would increase health gain, save money and help implement much needed expansion of services for neuropsychiatric conditions in low resource settings.


The rationale for BAFF inhibition in systemic lupus erythematosus.
BAFF (B-cell-activating factor) is a critical survival factor for transitional and mature B cells and is a promising therapeutic target for systemic lupus erythematosus (SLE). In 2010-2011, two phase 3 clinical trials showed that the addition of the anti-BAFF antibody belimumab to standard-of-care therapy in patients with moderately active SLE results in a better outcome at 52 weeks than standard-of-care therapy alone. Belimumab has been US Food and Drug Administration approved for the treatment of SLE, and other drugs that target BAFF are now in various stages of clinical testing. This review describes the function of BAFF and its homolog APRIL (a proliferation-inducing ligand) and addresses the rationale for the treatment of SLE with BAFF/APRIL inhibitors.


Inferior vena cava replacement: the role of antiplatelet therapy.
To evaluate the effect of ibuprofen on early thrombus formation following inferior vena cava (IVC) replacement, a 4-cm segment of IVC was replaced with a 5-cm (10-mm-i.d.) segment of reinforced polytetrafluoroethylene (PTFE) graft in 12 dogs. Autologous platelets and canine fibrinogen were labeled with 111In and 125I, respectively, and injected into each animal 24 hr prior to vena cava replacement. Six dogs served as controls and six were treated with 12.5 mg/kg ibuprofen intravenously 1 hr preoperatively. All dogs were heparinized with 100 U/kg intravenous heparin prior to crossclamping the IVC: heparin was not reversed at the end of the procedure. Three hours after normal circulation was restored, the grafts were removed and counts of radioactivity made. All grafts were patent. The mean platelet count for the control group was 12.8 X 10(6)/mm2, while in the grafts from the treated group it was 0.960 X 10(6)/mm2. The decreased platelet deposition was significant in all graft segments (P less than 0.01). Fibrin deposition was reduced from 3.38 micrograms/mm2 to 0.25 micrograms/mm2 (P less than 0.01) by ibuprofen. Although fibrin and red blood cells are the major constituents of venous thrombi, platelet aggregation appears to play an important role if prosthetic material is implanted into the venous system. Ibuprofen not only reduced platelet deposition by 13.5-fold, but also reduced fibrin deposition by 13.5-fold. The ratio of platelets to fibrin in control and treated animals was similar (3.84 and 3.79, respectively). These data suggest that antiplatelet medication combined with heparin therapy might decrease early thrombus formation in venous prostheses.


Uranium biosorption mechanism model of protonated Saccharomyces cerevisiae.
Further understanding absorption uranium mechanism of the regenerational biosorbent is very interesting in application of the biosorbent. The regeneration adsorbent of Saccharomyces cerevisiae biomass was made by hydrochloric acid. Using it to absorb uranium at low constant pH(2.50), accompanied with proton releasing the ratio almost 1:2 which is to be analyzed in this paper. The type and amount of functional groups in the biomass such as carboxyl, amino, phosphoryl were determined by Potentiometric titrations and FTIR analysis. Chemical modification showed that the contribution of functional groups to uranium adsorption was carboxyl, phosphoryl and amino in turn. Analysis of SEM-EDX and staining microscopy showed that uranium on the surface of cells did not exist in the form of precipitation at lower pH 2.98, but at higher pH 4.52. The effects of phosphorus release and pH on uranium species was analyzed by MINTEQ software 3.0. Based on the above boundary conditions of the model construction, a multi-site of functional groups model equation of ion exchange absorption mechanism was built in which the final uranium ion concentration and pH as functions. It could well describe the exchange equilibrium of proton with uranium ion at pH2.50 to pH4.00.


Expression of membrane-type-1-matrix metalloproteinase and metalloproteinase-2 in nonsmall cell lung carcinomas.
For the metastasis and invasion of cancer cells, destruction of extracellular matrix is essential. In this process, collagen is broken down by some matrix metalloproteinases. Matrix metalloproteinase 2 (MMP2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP2. We investigated the expressions of MT1-MMP and MMP2 and their relation to both clinicopathologic parameters and clinical outcome in non-small cell lung carcinomas (NSCLC). Eighty-nine specimens of NSCLC were examined using in situ hybridization and immunohistochemistry. Each metalloproteinase was expressed within the cytoplasm of tumor cells with or without stromal cells in NSCLC. Tumors in which tumor cells strongly stained for MT1-MMP mRNA or protein made up more than 50% of the tumor area were found in 44 and 26% of cases, respectively. The corresponding values for MMP-2 mRNA and protein, were 51 and 26%. Our analysis of clinicopathological findings revealed a significant positive relationship between MT1-MMP mRNA and p-M. The correlation between MMP2 protein-staining status and overall survival rate reached significance in the univariate analysis. However, an association was not demonstrated in the multivariate analysis. The detection of MT1-MMP and MMP2 is likely to be of limited value in informing the prognosis in NSCLC.


[Retrospective evaluation of PC IOL power after extracapsular cataract extraction].
Retrospective evaluation of PC IOL power calculation accuracy and comparison of the refractive errors after ECCE resulted from different methods of calculation. The PC IOL power in 100 eyes with senile cataract without significant refractive errors, was calculated using SRK II formula with two different biometers and based on primary refraction. The final IOL power was established by surgeon based on all mentioned calculations (surgeon choice). Half a year after surgery the refractive error was measured. The proper IOL power, which did not require additional correction, was calculated (ideal lens). 48 eyes did not require any distance correction. In 44 eyes small hyperopia (to +2.0 D) appeared and in 8 eyes myopia (to -1.5 D). The smallest error was made in cases where we implanted lenses according to surgeon choice. The average power of ideal lens was 20.32 D. We observed statistically significant difference between both ultrasound biometers. The most accurate results were achieved in cases where IOL power was chosen by the surgeon based on SRK II formula and primary refraction. Possible source of errors can be inadequate indications of biometers.


