Discordance of muscular dystrophy in monozygotic female twins: evidence supporting asymmetric splitting of the inner cell mass in a manifesting carrier of Duchenne dystrophy.
In 1990, Richards et al. reported dramatically skewed lyonization in a set of female monozygotic twins heterozygous for Duchenne muscular dystrophy (DMD). The skewed inactivation pattern was symmetrical in opposite directions, one twin being affected with DMD, the other one being normal. Here, we report an additional set of female monozygotic twins heterozygous for a mutation at the dystrophin locus. Similarly, one shows a manifesting carrier phenotype while one is normal. However, unlike the previous report, we find a skewed X inactivation pattern only in the affected twin, while the normal twin showed a random X inactivation pattern. Our results lend considerable experimental support for the models of twinning and X inactivation recently outlined by Nance in 1990, in that these twins probably represent asymmetric splitting of the inner cell mass (ICM): The affected twin likely arose when a small proportion of the ICM split off after lyonization had occurred. In this situation, the original ICM could give rise to the normal twin with random lyonization, while the newly split cells would experience catch-up growth and lead to the affected twin. Genetic studies of this family showed that the specific dystrophin gene mutation was an exon duplication that arose sporadically in the paternally derived X chromosome.


Impact of different laminae open angles on axial symptoms after expansive open-door laminoplasty.
The present study is a retrospective study.Axial symptoms are frequently encountered complication after laminoplasty. Some studies have reported the influencing factors and preventive measures of axial symptoms after laminoplasty. However, impact of different laminae open angles on the postoperative axial symptoms remains unclear.The objective of the present study was to explore the effect of different laminae open angles on postoperative axial symptoms and to discuss the possible mechanisms of the impact of different open angles on axial symptoms.We retrospectively analyzed 124 patients with multilevel cervical compression myelopathy who were treated with expansive open-door laminoplasty from February 2012 to January 2015. The operational level ranged from C3-C7 in all patients. The laminae open angles at the C4, C5, and C6 levels were measured 1 week postoperative. The mean value was taken for statistical analysis. The patients were divided into 2 groups, group A (open angles < 40°, 71 patients including 44 males and 27 females) and group B (open angles ≥ 40°, 53 patients including 32 males and 21 females). C2-C7 Cobb angle, range of cervical motion (ROM), Japanese Orthopedic Association (JOA) score, and visual analog scale (VAS) score for axial pain were compared between the 2 groups.All patients completed at least 2-year follow-up. Both groups gained significant JOA improvement postoperatively (P < .05). Preoperative and postoperative C2-C7 Cobb angle and ROM comparisons were significantly different (P < .05) in both groups. There were no significant difference for other clinical and radiography parameters between the groups (P > .05). At 2 weeks and 6 months after surgery, there was significant difference in axial symptoms between the 2 groups (P < .05). At final follow-up, the difference between the 2 groups was not statistically significant (P > .05).In different angles of the lamina open-door, incidence of axial symptoms has statistically difference between the 2 groups. When the lamina open-door angles are <40°, there are not only ensure adequate spinal cord decompression but reduces the incidence of early and midterm postoperative axial pain.


Bilateral simultaneous femoral neck fracture mimicking abdominal pain in a cerebral palsy patient.
Simultaneous bilateral femoral neck fractures are unusual lesions, generally associated with an underlying condition which causes impaired bone mineralization, triggered by an increased bone stress. We present a 24-year-old cerebral palsy patient, who was previously evaluated in another institution due to inability to walk, interpreted as abdominal pain. No alteration in blood analysis or abdominal X-rays was found. As no response to treatment was observed, a new abdominal X-ray was taken, which incidentally depicted bilateral medial femoral neck fracture. He was referred to our practice after a resection arthroplasty was offered in another institution. After admission, bilateral one-stage THA was performed. Several reports emphasize bone disease as a major precipitating factor, and there is an increased incidence of hip fractures in chronic epilepsy, renal osteodystrophy, and chronic steroid use. Femoral head resection has been proven to be effective in immobilized patients, whereas this was not a reasonable option in this patient who presented walking ability. Despite the treatment election, primary care physicians should be aware of and alert to the possibility of fractures in patients with neurological disorders and calcium metabolism alterations. Late diagnosis of orthopedic injuries in this type of patients may lead to permanent disability.


[How and why treat supraventricular tachycardias].
The present study deals with pathophysiological and clinical aspects of two major supraventricular tachyarrhythmias: atrial fibrillation and reciprocating tachycardia. The main hemodynamic effects and the most frequent complications are examined, and therapeutic indications are given concerning pharmacologic, surgical or electrical treatment. Twelve patients with supraventricular tachycardia (5 with intranodal reentry and 7 with A-V by-pass tract) were treated with Propafenone and evaluated by repeated electrophysiological testing. Acute infusion of Propafenone (2 mg/kg over 10 minutes) interrupted the induced tachycardia in 9 of 11 patients (81%); Propafenone prevented the induction of the arrhythmia in 60% of patients with nodal reentry and in none with A-V by-pass. Electrophysiological evaluation repeated after one week of oral treatment (300 mg three times daily) in 5 patients indicated complete protection in two patients; in three the arrhythmia was still inducible but had a significantly lower rate. Finally, with regard to electrical treatment, data are presented concerning 10 patients with supraventricular reentrant tachycardia (4 intranodal, 6 with A-V by-pass tract) in whom an antiarrhythmic pacemaker was implanted (5 type Pasar Telectronics, 5 type Medtronic SP 500). The results were highly favourable in 9 patients with complete control of the arrhythmia.


Metabolomic Signature of Coronary Artery Disease in Type 2 Diabetes Mellitus.
Coronary artery disease (CAD) is a common complication of type 2 diabetes mellitus (T2D). This case-control study was done to identify metabolites with different concentrations between T2D patients with and without CAD and to characterise implicated metabolic mechanisms relating to CAD. Fasting serum samples of 57 T2D subjects, 26 with (cases) and 31 without CAD (controls), were targeted for metabolite profiling of 163 metabolites. To assess the association between metabolite levels and CAD, partial least squares (PLS) analysis and multivariate logistic regression analysis with adjustment for CAD risk factors and medications were performed. We observed a separation of cases and controls with two classes of metabolites being significantly associated with CAD, including phosphatidylcholines, and serine. Four metabolites being independent from the common CAD risk factors displaying best separation between cases and controls were further selected. Addition of the metabolite concentrations to risk factor analysis raised the area under the receiver-operating-characteristic curve from 0.72 to 0.88 (p = 0.020), providing improved sensitivity and specificity for CAD classification. Serum phospholipid and serine levels independently discriminate T2D patients with and without CAD. Oxidative stress and reduced antioxidative capacity lead to lower metabolite concentrations probably due to changes in membrane composition and accelerated phospholipid degradation.


Relationships between Atmospheric Transport Regimes and PCB Concentrations in the Air at Zeppelin, Spitsbergen.
Polychlorinated biphenyls (PCBs) are persistent hazardous chemicals that are still detected in the atmosphere and other environmental media, although their production has been banned for several decades. At the long-term monitoring site, Zeppelin at Spitsbergen, different PCB congeners have been continuously measured for more than a decade. However, it is not clear what factors determine the seasonal and interannual variability of different (lighter versus heavier) PCB congeners. To investigate the influence of atmospheric transport patterns on PCB-28 and PCB-101 concentrations at Zeppelin, we applied the Lagrangian Particle Dispersion Model FLEXPART and calculated "footprints" that indicate the potential source regions of air arriving at Zeppelin. By means of a cluster analysis, we assigned groups of similar footprints to different transport regimes and analyzed the PCB concentrations according to the transport regimes. The concentrations of both PCB congeners are affected by the different transport regimes. For PCB-101, the origin of air masses from the European continent is primarily related to high concentrations; elevated PCB-101 concentrations in winter can be explained by the high frequency of this transport regime in winter, whereas PCB-101 concentrations are low when air is arriving from the oceans. For PCB-28, in contrast, concentrations are high during summer when air is mainly arriving from the oceans but low when air is arriving from the continents. The most likely explanation of this finding is that local emissions of PCB-28 mask the effect of long-range transport and determine the concentrations measured at Zeppelin.


[The reconstructive sequence in the 21st century. A reconstructive clockwork].
Mathes and Nahai introduced the conventional reconstructive ladder in 1982 to address tissue defects starting with primary and secondary closure of wounds followed by autologous skin grafting. Regional and local pedicled flaps, tissue expansion and free tissue transfer were further steps. Despite enormous achievements and refinements in these techniques, clinical situations and problems occur beyond the scope of these conventional reconstructive measures. Composite tissue allotransplantation (CTA) of partial faces or of unilateral or bilateral forearms and upper arms, are a novel part of transplantation medicine. The initially reported clinical results are encouraging, especially in light of the initial clinical reports of organ transplantation. However, short and long term problems such as potential tumor induction by immunosuppression and chronic rejection must be taken into consideration. Given the fact that patients receiving CTA have already undergone various reconstructive procedures before, patients often gain tremendous improvement in the quality of life. Robots such as the Da Vinci system for surgeons and the Penelope assistant robot have found their way into the surgical routine. While even microsurgical anastomosis has been accomplished using the Da Vinci system, the total amount of time and resources spent is beyond being practical at present. Regeneration and tissue engineering are of distinct interest in reconstructive surgery. Adipose-derived stem cell transfer is able not only to improve contour defects by volume effects, but also to improve the quality of the overlying skin. Therefore we would propose that these novel techniques, CTA, robotics, regeneration and tissue engineering should be considered as potential future integral cogs in the reconstructive mechanism for the 21st century with the patient being at the centre of the reconstructive efforts.


