Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia.
Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.


Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors.
The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism. To directly investigate the role of AML1-ETO in leukemogenesis, we used gene targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21). Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5 from a complete absence of normal fetal liver-derived definitive hematopoiesis and lethal hemorrhages. This phenotype was similar to that seen following homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained dysplastic multilineage hematopoietic progenitors that had an abnormally high self-renewal capacity in vitro. To further document the role of AML1-ETO in these growth abnormalities, we used retroviral transduction to express AML1-ETO in murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing cells were again found to have an increased self-renewal capacity and could be readily established into immortalized cell lines in vitro. Taken together, these studies suggest that AML1-ETO not only neutralizes the normal biologic activity of AML1 but also directly induces aberrant hematopoietic cell proliferation.


Location-based prospective memory.
This study explores location-based prospective memory. People often have to remember to do things when in a particular location, such as buying tissues the next time they are in the supermarket. For event cognition theory, location is important for structuring events. However, because event cognition has not been used to examine prospective memory, the question remains of how multiple events will influence prospective memory performance. In our experiments, people delivered messages from store to store in a virtual shopping mall as an ongoing task. The prospective tasks were to do certain activities in certain stores. For Experiment 1, each trial involved one prospective memory task to be done in a single location at one of three delays. The virtual environment and location cues were effective for prospective memory, and performance was unaffected by delay. For Experiment 2, each trial involved two prospective memory tasks, given in either one or two instruction locations, and to be done in either one or two store locations. There was improved performance when people received instructions from two locations and did both tasks in one location relative to other combinations. This demonstrates that location-based event structure influences how well people perform on prospective memory tasks.


High performance carbon nanotube-Si core-shell wires with a rationally structured core for lithium ion battery anodes.
Core-shell Si nanowires are very promising anode materials. Here, we synthesize vertically aligned carbon nanotubes (CNTs) with relatively large diameters and large inter-wire spacing as core wires and demonstrate a CNT-Si core-shell wire composite as a lithium ion battery (LIB) anode. Owing to the rationally engineered core structure, the composite shows good capacity retention and rate performance. The excellent performance is superior to most core-shell nanowires previously reported.


Meniscus-climbing behavior and its minimum free-energy mechanism.
Some insects can climb up the top of the meniscus surface generated by a hydrophilic wall by fixing their posture without moving their appendages [Baudoin, R. Bull. Biol. Fr. Belg. 1955, 89, 16. Hu, D. L.; Bush, J. W. M. Nature 2005, 437, 733]. To better understand this interesting phenomenon, we did meniscus-climbing experiments of bent copper sheets. It was found that the sheets do not always climb up the top of the meniscus surface but may stop and stably stay at various positions on the meniscus surface, depending upon their curvatures and masses, and that bent copper sheets can self-assemble into an oriented array (or an anisotropic form) through self-rotating on the water surface. The minimum energy mechanism of meniscus-climbing and self-rotating was then numerically studied. It was further shown that the meniscus-climbing and the rotating behavior is not only a general phenomenon for floating objects with hydrophilic surfaces, even those with fairly large sizes and weights (e.g., a metal bottle cap), but is also conditionally realizable for floating objects with hydrophobic surfaces.


Detection and spectral analysis of trifluoromethyl groups at a surface by sum frequency generation vibrational spectroscopy.
Sum frequency generation (SFG) vibrational spectroscopy was used to detect the presence of trifluoromethyl groups on the surface of 4-(trifluoromethyl)benzyl alcohol (TFMBA) in air. Supplementary data from infrared and Raman spectra were correlated to ab initio calculations by use of density functional theory (DFT) for TFMBA and three related compounds to reliably assign vibrational modes to the spectra. It was shown that strongly ordered CF3 groups dominate the surface of the TFMBA, and the vibrational modes of this functional group are strongly coupled to the benzene ring of the benzyl alcohol. This coupling, along with the SFG activity of the CF3 group, is removed with the insertion of an oxygen atom between the CF3 group and the benzene ring.


Response of proteome and morphological structure to short-term drought and subsequent recovery in Cucumis sativus leaves.
Drought is the primary limitation to plant growth and yield in agricultural systems. Cucumber (Cucumis sativus) is one of the most important vegetables worldwide and has little tolerance for water deficit. To understand the drought stress response strategy of this plant, the responses of cucumber to short-term drought and rewatering were determined in this study by morphological structure and proteomic analyses. The leaf relative water content was significantly decreased under drought, and the cell structure was altered, while rewatering obviously alleviated the symptoms of water shortage and cell damage. A total of 320 and 246 proteins exhibiting significant abundance changes in response to drought and recovery, respectively, were identified. Our proteome analysis showed that 63 co-regulated proteins were shared between drought and rewatering, whereas most of the responsive proteins were unique. The proteome is adjusted through a sequence of regulatory processes including the biosynthesis of secondary metabolites and the glutathione metabolism pathway, which showed a high correlation between protein abundance profile and corresponding enzyme activity. Drought and recovery regulated different types of proteins, allowing plants to adapt to environmental stress or restore growth, respectively, which suggests that short-term drought and recovery are almost fully uncoupled processes. As an important component of the antioxidant system in plants, glutathione metabolism may be one of the main strategies for regulating antioxidant capacity during drought recovery. Our results provide useful information for further analyses of drought adaptability in cucumber plants.


Unusual presentation of spontaneous pneumomediastinum.
Spontaneous pneumomediastinum (SPM) is an uncommon, self-limiting condition resulting from alveolar rupture in young adults. There are asthma, illicit drug use, and activities triggering a Valsalva maneuver as causes of developing SPM. We report two patients who were diagnosed with SPM in the absence of known predisposing factors and without any clinical sign of subcutaneous emphysema of the neck, the most common physical finding on presentation. Both of them developed dysphagia after swallowing a peach seed and boned rib of pork, respectively. SPM was suspected after performing lateral neck X-ray, and the diagnosis of SPM was confirmed by chest CT. These cases showed the importance of performing the lateral neck X-ray to screen SPM in patients with dysphagia.


[Historical and herbalogical studies on coloring crude drug (Part 1): "Langbacao"].
The name of Langbacao was described for the first time in Kai Bao Ben Cao in 10th century, in which Langbacao was introduced as an herb medicine for scours. While, as the name of Qu, Wujie, it was first described in Er Ya and as the name of Langyecao, it was first described in Ben Cao Shi Yi. Many investigators have confirmed that the original plant of Langbacao is to be Bidens tripartita L. In Japan, Langbacao is generally recognized as ta-u-ko-gi, while some investigators suggested that it is unlikely that ta-u-ko-gi is identical to Langbacao. In the old Chinese literature, Langbacao had been mentioned as a dye which could make hair dark. But in modern Chinese and Japanese literature, few papers reported the use of Bidens tripartita L. as a dye. The characteristics of the shapes of Langbacao between old and modern literature seem not to be consistent. Other names of Langbacao are confused even in the modern literature. It seems that Langbacao in the old literature includes species of the genus Bidens other than B. tripartita.


[Rhinolith - diagnosis and treatment features].
Exogenous foreign bodies enter the nasal cavity through the nostrils or in some cases through the choana and usually get stuck in the lower or middle nasal meatus. An alien body that has been in the nasal cavity for a long time serves as a nucleus around which calcium and magnesium salts, organic components, are deposited from the nasal secretions, and contributes to the formation of rhinolith (nasal stone, from Greek rhino - nose, lithos - stone). Endogenous material (thick mucous secret or a blood clot drying into the crusts, desquamated epithelium, an atypically located tooth, products of cellular lysis and necrosis of the mucous membrane) can also serve as a potential nucleus for salt deposition. Narrowing of the nasal passages due to the curvature of the nasal septum, hypertrophy of the nasal conchae, violation of mucociliary transport and inflammatory changes in the mucous membrane in chronic rhinitis or rhinosinusitis can lead to a delay in the mucous discharge in the nasal cavity, pH changes, excessive saturation of the secretion with crystalloids, initiate crystallization around the nucleus and deposition of salts. This article presents the results of clinical examination and surgical treatment of a patient with rhinolith formed by prolonged inhalation of construction dust.


LXR and PPAR activators stimulate cholesterol sulfotransferase type 2 isoform 1b in human keratinocytes.
Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are potent regulators of keratinocyte proliferation, differentiation, and epidermal permeability barrier homeostasis. Cholesterol sulfotransferase type 2B isoform 1b (SULT2B1b) is a key enzyme in the synthesis of cholesterol sulfate (CS), a critical regulator of keratinocyte differentiation and desquamation, as well as a mediator of barrier homeostasis. In this study, we assessed the effect of activators of LXR, PPARalpha, PPARbeta/delta, and PPARgamma on SULT2B1b gene expression and enzyme activity in cultured human keratinocytes (CHKs). Our results demonstrate that PPAR and LXR activators increase SULT2B1b mRNA levels, with the most dramatic effect (a 26-fold increase) induced by the PPARgamma activator ciglitazone. Ciglitazone upregulates SULT2B1b mRNA in a dose- and time-dependent manner. Moreover, the stimulation of SULT2B1b gene expression by LXR and PPAR activators occurs in both undifferentiated and differentiated CHKs. The upregulation of SULT2B1b mRNA by ciglitazone appears to occur at a transcriptional level, because the degradation of SULT2B1b is not accelerated by ciglitazone. In addition, cycloheximide almost completely blocks the ciglitazone-induced increase in SULT2B1b mRNA, suggesting that the transcription of SULTB1b mRNA is dependent on new protein synthesis. Finally, LXR and PPAR activators also increased the activity of cholesterol sulfotransferase. Thus, LXR and PPAR activators regulate the expression of SULT2B1b, the key enzyme in the synthesis of CS, which is a potent regulator of epidermal differentiation and corneocyte desquamation.