The Effects of Canopy Height and Bud Light Exposure on the Early Stages of Flower Development in Prunus persica (L.) Batsch.
The aims of this study were to investigate the sunlight requirements during floral initiation and differentiation for the development of flower buds in 'Autumn Bright' nectarine and to explore its source-sink relationship. In early January 2019 (111 days after full bloom), prior to floral initiation and differentiation, 12 new shoots were tagged on 14 trees, with four shoots in each of the low (0-1.2 m), middle (1.2-2.0 m), and high (>2.0 m) canopy heights. Three treatments (bud shading; leaf pluck; bud shading and leaf pluck) were applied to three shoots in each canopy height on the fourth and eighth bud, in addition to a fourth control shoot. Light penetration was measured at the different canopy heights. Buds were assessed in Spring for floral transition, number of floral buds per node, and fruit set. The treatments at the node level had no effect on floral initiation, indicating that sink strength was not promoted by additional light. Light penetration decreased with decreasing canopy height and corresponded with lower floral buds in the low zone. Fruit set was uninfluenced by all treatments. The results of this study emphasised the importance of the availability of photosynthetic assimilates for floral initiation in peach and nectarine trees. Balanced crop load management and summer pruning to enhance canopy sunlight distribution would increase the availability of nutrients for improved floral transition in this cultivar.


Thrombosis and degeneration of Hancock valves: clinical and pathological findings.
Of 415 Hancock valves implanted in 370 patients, 26 valve specimens were recovered at postmortem examination and 8 at reoperation. In 9 of these 34, thrombosis had formed without apparent alteration of the heterograft tissue (Group A). All were mitral prostheses, and the thrombi were attached to the sewing ring. Six of the patients died in the early postoperative period following prolonged low cardiac output syndrome and coagulation disturbances. Three patients had late valve thrombosis 12 to 26 months after operation and were in chronic atrial fibrillation with a very large left atrium. Four valve specimens (Group B) demonstrated degenerative changes of the heterograft leaflets such as shrinkage, perforation, and calcification. The clinical courses and possible pathogenesis are discussed.


Generation and expression of a Hoxa11eGFP targeted allele in mice.
Hox genes are crucial for body axis specification during embryonic development. Hoxa11 plays a role in anteroposterior patterning of the axial skeleton, development of the urogenital tract of both sexes, and proximodistal patterning of the limbs. Hoxa11 expression is also observed in the neural tube. Herein, we report the generation of a Hoxa11eGFP targeted knock-in allele in mice in which eGFP replaces the first coding exon of Hoxa11 as an in-frame fusion. This allele closely recapitulates the reported mRNA expression patterns for Hoxa11. Hoxa11eGFP can be visualized in the tail, neural tube, limbs, kidneys, and reproductive tract of both sexes. Additionally, homozygous mutants recapitulate reported phenotypes for Hoxa11 loss of function mice, exhibiting loss of fertility in both males and females. This targeted mouse line will prove useful as a vital marker for Hoxa11 protein localization during control (heterozygous) or mutant organogenesis.


Genetic linkage of a novel autosomal dominant restrictive cardiomyopathy locus.
In recent years, non-syndromic idiopathic cardiomyopathies have increasingly been characterised as autosomal dominant conditions caused by single gene mutations. Loci have been identified for hypertrophic and dilated cardiomyopathy, and in some cases the same loci are associated with restrictive cardiomyopathy (RCM). In a kindred with RCM that we previously reported, we ruled out the known cardiomyopathy loci and other candidate genes by linkage analysis and mutation screening. Here we report a genome-wide analysis in this family that has resulted in linkage to a region on chromosome 10. There are no genes in the interval that are known to cause idiopathic cardiomyopathy, and thus this linkage represents localisation of a new RCM locus.


Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing.
The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X-linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis. In this study, we used Sanger sequencing and next-generation sequencing (NGS)-based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease-causing gene defects carried by this family. We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co-segregating with the disease, causing a pseudodominant inheritance of GRM6-related autosomal recessive complete CSNB. This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein.


Ectopic thyroid tissue in the anterior mediastinum with a normally located gland: a case report.
Ectopic thyroid tissue occurs in about 7 to 10% of the general population. Localization in the anterior mediastinum is rare: seven cases reported in the literature, most associated with thyroid dysfunction. We report the case of a 77-year-old woman who presented ectopic thyroid tissue in the anterior mediastinum and a normally-located normally-functioning gland.


Infection profile and risk factors for mortality in patients with end-stage renal disease attributable to systemic lupus erythematosus: a two-center integrated study.
Renal impairment is a significant complication of systemic lupus erythematosus (SLE). Additionally, infection in patients with end-stage renal disease (ESRD) attributable to SLE is common, and it increases the risk of mortality. This study explored the infection profile and risk factors for mortality in patients with ESRD attributable to SLE. In this retrospective, observational study of 125 hospitalized patients, demographic, clinical, laboratory, treatment, and prognosis data were retrieved and analyzed. The 125 cases included 98 pulmonary infections (78.4%), 14 urinary infections (11.2%), and 13 intestinal infections (10.4%). Twenty-six patients died within 1 month after enrollment. Univariate Cox regression and Kaplan-Meier analyses revealed several possible indicators potentially influencing patient survival. Furthermore, multivariate Cox regression analysis identified a higher SLE Disease Activity Index-2000 score, recent higher-dose glucocorticoid use, hypertension, and catheter indwelling as risk factors for higher mortality. Infections were common in patients with advanced SLE and ESRD, and several risk factors might increase the risk of mortality. Once infection is identified, empiric antibiotics should be initiated immediately, and subsequent antibiotics should be applied per the results of drug sensitivity testing to clear the infection.


High levels of β-xylosidase in Thermomyces lanuginosus: potential use for saccharification.
A new strain of Thermomyces lanuginosus was isolated from the Atlantic Forest biome, and its β-xylosidases optimization in response to agro-industrial residues was performed. Using statistical approach as a strategy for optimization, the induction of β-xylosidases activity was evaluated in residual corn straw, and improved so that the optimum condition achieved high β-xylosidases activities 1003U/mL. According our known, this study is the first to show so high levels of β-xylosidases activities induction. In addition, the application of an experimental design with this microorganism to induce β-xylosidases has not been reported until the present work. The optimal conditions for the crude enzyme extract were pH 5.5 and 60°C showing better thermostability at 55°C. The saccharification ability of β-xylosidase in the presence of hemicellulose obtained from corn straw raw and xylan from beechwood substrates showed a xylo-oligosaccharide to xylose conversion yield of 80 and 50%, respectively, at 50°C. Our data strongly indicated that the β-xylosidases activities was not subjected to the effects of potential enzyme inhibitors often produced during fermentation process. These data suggest the application of this enzyme studied for saccharification of hemicellulose, an abundant residue in the American continents, thus providing an interesting alternative for future tests for energy production.