Improved homogeneous proximity-based screening assay of potential inhibitors of 17beta-hydroxysteroid dehydrogenases.
17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are substrate- and tissue-specific isoenzymes that regulate activation and inactivation of steroid hormones. Up-regulation and downregulation in expression of 17beta-HSDs are linked to onset of many steroid-dependent diseases, such as colon, prostate, and breast cancer; thus 17beta-HSDs are potential drug screening targets. Currently their enzymatic activities are usually measured using laborious chromatographic separations followed by radioactive detection of substrate and product. We have previously reported the use of a homogeneous luminescence resonance energy transfer-based immunoassay for 17beta-estradiol in screening of potential inhibitors of 17beta-HSD type 1 (17beta-HSD-1). By replacing the previously used cell-based enzyme reactions with recombinant enzyme reactions the sensitivity of the screening assay improved considerably. In addition, the single assay was able to detect the influence of a tested compound not only on 17beta-HSD-1 but also on 17beta-HSD type 2 (17beta-HSD-2), catalyzing the opposite reaction. The screening results of the tested molecules obtained from the optimized immunoassay were very similar when compared with the results of high performance liquid chromatography separation analysis. The Z factors were 0.79 and 0.83 for 17beta-HSD-1 and 17beta-HSD-2 assays, respectively. Thus the immunoassay measuring samples converted with the recombinant enzymes was a very suitable method for primary high throughput screening, and it could be used also in further characterization of potential drugs.


Smoking, the missing drug interaction in clinical trials: ignoring the obvious.
Tobacco use is universally recognized as the foremost preventable cause of cancer in the United States and globally and is responsible for 30% of all cancer-related deaths in the United States. Tobacco use, including exposure to secondhand smoke has been implicated as a causal or contributory agent in an ever-expanding list of cancers, including lung, oral cavity and pharynx, pancreas, liver, kidney, ureter, urinary bladder, uterine cervix, and myeloid leukemia. In addition to and independent of the etiologic effects of tobacco carcinogens in numerous cancers, there is a growing literature on the direct and indirect effects of smoking on treatment efficacy (short-term and long-term outcomes), toxicity and morbidity, quality of life (QOL), recurrence, second primary tumors (SPT), and survival time as summarized below. Oncology health professionals have called for increased advocacy for tobacco control. Despite the critical relevance of smoking to cancer outcomes, most oncology clinical trials do not collect data on smoking history and status unless the malignancy is widely acknowledged as smoking related (e.g., lung or head and neck cancer). Usually, these data are collected only at trial registration. Changes in smoking status during treatment or follow-up are monitored in very few trials and are infrequently reported in sample descriptions or included in analysis plans as a potential moderator of outcomes. Based on mounting evidence that tobacco use affects cancer treatment outcomes and survival, we recommend that smoking history and status be systematically collected as core data in all oncology clinical trials: at diagnosis, at trial registration, and throughout treatment and follow-up to long-term survival or death. We feel that the inclusion and analysis of such data in clinical trials will add important information to the interpretation of outcomes and the development of scientific knowledge in this area. Smoking status has been called another "vital sign" because of its relevance to a patient's immediate medical condition. We explain the critical value of knowing the smoking status of every patient with cancer at every visit by providing a brief overview of the following research findings: (a) the effects of tobacco use on cancer treatment and outcome; (b) recent findings on the role of nicotine in malignant processes; (c) some unexpected results concerning tobacco status, treatment, and disease outcome; and (d) identifying key questions that remain to be addressed. We provide a suggested set of items for inclusion in clinical trial data sets that also are useful in clinical practice.


Stereotactic Radiotherapy for Cervical Spinal Intramedullary Metastasis and Multiple Brain Metastases: A Case Report.
A case of cervical (C) spinal intramedullary metastasis and multiple small brain metastases from papillary thyroid carcinoma was presented. Spinal metastasis caused posterior neck and left shoulder pain, dysesthesia in both legs, and motor weakness in both legs and left arm, though the brain metastases were asymptomatic. Both the spinal and brain metastases were successfully treated by frameless stereotactic radiotherapy (SRT)/stereotactic radiosurgery (SRS). The patient's symptoms were almost entirely relieved within two months. A 76-year-old woman was diagnosed as having a thyroid tumor and lung metastasis by roentgenography and computed tomography. Biopsy of the thyroid tumor extending into the mediastinum revealed papillary thyroid carcinoma. She underwent surgical resection of thyroid with dissection of the mediastinum lymph node area. Internal oral radioisotope therapy was not effective for the multiple small lung metastases. She did well for 15 months, but later developed posterior neck and left shoulder pain and dysesthesia in the right leg and then dysesthesia and motor weakness in both legs. Then she experienced weakness in the left upper extremity. Magnetic resonance imaging (MRI) disclosed a small cervical spinal intramedullary mass lesion at the level of C6 and C7 on the left side as well as nine small brain lesions. The cervical spinal intramedullary metastatic tumor was treated by volumetric modulated arc radiotherapy (VMAT) SRT and the nine small brain metastatic tumors were treated by dynamic conformal arc (DCA) SRS uneventfully. A total dose of 39 Gy (100% dose) was delivered in 13 fractions for the spinal lesion (prescription, D95=95% dose; maximum dose=46.3 Gy). Single fraction SRS of 22 Gy (prescription, D95=100% dose) was performed for each of the nine small brain tumors. The spinal tumor was decreased in size on follow-up MRI two months after SRT. Three of the nine brain lesions had disappeared and six were decreased in size on follow-up MRI two months after SRS. Motor weakness in the left extremities and right leg was fully improved, and she could walk again without a cane within two months after SRT. She had only slight dysesthesia in the right leg, possibly due to lumbar spondylosis at the end of the six-month follow-up after SRT. The spinal tumor continued to decrease in size on follow-up MRI five months after SRT. Eight of the nine brain lesions had disappeared and one was decreased in size on follow-up MRI five months after SRS.


Utilising integrated urban water management to assess the viability of decentralised water solutions.
Cities worldwide are challenged by a number of urban water issues associated with climate change, population growth and the associated water scarcity, wastewater flows and stormwater run-off. To address these problems decentralised solutions are increasingly being considered by water authorities, and integrated urban water management (IUWM) has emerged as a potential solution to most of these urban water challenges, and as the key to providing solutions incorporating decentralised concepts at a city wide scale. To incorporate decentralised options, there is a need to understand their performance and their impact on a city's total water cycle under alternative water and land management options. This includes changes to flow, nutrient and sediment regimes, energy use, greenhouse gas emissions, and the impacts on rivers, aquifers and estuaries. Application of the IUWM approach to large cities demands revisiting the fundamental role of water system design in sustainable city development. This paper uses the extended urban metabolism model (EUMM) to expand a logical definition for the aims of IUWM, and discusses the role of decentralised systems in IUWM and how IUWM principles can be incorporated into urban water planning.


Diffuse cavernous hemangioma of the spleen.
Diffuse hemangioma of the spleen occurred in a 59-year-old man. The presenting features were a dull ache and heaviness in the left upper quadrant for 3 weeks, severe left-sided pain and fever immediately before hospitalization, and a tender mass in the left upper quadrant. The condition was diagnosed at laparotomy; splenectomy was performed. In this case intrahemangiomatous hemorrhage had occurred, but not rupture of the spleen, which is a potentially lethal complication. Other complications of diffuse splenic hemangioma are thrombosis, infarction, infection with abscess formation, and partial calcification of the vascular spaces. The condition is rare; only 56 cases have been reported.


Solvent-Free Nuclear Magnetic Resonance Spectroscopy of Charged Molecules.
Nuclear magnetic resonance (NMR) spectroscopy of small molecules protonated in a solvent-free environment was successfully demonstrated. The method is referred to as solvent-free protonation NMR (SoF-NMR). Leveraging matrix-assisted ionization (MAI), we generated protonated species of aniline, 4-chloroaniline, 4-aminobiphenyl, and benzocaine for NMR analysis under mild pressure and temperature conditions. The SoF-NMR spectra were compared to traditional solution NMR spectra, and the shift changes in nuclear spin resonance frequencies verify that these small molecules are protonated by 3-nitrobenzonitrile (3-NBN). As the sample pressure decreased, new spectral features appeared, indicating the presence of differently charged species. Several advantages of SoF-NMR are highlighted, such as the elimination of H/D exchange in labile protons, resulting in the precise observation of protons that are otherwise transient in solution. Notably, the data on benzocaine show evidence of neutral, N-protonated, and O-protonated species all in the same spectrum. SoF-NMR eliminates the solvent effects and interactions that can hinder important spectral features. Optimizing SoF-NMR will result in more cost-effective and efficient NMR experimentation to monitor high-temperature, solvent-free reactions. SoF-NMR has a viable future application for studying exchangeable protons, intermediates, and products in gas-phase chemistry.


Integration of the Forensic Dimension into Anti-Doping Strategies.
Traditionally, research in anti-doping has been stimulated by the need for technological improvements to accommodate the expansion of the list of prohibited substances and methods. Nevertheless, in recent years, anti-doping found itself at a crossroads due to the increasing complexity and constant refinement of doping methods. As illustrated by the 2012 USADA (United States Anti-Doping Agency) versus Lance Armstrong case, a change in paradigm was necessary. The exploration of new scientific avenues to understand the mechanisms of doping and pinpoint its practice was most needed to allow designing more efficient preventive or disruptive strategies. In this context, and at the time of writing in 2017, transposing the concept of forensic intelligence to anti-doping was identified as a promising approach to address the different aspects of doping, from the individual athlete to organized doping and trafficking of substances in a proactive rather than a reactive way. Indeed, collection, structuring, and logical processing of multiple sources of information, and not strictly results of bioanalytical testing of urinary and blood samples, can bring additional value to detect and describe potential, emerging, or existing doping issues. This anti-doping intelligence can provide anti-doping authorities and relevant stakeholders with timely, accurate, and usable information for decision making to solve, reduce, and/or prevent doping-related activities. The integration of intelligence to complement other anti-doping approaches is a potentially major step forward in the development of more effective and robust anti-doping strategies.