Sexually communicable micro-organisms in human semen samples to be used for artificial insemination by donor.
Two hundred and thirty seven semen samples from 10 institutes for artificial insemination by donor (AID) in Belgium and the Netherlands were tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, herpes simplex virus, and cytomegalovirus. The incidence of these micro-organisms in the semen samples was 0%, 6.3%, 4.6%, 35.9%, 0%, and 0.4% respectively, and 47% of all samples were infected with one or more of the micro-organisms. As the ejaculates from which the samples had been taken had already been, or would be, used for AID, the exclusion of microbiological contamination with sexually communicable micro-organisms before insemination is indicated.


Home-based music therapy for persons with dementia and their spouses as primary caregivers.
Music therapy has been found to be an effective intervention for persons with dementia (PWD) and their primary caregivers (PC), yet the implementation of musical strategies to improve daily care in the home environment requires further exploration. This study developed and examined a home-based music therapy (HBMT) work model that offers weekly joint music therapy sessions, and additional bi-weekly phone-counseling sessions with the PC. This was followed by an additional 12-week support period that included 3 therapy sessions and 3 phone counseling sessions once every other fortnight, so that the same type of session occurred at a frequency of once a month. Participants were five couples (PWD + spouse as PC) who live in their home. Findings based on the qualitative multiple case study research method showed the importance of the music therapist's (MT) continuous support. The MT's presence made it possible to address the needs of both spouses, separately and together, while maintaining the required balance. Moreover, the MT's presence enabled better implementation of the musical strategies independently and this was maintained during the intervention and the support period.


Numb chin with mandibular pain or masticatory weakness as indicator for systemic malignancy - A case series study.
Numb chin syndrome (NCS) is a critical sign of systemic malignancy; however it remains largely unknown by clinicians and dentists. The aim of this study was to investigate NCS that is more often associated with metastatic cancers than with benign diseases. Sixteen patients with NCS were diagnosed and treated. The oral and radiographic manifestations were assessed. Four (25%) of 16 patients with NCS were affected by nonmalignant diseases (19% by medication-related osteonecrosis of the jaw and 6% by osteopetrosis); yet 12 (75%) patient conditions were caused by malignant metastasis, either in the mandible (62%) or intracranial invasion (13%). NCS was unilateral in 13 cases and bilateral in three cases. Mandibular pain and masticatory weakness often dominate the clinical features in NCS associated with cancer metastasis. In two patients, NCS preceded the discovery of unknown malignancy (breast cancer and leukemia). In nine others, NCS heralded malignancy relapse and progression. Metastatic breast cancer in four (36%) cases accounted for the most common malignancy. Other metastatic diseases included two multiple myelomas, and one each of leukemia, prostate cancer, colon cancer, lung cancer, maxillary sinus adenoid cystic carcinoma and adrenal gland neuroblastoma. Radiographic examinations showed obvious mandibular metastasis with compression of the inferior alveolar nerve or mental nerve in nine patients, and leptomeningeal seeding or intracranial metastasis to the trigeminal nerve root at the skull base in two patients. NCS without obvious odontogenic causes or trauma often signals systemic malignancy. It may be the first clue of occult malignancy.


The effect of periodontal therapy on glycemic control and fasting plasma glucose level in type 2 diabetic patients: systematic review and meta-analysis.
Diabetic mellitus and periodontal disease have bilateral associations. However, there is a dilemma on the effect of periodontal therapy on glycemic control and/or fasting plasma glucose level in type 2 diabetic patients with periodontitis. Therefore, this review aimed to assess the effectiveness of periodontal therapy versus no periodontal therapy on glycated hemoglobin (HbA1c) and fasting plasma glucose level in type 2 diabetic patients. Article searching was done using four databases (MEDLINE, Cochrane library (CENTRAL), EMBASE and CINAHL) and a manual search (until December 2015). We included randomized controlled trials testing the effectiveness of periodontal therapy on glycated hemoglobin and fasting plasma glucose level in patients with type 2 Diabetes mellitus with periodontal disease. Studies published in English between 2005 and 2015 were included. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases. After the article selection process, seven Randomized controlled trials involving 940 participants with a primary outcome of change in glycated hemoglobin and/or fasting plasma glucose and having a minimum of 3 months follow-up were included. There was a reduction of glycated hemoglobin 0.48(95 % CI: 0.18-0.78) after 3 months follow-up and 0.53 (95 % CI: 0.24-0.81) at the end of the intervention period. There was also a significant reduction of fasting plasma glucose level, 8.95 mg/dl (95 % CI: 4.30-13.61) in the intervention group after the end of the intervention. The pooled analysis showed that patients with adjunctive antibiotic therapy and mouth wash had effect size of 0.51(0.03, 1.00, p = 0.04) and it was 0.53 (95 % CI: 0.19, 0.87; p = 0.002) in patients without adjunctive therapy. The publication bias of the studies was 0.066 according to Egger's test. In this systematic review and meta-analysis, there is a significant reduction of Glycated hemoglobin and Fasting plasma glucose level on type 2 diabetic and periodontal patients with non-surgical periodontal therapy.


Low concentrations of primaquine inhibit degradation but not receptor-mediated endocytosis of asialoorosomucoid by HepG2 cells.
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is undegraded, dissociated from the ASGP receptor, and contained within vesicular compartments distinct from lysosomes, plasma membrane, or endosomes. In addition, the effect of 80 microM primaquine on 125I-ASOR degradation is very slowly reversible (greater than 6 h), in contrast to primaquine's rapidly reversible effect on receptor recycling and ligand uptake (10 min). Furthermore, the effect is ligand-specific. 125I-asialofetuin, another ASGP receptor ligand, is internalized and degraded in lysosomes at normal rates in HepG2 cells exposed to 80 microM primaquine. These findings indicate that primaquine has multiple effects on the uptake and degradation of ligand occurring in the endosome-lysosome pathway. These effects of primaquine differ in their concentration-dependence, site of action, reversibility, and ligand selectivity.


Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study.
We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the Social and Family Well-Being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio (HR) for RFS by comparing such changes. The mean (SD) age of the patients was 35 (3.9) years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean (SD) SFWB score at baseline was 20.5 (5.0) out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.


Chemical Tools for Dissecting the Role of lncRNAs in Epigenetic Regulation.
Proper control and maintenance of gene expression is critical for cellular identity and maintenance. Transcription of RNA from the genome is intimately controlled by post-translational chemical modification of histone tails and DNA. Recent studies have demonstrated that chromatin-remodeling complexes seek out their target genomic loci through the help of noncoding RNA molecules. Within this Review, we will outline how the use of biochemical techniques has shed light on the mechanisms employed by RNA to guide these complexes and therefore control gene expression.


Regulation of Lung Immune Tone by the Gut-Lung Axis via Dietary Fiber, Gut Microbiota, and Short-Chain Fatty Acids.
Lung immune tone, i.e. the immune state of the lung, can vary between individuals and over a single individual's lifetime, and its basis and regulation in the context of inflammatory responses to injury is poorly understood. The gut microbiome, through the gut-lung axis, can influence lung injury outcomes but how the diet and microbiota affect lung immune tone is also unclear. We hypothesized that lung immune tone would be influenced by the presence of fiber-fermenting short-chain fatty acid (SCFA)-producing gut bacteria. To test this hypothesis, we conducted a fiber diet intervention study followed by lung injury in mice and profiled gut microbiota using 16S sequencing, metabolomics, and lung immune tone. We also studied germ-free mice to evaluate lung immune tone in the absence of microbiota and performed in vitro mechanistic studies on immune tone and metabolic programming of alveolar macrophages exposed to the SCFA propionate (C3). Mice on high-fiber diet were protected from sterile lung injury compared to mice on a fiber-free diet. This protection strongly correlated with lower lung immune tone, elevated propionate levels and enrichment of specific fecal microbiota taxa; conversely, lower levels of SCFAs and an increase in other fatty acid metabolites and bacterial taxa correlated with increased lung immune tone and increased lung injury in the fiber-free group. In vitro , C3 reduced lung alveolar macrophage immune tone (through suppression of IL-1β and IL-18) and metabolically reprogrammed them (switching from glycolysis to oxidative phosphorylation after LPS challenge). Overall, our findings reveal that the gut-lung axis, through dietary fiber intake and enrichment of SCFA-producing gut bacteria, can regulate innate lung immune tone via IL-1β and IL-18 pathways. These results provide a rationale for the therapeutic development of dietary interventions to preserve or enhance specific aspects of host lung immunity.


Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease.
Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-β (Aβ) protein by GO. Both in vivo and in vitro models were induced using Aβ1-42, and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels in vitro; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Aβ1-42-induced AD. This proved that GO loaded with Dau could protect against Aβ1-42-induced oxidative damage and apoptosis in both in vitro and in vivo AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD.


[Cor triatriatum. Anatomical forms and surgical treatment of 6 consecutive cases].
Six cases of cor triatriatum documented and operated on at Henri-Mondor hospital between 1980 and 1984 are reported. Ages at the time of surgery ranged from 8 months to 57 years. Four of the 6 patients presented with pulmonary hypertension. Anatomic types consisted of 4 diaphragmatic types and 2 more complex malformations. Associated lesions were present in all but one patients. They consisted mostly of interatrial defects (depending on their position with regard to the intra-atrial membrane, they play a determinant role in the symptomatology) and of a left superior vena cava (which might play a role in the embryogenesis of the malformation). Except for one early postoperative death, results of surgery were excellent for all patients, with a mean follow-up of 5 years. This series, compared with the literature, allows precising the embryologic and anatomic aspects of the malformation and the surgical techniques in complex types.


Comparison of Different Thoracic Aortic Wall Characteristics for Assessment of Disease Activity in Takayasu Arteritis: A Quantitative Study with 3.0 T Magnetic Resonance Imaging.
Determination of disease activity in Takayasu arteritis (TAK) is crucial for clinical management but challenging. The value of different magnetic resonance imaging (MRI) characteristics for the assessment of disease activity remains unclear. This study investigated the imaging findings of the thoracic aortic wall and elasticity by using a comprehensive 3.0 T MRI protocol. We prospectively enrolled 52 consecutive TAK patients. TAK activity was recorded according to the ITAS2010. All the patients underwent thoracic aortic MRI. The luminal morphology of the thoracic aorta and its main branches were quantitatively evaluated using a contrast-enhanced magnetic resonance angiography (MRA) sequence. The maximum wall thickness of the thoracic aorta, postcontrast enhancement ratio, and aortic wall edema were analyzed in each patient through pre- and post-enhanced T1-weighted and T2-weighted imaging. Pulse-wave velocity (PWV) of the thoracic aorta was calculated using a four-dimensional flow technique. The majority of the 52 patients had type V disease (34.62%, 18/52). Among all the MRI indicators of the thoracic aorta, the area under the curve was the largest for the maximal wall thickness (0.804, 95% confidence interval [CI] = 0.667-0.941). The maximal wall thickness (93.33%, 95% CI = 68.1%-99.8%) exhibited the highest sensitivity with a cutoff value of 3.12 mm. Wall edema (84.00%, 95% CI = 63.9%-95.5%) presented the highest specificity. A positive correlation was noted between PWV and patients' age (r = 0.54, p < 0.001), disease duration (r = 0.52, p < 0.001), and the maximum wall thickness (r = 0.45, p = 0.001). MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. Aortic maximal wall thickness was the most accurate indicator of TAK activity. The early phase was superior to the delay phase for aortic wall enhancement analysis for assessing TAK activity.


Malabsorption of fat after partial gastric resection. A study of pathophysiologic mechanisms.
The causes of fat malabsorption after gastric resection were studied in patients randomized to Billroth I gastroduodenostomy or Roux-en-Y gastrojejunostomy after antrectomy and selective gastric vagotomy for intractable prepyloric peptic ulcer. Eighteen patients were studied 2 years or more postoperatively. Assessment of food intake concerning protein, fat, carbohydrate, vitamins and minerals showed deficiency in seven cases, but without significant difference between the two operation types. Postoperative weight loss did not differ significantly between the two study groups, but the faecal excretion of fat was significantly larger (p less than 0.05) after gastrojejunostomy than after gastroduodenostomy. Since both the oro-caecal transit time and the breath excretion of hydrogen after a standardized test meal showed no intergroup difference, the results suggest that duodenal exclusion may be of particular pathophysiologic importance for the observed malabsorption of fat after gastric resection.


Quantification of marrow hematogones following autologous stem cell transplant in adult patients with plasma cell myeloma or diffuse large B-cell lymphoma and correlation with outcome.
In this retrospective study, we quantified the hematogone (normal B-lineage precursor) population by flow cytometric immunophenotyping in post-transplant bone marrow biopsy specimens from adult patients who received an autologous stem cell transplant for either plasma cell myeloma (n = 57) or diffuse large B-cell lymphoma (n = 73). The majority of patients (80%) had <5% marrow hematogones post-transplant. Extreme (>10%) hematogone percentages were quite rare, seen in only four patients, and were not associated with disease progression. There was a positive association between the post-transplant day and hematogone percentage within the first year after transplant, and a negative association thereafter. Plasma cell myeloma patients with ≥5% hematogones in any post-transplant flow cytometry study had a worse overall survival as did plasma cell myeloma patients with increased hematogones (as defined by percentile) at 100 days post-transplant. These findings require further study, ideally in a prospective study design.


Mucoepidermoid carcinoma of sublingual gland: a malignant neoplasm in an uncommon region.
Although mucoepidermoid carcinomas (MECs) are considered as the second most common malignant salivary gland neoplasm, only 0.5-1% of epithelial salivary gland tumours have been reported to arise from the sublingual salivary gland.1 The authors report a case of a low-grade MEC of the sublingual salivary gland in a 35-year-old woman. Wide excision of the tumour along with continuous marginal mandibulectomy was performed. There has been no recurrence till date.


Development of resistance to metronidazole and minocycline in vitro.
By local delivery of antibiotics to periodontal pockets, very high initial concentrations are often quickly succeeded by subinhibitory concentrations, which may facilitate development of bacterial resistance. The purpose of the present study was to investigate possible development of resistance in suspected periodontal pathogens after exposure to subinhibitory concentrations of metronidazole and minocycline. The minimal inhibitory concentration (MIC) of 18 reference strains and 12 clinical isolates was determined by a broth dilution method. Subsequently, all strains with MIC < 8 micrograms/ml were exposed to serial passage on plates containing subinhibitory and gradually increasing concentrations of antibiotics, until growth was inhibited. Initially, most strains were inhibited at < or = 0.250 microgram/ml of minocycline and < or = 0.5 microgram/ml of metronidazole, though A. actinomycetemcomitans was resistant to metronidazole. After growth at subinhibitory concentrations, 8 strains survived 1-2 x and 11 stains survived 8-32 x their initial MIC of metronidazole, growing at up to 8 micrograms/ml. All A. actinomycetemcomitans survived 8-64 x their initial MIC of minocycline, growing at > or = 2 micrograms/ml, while all other strains were inhibited at < or = 0.250 microgram/ml, corresponding to a 1-8 x increase in their initial MIC. Thus, development of resistance was observed for periodontal bacteria growing at up to 64 x their initial MIC, but the final level of resistance was moderate.


Angiotensin-converting enzyme regulates bradykinin receptor gene expression.
The angiotensin-converting enzyme (ACE) is a membrane-bound peptidyl dipeptidase known to act on a variety of peptide substrates in the extracellular space. Its most notable functions are the formation of angiotensin II and the degradation of bradykinin. In the current experiments, we found that exogenous ACE added to vascular smooth muscle cell culture strongly induces and upregulates the genes of bradykinin receptors B1 and B2. This transcriptional regulatory property of ACE was shown to be unrelated to its known enzymatic properties. Indeed, ACE at 3.75 microg/ml added in the culture medium of vascular smooth muscle cells was found to cause marked upregulation of the mRNA expression of the genes for the B1 and B2 receptors of bradykinin by 22- and 11-fold, respectively. This phenomenon was not altered by the addition of specific angiotensin II antagonists for the AT1 or AT2 receptors. Moreover, the ACE inhibitor captopril, which inhibited ACE enzymatic activity, did not block its effect at the bradykinin receptor gene transcription level. Expression of both receptor genes was completely abolished by actinomycin D. Furthermore, transcriptional upregulation was inhibited by curcumin, suggesting involvement of different transcriptional factors in this phenomenon. Electrophoretic mobility shift assay revealed increase in NF-kappaB and activator protein-1 protein binding for consensus sequences, between ACE-treated cells versus untreated cells. The data indicate a novel biological function of the ACE unrelated to its well-known enzymatic function as a peptidyl dipeptidase.


Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study.
Four-factor prothrombin complex concentrate (4F-PCC) was approved by the US Food and Drug Administration in 2013 for management of severely bleeding patients on warfarin therapy. We describe use of 4F-PCC at a large, suburban academic center. We retrospectively reviewed all patients receiving 4F-PCC from its introduction through 2016 at a large level 1 trauma center. Clinical and demographic data were obtained, including indications for anticoagulation and antiplatelet agents, comorbidities, concomitant medications, etiology and site of bleeding, as well as disposition, length of stay, mortality, and thrombotic events. One hundred eighty-four patients received 4F-PCC. Mean age was 72 years; 40.8% were female. Indications for 4F-PCC administration included: active bleeding (74%), reversal prior to a procedure (14%), and elevated international normalized ratio (12%). Warfarin was the most common concomitant medication (71.1%). Most patients were receiving anticoagulation for atrial fibrillation (63%). Concomitant treatments for bleeding included vitamin K (58.2%), packed red blood cells (50%), fresh frozen plasma (38%), and platelets (26.1%), amongst others. Median length of hospital stay was 8.4 days. Nine patients (4.9%) developed thrombosis within 90 days of 4F-PCC. Mortality was 24.5%, with notably higher rates amongst those who received 4F-PCC for off-label indications (19.1% on-label mortality vs. 37.7% off-label mortality on chi-square analysis, P=0.01). This study demonstrates that 4F-PCC is being utilized for indications other than the reversal of warfarin-induced coagulopathy. Further investigation is warranted to determine the efficacy and safety of 4F-PCC for these potential indications.


Post-hysteroscopy Ruptured Tubo-Ovarian Abscess With Atypical Bacteremia: A Case Report.
Hysteroscopies are commonly performed in the diagnosis and treatment of patients with abnormal uterine bleeding. Current research suggests a low rate of all types of complications following hysteroscopies. The rate of infectious complications has been reported as exceptionally low. We present a case of tubo-ovarian abscess with Escherichia coli bacteremia and eventual abscess rupture in a 51-year-old gravida 3, para 2012 (G3P2) woman who underwent a hysteroscopy with concurrent polypectomy. The patient had no risk factors that have historically been attributed to the development of post-hysteroscopy infection, such as a history of pelvic inflammatory disease or endometriosis. The patient also had no known intra-operational complications that might predispose her to infection. Further, the patient's clinical presentation was significantly atypical. Despite having E. coli bacteremia on admission, severe abdominal pain, lack of an adequate response to several days of intravenous broad-spectrum antibiotics, and eventually evidence of abscess rupture, the patient never met clinical criteria for sepsis, including a lack of leukocytosis. This case demonstrates a rare presentation of a rare complication and emphasizes the necessity of clinical vigilance in diagnosing and promptly treating gynecological infectious complications.


Functional cloning and characterization of the multidrug efflux pumps NorM from Neisseria gonorrhoeae and YdhE from Escherichia coli.
Active efflux of antimicrobial agents is one of the most important adapted strategies that bacteria use to defend against antimicrobial factors that are present in their environment. The NorM protein of Neisseria gonorrhoeae and the YdhE protein of Escherichia coli have been proposed to be multidrug efflux pumps that belong to the multidrug and toxic compound extrusion (MATE) family. In order to determine their antimicrobial export capabilities, we cloned, expressed, and purified these two efflux proteins and characterized their functions both in vivo and in vitro. E. coli strains expressing norM or ydhE showed elevated (twofold or greater) resistance to several antimicrobial agents, including fluoroquinolones, ethidium bromide, rhodamine 6G, acriflavine, crystal violet, berberine, doxorubicin, novobiocin, enoxacin, and tetraphenylphosphonium chloride. When they were expressed in E. coli, both transporters reduced the levels of ethidium bromide and norfloxacin accumulation through a mechanism requiring the proton motive force, and direct measurements of efflux confirmed that NorM behaves as an Na(+)-dependent transporter. The capacities of NorM and YdhE to recognize structurally divergent compounds were confirmed by steady-state fluorescence polarization assays, and the results revealed that these transporters bind to antimicrobials with dissociation constants in the micromolar region.


A comparison of lumbopelvic motion patterns and erector spinae behavior between asymptomatic subjects and patients with recurrent low back pain during pain-free periods.
The purpose of this study was to determine the patterns of lumbopelvic motion and erector spinae (ES) activity during trunk flexion-extension movements and to compare these patterns between patients with recurrent low back pain (LBP) in their pain-free periods and matched asymptomatic subjects. Thirty subjects participated (15 patients with disc herniation and recurrent LBP in their pain-free periods and 15 asymptomatic control subjects). A 3-dimensional videophotogrammetric system and surface electromyography (EMG) were used to record the angular displacements of the lumbar spine and hip in the sagittal plane and the EMG activity of the ES during standardized trunk flexion-extension cycles. Variables were maximum ranges of spine and hip flexion; percentages of maximum lumbar and hip flexion at the start and end of ES relaxation; average percentages of EMG activity during flexion, relaxation, and extension; and flexion-extension ratio of myoelectrical activity. Recurrent LBP patients during their pain-free period showed significantly greater ES activation both in flexion and extension, with a higher flexion-extension ratio than controls. Maximum ranges of lumbar and hip flexion showed no differences between controls and patients, although patients spent less time with their lumbar spine maximally flexed. This study showed that reduced maximum ranges of motion and absence of ES flexion-relaxation phenomenon were not useful to identify LBP patients in the absence of acute pain. However, these patients showed subtle alterations of their lumbopelvic motion and ES activity patterns, which may have important clinical implications.


Hollow fiber-based Fabry-Perot cavity for liquid surface tension measurement.
A Fabry-Perot (FP) cavity, formed by a single-mode fiber (SMF) fusion spliced with a section of hollow fiber, was proposed and experimentally used as a sensor for liquid surface tension measurement. Due to the FP cavity length changing with different liquids, the surface tension can be measured by monitoring the interference wavelength spacing. In our experiment, five kinds of liquids were measured, and the relationship between wavelength spacing and liquid surface tension was obtained. The experimental results show that the achieved sensitivity to liquid surface tension is 30.96 nm/(N/m), and the maximum error is 5.43%.


[A case of splenic abscess in a drug addict with acquired immunodeficiency syndrome].
The complex diagnostic procedure involved in a case of splenic abscess in a young drug addict as a result of septicaemia caused by streptococcus fascalis is described and discussed with an examination of the criteria in support of a more aggressive approach to the removal of septic foci in such patients with AIDS. It is concluded that such criteria are valid even when, as in the case described, splenectomy further depresses the immune system.


Removal of sulfamethoxazole and diclofenac from water: strategies involving O3 and H2O2.
Diclofenac (DCF) and Sulfamethoxazole (SMX) are two of the most frequently detected pharmaceutical compounds in water and are hardly removed by biological treatment systems. The presence of H2O2 was investigated in the ozonation of these two compounds. Experiments were carried out with both using distilled water and secondary effluent from a municipal wastewater treatment plant spiked with pharmaceuticals. Chemical oxygen demand (COD) abatement rate improved when H2O2 was added at the beginning of the ozonation process and when the ozone inlet concentration increased, attaining a maximum value of 91% and simultaneously a lower ozone waste for a H2O2 initial concentration of 5 mM and an ozone inlet concentration of 20 g Nm-3. For these operation conditions, the water matrix has no significant impact on SMX and DCF removal, which were totally degraded in 45 and 60 min, respectively. Nevertheless, lower COD degradation and ozone usage were obtained when the secondary effluent was used. Inorganic ions such as chloride, sulphate and nitrate and short-chain organic compounds were detected as by-products of the SMX and DCF oxidation. Vibrio fischeri luminescence inhibition tests revealed that simultaneous use of ozone and H2O2 reduced acute toxicity.


Clinical aspects of fungal infection in organ transplant recipients.
Fungal infections following solid organ transplantation remain a major cause of morbidity and mortality. Candida species and Aspergillus fumigatus continue to account for the majority of these infections, although the attack rate is higher among recipients of organs other than kidneys because those patients receive more immunosuppressive therapy. Although amphotericin B remains the drug of choice for treatment of invasive aspergillosis, its toxicity profile limits its widespread use. Recent experience suggests that fluconazole may be a safe and effective alternative for the treatment of fungal infections caused by Candida species or Cryptococcus neoformans. Prevention of fungal infections remains one of the most important goals in the field of transplantation. New approaches--such as the use of "preemptive therapy," or prophylaxis, for patients at greatest risk of developing infection--may assist in attainment of this goal.


Light and electron microscopic study of crocodile islets of Langerhans.
The tissue of the islets of Langerhans was studied in Alligator mississippiensis and Caiman niger. The distribution of the insular tissue in the pancreas was described from the picture in the light microscope, together with the incidence of characteristic islets, which frequently surround the duct tress, and of scattered insular cells. Five types of endocrine cells, distinguishable by their staining properties and typical electron microscopic image, were described in the insular tissue. In addition to A-, B- and D-cells, others which very probably correspond to EC- and PP-cells are described. Mixed cells were also found. The pancreatic interstitial connective tissue contains large numbers of nerve fibre bundles; isolated nerve fibres may penetrate to the insular cells. At the site of contact of a nerve ending with an endocrine cell, characteristic thickening of the membranes is sometimes found.


Immunofluorescence analysis of the primordial myosin detectable in embryonic striated muscle.
Immunofluorescence analysis showed that the earliest myosin detectable in both the embryonic chicken heart and somitic myotome, the precursor to skeletal muscle, was strongly reactive with two different monoclonal antibodies specific for the heavy chain of cardiac ventricular myosin, but it showed no reactivity with affinity-purified polyclonal antibodies specific for the heavy chains of either fast-twitch or slow-tonic skeletal myosins. The heart remained reactive exclusively with the antibodies to cardiac myosin throughout development, while late embryonic (day 20) skeletal muscles were strongly reactive only with their homologous skeletal myosin antibodies. Our findings suggest that the primordial myosin heavy chain detectable in both forms of embryonic chicken striated muscle, the myotome and the heart, is immunologically distinct from myosins expressed in later embryonic as well as adult skeletal muscles, but it contains antigenic determinants similar to those present in cardiac ventricular myosin.


Effect of micronized fenofibrate on microvascular complications of type 2 diabetes: a systematic review.
Micronized fenofibrate prevents the progression of microvascular complications in type 2 diabetes, but no systematic review has summarized these effects. Therefore, we performed a systematic review to investigate the effects of micronized fenofibrate on type 2 diabetes-related microvascular complications. The PubMed database was systematically searched for trials in English language published between January 1990 and November 2015 that examined the effects of fenofibrate on microvascular complications in patients with type 2 diabetes. Thirteen trials of the 290 clinical studies reviewed met the inclusion criteria. Fenofibrate significantly slowed the progression of early diabetic retinopathy by 30 to 40% within 4 to 5 years in patients with type 2 diabetes mellitus and pre-existing retinopathy at baseline. Fenofibrate also consistently reduced the progression of urinary albumin excretion in the trials studied. One large study demonstrated a significant effect (47% reduction) of the drug on diabetes-related minor amputations. The available evidence supports the adjunctive early use of fenofibrate in type 2 diabetes mellitus for the prevention of microvascular complications, particularly in individuals presenting with the first signs of the complication and during the initial stages of the disease.


Tunable Bragg reflectors on silicon-on-insulator rib waveguides.
We present the design, fabrication and characterization of Bragg reflectors on silicon-on-insulator rib waveguides. The fabrication is based on a new double lithographic process, combining electron-beam lithography for the grating and photolithography for the waveguides. This process allows the realization of low loss reflectors, which were fully characterized. The influence of the etching depth and of the waveguide geometry on the reflector performance is considered. We demonstrate a reflectivity larger than 80% over a bandwidth of 0.8 nm with an insertion loss of only 0.5 dB. A thermal tunability of the device is also considered, showing that a shift of the reflected wavelength of 77 pm/K is possible.


Circumcision in Australia: further evidence on its effects on sexual health and wellbeing.
To report on the prevalence and demographic variation in circumcision in Australia and examine sexual health outcomes in comparison with earlier research. A representative household sample of 4,290 Australian men aged 16-64 years completed a computer-assisted telephone interview including questions on circumcision status, demographic variables, reported lifetime experience of selected sexually transmissible infections (STIs), experience of sexual difficulties in the previous 12 months, masturbation, and sexual practices at last heterosexual encounter. More than half the men (58%) were circumcised. Circumcision was less common (33%) among men under 30 and more common (66%) among those born in Australia. After adjustment for age and number of partners, circumcision was unrelated to STI history except for non-specific urethritis (higher among circumcised men, OR=2.11, p<0.001) and penile candidiasis (lower among circumcised men, OR=0.49, p<0.001). Circumcision was unrelated to any of the sexual difficulties we asked about (after adjusting for age) except that circumcised men were somewhat less likely to have worried during sex about whether their bodies looked unattractive (OR=0.77, p=0.04). No association between lack of circumcision and erection difficulties was detected. After correction for age, circumcised men were somewhat more likely to have masturbated alone in the previous 12 months (OR=1.20, p=0.02). Circumcision appears to have minimal protective effects on sexual health in Australia.


Oviposition in the period genotypes of Drosophila melanogaster.
Two behavioral rhythm phenotypes, oviposition and locomotor activity, have been compared in the four period genotypes (per+, pers, per0, and per1) of Drosophila. Period, signal-to-noise ratio, and phase were all analyzed and the genetic penetrance of the two characters was estimated. Significant rhythmicity of both oviposition and locomotor activity was evident in all four genotypes. The entrained and free-running periods of the activity rhythms of per+, pers, and per1 were within the range reported for these flies by previous workers, and rhythmic behavior was also shown by the per0 flies. The free-running period of the oviposition rhythm varied similarly between the four genotypes and showed significant correlation with that of the locomotor activity rhythm. It is suggested that both rhythm phenotypes are determined by the period gene, and estimates of the genetic penetrance of rhythmicity in oviposition and locomotor activity, based on period and signal-to-noise ratios (SNRs) of the different strains, are consistent with this hypothesis. The phase of maximum oviposition and locomotor activity showed greater variability between the genotypes and was not significantly correlated with period, suggesting that this rhythm characteristic is independent of mutations at the period locus.


[Bacterial pathogens causing acute otitis media].
The objectives were to assess the prevalence of etiological agents of acute otitis media (AOM) in children, age distribution of patients, frequency of the disease throughout the year, prescribed antibiotics, risk factors and complications. Included in the study were 100 children and adolescents aged 0 to 18 years who had been diagnosed with AOM. From these patients, swabs for culture were obtained from the middle ear after paracentesis or perforation of the ear drum. Over the study period, a total of 111 isolates were obtained from 100 patients. The most prevalent etiological agents were Streptococcus pneumoniae (29 %), Streptococcus pyogenes (19 %) and Haemophilus influenzae (14 %). The frequency of other bacterial species was below 5 %; twenty-one isolates were negative (19 %). Staphylococcus aureus was identified in 15 cases (14 %); of those, 9 cases had another pathogen. The rates of agents were different in patients with spontaneous perforation. The most frequent etiological agents were Streptococcus pyogenes (24 %), Haemophilus influenzae (20 %), Staphylococcus aureus (17 %) and Streptococcus pneumoniae (15 %). Negative findings were noted in 20 %. The most prescribed antibiotic was amoxicillin-clavulanate (27 %), followed by phenoxymethylpenicillin (21 %) and cefuroxime (15 %). No antibiotics were administered in 20 % of cases and 3 % of patients received only local antibiotics. Complications (mastoiditis) developed in two children (2 %). The study showed that Streptococcus pneumoniae was the most prevalent etiological agent in children with OMA. After spontaneous perforation, however, these were replaced by Streptococcus pyogenes and Haemophilus influenzae. For empirical therapy, the most frequent drugs were amoxicillin-clavulanate, phenoxymethylpenicillin and cefuroxime. The initial empirical therapy had to be changed in only 2 % of the cases.


The effect of inlet gas temperatures on heated humidifier performance.
The aim of the current study was to determine the temperature range of gas at the point at which it passes into a heated humidifier within an intensive care unit and to experimentally examine the effect of different inlet gas temperatures on the performance of a heated humidifier. Various gas and ambient temperatures were measured in an intensive care unit and within ventilator circuits. Ventilator oxygen and air inlet temperatures, ventilator gas outlet temperatures, and humidifier gas inlet temperatures were measured in conjunction with the use of a number of ventilators. Ambient temperatures within the ward ranged from 22.8 degrees C to 28.9 degrees C, while typical ward humidifier gas inlet temperatures ranged from 24.3 degrees C to 28.8 degrees C. Humidity output from a heated humidifier was then determined in an experimental setup at controlled levels of inlet gas temperature using a constant gas flow. A decrease in humidity production, from approximately 36 mg/L at a humidifier inlet gas temperature of 18 degrees C, to 26 mg/L at a humidifier inlet gas temperature of 32 degrees C, was observed with increasing gas inlet temperature. We conclude that humidity output from a heated humidifier varies with inlet gas temperature, decreasing as inlet gas temperature increases. Inlet gas temperatures above 26 degrees C may result in inadequate humidification.


Phylogeny of the Procyonidae (Mammalia: Carnivora): molecules, morphology and the Great American Interchange.
The Procyonidae (Mammalia: Carnivora) have played a central role in resolving the controversial systematics of the giant and red pandas, but phylogenetic relationships of species within the family itself have received much less attention. Cladistic analyses of morphological characters conducted during the last two decades have resulted in topologies that group ecologically and morphologically similar taxa together. Specifically, the highly arboreal and frugivorous kinkajou (Potos flavus) and olingos (Bassaricyon) define one clade, whereas the more terrestrial and omnivorous coatis (Nasua), raccoons (Procyon), and ringtails (Bassariscus) define another clade, with the similar-sized Nasua and Procyon joined as sister taxa in this latter group. These relationships, however, have not been tested with molecular sequence data. We examined procyonid phylogenetics based on combined data from nine nuclear and two mitochondrial gene segments totaling 6534bp. We were able to fully resolve relationships within the family with strongly supported and congruent results from maximum parsimony, maximum likelihood, minimum evolution, and Bayesian analyses. We identified three distinct lineages within the family: a (Nasua, Bassaricyon) clade, a (Bassariscus, Procyon) clade, and a Potos lineage, the last of which is sister to the other two clades. These findings, which are in strong disagreement with prior fossil and morphology-based assessments of procyonid relationships, reemphasize the morphological and ecological flexibility of these taxa. In particular, morphological similarities between unrelated genera possibly reflect convergence associated with similar lifestyles and diets rather than ancestry. Furthermore, incongruence between the molecular supermatrix and a morphological character matrix comprised mostly of dental characters [Baskin, J.A., 2004. Bassariscus and Probassariscus (Mammalia, Carnivora, Procyonidae) from the early Barstovian (Middle Miocene). J. Vert. Paleo. 24, 709-720] may be due to non-independence among atomized dental characters that does not take into account the high developmental genetic correlation of these characters. Finally, molecular divergence dating analyses using a relaxed molecular clock approach suggest that intergeneric and intrageneric splits in the Procyonidae mostly occurred in the Miocene. The inferred divergence times for intrageneric splits for several genera whose ranges are bisected by the Panamanian Isthmus is significant because they suggest diversification well precedes the Great American Interchange, which has long been considered a primary underlying mechanism for procyonid evolution.


Microscopic Reservoir Characteristics of the Lacustrine Calcareous Shale: An Example from the Es4 s Shale of the Paleogene Shahejie Formation in Boxing Sag, Dongying Depression.
The Es4 s shale is taken as the main research object to understand and describe the reservoir characteristics in Boxing Sag, Dongying Depression. Through core observation, X-ray diffraction, thin section observation, field-emission scanning electron microscopy analysis, and low-pressure nitrogen gas adsorption experiment, the reservoir space of the Es4 s shale including pore types, pore size, and pore structure characteristics was elucidated. The study shows that the shale in the Boxing Sag has the following characteristics: (1) the reservoir space in the study area is diverse, with the development of inorganic pores, organic pores, and microfractures. The higher the content of calcite and organic matter, the more favorable the development of intergranular pores, dissolution pores, and organic matter pores and (2) complex pore structure. The average Barrett-Joyner-Halenda pore size of calcareous shale is 6.5-22.8 nm, and the Brunauer-Emmett-Teller cumulative specific surface area is 0.7588-4.744 m2/g. According to the morphological analysis of the adsorption and desorption curve, it is found that the shale samples in the target interval are mainly ink-bottle-shaped, cylindrical, and slit-shaped pores. The shale samples with relatively well-laminated intervals are mainly composed of ink-bottle-shaped and cylindrical pores, while the samples with relatively unlaminated intervals and high clay mineral content are mainly composed of slit-shaped pores. The contents of clay minerals and calcite are correlated with pore volume, specific surface area, and pore size, which further indicates the controlling effect of clay minerals and carbonate mineral components on pore structure parameters. This study not only helps us to understand the distribution of various micropores/nanopores in the lacustrine shale but also acts as a guiding note for the characterization of the shale oil reservoir, which ultimately offers a theoretical foundation for lacustrine shale oil exploration and development.


Cytochrome synthesis and its regulation in Spirillum itersonii.
Spirillum itersonii contains b- and c-type cytochromes as well as a carbon monoxide-binding pigment of the cytochrome o type. Synthesis of cytochromes b and c is increased by about two- and fourfold, respectively, when cells are transferred from high to low aeration. The increased concentration of cytochrome is not accompanied by an increase in the respiration rate of the cells. Both cytochrome b and cytochrome c are located in the particulate fraction of cells grown under high or low aeration, and both pigments are fully reducible by succinate. No evidence was found for the accumulation of the protein component of either cytochrome when synthesis of the prosthetic group was limited by iron deficiency, nor did heme or precursors accumulate when protein synthesis was prevented. It was therefore concluded that the formation of the heme prosthetic group is closely integrated with the synthesis of the protein moiety. delta-Aminolevulinate synthase was detected in extracts of the organism. Its activity was correlated with cytochrome synthesis; it was reduced by high aeration and increased under low aeration. The synthase was inhibited by hemin at concentrations of 10 mum or higher. The observations are consistent with a central role for the heme prosthetic group in the regulation of cytochrome synthesis.


Multiplex PCR for bla(CTX-M) & bla(SHV) in the extended spectrum beta lactamase (ESBL) producing gram-negative isolates.
Phenotyping is commonly used for detection of extended spectrum beta lactamase (ESBL) production in gram-negative isolates. ESBLs are mainly coded for by three important genes, namely bla(TEM), bla(SHV) and bla(CTX-M). In this study we used a multiplex PCR as a rapid method to identify two common genes (bla(CTX-M) & bla(SHV)) responsible for extended spectrum beta lactamase production in members of Enterobacteriaceae family isolated from different clinical samples from a specialty hospital at Chennai. A total of 260 non repetitive clinical isolates from 240 patients (some patients had more than one organism also), was selected for the study. Of these 33 were from sputum, 64 from urine, 46 from blood, 28 from pus aspirates, 58 from endotracheal secretions and 31 from other miscellaneous specimens. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) and phenotypic confirmatory double disk test (PCDDT) according to CLSI guidelines. Multiplex PCR for bla(CTX-M) and bla(SHV) was performed for the ESBL positive isolates. bla(SHV) like genes were found in 6 of 42 E.coli (14%), 7 of 46 Enterobacter species (15%), 28 of 62 Klebsiella species (45%) and bla(SHV) was not detected in any of the 50 isolates of non-fermenting gram-negative isolates. (Pseudomonas and Acinetobacter species) bla(CTX-M) like genes were found in 21 of 42 E. coli (50%), 13 of 46 Enterobacter species (28%), 25 of 62 (40%) Klebsiella species and 1 of 50 nonfermenting gram-negative bacilli (2%). Our study demonstrated rapid detection of bla(SHV) and bla(CTX-M) in isolates belonging to Enterobacteriaceae and other non-fermenting clinical isolates using multiplex PCR. This genotypic method provided a rapid and efficient differentiation of ESBLs in the laboratory.


Benefit of high negative pressure during endoscopic ultrasound-guided fine-needle aspiration with standard 22-gauge needles for pancreatic lesions: a retrospective comparative study.
Few studies are available on high negative pressure (HNP) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study compared the diagnostic yield between HNP and normal negative pressure (NNP) during EUS-FNA for solid pancreatic masses. Consecutive patients with pancreatic masses who underwent EUS-FNA using a 22-G needle with either HNP or NNP for both the first and second passes were retrospectively examined for diagnostic yield. Rapid on-site evaluation (ROSE) was unavailable at our center. The main outcome measures were the number of passes, diagnostic accuracy and quantity of histological samples. Two hundred patients underwent EUS-FNA (n = 97, HNP; n = 103, NNP) over a 22-month period. A significantly lower median number of passes was required for HNP than for NNP (2 vs. 3; p < .001). There was no significant difference in diagnostic accuracy between the two groups. The rate of obtaining a histological sample larger than a 10× power field in length was significantly higher for HNP than for NNP (76.4% vs. 59.6%; p = .0019). In the multivariate analysis, a large tumor size (>20 mm) and HNP were identified as factors influencing the acquisition of a larger histological sample. There was no significant difference in diagnostic accuracy between HNP and NNP. HNP required fewer passes without ROSE and was related to the acquisition of a larger histological sample. HNP may be useful when few samples are available for EUS-FNA with NNP or a larger histological sample is needed.


Expression of serine/threonine protein kinase SGK1F promotes an hepatoblast state in stem cells directed to differentiate into hepatocytes.
The rat pancreatic AR42J-B13 (B-13) cell line differentiates into non-replicative hepatocyte-like (B-13/H) cells in response to glucocorticoid. Since this response is dependent on an induction of serine/threonine protein kinase 1 (SGK1), this may suggest that a general pivotal role for SGK1 in hepatocyte maturation. To test this hypothesis, the effects of expressing adenoviral-encoded flag tagged human SGK1F (AdV-SGK1F) was examined at 3 stages of human induced pluripotent stem cell (iPSC) differentiation to hepatocytes. B-13 cells infected with AdV-SGK1F in the absence of glucocorticoid resulted in expression of flag tagged SGK1F protein; increases in β-catenin phosphorylation; decreases in Tcf/Lef transcriptional activity; expression of hepatocyte marker genes and conversion of B-13 cells to a cell phenotype near-similar to B-13/H cells. Given this demonstration of functionality, iPSCs directed to differentiate towards hepatocyte-like cells using a standard protocol of chemical inhibitors and mixtures of growth factors were additionally infected with AdV-SGK1F, either at an early time point during differentiation to endoderm; during endoderm differentiation to anterior definitive endoderm and hepatoblasts and once converted to hepatocyte-like cells. SGK1F expression had no effect on differentiation to endoderm, likely due to low levels of expression. However, expression of SGK1F in both iPSCs-derived endoderm and hepatocyte-like cells both resulted in promotion of cells to an hepatoblast phenotype. These data demonstrate that SGK1 expression promotes an hepatoblast phenotype rather than maturation of human iPSC towards a mature hepatocyte phenotype and suggest a transient role for Sgk1 in promoting an hepatoblast state in B-13 trans-differentiation to B-13/H cells.


Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation.
Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling. Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P<0.01). AdipoR1-KD markedly reduced globular adiponectin-induced nCDase activation, whereas AdipoR2-KD only slightly reduced. More importantly, small interfering RNA-mediated nCDase-KD markedly blocked the effect of adiponectin on TNFα-induced intercellular adhesion molecule-1 expression. AMP-activated protein kinase-KD failed to block adiponectin-induced nCDase activation and modestly inhibited adiponectin anti-inflammatory effect. In contrast, in caveolin-1 KD (Cav1-KD) cells, >87% of adiponectin-induced nCDase activation was lost. Whereas adiponectin treatment failed to inhibit TNFα-induced intercellular adhesion molecule-1 expression, treatment with sphingosine-1-phosphate or SEW (sphingosine-1-phosphate receptor agonist) remained effective in Cav1-KD cells. AdipoR1 and Cav1 colocalized and coprecipitated in human umbilical vein endothelial cells. Adiponectin treatment did not affect this interaction. There is weak basal Cav1/nCDase interaction, which significantly increased after adiponectin treatment. Knockout of AdipoR1 or Cav1 abolished the inhibitory effect of adiponectin on leukocyte rolling and adhesion in vivo. These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion.


Critical exploration of co-occurring Attention-Deficit/Hyperactivity Disorder, mood disorder and Substance Use Disorder.
Co-occurring disorders (CODs) describe a Substance Use Disorder (SUD) accompanied by a comorbid psychiatric disorder. Attention-Deficit/Hyperactivity Disorder (ADHD) and mood disorders are common CODs with high prevalence rates in SUD populations. It is proposed that literature on a tri-condition presentation of ADHD, mood disorder and SUD is limited. Areas covered: A literature search was conducted using a keyword search on EBSCOhost. Initially 2 799 records were identified, however, only two articles included all three conditions occurring concurrently in individuals. CODs constitute a major concern due to their overarching burden on society as a whole. Diagnosis and treatment of such patients is challenging. There is evidence that dysfunction of dopamine in the brain reward circuitry impacts the development or symptomology of all three disorders. Disparity exists regarding whether ADHD or mood disorders are greater modifiers for increased SUD severity. However, it has been reported that poor functional capacity may have a greater influence than comorbidities on SUD development. Expert commentary: Challenges exist which confound the clear distinction of CODs, however, with greater emergence of adult ADHD its screening in SUD populations should become standard practice to establish data on multi-condition presentations with the ultimate goal of improving clinical outcomes.


Social determinants associated with physical activity among Indigenous adults at the University of Saskatchewan.
Colonization impacts Indigenous Peoples' way of life, culture, language, community structure and social networks. Links between social determinants of health and physical activity (PA) among Indigenous Peoples in Saskatchewan, with 16% Indigenous residents, are unclear. This cross-sectional study, guided by Indigenous Community Advisors, compared moderate-to-vigorous PA (MVPA), traditional Indigenous PA and musculoskeletal PA with social determinants of Indigenous (n = 124), including First Nations (n = 80, including 57 Cree/Nehiyawak) and Métis (n = 41), adults in Saskatchewan. Participants completed Godin-Shephard Leisure-Time PA, Social Support Index and traditional Indigenous PA participation questionnaires. Regression associated positive perception of social support with MVPA (R = 0.306, p = 0.02), while residential school experiences (R = 0.338, p = 0.02) and community support (R = 0.412, p = 0.01) were associated with traditional Indigenous PA participation. Among Métis, discrimination experiences were associated with traditional Indigenous PA participation (R = 0.459, p = 0.01). Traditional Indigenous PA participation was associated with community support among First Nations (R = 0.263, p = 0.04), and also foster care placement (R = 0.480, p = 0.01) for Cree/Nehiyawak First Nations specifically. Among Cree/Nehiyawak, family support (R = 0.354, p = 0.04), discrimination experiences (R = 0.531, p = 0.01) and positive perceptions of support (R = 0.610, p = 0.003) were associated with musculoskeletal PA. Greater community, family and perceived social support, and experiences of discrimination, residential school and foster care are associated with more PA for Indigenous Peoples. Novelty: Positive support perceptions predict physical activity among Indigenous Peoples. Family support, discrimination experiences and positive support perceptions predict physical activity for Cree/Nehiyawak First Nations. Traditional physical activity was predicted by residential school experiences and community support (Indigenous Peoples), discrimination experiences (Métis), community support (First Nations), and foster care experiences (Cree/Nehiyawak).


The LEW.BN(2R) strain: a recombinant in the rat MHC.
Cell-mediated cytolytic (CMC) responses resulting from immunizations between rat strains considered to be RT1 (Ag-B) identical (LEW.B3:BN) are capable of detecting a membrane determinant(s) controlled by a locus linked to RT1, which has been designated Ag-L. The Ag-L gene region has been isolated in a recombinant line, tentatively designated as LEW.BN(2R), and has been assigned the RT1r5 haplotype. The data presented demonstrate that the genes responsible for MLR stimulation in the 2R strain are of LEW origin. In addition, LEW.B3 anti-BN CTL appear to recognize multiple specificities, only one of which is in the 2R strain. Some of the remaining specificities in BN may be the result of interactions between undetected genes that have been separated in the LEW.B3 and 2R strains.


A modified technique for the reconstruction of the alimentary tract after pancreatoduodenectomy.
The high death rate for those patients undergoing pancreatoduodenectomy, which is a result of leakage of biliary and pancreatic anastomoses in most instances, justifies the study of this technique for rebuilding the alimentary tract. The use of two separate intestinal loops for the biliary and pancreatic anastomoses is the basis of this method. This technique reduces the morbidity and the death rates which are the result of leakage in either anastomosis because it separates biliary and pancreatic fistulas.


Astrocyte calcium elevations: properties, propagation, and effects on brain signaling.
The possibility that astrocytes are involved in brain signaling began to emerge in the late 1970s, when it was first shown that astroglia in vitro possess numerous receptors for neurotransmitters. It was later demonstrated that cultured astroglia and astrocytes in situ respond to neurotransmitters with increases in intracellular second messengers, including cyclic AMP and calcium. Astrocyte calcium responses have since been extensively studied both in culture and in intact tissue. We continue to gather information regarding the various compounds able to trigger astrocyte calcium increases, as well as the mechanisms involved in their initiation, propagation as a calcium wave within and between astrocytes, and effects on signaling within the brain. This review will focus on each of these aspects of astrocyte calcium regulation, and attempt to sort out which effects are more likely to occur in developmental, pathological, and physiological conditions. While we have come far in our understanding of the properties or potential of astrocytes' ability to signal to neurons using our array of pharmacological tools, we still understand very little regarding the level of involvement of astrocyte signaling in normal brain physiology.


Rat cytosolic aspartate aminotransferase: molecular cloning of cDNA and expression in Escherichia coli.
cDNA clones for rat cytosolic aspartate aminotransferase (cAspAT, L-aspartate:2-oxoglutarate aminotransferase) [EC 22.214.171.124] were isolated from a rat cDNA library, and the primary structure of the gene for cAspAT was deduced from its cDNA sequence. Rat cAspAT consists of 412 amino acids and its molecular weight is 46,295. The deduced amino acid sequence of rat cAspAT was compared with the sequences of AspATs from other species. The degree of sequence identities of rat/mouse cAspAT, rat/pig cAspAT, rat/chicken cAspAT, rat/pig mAspAT, and rat/Escherichia coli AspAT were 97.1, 89.6, 81.7, 48.1, and 41.2%, respectively. A coding region of rat cAspAT cDNA was inserted into E. coli expression vector pUC9, and enzymatically active cAspAT was expressed as a beta-galactosidase-cAspAT hybrid protein. This hybrid protein represented about 18% of the soluble proteins in E. coli and its kinetic properties were comparable with those of cAspAT preparations purified from rat liver.


Informing parents about newborn screening.
To evaluate current rules and regulations for educating parents about newborn screening. Cross-sectional survey. Newborn screening program coordinators in all 50 states and the District of Columbia. Answers to a standardized semi-structured telephone survey in January 2004. Fifty programs provide standardized information about screening, and 32 of these have information available in multiple languages. Most programs (n=36) believe that parents should be informed about newborn screening as a part of prenatal care; however, none has rules or regulations requiring this. Five require documented informed consent; only one provides the consent form in a language other than English. Hospitals and birthing centers are required by many programs to educate families, including providing information (n=12), obtaining informed consent (n=5), informing parents of the right to refuse screening (n=13), and documenting refusal on institutionally developed forms (n=9). We found considerable variation in policy language across the newborn screening programs. The complexity of current newborn screening programs and the likelihood of expansion in the number of conditions on newborn screening panels present a unique opportunity and challenge for public health nurses to ensure that these programs are effective and that care is integrated.


Challenges to be faced in the reconstruction of metabolic networks from public databases.
In the post-genomic era, the biochemical information for individual compounds, enzymes, reactions to be found within named organisms has become readily available. The well-known KEGG and BioCyc databases provide a comprehensive catalogue for this information and have thereby substantially aided the scientific community. Using these databases, the complement of enzymes present in a given organism can be determined and, in principle, used to reconstruct the metabolic network. However, such reconstructed networks contain numerous properties contradicting biological expectation. The metabolic networks for a number of organisms are reconstructed from KEGG and BioCyc databases, and features of these networks are related to properties of their originating database.


Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.
Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. Case series. Academic peripheral neuropathy clinic. Eight patients with CD and neuropathy symptoms. Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. Clinical data and ENF density. All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.


CellDestiny: A RShiny application for the visualization and analysis of single-cell lineage tracing data.
Single-cell lineage tracing permits the labeling of individual cells with a heritable marker to follow the fate of each cell's progeny. Over the last twenty years, several single-cell lineage tracing methods have emerged, enabling major discoveries in developmental biology, oncology and gene therapies. Analytical tools are needed to draw meaningful conclusions from lineage tracing measurements, which are characterized by high variability, sparsity and technical noise. However, the single cell lineage tracing field lacks versatile and easy-to-use tools for standardized and reproducible analyses, in particular tools accessible to biologists. Here we present CellDestiny, a RShiny app and associated web application developed for experimentalists without coding skills to perform visualization and analysis of single cell lineage-tracing datasets through a graphical user interface. We demonstrate the functionality of CellDestiny through the analysis of (i) lentiviral barcoding datasets of murine hematopoietic progenitors; (ii) published integration site data from Wiskott-Aldrich Symdrome patients undergoing gene-therapy treatment; and (iii) simultaneous barcoding and transcriptomic analysis of murine hematopoietic progenitor differentiation in vitro. In summary, CellDestiny is an easy-to-use and versatile toolkit that enables biologists to visualize and analyze single-cell lineage tracing data.


Discoid lateral meniscus in children: limited knee extension and meniscal instability in the posterior segment.
Limited knee extension is a well-known sign in children with discoid meniscus, but its causative mechanism is controversial. The purpose of this study was to characterize discoid meniscus with this clinical manifestation with a focus on instability of the posterior segment and its morphologic features. The authors retrospectively reviewed magnetic resonance imaging and intraoperative arthroscopic videos of 34 knees in 32 consecutive patients (age range, 4.5-15.0 years) who underwent arthroscopic treatment for symptomatic discoid lateral meniscus. Knees were classified into 2 groups, depending on the presence (n = 19) or absence (n = 15) of an extension block, which was defined as a limitation of knee extension by 10 degrees or more under general anesthesia. Meniscal instability in the posterior segment was determined based on arthroscopic findings, and its correlation with knee extension block was analyzed. Using magnetic resonance imaging, the thicknesses of anterior and posterior segments were measured to assess significance of the thickness differences by a presence of knee extension block and by the posterior segment instability. There were 13 knees with a stable posterior segment and 21 knees with an unstable posterior segment. Meniscal instability in the posterior segment was observed in the knees with a surface tear (n = 12), in a hypermobile posterior rim despite the absence of a surface tear (n = 5), and in knees with a freely movable posterior rim without posterior tibial attachment (n = 4). Knee extension block occurred exclusively in complete type menisci and was significantly correlated with meniscal instability in the posterior segment. Magnetic resonance imaging observations suggested that morphologic features characteristic of thick anterior and thin posterior segments were significantly associated with meniscal instability in the posterior segment. Clinically, knee extension block disappeared in all cases within 4 months of arthroscopic treatment. A redundant anterior segment associated with meniscal instability in the posterior segment is likely to cause limited knee extension in children with discoid lateral meniscus. This correlation mandates that discoid menisci be thoroughly evaluated during arthroscopic treatment to identify any instability that might require stabilization.


Does a pelvic belt reduce hip adduction weakness in pregnancy-related posterior pelvic girdle pain? A case-control study.
The cause of non-specific lumbopelvic pain is unknown. Pregnancy-related pelvic girdle pain seems to be a subgroup that deserves a specific treatment. One of the options is the use of a pelvic belt. To objectify the influence of a pelvic belt in patients with pelvic girdle pain. Case-control study. Outpatient clinic. A total of 49 women with long-lasting posterior pelvic girdle pain and 37 parous women of the same age group without pelvic girdle pain. Hip adduction force was measured by asking the participant to squeeze a hand-held dynamometer between the knees. This was firstly performed without a pelvic belt and then with a pelvic belt. The increase of hip adduction force after applying the pelvic belt was expressed in percentages. After tightening a pelvic belt hip adduction force increased 25.9±33.9% in patients with pelvic girdle pain (P<0.0001) and 1.0±8.6% in participants without (P=0.67). The difference between groups was significant (P<0.00001). A pelvic belt has a positive influence on hip adduction force in pregnancy-related posterior pelvic girdle pain. The results show an objective positive effect of the pelvic belt in women with long-lasting pregnancy-related posterior pelvic girdle pain in a test-situation. The results support the idea that the use of a belt could be part of a multidisciplinary rehabilitation of those patients.


Evidence for increased clinical severity of familial and sporadic Paget's disease of bone in Campania, southern Italy.
The analysis of 236 Italian patients with Paget's bone disease showed higher clinical severity and greater frequency of neoplastic degeneration among patients who live or descend from individuals living in the Campania region (southern Italy). A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region. The Campania region in southern Italy has been recently indicated as a high prevalence area for Paget's disease of bone (PDB), and most pagetic families with multiple occurrence of neoplasms in affected members were from this geographical region. We evaluated the PDB epidemiological characteristics in 125 patients from Campania in comparison with 111 patients from other Italian regions. Twenty-three patients from Campania and 26 patients from other Italian areas had at least one first-degree relative affected by PDB (familial cases). The remaining patients made up the sporadic cases. Among subjects from Campania, the patients in the familial group tended to come from larger families and showed at diagnosis higher serum total alkaline phosphatase, larger extension of disease, and earlier mean age with respect to patients with PDB of the sporadic group. The skull, spine, and humerus were the sites preferentially involved in the familial cases. In contrast, no such differences were observed between familial and sporadic PDB cases among patients from the other geographical areas, except for a lower age at diagnosis. An increased PDB clinical severity was finally observed in the PDB cohort from Campania in comparison with patients from other Italian regions. Neoplastic degeneration of pagetic bones (osteosarcoma and giant cell tumor) was exclusively observed in patients with polyostotic PDB from Campania. We showed a higher clinical severity of PDB with occurrence of neoplastic degeneration in the high prevalence area of Campania, with its maximum expression in cases with familial disease. This peculiar pattern might be traced to genetic predisposition and/or to the abnormal impact of a still undefined environmental trigger.


[Hemodialysis without risk of hemorrhage. Introduction of an APTT bedside method for exact heparin monitoring--a review].
A summarized account of our experiences over 1 1/2 years is given, in relation to a minimum heparinisation technique during haemodialysis. This novel technique was made possible by the introduction of an APTT bedside method. In a comparison between the techniques employed so far for preventing a heparin-caused risk of haemorrhage and our method, the clear advantage of our method was apparent. In addition to a discussion of our methods, we describe the cases treated so far. The amounts of heparin required for dialysis are so small that a necessary coagulation can occur even in a part of the organism where there is a danger of haemorrhage. Thereby it was possible to extend the range of indication for haemodialysis substantially. By using minimum heparinisation, it is possible to perform an immediate postoperative haemodialysis. The healing of wounds, which is impaired in cases of renal insufficiency, may be improved by early dialysis without the risk of haemorrhage. Our results show that the minimum heparinisation signifies a decisive achievement in acute dialysis therapy.


[Cholesterol: consensus and controversies, what is the trend in 1993?].
Anatomopathological, biological and epidemiological studies suggest that raised cholesterol concentrations are associated with heightened risk for coronary heart disease. Preventive measures have been recommended by consensus conferences (prudent diet and cholesterol lowering drugs) for a "desirable" level of plasma total cholesterol, i.e.: 1.80 g/l before thirty years and 2 g after thirty years. The debates about the advantage of plasma cholesterol lowering have boosted many controversies after the completion of randomized primary and secondary prevention trials analyses. It was showed an increase in total mortality and a no reduction in fatal coronary events. A series of papers have tried to discourage physicians from identifying subjects with high risk. One has to continue to detect subjects with familial hypercholesterolemia and to treat them following the recommendations of consensus conferences. In the other cases, one has to attach value to HDL-cholesterol and plasma triglyceride levels, especially in patients with hyperinsulinemia, insulin resistance, hypertension and visceral obesity. As lipid oxidation products toxicity, protective diets, as the traditional mediterranean diet containing antioxidant components are important too. Relationships between lipoprotein status and hypercoagulability remains to be investigated to identify predictive factors better than cholesterol for atherothrombosis diseases in subjects at risk.


Culex pipiens crossing type diversity is governed by an amplified and polymorphic operon of Wolbachia.
Culex pipiens mosquitoes are infected with Wolbachia (wPip) that cause an important diversity of cytoplasmic incompatibilities (CIs). Functional transgenic studies have implicated the cidA-cidB operon from wPip and its homolog in wMel in CI between infected Drosophila males and uninfected females. However, the genetic basis of the CI diversity induced by different Wolbachia strains was unknown. We show here that the remarkable diversity of CI in the C. pipiens complex is due to the presence, in all tested wPip genomes, of several copies of the cidA-cidB operon, which undergoes diversification through recombination events. In 183 isofemale lines of C. pipiens collected worldwide, specific variations of the cidA-cidB gene repertoires are found to match crossing types. The diversification of cidA-cidB is consistent with the hypothesis of a toxin-antitoxin system in which the gene cidB co-diversifies with the gene cidA, particularly in putative domains of reciprocal interactions.


Converting Organic Wastewater into CO Using MOFs-Derived Co/In2O3 Double-Shell Photocatalyst.
The photocatalytic conversion of organic wastewater into value-added chemicals is a promising strategy to solve the environmental issue and energy crisis. Herein, Co/In2O3 nanotubes with a double-shell structure, as a highly efficient photocatalyst, are synthesized by a one-step calcination method. The Co/In2O3 heterostructure shows an outstanding photocatalytic CO2 reduction performance of 4902 μmol h-1 g-1. Notably, these Co/In2O3 photocatalysts also achieve CO2 self-generation and in situ reduction conversion in acid organic wastewater (phenol solution), in which the high CO2 (47.5 μmol h-1 g-1) and CO (0.9 μmol h-1 g-1) evolution rates are demonstrated under solar irradiation. Transient photovoltage (TPV) tests demonstrate that Co nanoparticles on Co/In2O3 double-shell heterostructure serve as the CO2 reduction sites for the effective capture and stabilization of the photogenerated electrons.


Adrenal SGLT1 or SGLT2 as predictors of atherosclerosis under chronic stress based on a computer algorithm.
Chronic stress promotes the development of atherosclerosis, causing disruptions in the body's hormone levels and changes in the structural function of organs. The purpose of this study was to investigate the pathological changes in the adrenal gland in a model of atherosclerosis under chronic stress and to verify the expression levels of Sodium-glucose cotransporter (SGLT) 1 and SGLT2 in the adrenal gland and their significance in the changes of adrenal gland. The model mice were constructed by chronic unpredictable stress, high-fat diet, and Apoe-/- knockout, and they were tested behaviorally at 0, 4, 8 and 12 weeks. The state of the abdominal artery was examined by ultrasound, and the pathological changes of the aorta and adrenal glands were observed by histological methods, and the expression levels and distribution of SGLT1 and SGLT2 in the adrenal gland were observed and analyzed by immunofluorescence and immunohistochemistry. The predictive value of SGLT1 and SGLT2 expression levels on intima-media thickness, internal diameter and adrenal abnormalities were verified by receiver operating characteristic (ROC) curves, support vector machine (SVM) and back-propagation (BP) neural network. The results showed that chronic stress mice had elevated expression levels of SGLT1 and SGLT2. The model mice developed thickening intima-media and smaller internal diameter in the aorta, and edema, reticular fiber rupture, increased adrenal glycogen content in the adrenal glands. More importantly, analysis of ROC, SVM and BP showed that SGLT1 and SGLT2 expression levels in the adrenal glands could predict the above changes in the aorta and were also sensitive and specific predictors of adrenal abnormalities. SGLT1 and SGLT2 could be potential biomarkers of adrenal injury in atherosclerosis under chronic stress.