Morphological changes of intermingled skin transplants on rats.
Experiments with rats demonstrate that free skin transplants between genetically distinct strains become totally rejected after no longer than 3 weeks. In intermingled skin transplants, however, the autogenic epidermis directly covers the allodermis, which results in a definitively covered wound with a mostly normal skin texture. It seems that during the first phase after the burn the allodermis is accepted as donor skin. In the second phase it becomes covered by the epidermis and surrounded by the connective tissue of the recipient. During this process all structures of ectodermal origin like skin adnexa are rejected. Since for the most part the elastic fibres in the allograft remain unchanged after a successful intermingled skin transplantation, the transplant shows elasticity similar to a mesh autograft, but it is incapable of regenerating skin adnexa. After complete healing cellular and humoral infiltrates, as in the case of immunological rejections, could no longer be detected.


Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) is induced in rabbit articular chondrocytes by cotreatment with interleukin 1 beta and a protein kinase C activator.
The synthesis of an 88-kDa gelatinolytic enzyme, identified as a zymogen of matrix metalloproteinase (proMMP)-9, was induced in the primary culture of rabbit articular chondrocytes by cotreatment with recombinant interleukin 1 beta (rIL-1 beta) and the protein kinase C (PKC) agonists, phorbol 12,13-dibutyrate (PDBu) or mezerein. Negligible 88-kDa gelatinolytic activity was produced by unstimulated cells or cells treated with a PKC activator alone at concentrations up to 100 ng/ml, and only a modest induction occurred with rIL-1 beta alone at concentrations of 1-100 ng/ml. However, when these cells were treated with a PKC activator in the presence of IL-1 beta (1 ng/ml), induction was striking, with enzymic activity detectable at a concentration as low as 1 ng/ml of mezerein or 10 ng/ml of PDBu. Rabbit chondrocytes in culture constitutively produced the zymogen of MMP-2 (proMMP-2) and its production was not altered by treatment with IL-1 beta or PKC agonists alone or in combination. Recombinant tumor necrosis factor alpha (rTNF alpha) did not substitute for IL-1 beta in inducing proMMP-9 in the presence of PKC activators, nor was the combination of IL-1 beta or TNF alpha alone effective. These data indicate that rabbit articular chondrocytes have a potential to synthesize and secrete proMMP-9 under certain biological and pathological conditions but that the expression of proMMP-9 is differently regulated from that of other MMPs.


The Clinical Outcomes of Marginal Donor Hearts: A Single Center Experience.
Although the shortage of donor is a common problem worldwide, a significant portion of unutilized hearts are classified as marginal donor (MD) hearts. However, research on the correlation between the MD and the prognosis of heart transplantation (HTx) is lacking. This study was conducted to investigate the clinical impact of MD in HTx. Consecutive 73 HTxs during 2014 and 2021 in a tertiary hospital were analyzed. MD was defined as follows; a donor age >55 years, left ventricular ejection fraction <50%, cold ischemic time >240 minutes, or significant cardiac structural problems. Preoperative characteristics and postoperative hemodynamic data, primary graft dysfunction (PGD), and the survival rate were analyzed. Risk stratification by Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was performed to examine the outcomes according to the recipient state. Each group was sub-divided into 2 risk groups according to the IMPACT score (low <10 vs. high ≥10). A total of 32 (43.8%) patients received an organ from MDs. Extracorporeal membrane oxygenation was more frequent in the non-MD group (34.4% vs. 70.7, p=0.007) There was no significant difference in PGD, 30-day mortality and long-term survival between groups. In the subgroup analysis, early outcomes did not differ between low- and high-risk groups. However, the long-term survival was better in the low-risk group (p=0.01). The outcomes of MD group were not significantly different from non-MD group. Particularly, in low-risk recipient, the MD group showed excellent early and long-term outcomes. These results suggest the usability of selected MD hearts without increasing adverse events.


DFT studies, vibrational spectra and conformational stability of 4-hydroxy-3-methylacetophenone and 4-hydroxy-3-methoxyacetophenone.
The FT-IR and FT-Raman spectra of 4-hydroxy-3-methylacetophenone (HMA) and 4-hydroxy-3-methoxyacetophenone (HMOA) have been recorded. The total energy calculations of HMA and HMOA were tried for various possible conformers. The spectra were interpreted with the aid of normal coordinate analysis based on density functional theory (DFT) using standard B3LYP/6-31G* and B3LYP/6-311+G** methods and basis sets combinations for the most optimized geometries. Normal coordinate calculations were performed with the DFT force field corrected by a recommended set of scaling factors yielding fairly good agreement between observed and calculated frequencies. On the basis of the comparison between calculated and experimental results, assignments of fundamental modes were examined.


Electrogenerated chemiluminescence of tris(2,2'-bipyridine)ruthenium(II) using N-(3-aminopropyl)diethanolamine as coreactant.
Coreactant plays a critical role for the application of electrochemiluminescence (ECL). Herein, N-(3-aminopropyl)diethanolamine (APDEA) has been explored as a potential coreactant for enhancing tris(2,2'-bipyridyl)ruthenium(II) ECL. It is much more effective than tripropylamine at gold and platinum electrodes although it has one primary amine group besides a tertiary amine group. The presence of primary amine group and hydroxyl groups in APDEA promotes the oxidation rates of amine and thus remarkably increases ECL intensity. The ECL intensities of the Ru(bpy)3 (2+)/APDEA system are approximately 10 and 36 times stronger than that of Ru(bpy)3 (2+)/tripropylamine system and about 1.6 and 1.14 times stronger than that of Ru(bpy)3 (2+)/N-butyldiethanolamine system at Au and Pt electrodes, respectively. The ECL intensity of the Ru(bpy)3 (2+)/APDEA system is 2.42 times stronger than that of Ru(bpy)3 (2+)/N-butyldiethanolamine at glassy carbon electrodes.


Biofilm on the apical region of roots in primary teeth with vital and necrotic pulps with or without radiographically evident apical pathosis.
To evaluate, by scanning electron microscopy (SEM), the presence of biofilms on the external surfaces of the apical third of roots of human primary teeth with vital or necrotic pulps with and without radiographically evident periradicular pathosis. Eighteen teeth were selected: group I - normal pulp (n = 5), group II - pulp necrosis without radiographic evidence of periapical pathosis (n = 7) and group III - pulp necrosis with well-defined radiographic periapical pathosis (n = 6). After extraction, the teeth were washed with saline and immersed in 0.03 g mL(-1) trypsin solution for 20 min. The teeth were then washed in sodium cacodilate buffer and stored in receptacles containing modified Karnovsky solution. The teeth were sectioned, dehydrated in an ethanol series, critical-point dried with CO(2), sputter coated with gold and the external root surface in the apical third examined by SEM. In the teeth of groups I and II, the apical root surfaces were covered by collagen fibres, with no evidence of bacteria (100%). In the teeth of group III, the root apices had no collagen fibres but revealed resorptive areas containing microorganisms (cocci, bacilli, filaments and spirochetes) in all cases (100%). Microorganisms organized as biofilms on the external root surface (extraradicular infection) were detected in primary teeth with pulp necrosis and radiographically visible periapical pathosis.