Small molecule perturbation of the CAND1-Cullin1-ubiquitin cycle stabilizes p53 and triggers Epstein-Barr virus reactivation.
The chemical probe C60 efficiently triggers Epstein-Barr Virus (EBV) reactivation from latency through an unknown mechanism. Here, we identify the Cullin exchange factor CAND1 as a biochemical target of C60. We also identified CAND1 in an shRNA library screen for EBV lytic reactivation. Gene expression profiling revealed that C60 activates the p53 pathway and protein analysis revealed a strong stabilization and S15 phosphorylation of p53. C60 reduced Cullin1 association with CAND1 and led to a global accumulation of ubiquitylated substrates. C60 also stabilized the EBV immediate early protein ZTA through a Cullin-CAND1-interaction motif in the ZTA transcription activation domain. We propose that C60 perturbs the normal interaction and function of CAND1 with Cullins to promote the stabilization of substrates like ZTA and p53, leading to EBV reactivation from latency. Understanding the mechanism of action of C60 may provide new approaches for treatment of EBV associated tumors, as well as new tools to stabilize p53.


The Rhizobium meliloti ExoK and ExsH glycanases specifically depolymerize nascent succinoglycan chains.
The Rhizobium meliloti ExoK and ExsH glycanases have been proposed to contribute to production of low molecular weight (LMW) succinoglycan by depolymerizing high molecular weight succinoglycan chains in R. meliloti cultures. We expressed and purified ExoK and ExsH and determined that neither enzyme can extensively cleave succinoglycan prepared from R. meliloti cultures, although neutral/heat treatment and acid/heat treatment convert succinoglycan to forms that can be cleaved efficiently by both enzymes. These results were somewhat surprising, given that the exoK+ and exsH+ genes play a crucial role in production of LMW succinoglycan in R. meliloti cultures. We demonstrated by Western blot analyses that R. meliloti expresses ExoK and ExsH, that both proteins can be detected extracellularly, and that ExsH secretion depends on the prsD+/prsE+ genes, consistent with previous predictions based on mutant analyses. Furthermore, we determined that the depolymerization activities associated with purified ExoK and ExsH are comparable with exoK+ and exsH+-dependent depolymerization activities expressed in R. meliloti cultures. We resolved the apparent contradiction between the results of our previous genetic analyses and depolymerization assays by determining that ExoK and ExsH can cleave high molecular weight succinoglycan that is being produced actively by R. meliloti, but not succinoglycan that has accumulated in cultures, to yield LMW succinoglycan. We propose that ExoK and ExsH dynamically regulate the molecular weight distribution of succinoglycan by cleaving nascent succinoglycan only during a limited period after its synthesis, perhaps before it undergoes a time-dependent change in its conformation or aggregation state.


Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.
The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.


Effect of L-arginine intake on exercise-induced hypotension.
to verify if one single dose of L-arginine improves post-exercise hypotension (PEH) in hypertensive. double-blind, placebo, randomized with 20 hypertensive (51.47 ± 1.24 years). Two sessions of aerobic exercise were performed proceeded for the ingestion of one dose of 7 g of L-arginine (EX-LARG) or placebo (EX-PLA), plus one session only with L-arginine ingestion (L-ARG). Blood pressure (BP) was measured at rest, and each ten minutes for a period of 60 minutes recovery after exercise. Blood samples were taken before and after exercise for analysis of plasma concentration of nitrite and malondialdehyde (MDA). One-way ANOVA tests were used to compare the baseline conditions and two-way ANOVA, to evaluate possible differences in pressure responses between procedures. both sessions EX-LARG and EX-PLA showed similar peak reduction for the mean systolic blood pressure (-6.58 ± 0.95 mmHg and -8.38 ± 1.29 mmHg respectively, p = 0.28). On the other hand, for the diastolic component, only L-ARG was able to promote PEH (-1.85 ± 0.44 mmHg), significantly better than EX-PLA (+2.13 ± 0.62 mmHg; p < 0.01). L-ARG alone did not result in significant changes in BP. Nitrite and MDA behaved similarly between procedures. a single dose of L-arginine before exercise improves diastolic PEH.


Veterans' views on military tobacco use and tobacco control policy.
National military and veteran service organizations (MVSOs) have the potential to be advocates for stronger military tobacco control. This study consisted of qualitative analysis of interviews with 5 MVSO leaders (or their designees) and 6 focus groups conducted with veterans, to explore the opinions of MVSO leaders and veterans about military tobacco use and tobacco control policy, and to assess their current knowledge, attitudes, and likelihood of engaging with civilian tobacco control. Themes discussed include the impact of tobacco use on the military mission and on veterans; the possibility of stronger military tobacco control policies; and the idea that such policies would affect the rights of military personnel. Participants considered whether tobacco use impacts the military mission in the most literal sense (e.g., giving away patrol locations), ignoring larger scale effects on long term health and costs. While familiar with tobacco's impacts on veterans' health, MVSO leaders did not endorse stronger policies, although some veterans did. Participants were largely unaware of the impact of tobacco use on military readiness. Establishment of better alliances among MVSOs and civilian public health groups for mutual education about tobacco's many negative effects on the military's mission may be necessary to achieve a tobacco-free military.


CAPD in patients above 70 years of age.
This report shows our experience with 13 patients aged 70-83 years who started CAPD treatment 1981-1989. There were 7 females and 6 males. The total treatment time was 298 months (range 4-104). Nine of the patients were able to perform all CAPD procedures while 4 patients needed some help. The patients who were able to take care of all procedures had the lowest period of terminal care, i.e. the period preceding death when the patients had to be taken care of by the hospital staff. The terminal care period was 5.1% of the total treatment period. In the patients who needed help from the beginning of the treatment, the terminal care was 17.2% of the total treatment period. The frequency of peritonitis was 1 per 10.2 treatment month. The main cause for hospitalization was peritonitis and terminal care at the end of the lives of the patients. No patients died due to peritonitis. However, two patients were transferred to hemodialysis due to recurrent peritonitis and ultrafiltration loss, one was transplanted and one was transferred to IPD due to weakness. The causes of death were myocardial infarction, cerebral stroke and cardiac insufficiency. No deaths were due to peritonitis. CAPD in patients above 70 years of age is acceptable both on the basis of the somatic situation and of quality of life.


The neonatal Fc receptor in cancer FcRn in cancer.
Since the neonatal IgG Fc receptor (FcRn) was discovered, it was found to be involved in immunoglobulin recycling and biodistribution, immune complexes routing, antigen presentation, humoral immune response, and cancer immunosurveillance. The latest data show that FcRn plays a part in cancer pathophysiology. In various types of cancers, such as lung and colorectal cancer, FcRn has been described as an early marker for prognosis. Dysregulation of FcRn expression by cancer cells allows them to increase their metabolism, and this process could be exploited for passive targeting of cytotoxic drugs. However, the roles of this receptor depend on whether the studied cell population is the tumor tissue or the infiltrating cells, bringing forward the need for further studies.


Sinusitis as a source of dental pain.
Sinusitis is a common medical problem that can occasionally manifest as dental pain. If the patient is experiencing dental pain in the maxillary posterior teeth, then it is appropriate for the dentist to rule out sinusitis as a source of the problem before proceeding with definitive dental treatment. Often there is an obvious odontogenic source of the pain, and this should be resolved first, but in other situations it is difficult to determine the cause of the symptoms. In some patients, the source of the pain is so equivocal that it may be necessary to treat the patient for sinusitis to eliminate this as the source of the dental pain (Table 7). In this process, the dentist has one of 2 options: either refer the patient to a physician or treat the sinusitis. The option chosen regarding patient management is made by the dentist and depends on the particular clinical situation and the dentist's training and experience.


GeoSES: A socioeconomic index for health and social research in Brazil.
The individual's socioeconomic conditions are the most relevant to predict the quality of someone's health. However, such information is not usually found in medical records, making studies in the area difficult. Therefore, it is common to use composite indices that characterize a region socioeconomically, such as the Human Development Index (HDI). The main advantage of the HDI is its understanding and adoption on a global scale. However, its applicability is limited for health studies since its longevity dimension presents mathematical redundancy in regression models. Here we introduce the GeoSES, a composite index that summarizes the main dimensions of the Brazilian socioeconomic context for research purposes. We created the index from the 2010 Brazilian Census, whose variables selection was guided by theoretical references for health studies. The proposed index incorporates seven socioeconomic dimensions: education, mobility, poverty, wealth, income, segregation, and deprivation of resources and services. We developed the GeoSES using Principal Component Analysis and evaluated its construct, content, and applicability. GeoSES is defined at three scales: national (GeoSES-BR), Federative Unit (GeoSES-FU), and intra-municipal (GeoSES-IM). GeoSES-BR dimensions showed a good association with HDI-M (correlation above 0.85). The model with the poverty dimension best explained the relative risk of avoidable cause mortality in Brazil. In the intra-municipal scale, the model with GeoSES-IM was the one that best explained the relative risk of mortality from circulatory system diseases. By applying spatial regressions, we demonstrated that GeoSES shows significant explanatory potential in the studied scales, being a compelling complement for future researches in public health.


Acetate kinase in the genus Veillonella: effect of succinate, serological cross-reactivity, and separation by electrophoresis.
Acetate kinases from the genus Veillonella were divided into two types: a succinate-stimulated enzyme and a succinate-independent enzyme. Three strains, V. parvula ATCC 17743 (antigenic group II), V. parvula ATCC 17744 (V), and V. parvula ATCC 10790 (VI), contained the succinate-stimulated enzyme. Among four types strains of V. alcalescens, three strains, ATCC 17747 (I), ATCC 17746 (III), and ATCC 17748 (VII), contained the succinate-independent enzyme, whereas only one strain, ATCC 17745 (IV), contained the succinate-stimulated enzyme. Small amounts of antiserum to the purified acetate kinase from V. alcalescens ATCC 17748 completely inhibited the purified and crude enzyme activity from the strain. Classification of the enzymes on the basis of stimulation by succinate was consistent with classification based on serological reactions using the antiserum as an independent parameter. The succinate-stimulated enzyme could be separated into two classes according to the degree of sensitivity to succinate: (i) enzymes from V. parvula ATCC 17744 and V. alcalescens ATCC 17745, which could be demonstrated on gel after electrophoresis by a histochemical method to be highly stimulated by the presence of succinate in the reaction mixture, and (ii) enzymes from V. parvula ATCC 10790 and V. parvula ATCC 17743, which could be easily demonstrated without succinate. Four groups of acetate kinases from the genus Veillonella were separated by gel electrophoretic mobility. The results showed that almost all enzymes from the seven type strains were heterogeneous at the molecular level.


Progressive Glass Segmentation.
Glass is very common in the real world. Influenced by the uncertainty about the glass region and the varying complex scenes behind the glass, the existence of glass poses severe challenges to many computer vision tasks, making glass segmentation as an important computer vision task. Glass does not have its own visual appearances but only transmit/reflect the appearances of its surroundings, making it fundamentally different from other common objects. To address such a challenging task, existing methods typically explore and combine useful cues from different levels of features in the deep network. As there exists a characteristic gap between level-different features, i.e., deep layer features embed more high-level semantics and are better at locating the target objects while shallow layer features have larger spatial sizes and keep richer and more detailed low-level information, fusing these features naively thus would lead to a sub-optimal solution. In this paper, we approach the effective features fusion towards accurate glass segmentation in two steps. First, we attempt to bridge the characteristic gap between different levels of features by developing a Discriminability Enhancement (DE) module which enables level-specific features to be a more discriminative representation, alleviating the features incompatibility for fusion. Second, we design a Focus-and-Exploration Based Fusion (FEBF) module to richly excavate useful information in the fusion process by highlighting the common and exploring the difference between level-different features. Combining these two steps, we construct a Progressive Glass Segmentation Network (PGSNet) which uses multiple DE and FEBF modules to progressively aggregate features from high-level to low-level, implementing a coarse-to-fine glass segmentation. In addition, we build the first home-scene-oriented glass segmentation dataset for advancing household robot applications and in-depth research on this topic. Extensive experiments demonstrate that our method outperforms 26 cutting-edge models on three challenging datasets under four standard metrics. The code and dataset will be made publicly available.


Hsa-circ_0000064 accelerates the malignant progression of gastric cancer via sponging microRNA-621.
Gastric cancer (GC) is one of the most common digestive system tumors in the world. Many circular RNAs (circRNAs) are involved in the progression of GC. The purpose of this study was to delve into the expression characteristics and biological functions of circ_0000064 in GC, and further study its mechanisms. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0000064 expression in 61 GC tissues and cell lines. Circ_0000064 knockdown was successfully modeled with siRNA. The effects of circ_0000064 on the biological functions of GC cells were analyzed by CCK-8, BrdU, and Transwell assays. Bioinformatics and dual-luciferase reporter gene assay were adopted to explore the relations between circ_0000064 and microRNA-621 (miR-621). Western blot was used to examine the regulatory function of circ_0000064 and miR-621 on SYF2 pre-mRNA splicing factor 2. Cric_0000064 expression was elevated in GC tissues and cell lines. Knocking down cric_0000064 could inhibit the viability, migration, and invasion of GC cells. Dual-luciferase reporter gene assay showed that miR-621 could bind circ_0000064 and SYF2 3'UTR; in addition, miR-621 overexpression or SYF2 knockdown could partially weaken the cancer-promoting effect of circ_0000064 on GC cells. Circ_0000064 expression was negatively correlated with miR-621 expression in GC tissues while positively with SYF2 expression. Circ_0000064 can participate in the GC progression via modulating miR-621/SYF2 axis. This implies that circ_0000064 may be a new diagnosed biomarker or a new therapeutic target of GC.


Selective and benign alkylation of sulfido-oxo stannate clusters with propyl, pentyl, or hexyl substituents.
Chalcogenido metalate compounds that are based on tetrahedral clusters have been extensively studied in recent years due to their rich structural chemistry and uncommon chemical and physical properties. Recently it was shown that partial butylation of the inorganic cluster core by ionothermal reactions allowed access to tetrahedral sulfido-oxo stannate clusters with reasonable solubility in conventional solvents at the retainment of their opto-electronic features. We have expanded this mild alkylation approach, and herein report success in receiving the first sulfido-oxo stannate clusters that are selectively propylated, pentylated, and hexylated. This was achieved in a unique way by preparing symmetrically 1,3-substituted imidazolium bromides in preparative scale and using them as both the reaction medium and alkylatoin reagent. We discuss the effect of the organic groups attached to the cluster and present in the counterions of the products on the compounds' structural and opto-electronic properties.


Adiposis dolorosa.
We report a 46-year-old woman with a nine-year history of obesity; chronic diffuse pain in the adipose tissue of her medial upper arms, lower trunk, and thighs; multiple biopsy-proven lipomas and angiolipomas; and a lipomatous pseudomass of the breast. Her systemic symptoms included generalized weakness, fatigue, memory impairment, and arthralgias. Although some of the lesions were tender, most were only appreciated with palpation. Her clinical history and histopathologic data suggested adiposis dolorosa (Dercum's disease). Owing to the chronic pain, an interdisciplinary approach with the use of analgesics and doxycycline has been initiated.


Effects of Inflammasome Activation on Secretion of Inflammatory Cytokines and Vascular Endothelial Growth Factor by Retinal Pigment Epithelial Cells.
Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of AMD. Lipofuscin phototoxicity activates the inflammasome in RPE cells by inducing lysosomal membrane permeabilization (LMP). We investigated the effects of LMP-induced inflammasome activation on the secretion of inflammation-related cytokines and VEGF by RPE cells. In primary human RPE cells and ARPE-19 cells, the inflammasome was activated by L-leucyl-L-leucine methyl ester (Leu-Leu-OMe)- or lipofuscin phototoxicity-induced LMP. Cytokine secretion was measured by protein dot blot and enzyme-linked immunosorbent assays. The polarization of cytokine secretion was assessed in RPE monolayers on permeable membranes. We analyzed the chemotactic and angiogenic effects of secreted cytokines on murine embryonic stem cell-derived microglia cells and human umbilical vascular endothelial cells, respectively. Inflammasome activation in RPE cells was associated with caspase-1-dependent secretion of IL-1β, IL-6, IL-18, GM-CSF, and GRO (CXCL1/2/3), whereas constitutive secretion of VEGF was reduced. Secretion of IL-1β and IL-18 was highly polarized to the apical cell side. Incubation with conditioned media of inflammasome-activated RPE cells induced directed migration of microglia cells (11.0-fold increase) and diminished vascular endothelial cells proliferation (39.0% reduction) and migration (69.3% reduction) as compared with conditioned media of untreated control RPE cells. Lysosomal membrane permeabilization-induced activation of the NLRP3 inflammasome in RPE cells results in apical secretion of inflammatory cytokines with chemotactic effects on microglia cells and reduced constitutive secretion of VEGF. Via these mechanisms, lipofuscin phototoxicity may contribute to local immune processes in the outer retina as observed in AMD.


Fluorogenic Templated Reaction Cascades for RNA Detection.
Nucleic acids detection is essential to the study of biological processes and to diagnosis of pathological states. Although PCR is highly effective in vitro, methods that can function without prior sample preparation, thermal cycling, or enzymes are of interest due to their simplicity. Most current non-PCR detection methods rely on linear signal amplification, which hinders the detection of small amounts of genetic material. To address this limitation, we tested a new strategy for attaining higher-order signal amplification, in which a target sequence templates a chemical ligation, and the product of this reaction is in turn detected with a second templated reaction. The method is nonenzymatic, isothermal, and fluorogenic, allowing the direct detection of nucleic acids in complex matrices. Using this approach, as little as 500 attomoles (10 pM) could be detected with single nucleotide resolution. In a test of selectivity, single nucleotide substitutions and deletions could successfully be detected, including a deletion that is associated with tetracycline resistance in Helicobacter pylori. Compatibility with biological matrices was demonstrated by the direct detection of rRNA in bacterial lysate. Imaging and detection of target sequences on a solid support further illustrates the potential of the new approach for high-throughput analysis.


Pericentric inversion of chromosome No. 8.
Chromosome studies of an infant with multiple malformations were made by means of the trypsin-Giemsa banding as well as conventional Giemsa staining methods. The propositus showed 46, XY +3, -C, and it was indicated that the abnormal metacentric chromosome was induced by the pericentric inversion of chromosome No. 8, in which chromosomal breakage had occurred most likely at the bands 8p23 and 8q23. The probable formula of the inversion is 46, XY, inv (8) (p23q23). Karyotypic analyses of the parents revealed no abnormalities, and the inversion therefore occurred spontaneously. Clinical features of the porpositus are postulated to be caused by a loss of very small portions of the chromosomal material with the occurrence of the pericentric inversion.