Could this patient's symptoms be related to an environmental problem?
Environmental hazards attract a lot of media attention with many patients aware of these as a possible cause of their illness. This article provides an overview for an approach to this type of problem and reinforces the fact that considering the possibility is the first step in management. A specific disorder is often not identified and treatment is aimed at symptomatic relief.


Contribution of protein Z and protein Z-dependent protease inhibitor in generalized Shwartzman reaction.
Sepsis, a leading cause of mortality in critically ill patients, is closely linked to the excessive activation of coagulation and inflammation. Protein Z, a cofactor for the protein Z-dependent protease inhibitor, enhances the inhibition of coagulation factor Xa, and protein Z-dependent protease inhibitor inhibits factor XIa in a protein Z-independent fashion. The functions of protein Z and protein Z-dependent protease inhibitor in the inflammatory and coagulant responses to septic illness have not been evaluated. For induction of generalized Shwartzman reaction, dorsal skinfold chamber-equipped mice were challenged twice with lipopolysaccharide (0.05 mg/kg on day -1 and 5 mg/kg body weight 24 hr later). Time-matched control animals received equal volumes of saline. University research laboratory. Using intravital fluorescence microscopy in protein Z-dependent protease inhibitor deficient (ZPI) and protein Z deficient (PZ) mice, as well as their wild-type littermates (ZPI, PZ), kinetics of light/dye-induced thrombus formation and microhemodynamics were assessed in randomly chosen venules. Plasma concentrations of chemokine (C-X-C motif) ligand 1, interleukin-6, and interleukin-10 were measured. Liver and lung were harvested for quantitative analysis of leukocytic tissue infiltration and thrombus formation. After induction of generalized Shwartzman reaction, all mice showed significant impairment of microhemodynamics, including blood flow velocity, volumetric blood flow, and functional capillary density, as well as leukocytopenia and thrombocytopenia. Thrombus formation time was markedly prolonged after induction of generalized Shwartzman reaction in all mice, except of ZPI mice, which also had a significantly higher fraction of occluded vessels in liver sections. PZ mice developed the highest concentrations of interleukin-6 and interleukin-10 in response to generalized Shwartzman reaction and showed greater leukocytic tissue infiltration than their wild-type littermates. In this murine model of generalized Shwartzman reaction, protein Z-dependent protease inhibitor deficiency enhanced the thrombotic response to vascular injury, whereas protein Z deficiency increased inflammatory response.


Increased bone mineral density in the non-resurfaced patella after total knee arthroplasty: a clinical and densitometric study.
We report the results of a longitudinal study of 40 patients with osteoarthritis who had primary prosthetic replacement without patellar resurfacing, and were followed at 6 months postoperatively with a densitometric study and clinically at a minimum follow-up of 2 years. Densitometric analysis showed a mean preoperative density at the affected knee of 0.69 g/cm(2) (CI: 0.62-0.76), compared to 0.86 g/cm(2) (CI: 0.79-0.93) for the opposite knee (p = 0.002). In our study population, the return to load and motion to the retained patella led to a significant increase in patellar bone density as measured by densitometry studies. This observation correlated with significant improvement in knee functional score.


Penta-aqua-(5-carb-oxy-pyridine-2-carboxyl-ato-κN,O)(pyridine-2,5-dicarboxyl-ato-κN,O)cerium(III) tetra-hydrate.
In the title compound, [Ce(C(7)H(3)NO(4))(C(7)H(4)NO(4))(H(2)O)(5)]·4H(2)O, the Ce(3+) ion is nine-coordinated by two O atoms and two N atoms from one single and from one double deprotonated pyridine-2,5-dicarboxyl-ate ligand and five water mol-ecules in a distorted monocapped square-anti-prismatic geometry. In the crystal, extensive O-H⋯O hydrogen-bonding inter-actions result in a three-dimensional supra-molecular architecture.


Rehydration with drinks differing in sodium concentration and recovery from moderate exercise-induced hypohydration in man.
To investigate how differing moderate sodium chloride concentrations affect rehydration after exercise and subsequent exercise capacity, eight males lost 1.98 +/- 0.1% body mass exercising in the heat, then consumed one of four drinks in a volume equivalent to 150% of mass loss. Drinks were identical except for sodium chloride content (1 +/- 1, 31 +/- 1, 40 +/- 1, 50 +/- 1 mmol/l). After 4 h recovery subjects cycled for 5 min at 70% VO(2peak) then at 95% VO(2peak) until volitional fatigue. Urine output was inversely related to sodium intake: more was produced with the 1 than the 40 and 50 mmol/l drinks (P < 0.01). Time to exhaustion in the exercise capacity test was not different between treatments (P = 0.883). The addition of 40 or 50 mmol/l of sodium chloride to a rehydration beverage reduced subsequent urine output, thereby providing more effective rehydration than a sodium-free drink. This did not, however, result in improved performance 4 h after the end of the rehydration period.