Parameter estimation for mathematical models of NKCC2 cotransporter isoforms.
An optimization problem, formulated using a nonlinear least-squares approach, was used to estimate parameters for kinetic models of the three isoforms of the kidney-specific Na-K-2Cl (NKCC2) cotransporter. Specifically, the optimization problem estimates the magnitude of model parameters (i.e., off-binding and translocation rate constants) by minimizing the distance between model unidirectional fluxes and published unidirectional (86)Rb(+) uptake curves for the A, B, and F isoforms of the NKCC2 cotransporter obtained in transfected Xenopus oocytes. By using different symmetry assumptions, NKCC2 models with five, six, seven, or eight parameters were evaluated. The optimization method identified parameter sets that yielded computed unidirectional fluxes consistent with the uptake data. However, the parameter values were not unique, in that systematic exploration of the parameter space revealed alternative parameter sets that fit the data with similar accuracy. Finally, we demonstrate that the optimization method can identify parameter sets for the three transporter isoforms that differ only in ion binding affinities, a result that is consistent with a published mutagenesis analysis of the molecular and structural bases for the differences in (86)Rb(+) uptake among the A, B, and F isoforms. These NKCC2 cotransporter models will facilitate the development of larger scale models of ion transport by thick ascending limb cells.


Responsiveness, affinity constants and beta 2-adrenoceptor reserves for isoprenaline on portal veins from normo- and pre- and hypertensive rats.
1. This study used contractility methods with the portal veins of 5- and 14-week-old Wistar-Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs). The SHRs are prehypertensive at 5 weeks. 2. The first part of our study was to determine whether the responsiveness to isoprenaline and forskolin was altered in the maturation of portal veins from normo- and prehypertensive rats. The responses to forskolin were similar on the portal veins of 5- and 14-week-old WKY and SHRs. 3. The sensitivity and maximum responses to isoprenaline were similar on portal veins of 5- and 14-week-old WKY. The sensitivity and maximum responses to isoprenaline were lower on the portal veins of 5-week-old SHRs (pD2 = 8.25, maximum = 85%) than age-matched WKY (pD2 = 8.79, maximum = 96%); these differences are not caused by hypertension. At 14 weeks, the sensitivity was similar (WKY pD2 = 8.74, SHR pD2 = 8.65) but the maximum responses to isoprenaline were lower on the portal veins SHRs (77%) than WKY (97%). Thus, the sensitivity to isoprenaline increases with the development of hypertension in the SHR portal vein. 4. The second part of the study was to determine whether the affinity for isoprenaline at beta2-adrenoceptors and the fractional beta2-adrenoceptor occupancy-response relationships on the portal vein were altered in maturation from normo- and pre-hypertensive rats. The effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor blocker, on the isoprenaline responses of 5- and 14-week-old WKY and SHRs were studied. Maturation of the WKY portal vein between 5 and 14 weeks was associated with a loss of affinity for isoprenaline (from pKA of 7.13 to 7.87), and increase in beta2-adrenoceptor reserve (from 72 to 92% at the 95% response). There were similar affinity and reserve findings in the maturation of the SHR portal vein. Thus, there are major changes in beta2-adrenoceptor structure and reserve in maturation on the portal vein that are irrespective of the development of hypertension.


Göteborg Metoprolol Trial: tolerance.
During a 3-month follow-up, 131 patients (19.1%) withdrew from blind treatment in both metoprolol- and placebo-treated groups. More metoprolol-treated than placebo-treated patients withdrew because of cardiovascular adverse experience mainly during the very early phase. In all, 45 (6.5%) metoprolol-treated vs 14 (2.0%) placebo-treated patients were not given either a full intravenous dose or a full oral dose 15 minutes later. Bradycardia and hypotension were more common in the metoprolol group, whereas severe atrioventricular block did occur in a similar number of patients in both groups and severe congestive heart failure was more common in the placebo group. Results indicate that tolerance is generally good after intravenous and oral treatment with metoprolol in patients with suspected acute myocardial infarction.


Oral extracellular vesicles in early pregnancy can identify patients at risk of developing gestational diabetes mellitus.
To isolate and characterize oral extracellular vesicles from gingival crevicular fluid at 11-14 weeks and evaluate their capacity to identify patients at risk of developing gestational diabetes mellitus. A case-control study was conducted, including patients who developed gestational diabetes mellitus (n = 11) and healthy pregnant controls (n = 23). Obstetric and periodontal histories were recorded at 11-14 weeks of gestation, and samples of gingival crevicular fluid obtained. Extracellular vesicles were isolated from gingival crevicular fluid by ExoQuick. Nanoparticle tracking analysis, ELISA and transmission electron microscopy were used to characterize extracellular vesicles. Total extracellular vesicles isolated from gingival crevicular fluid were significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (6.3x109 vs 1.7 x1010, p value = 0.0026), and the concentration of the extracellular vesicles delivered an area under the ROC curve of 0.81. The distribution size of extracellular vesicles obtained using ExoQuick was around 148 ± 57 nm. There were no significant differences in the periodontal status between cases and controls. The exosome transmembrane protein CD63 was also detected in the extracellular vesicles of gingival crevicular fluid. We were able to isolate extracellular vesicles from gingival crevicular fluid using a method that is suitable to be applied in a clinical setting. Our results provide an insight into the potential capacity of first trimester oral extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus in pre-symptomatic women.


[Hormone therapies in pregnancy].
Maternal endocrine disorders can have detrimental effects on the fetus and the pregnancy can affect the course of a pre-exisiting endocrinopathy or induce the onset of one of these disorders. Therapies for endocrine disorders are not always safe to administer during pregnancy. Before administering any therapy to the mother, the effects on the fetus, the degree of placental trespassing as well as the potential damaging effects must be assessed. An accurate evaluation of the risks/benefits of any drug to be used on the mother is needed, assessing above all a potential theratogenic effect. In this review, the incidence of the main endocrine disorders, their evolution during pregnancy, their effects on mothers and fetuses and new acquisition on the treatment during pregnancy are discussed.


Calcium-dependent regulation of rab3 in short-term plasticity.
The Rab3 proteins are monomeric GTP-binding proteins associated with secretory vesicles. In their active GTP-bound state, Rab3 proteins are involved in the regulation of hormone secretion and neurotransmitter release. This action is thought to involve specific effectors, including two Ca2+-binding proteins, Rabphilin and Rim. Rab3 acts late in the exocytotic process, in a cell domain in which the intracellular Ca2+ concentration is susceptible to rapid changes. Therefore, we examined the possible Ca2+-dependency of the regulatory action of GTP-bound Rab3 and wild-type Rab3 on neuroexocytosis at identified cholinergic synapses in Aplysia californica. The effects of recombinant GTPase-deficient Aplysia-Rab3 (apRab3-Q80L) or wild-type apRab3 were studied on evoked acetylcholine release. Intraneuronal application of apRab3-Q80L in identified neurons of the buccal ganglion of Aplysia led to inhibition of neurotransmission; wild-type apRab3 was less effective. Intracellular chelation of Ca2+ ions by EGTA greatly potentiated the inhibitory action of apRab3-Q80L. Train and paired-pulse facilitation, two Ca2+-dependent forms of short-term plasticity induced by a rise in intraterminal Ca2+ concentration, were increased after injection of apRab3-Q80L. This result suggests that the inhibition exerted by GTP-bound Rab3 on neuroexocytosis is reduced during transient augmentations of intracellular Ca2+ concentration. Therefore, a Ca2+-dependent modulation of GTP-bound Rab3 function may contribute to short-term plasticity.


Association of selected risk factors with variation in child and adolescent firearm mortality by state.
This study examined relationships between variation in child and adolescent firearm mortality by state and the following variables: childhood poverty rate, percent single parent families, percent population that is African American, percent population that is Hispanic, percent students carrying a gun, percent students carrying a weapon, percent students feeling unsafe, percent students feeling sad/hopeless, percent students academically at-risk, percent students involved infighting, percent students engaging in binge drinking behavior, violent crime rate for youths, individual gun laws in each state, prevalence of firearm ownership, and percent residing in urban area. Stepwise regression was calculated and one independent variable, prevalence of firearm ownership in the state, emerged as a significant predictor of child and adolescent firearm mortality. This variable predicted 47% of the variance from state to state in the child and adolescent firearm mortality. Schools need to address firearm safety and advocate for elimination of firearms accessible to youth.


A prospective study of the cognitive-stress model of depressive symptoms in adolescents.
This prospective study investigated a cognitive diathesis-stress model of depression in adolescents across the transition from 6th to 7th grade using individual, additive, weakest link, and keystone approaches to operationalizing the cognitive vulnerability. Participants were 240 young adolescents (mean age = 11.87 years, SD = 0.57) who differed in risk for mood disorders based on their mother's history of depression. Results of the hierarchical multiple regression analyses indicated some support for the individual, additive, weakest link, and keystone diatheses. In particular, the weakest link diathesis interacted with stress and gender to predict increases in depressive symptoms in 7th grade; the form of this interaction was consistent with the cognitive diathesis-stress model for boys, whereas for girls the pattern of relations reflected more of a dual-vulnerability model. That is, high levels of depressive symptoms were found for all girls except those with more positive cognitive styles and low stress levels. These findings highlight the utility of examining different approaches to combining measures of cognitive vulnerability in conjunction with stress in predicting depressive symptoms, and the importance of exploring gender differences with regard to the cognitive diathesis-stress model.


Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells.
Despite their therapeutic potential, progress in generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuraxis. GABAergic interneuron precursors have the remarkable ability to migrate extensively and survive after transplantation into postnatal cortex, making them an attractive candidate for use in cell-based therapy for seizures or other neuropsychiatric disorders. We have modified a mouse ESC line with an Lhx6-GFP reporter construct that allows for the isolation of newly generated cortical interneuron precursors. When transplanted into postnatal cortex, these cells can migrate into the cortical parenchyma, survive for months, and display morphological, neurochemical, and electrophysiological properties characteristic of mature interneurons. This work demonstrates that forebrain neuronal subtypes with complex traits can be generated from embryonic stem cells, and provides a novel approach to the study of cortical interneuron development and to the establishment of cell-based therapies for neurological disease.


Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+)CD56(bright) cells.
Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK) cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright) NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright) population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright) NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright) cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.


The early development of Kraepelin's ideas on classification: a conceptual history.
Psychiatry still lives in a Kraepelinian world and scholarship on the work of Kraepelin has consequently been unhistorical. Selective exegesis of the various editions of his textbook has led to a rigid view of his contribution. However, Kraepelin lived and wrote during an important period of European intellectual history and his work can only be understood against this background. This paper analyses the development of his views in terms of the 'Research Programme' he planned early in his life and whose objective was the creation of a stable description and classification of the psychoses. This Kraepelin eventually achieved by longitudinally studying patient cohorts in terms of methodological criteria such as illness course and incurability. In the event, this methodology allowed him to identify by correlation 'clinical pictures' that both represented the 'essence' of the disease and provided a taxonomic criterion. Although avowedly atheoretical, Kraepelin thus managed to construct (influenced by Kahlbaum and Wundt) an empirical support for his Kantian categorization of the psychoses. A discussion of the cultural variables that moulded these ideas is included.


Daughter-in-law's burden: An exploratory study of caregiving in Japan.
This exploratory study examines home caregiving of elderly family members in rural central Japan. The extent of the daughter-in-law's involvement with severely cognitively and physically impaired relatives is discussed within the context of traditional co-residence patterns. Findings from a preliminary survey, interviews and observations indicate limited modification of the physical environment, high levels of burden, and utilization of the limited respite services available. Despite expectations that daughters-in-law will care for the elderly, voices for change are growing louder.


Toxicokinetics of fumonisin B2 in ducks and turkeys.
Two extraction steps combined with HPLC with fluorescence detection were developed to determine the toxicokinetics of fumonisin B(2) (FB(2)) in ducks and turkeys. The limit of quantification of the method was 25 ng of FB(2)/mL. The mean extraction was 63%. After intravenous administration (single dose: 1 mg of FB(2)/kg of BW), plasma concentration time curves were best described by a 2-compartment open model. In ducks, elimination half-life, mean residence time, and clearance of FB(2) were 32 min, 12.9 min, and 9.3 mL/min per kilogram, respectively. In turkeys, these toxicokinetics parameters were 12.4 min, 5 min, and 8.7 mL/min per kilogram, respectively. Only a small amount of FB(2) was detected in plasma after oral dosing of 10 mg of FB(2)/kg of BW.


Enabling mothers of young children in a low SES area to co-design the support they are seeking for the adoption of healthy behaviours.
There is a need for interventions that meet the needs of low socioeconomic status (SES) groups, to encourage the adoption of healthy diets and physical activity, in line with current public health guidance. This qualitative research used co-production, a method which actively involves the relevant community, to identify and describe public health interventions to support a group of mothers of young children living in a low SES area. A group of 20 mothers took part in three in-depth qualitative interviews to discuss in detail the type of support that would be of value to them for the adoption and maintenance of healthy behaviours. The mothers were subsequently invited to take part in a public engagement project, a community-based self-help group. Four themes explained the principles of interventions that would be of value in supporting the mothers with the adoption of healthy behaviours, namely, a community-based self-help group, support for the whole family and support in the home and influencing the environment. These were then further developed into two types of intervention (1) learning for self-help and family care, which encompassed the first three learning-based themes and (2) community of support, which covered influencing the environment and the experience of the community-based self-help group. Co-production enabled a group of mothers of young children, from a low SES area, to describe the type of support that would help them with the establishment and maintenance of healthy lifestyle behaviours. A community-based self-help group warrants further research.


[Capillaria brochieri n. sp. (Nematoda: Capillariinae) intestinal parasite of the chimpanzee (Pan paniscus) in Zaire].
Capillaria brochieri n. sp. is described in a chimpanzee (Pan paniscus Schwartz, 1929) deceased from diarrhea. The male shows a unique structure of the caudal extremity: two flat paddles, with distal insertion, extend forward on each side of the ventral genital opening. The spicule (1,750 microns in length) shows a flattened anterior extremity and a tapered, curved posterior extremity. The cirrus is non-spiny and very long. Two narrow and very long lateral alae are present. The female bears a vulvar appendage. The egg shell shows an internal dense layer and an external layer of irregular width, showing pores and striations. The paper includes a study of the literature on Capillaria and Anatrichosoma from Primates and Man. C. brochieri is the first species of Capillaria described from the intestine of the chimpanzee. Because of the close analogies between chimpanzee's and man's helminthes, it is possible that C. brochieri has to be considered in human pathology.


Unifying Concepts of Statistical and Spectral Quantitative Ultrasound Techniques.
Quantitative ultrasound (QUS) techniques using radiofrequency (RF) backscattered signals have been used for tissue characterization of numerous organ systems. One approach is to use the magnitude and frequency dependence of backscatter echoes to quantify tissue structures. Another approach is to use first-order statistical properties of the echo envelope as a signature of the tissue microstructure. We propose a unification of these QUS concepts. For this purpose, a mixture of homodyned K-distributions is introduced to model the echo envelope, together with an estimation method and a physical interpretation of its parameters based on the echo signal spectrum. In particular, the total, coherent and diffuse signal powers related to the proposed mixture model are expressed explicitly in terms of the structure factor previously studied to describe the backscatter coefficient (BSC). Then, this approach is illustrated in the context of red blood cell (RBC) aggregation. It is experimentally shown that the total, coherent and diffuse signal powers are determined by a structural parameter of the spectral Structure Factor Size and Attenuation Estimator. A two-way repeated measures ANOVA test showed that attenuation (p-value of 0.077) and attenuation compensation (p-value of 0.527) had no significant effect on the diffuse to total power ratio. These results constitute a further step in understanding the physical meaning of first-order statistics of ultrasound images and their relations to QUS techniques. The proposed unifying concepts should be applicable to other biological tissues than blood considering that the structure factor can theoretically model any spatial distribution of scatterers.


Nuclear transcription factor-kappaB as a target for cancer drug development.
Nuclear factor kappa B (NF-kappaB) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-kappaB has become one of the major targets for drug development. Here, we review our current knowledge of NF-kappaB, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-kappaB signaling pathway for cancer drug development.


[Thrombinogenesis in chronic myeloproliferative syndromes].
Haemostatic disturbances are important in clinical complications in patients with chronic myeloproliferative syndromes and sometimes the reason of death. Pathogenesis of thrombo-embolic disease during these states is not clear. The aim of study was the evaluation of the risk of thrombosis in patients with chronic myeloproliferative syndromes using very detailed test to measure the concentration of TAT (thrombin-antithrombin) complexes. The study was performed in 73 patients: in 22 with chronic myeloid leucaemia (CML), in 25 with polycythemia vera (PV), in 21 with essential thrombocytemia (ET) and in 5 with myelofibrosis (MF). The control group consisted of 29 healthy volunteers. In the blood plasma of studied persons concentration of TAT complexes and antithrombin (AT) activity were detected. We observed in patients, except MF, significant increase of TAT but diminished AT activity. Increased TAT complexes in chronic myeloproliferative syndromes is the evidence of significant thrombinogenesis. AT activity diminished in PV showes too high consumption of it with concomitant low synthesis.


Spin-Dependent Weakly-Interacting-Massive-Particle-Nucleon Cross Section Limits from First Data of PandaX-II Experiment.
New constraints are presented on the spin-dependent weakly-interacting-massive-particle–- (WIMP-)nucleon interaction from the PandaX-II experiment, using a data set corresponding to a total exposure of 3.3×10^{4} kg day. Assuming a standard axial-vector spin-dependent WIMP interaction with ^{129}Xe and ^{131}Xe nuclei, the most stringent upper limits on WIMP-neutron cross sections for WIMPs with masses above 10 GeV/c^{2} are set in all dark matter direct detection experiments. The minimum upper limit of 4.1×10^{-41} cm^{2} at 90% confidence level is obtained for a WIMP mass of 40 GeV/c^{2}. This represents more than a factor of 2 improvement on the best available limits at this and higher masses. These improved cross-section limits provide more stringent constraints on the effective WIMP-proton and WIMP-neutron couplings.


Binding proteins for insulin-like growth factors in the human ovary: identification, follicular fluid levels and immunohistological localization of the 29-32 kd type 1 binding protein, IGF-bp1.
The occurrence of pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 29-32 kd insulin-like growth factor binding protein, now termed type 1 or IGF-bp1, has been examined in the human ovary by monoclonal and polyclonal antibody based radioimmunoassay and immunohistological techniques. Follicular fluids aspirated from 51 follicles of 32 women undergoing hyperstimulation involving buserelin or clomiphene-based protocols contained 35.5-276.0 ng/ml (mean 101.0 mg/ml) of immunoreactive IGF-bp1. Mean fluid concentrations were three times the level of IGF-bp1 detected in paired serum samples, available for 21 women. Immunoreactive IGF-bp1 in follicular fluid exhibited similar dose-response curves to purified protein and amniotic fluid and immunoreactive IGF-bp1 coeluted in gel filtration with a peak of [125I]-IGF-1 binding corresponding to the elution profile of purified IGF-bp1. Gel filtration also revealed the presence in follicular fluid of a greater than 100 kd binding protein with a binding capacity equal to IGF-bp1 under the conditions employed. A highly significant correlation (P less than 0.001) was found between follicular fluid progesterone and IGF-bp1 and a correlation of lower significance was found between oestradiol and IGF-bp1 (P less than 0.05). However, only low levels of immunoreactive IGF-bp1 were detected in supernatant media of granulosa cells in culture (range undetectable to 2.3 ng/ml). Employing monoclonal antibody-based immunohistology, immunoreactive IGF-bp1 was consistently associated with luteinized granulosa cells of corpora lutea rather than paraluteal cells and its intensity of reactivity appeared to reflect luteal phase steroid hormone profiles. No consistent reactivity was detected in preovulatory follicles and granulosa cells in culture, although reactivity was associated with primordial oocytes. Immunoreactive IGF-bp1 was detected in six of nine supernatant media of explants of luteal tissue obtained from five corpora lutea, with levels ranging from undetectable to greater than 200 ng/ml. These observations suggest that IGF-bp1 is primarily related to luteinization of the granulosa and the resultant luteal cells, and if produced by the luteal cells, additional exogenous factors are required to induce production by granulosa cells in vitro.


Clinical risk factors associated with intraoperative floppy iris syndrome: a prospective study.
To evaluate the incidence of and factors associated with intraoperative floppy iris syndrome (IFIS) in patients undergoing cataract phacoemulsification. In total, 319 eyes of 319 patients who underwent phacoemulsification with implantation of an intraocular lens (IOL) into the posterior chamber were included in this study. Direct injection of epinephrine into the anterior chamber was performed in all cases. The following patient information was collected: gender, age, axial length of the eye, presence of pseudoexfoliation syndrome, glaucoma, diabetes mellitus, hypertension, current use of medications including alpha1 adrenergic receptor antagonists (alpha1-ARAs), finasteride, and benzodiazepines, duration of intake of alpha1-ARAs and finasteride, and duration of the surgery. Patients were classified as IFIS or non-IFIS after the surgery. Univariate and multivariate logistic regression analyses were performed. The overall incidence of IFIS was 9.09% (29/319 eyes). The multivariate analysis revealed that tamsulosin use (P = 0.004), finasteride use (P = 0.014), and increasing age (P = 0.006) were significantly associated with IFIS. Male gender and benzodiazepine use were significantly associated with IFIS in the univariate analysis, but not in the multivariate analysis. The non-selective alpha1-ARA doxazosin was not found to be associated with IFIS. The findings suggest that finasteride use and aging are risk factors for IFIS and confirm the association of tamsulosin use with IFIS. Further, doxazosin appears to be a relatively safe drug with respect to the occurrence of IFIS.


The predictive validity of the university of rhode island change assessment questionnaire in a heroin-addicted polysubstance abuse sample.
The purpose of this investigation was to examine the predictive utility of the stages-of-change scales of the University of Rhode Island Change Assessment (URICA; E. A. McConnaughy, J. O. Prochaska, & W. F. Velicer, 1983) questionnaire in a heroin-addicted polysubstance-abusing treatment sample. Ninety-six participants completed the URICA at the beginning of a 29-week treatment period that required thrice-weekly urine drug screens. Multivariate multiple regression analysis indicated that after controlling for demographic variables, substance abuse severity, and treatment assignment, the stages-of- change scales added significant variance to the prediction of heroin- and cocaine-free urine samples. The Maintenance scale was positively related to cocaine-free urines and length in treatment. The implications of these findings for treatment and for measuring readiness among individuals using multiple substances while taking maintenance medications are discussed.


Polysaccharide κ-Carrageenan as Doping Agent in Conductive Coatings for Electrochemical Controlled Release of Dexamethasone at Therapeutic Doses.
Smart conductive materials are developed in regenerative medicine to promote a controlled release profile of charged bioactive agents in the vicinity of implants. The incorporation and the active electrochemical release of the charged compounds into the organic conductive coating is achieved due to its intrinsic electrical properties. The anti-inflammatory drug dexamethasone was added during the polymerization, and its subsequent release at therapeutic doses was reached by electrical stimulation. In this work, a Poly (3,4-ethylenedioxythiophene): κ-carrageenan: dexamethasone film was prepared, and κ-carrageenan was incorporated to keep the electrochemical and physical stability of the electroactive matrix. The presence of κ-carrageenan and dexamethasone in the conductive film was confirmed by µ-Raman spectroscopy and their effect in the topographic was studied using profilometry. The dexamethasone release process was evaluated by cyclic voltammetry and High-Resolution mass spectrometry. In conclusion, κ-carrageenan as a doping agent improves the electrical properties of the conductive layer allowing the release of dexamethasone at therapeutic levels by electrochemical stimulation, providing a stable system to be used in organic bioelectronics systems.


Characterization of a chromosomal type II toxin-antitoxin system mazEaFa in the Cyanobacterium Anabaena sp. PCC 7120.
Cyanobacteria have evolved to survive stressful environmental changes by regulating growth, however, the underlying mechanism for this is obscure. The ability of chromosomal type II toxin-antitoxin (TA) systems to modulate growth or cell death has been documented in a variety of prokaryotes. A chromosomal mazEaFa locus of Anabaena sp. PCC 7120 has been predicted as a putative mazEF TA system. Here we demonstrate that mazEaFa form a bicistronic operon that is co-transcribed under normal growth conditions. Overproduction of MazFa induced Anabaena growth arrest which could be neutralized by co-expression of MazEa. MazFa also inhibited the growth of Escherichia coli cells, and this effect could be overcome by simultaneous or subsequent expression of MazEa via formation of the MazEa-MazFa complex in vivo, further confirming the nature of the mazEaFa locus as a type II TA system. Interestingly, like most TA systems, deletion of mazEaFa had no effect on the growth of Anabaena during the tested stresses. Our data suggest that mazEaFa, or together with other chromosomal type II TA systems, may promote cells to cope with particular stresses by inducing reversible growth arrest of Anabaena.


Area postrema lesions impair flavor-toxin aversion learning but not flavor-nutrient preference learning.
Rats with lesions of the area postrema (APX) or sham lesions were trained to associate flavored solutions with positive or negative postingestive consequences. The APX rats were similar to controls in learning preferences for flavors paired with concurrent intragastric infusions of maltodextrin or corn oil and for a flavor paired with delayed maltodextrin infusions. In contrast, the APX rats displayed impaired aversion learning for flavors paired with toxic drug treatments (lithium chloride infusion or methylscopolamine injection). The aversion learning deficit ranged from mild to total, depending on training procedures. These findings confirm the important role of the area postrema in flavor-toxin learning but provide no evidence for its involvement in flavor-nutrient conditioning.


Measurement of brain oxygen utilization with radioactive oxygen-15: experimental verification.
This study was designed to provide direct experimental evidence in support of the method employing radioactive 15O-tagged hemoglobin for the in vivo and regional measurement of the cerebral oxygen utilization rate (CMRO2). This was accomplished by simultaneously measuring in vivo the mean CMRO2 in monkeys and human beings by the 15O method and a direct appeal to the Fick principle using measured arteriovenous oxygen differences of brain. The correlation between the 2 methods was excellent, with a correlation coefficient of 0.90 (P less than 0.001) in monkeys and 0.88 (P less than 0.001) in human beings.


Symposium on infectious complications of neoplastic disease (Part I). Introduction and epidemiology.
An approach to infections in cancer patients is outlined that divides such infections into those due to underlying disease, those related to underlying disease plus therapy, and those related to therapy alone. The incidence of such infections in each of the categories is discussed, together with a general outline of patterns and trends in regard to involved microorganisms. Several specific areas discussed include: problems of superinfection with newer antimicrobial agents; the current inadequacy of diagnostic techniques; the potential for early treatment with monoclonal antibodies; the potential for augmenting one or more host defenses prior to sundering other defenses during antitumor chemotherapy; the potential value of a variety of nutrients that either may be depleted or might be of benefit in enhancing host defense mechanisms.


Spectroelectrochemistry of a photochromic [2.2]paracyclophane-bridged imidazole dimer: clarification of the electrochemical behavior of HABI.
The photochromic behavior of the imidazole dimers can be attributable to the photoinduced homolytic cleavage of the C-N bond between the two imidazole rings. On the other hand, although the simultaneous formation of the imidazolyl radical and imidazole anion by the one-electron reduction of an imidazole dimer was reported, no definitive evidence for this electrochemical reaction has been demonstrated. We report the first direct evidence for the electrochemical generation of the imidazolyl radical from the radical anion of the imidazole dimer by conducting the UV-vis-NIR spectroelectrochemical analysis of the [2.2]paracyclophane-bridged imidazole dimer.


Adsorbent 2D and 3D carbon matrices with protected magnetic iron nanoparticles.
We report on the synthesis of two and three dimensional carbonaceous sponges produced directly from graphene oxide (GO) into which functionalized iron nanoparticles can be introduced to render it magnetic. This simple, low cost procedure, wherein an iron polymeric resin precursor is introduced into the carbon framework, results in carbon-based materials with specific surface areas of the order of 93 and 66 m(2) g(-1), compared to approx. 4 m(2) g(-1) for graphite, decorated with ferromagnetic iron nanoparticles giving coercivity fields postulated to be 216 and 98 Oe, values typical for ferrite magnets, for 3.2 and 13.5 wt% Fe respectively. The strongly magnetic iron nanoparticles are robustly anchored to the GO sheets by a layer of residual graphite, on the order of 5 nm, formed during the pyrolysis of the precursor material. The applicability of the carbon sponges is demonstrated in their ability to absorb, store and subsequently elute an organic dye, Rhodamine B, from water as required. It is possible to regenerate the carbon-iron hybrid material after adsorption by eluting the dye with a solvent to which it has a high affinity, such as ethanol. The use of a carbon framework opens the hybrid materials to further chemical functionalization, for enhanced chemical uptake of contaminants, or co-decoration with, for example, silver nanoparticles for bactericidal properties. Such analytical properties, combined with the material's magnetic character, offer solutions for environmental decontamination at land and sea, wastewater purification, solvent extraction, and for the concentration of dilute species.