Ultrasound indentation of bovine knee articular cartilage in situ.
We have earlier developed a handheld ultrasound indentation instrument for the diagnosis of articular cartilage degeneration. In ultrasound indentation, cartilage is compressed with the ultrasound transducer. Tissue thickness and deformation are calculated from the A-mode ultrasound signal and the stress applied is registered with the strain gauges. In this study, the applicability of the ultrasound indentation instrument to quantify site-dependent variation in the mechano-acoustic properties of bovine knee cartilage was investigated. Osteochondral blocks (n=6 per site) were prepared from the femoral medial condyle (FMC), the lateral facet of the patello-femoral groove (LPG) and the medial tibial plateau (MTP). Cartilage stiffness (dynamic modulus, E(dyn)), as obtained with the ultrasound indentation instrument in situ, correlated highly linearly (r=0.913, p<0.01) with the values obtained using the reference material-testing device in vitro. Reproducibility (standardized coefficient of variation) of the ultrasound indentation measurements was 5.2%, 1.7% and 3.1% for E(dyn), ultrasound reflection coefficient of articular surface (R) and thickness, respectively. E(dyn) and R were site dependent (p<0.05, Kruskall-Wallis H test). E(dyn) was significantly higher (p<0.05, Kruskall-Wallis Post Hoc test) in LPG (mean+/-SD: 10.1+/-3.1MPa) than in MTP (2.9+/-1.4MPa). In FMC, E(dyn) was 4.6+/-1.3MPa. R was significantly (p<0.05) lower at MTP (2.0+/-0.7%) than at other sites (FMC: 4.2+/-0.9%; LPG: 4.4+/-0.8%). Cartilage glycosaminoglycan concentration, as quantified with the digital densitometry, correlated positively with E(dyn) (r=0.678, p<0.01) and especially with the equilibrium Young's modulus (reference device, r=0.874, p<0.01) but it was not associated with R (r=0.294, p=0.24). We conclude that manual measurements are reproducible and the instrument may be used for detection of cartilage quality in situ. Especially, combined measurement of thickness, E(dyn) and R provides valuable diagnostic information on cartilage status.


Posterior reversible encephalopathy syndrome after lung transplantation: Risk factors and management.
Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.


Aspects of ischemic stroke biomechanics derived using ex-vivo and in-vitro methods relating to mechanical thrombectomy.
Establishing the underlying biomechanics of acute ischemic stroke (AIS) and its treatment is fundamental to developing more effective clinical treatments for one of society's most impactful diseases. Recent changes in AIS management, driven by clinical evidence of improved treatments, has already led to a rapid rate of innovation, which is likely to be sustained for many years to come. These unprecedented AIS triage and treatment innovations provide a great opportunity to better understand the disease. In this article we provide a perspective on the recreation of AIS in the laboratory to inform contemporary device design and procedural techniques in mechanical thrombectomy. Presentation of these findings, which have been used to solve the applied problem of designing mechanical thrombectomy devices, is intended to help inform the development of basic biomechanics solutions for AIS.


Age, pelvic incidence, facet joint angle and pedicle-facet angle as correlative factors for isthmic spondylolisthesis: a retrospective case control study.
Isthmic spondylolisthesis (IS) is a common clinical disease with a high incidence rate. However, most current researches explain the clear pathogenesis from a single perspective. The aim of our study was to explore the relationships between multiple parameters in patients and find the potential risk factors of this disease. Our study retrospectively included 115 patients who were diagnosed with isthmic spondylolisthesis and the same number of individuals without spondylolisthesis. The following parameters were measured or collected: age, pelvic incidence (PI), facet joint angle (FJA) and pedicle-facet angle (P-F angle). The radiographic files were imported into Mimics Medical 20.0 and all collected data were analyzed using SPSS, version 26.0, statistical software. The age was higher in IS group than in control group. PI was also higher in the IS group (50.99 ± 7.67) than in the control group (43.77 ± 9.30) significantly (P = 0.009). There was significant difference in cranial and average FJA tropism in L3-L4 level (P = 0.002, P = 0.006, respectively) and in L4-L5 level (P < 0.001). P-F angle of L4-L5 level showed significantly larger in IS group than in control group (P = 0.007).The logistic regression analysis showed a larger age, a greater L3-L4 cranial FJA tropism, and a greater L4-L5 cranial FJA tropism were potential predictors of IS, with an OR of 1.07, 1.28, and 1.39 respectively. The thresholds of the predictors were 60 years, 5.67°, and 8.97° according to the ROC curve. The linear regression equation was established: degree of slippage (%) = 0.220*age - 0.327* L3-4 cranial FJA tropism - 0.346* L4-5 average FJA tropism (F = 3.460, P = 0.011, r = 0.659). Our study revealed that isthmic spondylolisthesis may be related to multiple factors rather than a single factor. Age, PI, PJA and P-F angle are potentially associated with spondylolisthesis.


P300 from identical twins.
The P300 component was obtained from ten pairs of identical twins and matched control subjects with an auditory discrimination task. The event-related brain potentials (ERPs) from the identical twins were strikingly similar in amplitude and latency compared to control subject pairs. The data suggest that individual variations in ERP waveform morphology are determined by the structure of the neurophysiological mechanisms responsible for P300 generation.


Cross-mating study on bone mass in the spontaneously osteoporotic mouse (SAM-P/6).
Genetic control of bone mass in the spontaneously osteoporotic mouse (SAM-P/6) was examined by classical cross-mating experiments, in which SAM-P/2 with a high bone mass was used as a control. Femoral bone mass corrected by size (= bone density) was assayed photometrically. F1 hybrids exhibited intermediate values between those of the two parental strains, i.e. higher than SAM-P/6 and lower than SAM-P/2. F2 hybrids showed a more widely distributed pattern with a mean value quite similar to that of F1 hybrids. The values for backcrosses were between those of F1 and the respective parental strains. They did not show segregations expected in cases of a single-gene control. Numerical analysis of data distribution in each generation suggested that strain-specific bone mass in these strains of mice is inherited as a polygenic characteristic and controlled by a relatively small number of genes.


Inhibition of autophagy modulates astaxanthin and total fatty acid biosynthesis in Chlorella zofingiensis under nitrogen starvation.
The present study showed that inhibition of autophagy significantly increased cellular levels of reactive oxygen species in Chlorella zofingiensis under nitrogen starvation. This was accompanied with increased expression of PSY, and enhanced accumulation of astaxanthin after 48h of cultivation. Nevertheless, the proportion of astaxanthin in secondary carotenoids remained unchanged. Meanwhile, the expression level of ACCase was also elevated in the 3-MA-treated cells compared to the control despite a >20% lower content of fatty acid in the former than the latter. This phenomenon might be due to inhibition of recycling of cellular components by 3-MA and suggests the potential involvement of post-transcriptional regulation in fatty acid biosynthesis. In summary, our work has been the first to report a potentially important role of autophagy in fatty acid and astaxanthin accumulation in C. zofingiensis under stress conditions. The findings might provide valuable insights to guide further research in this area.


Control of feeding rhythm in the terrestrial slug Incilaria bilineata.
A modulatory neuron of feeding rhythm was newly identified in the buccal ganglia of the isolated central nervous system (CNS) of the terrestrial slug Incilaria bilineata. This neuron was termed the "feeding rhythm modulator" (FRM). Its morphological and electrical properties were compared with those of the MGC (metacerebral giant cell, a cerebral modulatory neuron of feeding rhythm). There was no direct connection between FRM and MGC. In order to investigate the control mechanism of the buccal central pattern generator, feeding rhythm was observed by varying the activities of MGC and FRM simultaneously. At a lower level of activity of MGC, feeding rhythm was not only sensitive to the activity of MGC but also to that of FRM. As the level of activity of MGC increased, feeding rhythm was exclusively controlled by the activity of MGC, and became unaffected by the activity of FRM. This indicates that cerebral neurons such as MGC primarily control feeding rhythm and modulate the contribution of FRM in a hierarchical manner.


Medicare services provided by cardiologists in the United States: 1999-2008.
Services provided by cardiologists represent a major portion of Medicare expenditures for specialist physicians. The absolute growth and distribution of these services over the past decade have not been well described. We analyzed fee-for-service Medicare Part B claims for each year from 1999-2008 and selected claims from physicians whose specialty code was cardiology. We then grouped approximately 1000 CPT-9 codes into 45 specific service groups that were then further aggregated into 3 broad service categories: evaluation and management, noninvasive procedures, and invasive procedures. Our main outcome measures were services and allowed charges per 1000 beneficiaries. Sample size ranged from 30.9 million beneficiaries in 1999 to 31.7 million in 2008. During this 10-year period, the number of claims from cardiologists increased 44% (from 2082-2997 per 1000 beneficiaries) while the allowed charges increased 28% after adjusting for inflation (in 2008 dollars, from $181,397-231,728 per 1000 beneficiaries). Evaluation and management services and invasive procedures contributed relatively little to this growth. Instead, most of the growth involved noninvasive procedures--with a 70% increase in claims. Although the most dramatic increases in noninvasive procedures involved emerging imaging technologies (cardiac CT, MRI, and PET scanning), the bulk of the growth occurred in two established technologies: resting echocardiograms and stress tests with nuclear imaging. Most of the growth in services provided by cardiologists over the past decade is the result of increased noninvasive imaging.


Cerebral gigantism of hypothalamic origin.
In five cases of Sotos Syndrome serum somatomedin activities were measured. In two of these cases elevated levels and an increased secretion of growth hormone was observed. In one case (index case) a suspected hypothalamic tumor mass could be excluded, but hydrocephalus with increased intracranial pressure was present. The pathogenesis of gigantism in this syndrome is discussed.


Prospective case series on possible effects of local factors on the development of halitosis in new complete denture wearers.
To assess the development of halitosis in participants wearing new removable complete dentures (RCD). Seventy-five completely edentulous patients receiving RCD were recruited. Halitosis was assessed by means of FitScan Breath Checker on the day of denture insertion (T0), as well as after 1 month (T1), and after 2 months (T2). Risk factors were studied using a validated questionnaire about oral and denture hygiene, and tongue scoring followed for each participant. A modified plaque scoring technique assessed the percentage of newly formed biofilms accumulated on all surfaces of the RCD. At T0, 44% of the participants revealed halitosis. This percentage insignificantly increased at T1 (66.7%) and T2 (65.6%), respectively (P > .109). At T1, halitosis was significantly lower among persons who reported tongue brushing compared to refraining participants (14.3% vs 72.6%; P = .002). At T2, halitosis was significantly higher among patients suffering from moderate to heavy tongue coatings compared to those with no or only light coatings (83.3% vs 50.0%; P = .006), those who did wear their dentures during sleeping (77.5% vs 45.8%; P = .010), and those who did not brush their tongues at all (87.5% vs 29.2%; P < .0001). With a 16-fold increased probability (95% CI 10.0 to 23.31; P < .001), the multivariate analysis revealed that non-brushing the tongue was the only variable significantly linked to halitosis at both follow-ups. Non-brushing of tongues as well as sleeping with dentures seems to be the main causes of halitosis in new RCD wearers.


HapMap-based study: CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers.
The aim of this study was to evaluate the association between CYP2A13 polymorphisms and lung cancer susceptibility using the HapMap database. A case-control analysis of 532 subjects with lung cancer and 614 controls with no personal history of the disease was performed. The tag SNPs rs1645690 and rs8192789 for CYP2A13 were selected, and the genetic polymorphisms were confirmed experimentally through real-time PCR, cloning, and sequencing assay. SNP frequency in this study was consistent with the HapMap Project database of Han-Chinese and lung cancer risk was associated with CYP2A13 polymorphisms in non-smokers. CYP2A13 shares a 93.5% identity with CYP2A6 in the amino acid sequence and the homologous sequences may interfere with the study of SNPs of CYP2A13. CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers. The common polymorphisms of CYP2A13 may be candidate biomarkers for lung cancer susceptibility in Han-Chinese.


Combined modality treatment for central nervous system malignancies.
This review summarizes the current status and future prospects for combined modality treatment of primary and metastatic central nervous system malignancies. The laboratory and clinical basis for multimodality therapy, including surgery, ionizing radiation, and drug therapy, are outlined and critically reviewed. The central nervous system diseases discussed include: glioma (low and high grade), brain metastases, and primary central nervous system lymphoma. Collectively, these data suggest a shift favoring combined modality approaches in several of these diseases; however, the incremental gains are indeed modest. The individual practitioner must weigh these with the additional toxicities before making a therapeutic decision for a particular patient. The future direction of combined modality therapy in these diseases will likely revolve around the increased use of molecular diagnostics resulting in the application of targeted therapy. Clearly, such promising innovations must be delineated in the context of continued preclinical studies and controlled clinical trials.


Autonomic dysreflexia: incidence in persons with neurologically complete and incomplete tetraplegia.
Autonomic dysreflexia (AD) is a common problem in patients with spinal cord injury (SCI) above the T6 neurologic level and may cause serious medical complications if untreated. Previous studies have focused on patients with complete SCI. Prospective analysis of a historic cohort. A retrospective review of a subset of the cohort also was performed. To examine the percentage of persons with complete and incomplete tetraplegia who developed AD and determine whether patients with incomplete injuries were at risk for developing AD; and to study the onset of AD and determine the time period that patients are at risk for developing AD. Data were collected prospectively on 332 patients with tetraplegia to determine American Spinal Injury Association (ASIA) impairment score, neurologic level, presence of AD, and length of hospital stay. The charts of 34 patients who developed AD were then reviewed retrospectively for further data such as onset and contributing factors of AD. Also obtained were data from the National SCI Statistical Center database for comparison of percentage of patients with complete and incomplete injuries who developed AD. Patients with motor-complete SCI (ASIA A or ASIA B) had a higher percentage of AD (P = 0.001) during their initial hospitalization than did patients with motor-incomplete SCI. However, patients with motor-incomplete injuries also were at risk for developing AD. The onset of AD occurred between 1 and 6 months after injury. Patients with incomplete tetraplegia are at risk for developing AD. As hospital lengths of stay decrease, patients may be discharged before onset of symptoms. Patient and family education about AD is, therefore, increasingly important for all patients with tetraplegia.