Determinants of peritubular capillary fluid uptake in hydropenia and saline and plasma expansion.
Hydrostatic (HPc) and oncotic (phic) pressures within the peritubular capillary, tubular pressure (Pt), nephron filtration rate, and plasma flow, and proximal fractional and absolute reabsorption (APR) were measured in anesthetized rats during hydropenia and plasma and saline expansion. Net interstitial pressure (phii-HPi) was estimated from subcapsular hydrostatic and oncotic pressures during saline expansion and these data were applied to a mathematical model of peritubular capillary fluid uptake to determine the profile of effective reabsorption pressure (ERP) with distance (x*) alongthe capillary and calculate the peritubular capillary permeability coefficient (LpAr). ERPX* = (PHIC MINUS HPC)X* MINUS (PHII MINUS HPi) and APR = ERPX*LpAr. During saline expansion phii minus HPi was -12.1 plus or minus 0.8 mmHg and ERP,3.8 mm. The LpAr was 0.07 nl/s per g KW per mmHg, and this value was applied to hypropenia and plasma expansion to determine ERP and phii minus HPi. The phiiminus HPi was +6.0 and +5.0 mmHg, respectively, and ERP was 4.1 and 3.5 mmHg. Efective reabsorptive pressure remained positive along x* in all states, and phii minus HPi correlated best changes in phic and poorly with changes in efferent plasma flow. The APR did not correlate with either calculated phii minus HPi or the transepithelial driving pressure, Pt + phii minus HPi.


Developmental changes in hemoglobin F levels during the first two years of life in normal and heterozygous beta-thalassemia infants.
To study the developmental pattern of hemoglobin F (HbF) during the first two years of life, levels of HbF were estimated in two groups of infants: 117 normal infants and 98 heterozygotes for beta-thalassemia, all aged between 1 and 24 months. The results may be summarized as follows: (1) Levels of HbF in beta-thalassemia heterozygotes were significantly higher than those of normal infants of the same age (P less than .01). (2) A reference curve for the decline of HbF in infants with beta-thalassemia trait was established to facilitate the diagnosis of heterozygotes during this period of life. (3) Hemoglobin A2 (HbA2) was also higher in beta-thalassemia heterozygotes than in normal infants of the same age. HbA2 increases with increasing age, reaching normal adult values at age 5 to 6 months. It is postulated that the higher level of HbF in heterozygous infants during the first two years of life is associated with the presence of the beta-thalassemia gene, which influences the increased synthesis of HbF in red cell.


Nonstationary spatio-temporal small rodent dynamics: evidence from long-term Norwegian fox bounty data.
1. The geographical pattern in Fennoscandian small rodent population dynamics with a southern noncyclic and a northern cyclic region, and with latitudinal gradients in density-dependent structure, cycle period length and spatial synchrony within the northern cyclic region, has been widely publicized and interpreted in the ecological literature. However, the time-series data on which these inferences have been established are relatively short and originate from a specific time period (mostly around 1970-90). Hence, it can be questioned whether the geographical population dynamics patterns are consistent over time (i.e. whether they are stationary). 2. Here we analyse an almost century long (1880-1976) panel of fox bounty time series including 18 counties of Norway, thus spanning the whole range of latitudes of Fennoscandia (i.e. 15 latitudinal degrees). These fox time series mirror the dynamics of their dominant small rodent prey, in particular, with respect to cycle period length and spatial synchrony. 3. While we found some evidence consistent with previous analyses showing a clearly patterned dynamics according to latitude, such patterns were not stationary on a longer time-scale. In particular, we observed a shift from an extensively synchronous (i.e. regionalized) 4-year cycle north of 60 degrees N just after the 'Little Ice Age' (1880-1910) to a diversification of cycle period length (3-5 years) and eventually, partial loss of cyclicity and synchronicity in later periods. Incidents of loss of cyclicity appeared to be preceded by changes in cycle period (i.e. period lengthening and shortening). 4. These results show that the dynamics of Fennoscandian small rodents, and their associated guild of predators, are more prone to change than previously acknowledged.


Thyroid Cancer Detection by Ultrasound Among Residents Ages 18 Years and Younger in Fukushima, Japan: 2011 to 2014.
After the Great East Japan Earthquake and Tsunami in March 2011, radioactive elements were released from the Fukushima Daiichi Nuclear Power Plant. Based on prior knowledge, concern emerged about whether an increased incidence of thyroid cancer among exposed residents would occur as a result. After the release, Fukushima Prefecture performed ultrasound thyroid screening on all residents ages ≤18 years. The first round of screening included 298,577 examinees, and a second round began in April 2014. We analyzed the prefecture results from the first and second round up to December 31, 2014, in comparison with the Japanese annual incidence and the incidence within a reference area in Fukushima Prefecture. The highest incidence rate ratio, using a latency period of 4 years, was observed in the central middle district of the prefecture compared with the Japanese annual incidence (incidence rate ratio = 50; 95% confidence interval [CI] = 25, 90). The prevalence of thyroid cancer was 605 per million examinees (95% CI = 302, 1,082) and the prevalence odds ratio compared with the reference district in Fukushima Prefecture was 2.6 (95% CI = 0.99, 7.0). In the second screening round, even under the assumption that the rest of examinees were disease free, an incidence rate ratio of 12 has already been observed (95% CI = 5.1, 23). An excess of thyroid cancer has been detected by ultrasound among children and adolescents in Fukushima Prefecture within 4 years of the release, and is unlikely to be explained by a screening surge.


Virtual Surgical Planning Decreases Operative Time for Isolated Single Suture and Multi-suture Craniosynostosis Repair.
Cranial vault reconstruction is a complex procedure due to the need for precise 3-dimensional outcomes. Traditionally, the process involves manual bending of calvarial bone and plates. With the advent of virtual surgical planning (VSP), this procedure can be streamlined. Despite the advantages documented in the literature, there have been no case-control studies comparing VSP to traditional open cranial vault reconstruction. Data were retrospectively collected on patients who underwent craniosynostosis repair during a 7-year period. Information was collected on patient demographics, intraoperative and postoperative factors, and intraoperative surgical time. High-resolution computed tomography scans were used for preoperative planning with engineers when designing osteotomies, bone flaps, and final positioning guides. A total of 66 patients underwent open craniosynostosis reconstruction between 2010 and 2017. There were 35 control (non-VSP) and 28 VSP cases. No difference in age, gender ratios, or number of prior operations was found. Blood loss was similar between the 2 groups. The VSP group had more screws and an increased length of postoperative hospital stay. The length of the operation was shorter in the VSP group for single suture and for multiple suture operations. Operative time decreased as the attending surgeon increased familiarity with the technique. VSP is a valuable tool for craniosynostosis repair. We found VSP decreases surgical time and allows for improved preoperative planning. Although there have been studies on VSP, this is the first large case-control study to be performed on its use in cranial vault remodeling.


Conn syndrome and Crohn disease in a pediatric case: an interesting parallel.
Conn syndrome is characterized by surreptitious secretion of aldosterone in which patients are found to have hypertension, hypokalemia, and metabolic alkalosis. Although rare, the most common presentation in the pediatric population is bilateral hyperplasia of the adrenal glands as opposed to an adenoma. Crohn disease is part of the spectrum of inflammatory bowel disease, which manifests in children as flare-ups of bloody diarrhea and abdominal pain. The association of concurrent Conn syndrome and Crohn disease has been previously presented in two cases in adults. This is the first pediatric case to be reported in the literature.


A Comprehensive Review of the Role of Artificial Intelligence in Obstetrics and Gynecology.
The exponential growth of artificial intelligence (AI) has fascinated its application in various fields and so in the field of healthcare. Technological advancements in theories and learning algorithms and the availability of processing through huge datasets have created a breakthrough in the medical field with computing systems. AI can potentially drive clinicians and practitioners with appropriate decisions in managing cases and reaching a diagnosis, so its application is extensively spread in the medical field. Thus, computerized algorithms have made predictions so simple and accurate. This is because AI can proffer information accurately even to many patients. Furthermore, the subsets of AI, namely, machine learning (ML) and deep learning (DL) methods, have aided in detecting complex patterns from huge datasets and using such patterns in making predictions. Despite numerous challenges, AI implementation in obstetrics and gynecology is found to have a spellbound development. Therefore, this review propounds exploring the implementation of AI in obstetrics and gynecology to improve the outcomes and clinical experience. In that context, the evolution and progress of AI, the role of AI in ultrasound diagnosis in distinct phases of pregnancy, clinical benefits, preterm birth postpartum period, and applications of AI in gynecology are elucidated in this review with future recommendations.


[Cardiovascular risk in polycystic kidney disease].
Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications.


Coexistence of granulomatous enteric inflammation and neoplasia in an adult sheep.
A 7-year-old dairy sheep suffering from chronic loss of weight without diarrhea or anorexia was euthanized after failing to respond to any treatment (antibiotic and antiparasitic). The main findings at the necropsy of this animal were multifocal miliary nodules in several organs, mainly in the Peyer's patches of the small intestine, and a segmental thickening of the jejunal wall. Histologic examination of the samples taken at the necropsy showed a multifocal chronic granulomatous inflammation, with mineralization and caseous necrosis at the core of the larger granulomas and scarce intrahistiocytic acid-fast bacilli consistent with a disseminated digestive tuberculosis. Polymerase chain reaction and bacteriological culture from these samples confirmed Mycobacterium avium subsp avium to be the etiologic agent of this infection. Histologically, the cause of the segmental thickening of the jejunal wall was found to be a small intestine adenocarcinoma, which in some areas coexisted with the granulomatous lesion.