Promising leads and pitfalls: a review of dietary supplements and hormone treatments to prevent postpartum blues and postpartum depression.
Prevention of postpartum depression (PPD) is important because it typically has a 13% prevalence rate, impactful immediate symptoms with greater risk of suicide, and higher long-term risk of psychiatric symptoms in both the mother and family. There are no universal approaches across all childbearing women that have proven to be preventative for PPD, so it is hoped that dietary and/or hormonal interventions will be developed. There are some effective preventative approaches for PPD, such as psychotherapy and medical management, for the highest risk cases, like when there is a past history of a major depressive episode. The purpose is to review studies that assess dietary and hormonal interventions for prevention of PPD and/or postpartum blues, a high-risk state for PPD. Studies that assess dietary and hormonal interventions for prevention of PPD which included a comparison group were reviewed, including omega-3 fatty acids, mineral and vitamin supplements, amino acid combinations, allopregnanolone, progesterone, and thyroxine. Presently, development of dietary supplements and hormonal products for prevention of PPD is at an early stage with most trials showing results that are either preliminary, not definitive, trend level or variable across studies. Even so, a few directions are not recommended for further investigation such as progesterone and thyroxine. On the other hand, studies of allopregnanolone for prophylaxis of PPD are needed. Also, given the number of trend level findings and the multifactorial etiology of PPD, it may be prudent to investigate combined interventions rather than monotherapies. There is still a major need to develop a dietary supplement that creates resiliency against the biological changes in early postpartum associated with risk for mood disorders and/or PPD.


A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates.
Some people believe that likelihood ratios provide diagnostic information that is more useful than sensitivity and specificity estimates. To assess how physicians' estimates about probability of illness are affected by the presentation of a diagnostic test's value as an estimate of sensitivity and specificity versus a likelihood ratio or an inexact numerical graphic. Random assignment of vignettes with different presentation formats of diagnostic test accuracy. Auditorium at a continuing medical education conference. 183 physicians. After estimating probabilities of 6 common illnesses described in patient vignettes, physicians reviewed pertinent test results presented in 1 of 3 formats. Physicians' probability estimates of illness before and after receiving test information, and post-test probability estimates based on the Bayes theorem. Absolute percentage point differences between the physicians' estimated and the Bayes-based post-test probabilities varied from -7 to 31, from -7 to 28, and from 1 to 29 for the sensitivity and specificity, likelihood ratio, and graphical groups, respectively. Mean differences of probability estimates between the sensitivity and specificity and the likelihood ratio groups were small for all vignettes (-2 to 3 percentage points; summary mean z value across the 6 vignettes, 0.04 [95% CI, -0.14 to 0.21]). The small pool of participants (who were potentially selected) and the limited number of vignettes prevented a more detailed analysis of relationships between the interpreted strength of diagnostic evidence and estimations of illness probability. These findings suggest that presenting diagnostic test accuracy with likelihood ratios does not affect some physicians' estimates of illness probability compared with presenting diagnostic test results as sensitivity and specificity.


Revision surgery after total joint arthroplasty: a complication-based analysis using worldwide arthroplasty registers.
The authors performed a complication-based analysis of total knee (TKA), total hip (THA), and total ankle arthroplasty (TAA) using worldwide arthroplasty registers. We extracted data with respect to reason for revision surgery and pooled causes. The most common causes for revisions in THA were aseptic loosening (55.2%), dislocation (11.8 %), septic loosening (7.5%), periprosthetic fractures (6%), and others. The most common causes in TKA were aseptic loosening (29.8%), septic loosening (14.8%), pain (9.5%), wear (8.2%), and others. The most common causes in TAA were aseptic loosening (38%), technical errors (15%), pain (12%), septic loosening (9.8%), and others. Revisions in TKA and THA differ with respect to type of complication. However, in case of TAA, higher rates of technically related complications are reported.


Sleep and behavioral problems in rolandic epilepsy.
Although patients with benign childhood epilepsy with centrotemporal spikes exhibit a benign course of the disease, some of them display sleep and behavioral problems. Sixty-one patients with rolandic epilepsy, aged 6-11 years, were included in this study. The patients were divided into two subgroups according to the presence of seizures over the preceding 6 months. The control group comprised 25 patients without epilepsy and with similar characteristics in terms of age and sex. All patients underwent evaluation of sleep (Sleep Disturbance Scale for Children) and behavior (Lithuanian version of the Child Behaviour Checklist). Only patients who had had seizures over the preceding 6 months displayed significantly higher scores for sleep problems (disorders of excessive daytime sleepiness, disorders of sleep-wake transition, and scores for total sleep problems), worse sleep quality (longer sleep-onset latency), and behavioral problems (anxiety/depression, social problems, thought problems, attention problems, and aggressive behavior) than the patients of the control group. Our data add to evidence that active epilepsy has an impact on sleep and behavior. Clinically significant sleep problems were related to the higher risk of behavioral problems. Parents' ratings for existing sleep problems were sensitive to Sleep Disturbance Scale for Children scores above normal values.


Covariation of fetal skull and maternal pelvis during the perinatal period in rhesus macaques and evolution of childbirth in primates.
A large brain combined with an upright posture in humans has resulted in a high cephalopelvic proportion and frequently obstructed labor. Fischer and Mitteroecker [B. Fischer, P. Mitteroecker, Proc. Natl. Acad. Sci. U.S.A. 112, 5655-5660 (2015)] proposed that the morphological covariations between the skull and pelvis could have evolved to ameliorate obstructed labor in humans. The availability of quantitative data of such covariation, especially of the fetal skull and maternal pelvis, however, is still scarce. Here, we present direct evidence of morphological covariations between the skull and pelvis using actual mother-fetus dyads during the perinatal period of Macaca mulatta, a species that exhibits cephalopelvic proportions comparable to modern humans. We analyzed the covariation of the three-dimensional morphology of the fetal skull and maternal pelvis using computed tomography-based models. The covariation was mostly observed at the pelvic locations related to the birth canal, and the forms of the birth canal and fetal skull covary in such a way that reduces obstetric difficulties. Therefore, cephalopelvic covariation could have evolved not only in humans, but also in other primate taxa in parallel, or it could have evolved already in the early catarrhines.


Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro.
To investigate effect and possible mechanisms of silencing human WFDC2 (HE4) gene on biological behavior changes as cell proliferation, apoptosis, movement and invasion of human serous ovarian cancer cell line SKOV3. Lentiviral WFDC2 gene sequence of small interfering siRNA was stablely transfected into SKOV3 identified by Q-PCR and western-blot. Obtained SKOV3 stable strains with silenced HE4 were measured by proliferation, apoptosis, migration, and invasion. Gene sequencing showed that the oligonucleotides were successfully inserted into the expected site. After silencing HE4 in the SKOV3, proliferation was significantly inhibited (P<0.05). G(0)/G(1) phase was arrested by the cell cycle (P<0.01) and capacity of the migration and invasion decreased significantly (P<0.01). Slight early apoptosis ratio and no change of late apoptosis were found without change of Caspase-3 or Bcl-2 protein. Proteins involved in ERK pathway as phosphorylated protein as p-EGFR, p-ERK decreased and protease protein involved in tissue remodeling as matrix metalloproteinases MMP-9, MMP-2 and cathepsin B decreased compared with control group. HE4 gene plays an important role in regulating proliferation, apoptosis, migration, invasion of serous ovarian cancer cells by ERK pathway and protease system. Its role in apoptosis needs to be further explored, and it may be a potential target for serous ovarian cancer.


Genome-wide association study of coronary artery disease in the Japanese.
A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 × 10(-34)), HLA-DQB1 on 6p21 (P=4.7 × 10(-7)), and CDKN2A/B on 9p21 (P=6.1 × 10(-16)). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 × 10(-40)). On 6p21, an HLA allele, DQB1(*)0604, could show one of the most prominent association signals in an ∼8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects - population specific and common - on susceptibility to CAD.


The Portuguese version of the visual vertigo analog scale.
Visual vertigo occurs after a vestibular disorder compromising daily living. It can be assessed by "the Visual Vertigo Analogue Scale" (VVAS), a self-administered questionnaire without Portuguese version. To perform the translation, cross cultural adaptation, and validation of VVAS from English to Portuguese. Prospective study involving the translation and cross-cultural adaptation of the VVAS into the Portuguese language, according to recognized guidelines. It was completed by 63 healthy controls and 198 participants with vestibulopathy who also completed the Dizziness Handicap Inventory (DHI) to further explore the link between DHI and VVAS. Groups were compared for severity of visual vertigo and VVAS reliability and internal consistency were tested. The VVAS score was significantly higher in vestibular group (p < 0.001). A Cronbach's α of 0.9 confirmed the valid internally consistent of the applied version. The severity score of VVAS showed a positive strong correlation with DHI (p < 0.0001). The present Portuguese translation of the scale showed satisfactory properties for the assessment of self-perceived and severity of visual vertigo in a significant group of vestibular Portuguese patients.


Food craving-like episodes during pregnancy are mediated by accumbal dopaminergic circuits.
Preparation for motherhood requires a myriad of physiological and behavioural adjustments throughout gestation to provide an adequate environment for proper embryonic development1. Cravings for highly palatable foods are highly prevalent during pregnancy2 and contribute to the maintenance and development of gestational overweight or obesity3. However, the neurobiology underlying the distinct ingestive behaviours that result from craving specific foods remain unknown. Here we show that mice, similarly to humans, experience gestational food craving-like episodes. These episodes are associated with a brain connectivity reorganization that affects key components of the dopaminergic mesolimbic circuitry, which drives motivated appetitive behaviours and facilitates the perception of rewarding stimuli. Pregnancy engages a dynamic modulation of dopaminergic signalling through neurons expressing dopamine D2 receptors in the nucleus accumbens, which directly modulate food craving-like events. Importantly, persistent maternal food craving-like behaviour has long-lasting effects on the offspring, particularly in males, leading to glucose intolerance, increased body weight and increased susceptibility to develop eating disorders and anxiety-like behaviours during adulthood. Our results reveal the cognitively motivated nature of pregnancy food cravings and advocates for moderating emotional eating during gestation to prevent deterioration of the offspring's neuropsychological and metabolic health.


Congenital sinus bradycardia combined with congenital total atrioventricular block.
Sinus bradycardia and total atrioventricular block were found at the age of seven months in a boy who is now 16 1/2 years old. According to Yaters (1929) criteria, these are likely to be congenital disorders. While the frequency of the ventricular impulse generator in the upper bundle of His only slowed in accordance with age during the period of observation, the sinus node activity deteriorated considerably. Finally potentials could only be sporadically demonstrated. Under heavy stress and with a simultaneous slight increase in ventricular frequency, a re-occurence of regular but slow sinus node activity came about. The cause of this binodal disorder of rhythm is unknown. There is no indication of family affliction or of myocarditis in early childhood. Congenital heart disease could also be excluded.


Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy.
We examined the correlation among the levels of urinary monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), hyperglycemia, and renal injuries in patients with type 2 diabetic nephropathy. The levels of urinary MCP-1, IL-8, protein excretion, blood urea nitrogen (BUN), serum creatinine (s-Cr), glycohemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) were measured in 24 patients with type 2 diabetic nephropathy and 14 healthy adults as controls. Diabetic nephropathy was classified into three stages: stage 1 = normoalbuminuric, stage 2 = microalbuminuric, and stage 3 = macroalbuminuric. All of the patients showed normal ranges in renal function tests. Levels of urinary MCP-1 in all patients with diabetic nephropathy were significantly higher than those in healthy adults (P < 0.05). The levels of urinary MCP-1 in patients with diabetic nephropathy increased gradually according to the clinical stage of this disease. In contrast, the levels of urinary IL-8 in patients with diabetic nephropathy increased in stages 2 and 3. There was a significant correlation between the levels of urinary IL-8 and those of HbA1c. High glucose may stimulate MCP-1 and/or IL-8 production and their excretion into the urine independently of the phases or pathological lesions of this disease. It appears that IL-8 increased in the early stage of diabetic nephropathy, and MCP-1 increased in the advanced stage of this disease. It was concluded that measurement of urinary MCP-1 and IL-8 may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy.