Cause-specific mortality among patients with different molecular subtypes of T1-2N0M0 breast cancer: A population-based study.
The objective of our study is to investigate mortality pattern and quantitatively assess prognostic risk for cause-specific death among T1-2N0M0 breast cancer survivors.The representative data of T1-2N0M0 breast cancer patients diagnosed between 2010 and 2016 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) were calculated taking US population as a reference. Cox regression analysis was conducted to analyze the potential prognostic factors for cause-specific mortality.A total of 161,966 patients were identified from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 41 months, mortality occurred in 10,567 patients, of which 30.9% and 22.7% were attributed to breast cancer and cardiovascular diseases (CVDs). The standardized mortality ratios of CVD were 4.78, 4.27, 3.78, and 4.95 in patients with HR+/HER2+, HR-/HER2+, HR+/HER2-, and HR-/HER2- breast cancer compared to general US population, respectively. Cox proportional hazards regression analysis showed that the adjusted HRs of breast cancer-specific mortality were 0.999 (95% confidence interval [CI]: 0.879-1.135), 1.454 (95% CI: 1.246-1.697), 2.145 (95% CI: 1.962-2.345) for HR+/HER2+, HR-/HER2+, and HR-/HER2- breast cancer, respectively, as compared with HR+/HER2- subtype; HRs of CVD-specific death were 1.215 (95% CI: 1.041-1.418), 1.391 (95% CI: 1.209-1.601), and 1.515 (95% CI: 1.213-1.892), respectively. In addition, we found that older age at diagnosis, and black race were also independent predictors of CVD-specific death.In the present study, we revealed the mortality pattern of cause-specific mortality, and identified prognostic factors of overall mortality, breast cancer-specific mortality, and CVD-specific mortality in T1-2N0M0 breast cancer survivors, supporting early detection and more efficient CVD care for these patients.


Interaction of poly(rC)-binding protein 2 domains KH1 and KH3 with coxsackievirus RNA.
Recombinant hnRNP K-homology (KH) domains 1 and 3 of the poly(rC)-binding protein (PCBP) 2 were purified and assayed for interaction with coxsackievirus B3 RNA in electrophoretic mobility shift assays using in vitro transcribed RNAs which represent signal structures of the 5'-nontranslated region. KH domains 1 and 3 interact with the extended cloverleaf RNA and domain IV RNA of the internal ribosome entry site (IRES). KH1 but not KH3 interacts with subdomain IV/C RNA, whereas KH3 interacts with subdomain IV/B. All in vitro results are consistent with yeast three-hybrid experiments performed in parallel. The data demonstrate interaction of isolated PCBP2 KH1 and KH3 domains to four distinct target sites within the 5'-nontranslated region of the CVB3 genomic RNA.


Arx is required for normal enteroendocrine cell development in mice and humans.
Enteroendocrine cells of the gastrointestinal (GI) tract play a central role in metabolism, digestion, satiety and lipid absorption, yet their development remains poorly understood. Here we show that Arx, a homeodomain-containing transcription factor, is required for the normal development of mouse and human enteroendocrine cells. Arx expression is detected in a subset of Neurogenin3 (Ngn3)-positive endocrine progenitors and is also found in a subset of hormone-producing cells. In mice, removal of Arx from the developing endoderm results in a decrease of enteroendocrine cell types including gastrin-, glucagon/GLP-1-, CCK-, secretin-producing cell populations and an increase of somatostatin-expressing cells. This phenotype is also observed in mice with endocrine-progenitor-specific Arx ablation suggesting that Arx is required in the progenitor for enteroendocrine cell development. In addition, depletion of human ARX in developing human intestinal tissue results in a profound deficit in expression of the enteroendocrine cell markers CCK, secretin and glucagon while expression of a pan-intestinal epithelial marker, CDX2, and other non-endocrine markers remained unchanged. Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations.


Modulation of Virulence Gene Expression in Salmonella enterica subsp. enterica typhimurium by Synthetic Milk-Derived Peptides.
The hydrolysis of milk proteins produces valuable bioactive peptides, some of which show antivirulence activity. In this study, five synthetic milk-derived peptides (β-LG f(9-18), β-CN f(5-15), β-CN f(17-27), β-CN f(94-106), and β-CN f(129-137)) were shown to decrease the expression of virulence genes in Salmonella enterica subsp. enterica typhimurium when tested at four concentrations (0.02, 0.05, 0.1, and 0.2 mg/ml). A mixture of these synthetic peptides at concentrations of 0.02 and 0.2 mg/ml each significantly downregulated the expression of both hilA and ssrB virulence genes in Salmonella typhimurium after a 3-h incubation. Individually, β-CN f(17-27) at 0.02 mg/ml caused a significant decrease in both hilA and ssrB gene expressions. These results suggest a synergistic interaction between bioactive peptides. Depending on dose and amino acid sequence, these five peptides were able to affect the expression of some virulence genes in Salmonella typhimurium.


Influence of aging on the in vivo properties of human patellar tendon.
Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study.


Comparison of helicopter and ground transportation in pediatric trauma patients.
Decision making regarding transportation mode after a traumatic injury may have a significant impact on outcomes, due to differences in time to definitive care. The objective of this study was to determine if transport mode had an impact on in-hospital mortality and discharge disposition in pediatric trauma patients. Data were abstracted from the National Trauma Data Bank from 2007 to 2016 comparing helicopter and ground transportation modes effects on mortality and discharge outcomes. The primary outcome was in-hospital death, while the secondary outcome was discharge home without services (DCHWOS). Analyses included logistic regression modeling and propensity score matching. Significant variables from univariate analysis were included in the multivariate, propensity-matched regression model. Pediatric trauma patients transported by helicopter had lower odds of mortality (OR 0.69 [0.64,0.75]) and higher odds of DCHWOS (1.29 [1.20,1.39]). There were no differences in overall mechanism, but individual injury patterns showed higher odds of mortality. Critical decisions regarding triage of patients by different modes of transport occur every day. This study supports the current literature on the topic and shows a potential additional benefit of a meaningful discharge outcome for those transported by helicopter. This study may impact prehospital triage decision making process for pediatric trauma patients on mortality. Prehospital transport mode may contribute to pediatric trauma discharge outcomes. Highlights the need for future research regarding non-clinical data that is unable to be abstracted from national databases (e.g., family dynamics, insurance status, weather, access to post-discharge resources).


Effect of tinofedrine (Homburg D8955) on cerebral blood flow in multi-infarct dementia.
Tinofedrine, a new derivative of l-norephedrine, was examined for cerebral vasodilator activity in man. Ten patients with reduced cerebral blood flow (CBF) and multi-infarct dementia were given the drug intravenously. Cerebral blood flow increased significantly by 28% from a mean of 43.3 to 55.5 ml/100 g/min.


Molecular imaging approaches to facilitate bacteria-mediated cancer therapy.
Bacteria-mediated cancer therapy is a potential therapeutic strategy for cancer that has unique properties, including broad tumor-targeting ability, various administration routes, the flexibility of delivery, and facilitating the host's immune responses. The molecular imaging of bacteria-mediated cancer therapy allows the therapeutically injected bacteria to be visualized and confirms the accurate delivery of the therapeutic bacteria to the target lesion. Several hurdles make bacteria-specific imaging challenging, including the need to discriminate therapeutic bacterial infection from inflammation or other pathologic lesions. To realize the full potential of bacteria-specific imaging, it is necessary to develop bacteria-specific targets that can be associated with an imaging assay. This review describes the current status of bacterial imaging techniques together with the advantages and disadvantages of several imaging modalities. Also, we describe potential targets for bacterial-specific imaging and related applications.


Procedural outcomes with use of the flash ostial system in aorto-coronary ostial lesions.
The Flash Ostial system (Ostial Corporation, Sunnyvale, CA) was designed to optimize implantation of aorto-ostial coronary stents by flaring the proximal stent struts against the aortic wall. We retrospectively reviewed the medical record, angiograms, and intravascular ultrasound images of 22 aorto-ostial percutaneous coronary interventions performed at our institution between March and September 2015. The Flash Ostial system was used in 13 cases (59%). Mean age was 67 ± 8 years and all patients were men. The target vessel was the right coronary artery (59%), left main (27%), or a saphenous vein graft (14%); 59% of the lesions had moderate/severe calcification. The mean number of predilation balloons was 1.8 ± 1.6, mean Flash ostial balloon diameter was 3.3 ± 0.5 mm and mean inflation pressure was 13.1 ± 4.0 atmospheres. Intravascular ultrasonography (available for 19 patients) revealed mean ostial minimum lumen cross-sectional area (MLA) of 9.2 ± 3.0 mm2 and reference MLA of 8.5 ± 2.7 mm2 . The percent difference between ostial and reference MLA was higher in cases in which the Flash Ostial system was used versus those where it was not (9.6 ± 5.5% vs. 4.0 ± 2.8%, P = 0.03). All stent struts were well apposed. Technical success was 100%. One patient developed a left groin pseudoaneurysm treated with thrombin injection and one patient had a periprocedural myocardial infarction. Median contrast, fluoroscopy time, and procedure time were 235 mL, 33 min, and 118 min, respectively. The Flash Ostial system can be successfully used in aorto-ostial stenting, resulting in large ostial vessel MLA. © 2016 Wiley Periodicals, Inc.


[Pulmonary embolism and disseminated coagulopathy syndrome after first trimester termination of pregnancy--a case report].
We present a rare case report of first trimester termination of pregnancy by suction curettage because of missed abortion complicated by pulmonary thrombembolism and disseminated coagulopathy. The diagnosis was confirmed by clinical, sonographical and laboratory means. The relative risk of such complications after first trimester termination of pregnancy is discussed.


A unique neurofilament from Torpedo electric lobe: sequence, expression, and localization analysis.
A set of cDNA clones encoding a protein highly homologous to the mammalian middle-size class of neurofilaments (NF-M) was characterized. The amino acid similarity between the Torpedo and rat NF-M approaches 90% in the amino-terminal "rod-like" domain and is significantly lower in the carboxy-terminal tail. The Torpedo protein contains 13 tandem repeats of a unique six amino acid core, containing a Lys-Ser-Lys putative phosphorylation site. Surprisingly, the 3' untranslated region contains stretches of 80-90% nucleic acid homology with the mammalian, but not with the chicken sequences. This homology is greater than much of the coding region, suggesting that the 3' untranslated region of the message has an important functional role, perhaps governing RNA stability or localization. This Torpedo NF-M mRNA is expressed specifically in the electric lobe and was not detected in other tissues, including brain and spinal cord. A polyclonal antibody generated against a fusion protein synthesized in E. coli detects a 150-kDa protein in the electric lobe and organ, as well as a small amount of material in the brain. Cytochemical studies reveal immunoreactivity in electromotor neuron axons and terminals. Specific expression of neurofilament genes in subsets of central neurons may be important in determining the morphology and functional characteristics of specific neuronal subtypes.


Identification and quantification of antimicrobial activity in commercially available chicken meat in a large urban centre in Pakistan.
Large-scale use and misuse of antibacterial agents for infection prevention and growth promotion in chicken has grown alongside mass production of poultry as a primary protein source in human diet. This has led to concern about promotion of antibiotic resistance among bacteria of clinical significance to human disease. The objectives of this study are to identify which, if any, antimicrobials are commonly found in commercially available broiler chicken and determining the minimum amount of meat with enough microbial inhibitory activity that can be measured in routine culture. Four test organisms, namely ATCC 25922, ATCC 51299, clinical isolate MRSA and clinical isolate E. coli were used. The antimicrobial sensitivity profiles of the test organisms were determined against beta-lactams, tetracyclines, aminoglycosides, sulphonamides, fluoroquinolones and phenicols. 8 mm tissue pieces of liver, muscle and kidney samples were obtained and plated on all four plates of our test organisms. The zones of inhibition, if any, around the tissue samples determined the presence of antimicrobial residues in meat. 270 tissue samples of liver, muscle and kidney were tested for the presence of antimicrobial residues. In total 90 freshly butchered broiler chicken samples were collected, each contributing a liver, kidney and a muscle tissue sample. The samples were collected randomly from butcher shops across geographical bins of the city of Lahore. The results showed that 73.3% of the samples were positive for antimicrobial activity. Of these 69.6% of the samples were positive for the presence of sulfonamides, 9.3% had flurphenicol, 7.0% had quinolone activity, 6.7% had aminoglycoside activity and 3.7% had tetracyclines in them.


Reinstating Elective Surgeries in MedStar Health: A Roadmap for Healthcare Organizations.
Coronavirus disease 2019 (COVID-19) infections have strained hospital resources worldwide. As a result, many facilities have suspended elective operations and ambulatory procedures. As the incidence of new cases of COVID-19 decreases, hospitals will need policies and algorithms to facilitate safe and orderly return of normal activities. We describe the recommendations of a task force established in a multi-institutional healthcare system for resumption of elective operative and ambulatory procedures applicable to all hospitals and service lines. MedStar Health created a multidisciplinary task force to develop guidelines for resumption of elective surgeries/procedures. The primary focus areas included the establishment of a governance structure at each healthcare facility, prioritization of elective cases, preoperative severe acute respiratory syndrome coronavirus 2 testing, and an assessment of the needs and availability of staff, personal protective equipment, and other essential resources. Each hospital president was tasked with establishing a local perioperative leadership team answering directly to them and granted the authority to prioritize elective surgery and ambulatory procedures. An elective surgery algorithm was established using a simplified Medically Necessary Time Sensitive score, with multiple steps requiring a "go/no-go" assessment based on local resources. In addition, mandatory preoperative COVID testing policies were developed and operationalized. Even when the COVID pandemic has passed, hospitals and surgical centers will require COVID screening and testing, case prioritization, and supply chain management to provide care essential to the surgical patient while protecting their safety and that of staff. Our guidelines consider these factors and are applicable to both tertiary academic medical centers and smaller community facilities.


Diagnostic features of a unilateral fused kidney with a lower-pole inflamed, hemorrhagic cyst.
Numerous imaging procedures contributed to the diagnosis of unilateral fused kidney with an associated lower-pole mass in a 68-year old man with back and right lower quadrant pain. 99mTc-DMSA renal scintigraphy provided the best global picture of the renal anomaly and a lower-pole contour defect suggesting a mass.


Oral microbiota-induced periodontitis: a new risk factor of metabolic diseases.
It has recently become evident that the periodontium (gingiva, desmodontal ligament, cementum and alveolar bone) and the associated microbiota play a pivotal role in regulating human health and diseases. The oral cavity is the second largest microbiota in the body with around 500 different bacterial species identified today. When disruption of oral cavity and dysbiosis occur, the proportion of strict anaerobic Gram-negative bacteria is then increased. Patients with periodontitis present 27 to 53% more risk to develop diabetes than the control population suggesting that periodontitis is an aggravating factor in the incidence of diabetes. Moreover, dysbiosis of oral microbiota is involved in both periodontal and metabolic disorders (cardiovascular diseases, dyslipidaemia …). The oral diabetic dysbiosis is characterized by a specific bacteria Porphyromonas, which is highly expressed in periodontal diseases and could exacerbate insulin resistance. In this review, we will address the nature of the oral microbiota and how it affects systemic pathologies with a bidirectional interaction. We also propose that using prebiotics like Akkermansia muciniphila may influence oral microbiota as novel therapeutic strategies. The discovery of the implication of oral microbiota for the control of metabolic diseases could be a new way for personalized medicine.


Using experimental de-worming to measure the immunological and pathological impacts of lungworm infection in cane toads.
The immunological and pathological consequences of parasite infection can be more rigorously assessed from experimental manipulation than from correlational studies of natural infections. We used anthelmintic treatment to experimentally decrease intensities of lungworm infection in captive and free-ranging wild cane toads to assess parasite impacts on host immune responses. First, we administered the anthelmintic drug Ivermectin to both infected and uninfected toads, to distinguish drug effects per se from the impacts of killing lungworms. Worms began dying and decomposing <48 h after injection. The only immunological variables that were affected by anthelmintic treatment were bactericidal capacity of the blood which increased in parasitized toads (presumably triggered by decomposing worms in the lungs), and the phagocytic capacity of blood (which increased in both infected and uninfected toads); the latter effect presumably was caused by the injection of Ivermectin per se rather than removal of parasites. Second, we looked at correlates of variation in the infection intensity induced by de-worming (in both captive and free-ranging toads) over an eight-week period. Heavier lungworm infection was associated with increased phagocytic ability of the host's blood, and a reduction in the host's liver mass (and hence, energy stores). Experimental de-worming thus revealed pathological and immunological costs of the presence of lungworms, and of their removal by anthelmintic injection.


Alprazolam in the treatment of panic attack patients with and without major depression.
Sixteen patients with panic attacks were treated with alprazolam at an anxiety clinic between March 1982 and April 1983. For all patients charts were reviewed for baseline data and treatment results at 1 and 6 months. Quantitated self-rating scales and the Clinical Global Impressions scale were used to assess progress. Alprazolam appeared effective for panic, agoraphobia, and depressive symptoms in 7 of 11 patients with either panic disorder or agoraphobia with panic attacks (DSM-III-defined diagnoses); side effects occurred in 4 of the 11 patients, were limited to oversedation, and resulted in no discontinuations of drug. However, alprazolam was ineffective in controlling panic, agoraphobia, and depression in 5 patients with panic attacks and secondary major depressive episode; for this group of patients, side effects were apparently paradoxical and required drug discontinuation in 3 of these 5 patients.


Stable N,N'-Diarylated Dihydrodiazaacene Radical Cations.
Three stable N,N'-diarylated dihydroazaacene radical cations were prepared by oxidation of neutral N,N'-diarylated dihydroazaacenes synthesized via palladium-catalyzed Buchwald-Hartwig aminations of aryl iodides with N,N'-dihydroazaacenes. Both neutral as well as oxidized species were investigated via UV-vis spectroscopy, single crystal analysis, and DFT calculations. All the radical cations are surprisingly stable-their absorption spectra in dichloromethane remain unchanged in ambient conditions for at least 24 hours.


Comparison of models to evaluate microbial sulphide generation and transport in the near field of a SF/HLW repository in Opalinus Clay.
In a deep geological repository for radioactive waste in the Opalinus Clay, disposal canisters may be corroded due to sulphide produced by sulphate reducing bacteria (SRB). This paper presents two computational models, a reactive transport model (RTM) and a simplified semi-analytical model (SM), to evaluate the potential of SRB to generate elevated sulphide concentrations, to assess sulphide fluxes to the canister and, in a simplified manner, the resulting canister corrosion. Calculations performed in the context of the repository's safety assessment based on a shared conceptual model reveal that the two computational models are complementary. The reactive transport model incorporates state-of-the-art understanding of the system's geochemistry, but is currently too computationally demanding to be applied in probabilistic safety assessment sensitivity analyses. The simplified model is fast and efficient, but some of its assumptions need to be verified, and some parameter values need to be calibrated using the more complete reactive transport model. Nonetheless, given the same set of assumptions, the two models predict comparable magnitudes of sulphide fluxes to the canister and comparable canister corrosion depths.


Anti-angiogenic effect of nano-formulated water soluble kaempferol and combretastatin in an in vivo chick chorioallantoic membrane model and HUVEC cells.
The present study evaluated the efficacy of nano-formulated water-soluble kaempferol and combretastatin alone and combined against the native kaempferol and combretastatin on angiogenesis. The solvent evaporation method was used to synthesize the nano-formulated water-soluble kaempferol and combretastatin and characterized using various analyses such as dynamic light scattering (DLS) and Fourier-transform infrared (FT-IR) spectroscopy.The anti-angiogenic activity of native, nano-formulated water-soluble kaempferol and combretastatin was investigated by cell viability on HUVEC and A498 cell lines, while chick chorioallantoic membrane (CAM) assay was utilized to assess morphometric and histopathological changes, and mRNA expressions of VEGF-A and FGF2 using qRT-PCR. MTT assay results revealed that the combination of nano-formulated water-soluble kaempferol and combretastatin significantly reduced the cell viability compared to control, individual treatments of native, nano-formulated water-soluble kaempferol, and combretastatin. Morphometric analysis of CAM showed that treatment with nano-formulated water-soluble kaempferol and combretastatin caused a substantial decrease in density, vessel network, branch points, and nets of CAM blood vessels. The histopathological results of CAM showed the irregular shape of blood vessels at the thin stratum of chronic endoderm, and blood capillaries were diminished compared to the control. In addition, the mRNA expression levels of VEGF-A and FGF2 were significantly decreased compared with native forms. Therefore, the findings of this study indicate that nano-formulated water-soluble combretastatin and kaempferol suppress angiogenesis by preventing the activation of endothelial cells and suppressing factors of angiogenesis. Moreover, a combination of nano-formulated water-soluble kaempferol and combretastatin worked much better than individual treatments.


Allosteric activation of brain mitochondrial Ca2+ uptake by spermine and by Ca2+: brain regional differences.
Analysis of the initial rates of 45Ca2+ uptake by rat brain mitochondria in Ca2+-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid buffers indicated that nontelencephalic mitochondria exhibited both a much less pronounced stimulatory effect of spermine and significantly more hyperbolic kinetics of Ca2+ uptake than telencephalic mitochondria. Nontelencephalic mitochondria were also markedly less susceptible to a Ca2+-induced hysteretic allosteric activation of the Ca2+ uniporter. A new Ca2+ loading procedure, which strikingly illustrates differences in mitochondrial Ca2+ buffering characteristics, is also described. In this procedure, low concentrations of Ca2+ (1, 2, or 5 microM) were repetitively added to mitochondria every 30 s while changes in free Ca2+ concentration were recorded. Spermine induced a marked attenuation of the rise in free Ca2+ level under these conditions. Steady-state rates of Ca2+ uptake were determined by a quantitative analysis of the buffering of repetitive Ca2+ additions, and, again, brain regional differences were qualitatively similar to those observed in the initial rate kinetics; Ca2+ uptake by nontelencephalic mitochondria in the steady state was markedly less responsive to stimulation by spermine and appeared to have a more hyperbolic dependence on Ca2+ in the absence of spermine. These results also suggest that there is a lag time in the activation of the uniporter by Ca2+, in addition to the hysteresis that has previously been observed in the deactivation of the uniporter.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of acute starvation on insulin resistance in obese patients with and without type 2 diabetes mellitus.
Starvation decreases insulin sensitivity and glucose tolerance in both lean and obese (OB) non-diabetic subjects. Influence of drastic calorie reduction on insulin resistance in patient with type 2 diabetes (T2DM) is not known. We enrolled 10 T2DM (diabetes duration 11.1+/-7.9 years) and 10 OB age and weight-matched subjects and performed isoglycaemic hyperinsulinaemic clamp (two 120 min phases of 60 and 120 mIU min-1 m-2 i.v. insulin) with indirect calorimetry at baseline and after 60 h of fasting. After starvation insulin-mediated glucose disposal decreased significantly in both hyperinsulinaemic phases in T2DM (phase 1: from 46+/-28 to 33+/-17, P<0.04; phase 2 from 122+/-47 to 80+/-30 microg kg-1 min-1, P<0.01) as well as in OB (phase 1: from 94+/-52 to 52+/-24, P<0.04; phase 2: from 131+/-46 to 106+/-43 microg kg-1 min, P<0.01). Both oxidative and non-oxidative components of glucose disposal tended to be reduced after fasting. A change of insulin sensitivity was found to be highly dependent upon pre-starvation conditions: more insulin resistant subjects tended to maintain (or modestly improve) insulin resistance whilst subjects with better insulin sensitivity tended to worse it. Insulin sensitivity worsens similarly in both T2DM and OB subjects during 60-h fast. The change is probably predictable according to pre-starvation insulin sensitivity.


Cyclooxygenase-2 expression and its association with angiogenesis, Helicobacter pylori, and clinicopathologic characteristics of gastric carcinoma.
Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.


Semi-continuous ultrasonic sounding and changes of ultrasonic signal characteristics as a sensitive tool for the evaluation of ongoing microstructural changes of experimental mortar bars tested for their ASR potential.
Semi-continuous ultrasonic sounding of experimental mortar bars used in the accelerated alkali silica reactivity laboratory test (ASTM C1260) is proposed as a supplementary measurement technique providing data that are highly sensitive to minor changes in the microstructure of hardening/deteriorating concrete mixture. A newly designed, patent pending, heating chamber was constructed allowing ultrasonic sounding of mortar bars, stored in accelerating solution without necessity to remove the test specimens from the bath during the measurement. Subsequent automatic data analysis of recorded ultrasonic signals proved their high correlation to the measured length changes (expansion) and their high sensitivity to microstructural changes. The changes of P-wave velocity, and of the energy, amplitude, and frequency of ultrasonic signal, were in the range of 10-80%, compared to 0.51% change of the length. Results presented in this study thus show that ultrasonic sounding seems to be more sensitive to microstructural changes due to ongoing deterioration of concrete microstructure by alkali-silica reaction than the dimensional changes.


Strategies for retrovirus-based correction of severe, combined immunodeficiency (SCID).
Severe combined immunodeficiencies (SCIDs) appear as optimal disease targets to challenge potential efficacy of gene therapy. Ex vivo, retrovirally mediated gene transfer into hematopoietic progenitor cells has been shown to provide sustained correction of two forms of SCID, that is, SCID-X1 and adenosine deaminase deficiencies. In the former case, however, genotoxicity was observed in a minority of patients as a consequence of retroviral integration into proto-oncogenes loci and transactivation. Design of vectors in which the enhancer element of retroviral LTR has been deleted and an internal promoter added (self-inactivated vectors) could provide both safe and efficient gene transfer as being presently tested.


Characterization and localization of the muscarinic cholinergic receptor in human prostatic tissue.
Radioligand receptor binding and autoradiography were used to characterize and localize the muscarinic cholinergic receptor in human benign prostatic hyperplastic tissue. These methods have not been used previously to investigate the autonomic innervation of the human prostate. The binding of [3H]N-methylscopolamine ([3H]NMS), a muscarinic cholinergic antagonist, to homogenates of human prostate was saturable and of high affinity. The equilibrium dissociation constant, (Kd), for [3H]NMS binding to human prostate homogenates was 0.10 +/- 0.03 nM (mean +/- SEM). The values of the Kd's for [3H]NMS binding to prostates of man (0.10 nM), dog (0.20 nM), pig (0.11 nM), rat (0.07 nM) and rabbit (0.15 nM) were similar, suggesting homogeneity of muscarinic cholinergic receptors in varying species. The mean density, B(max), of muscarinic cholinergic receptors identified in the human prostate was 2.1 fmol./mg. prostate wet weight. The relative density of receptors in the human prostates were similar in the homogenates and slide-mounted tissue sections. The pharmacology of NMS binding sites on slide-mounted tissue sections was evaluated by competitive binding experiments using [3H]NMS and atropine. The IC50 corrected of atropine on slide-mounted tissue sections (0.42 nM) was similar to values obtained in prostate homogenates (1.16 nM). Autoradiography on slide-mounted tissue sections demonstrated that the muscarinic cholinergic receptors were localized to the epithelium of the prostate. The ratio of specific NMS binding in the epithelial and stromal components of the prostate, expressed as autoradiographic grains/unit area and autoradiographic grains/cell, was 71:1 and 33:1 respectively. Because prostatic secretion is dramatically enhanced by muscarinic cholinergic agonists, localization of muscarinic cholinergic receptors to the epithelium is consistent with the neuropharmacology of prostatic secretion. These studies have provided basic insight into the neuropharmacology of the prostate. Future studies will be necessary to characterize and localize other neurotransmitters in the human prostate in order to further enhance our understanding of prostatic function.


Facultative non-mutualistic behaviour by an "Obligate" mutualist: "Cheating" by Yucca moths.
The interaction between yucca moths (Tegeticula spp., Incurvariidae) and yuccas (Yucca spp., Agavaceae) is an obligate pollination/seed predation mutualism in which adult female yucca moths pollinate yuccas, and yucca moth larvae feed on yucca seeds. In this paper we document that individual yucca moths, which are capable of acting as mutualists, facultatively "cheat" by ovipositing in yucca pistils without attempting to transfer pollen. Additionally, a high proportion of flowers are unlikely to receive pollen even when pollination is attempted, because many yucca moths carry little or no pollen. The probability of occurrence of non-mutualistic behaviour is not affected by the amount of pollen a moth carries: moths with full pollen loads are just as likely to act non-mutualistically as moths carrying little or no pollen. We propose four hypotheses that could explain facultative non-mutualistic behaviour in yucca moths.


Femoral Origin Anatomy of the Medial Patellofemoral Complex: Implications for Reconstruction.
To report the shape and orientation of the medial patellofemoral complex (MPFC) footprint on the medial femur and describe the difference between the proximal (medial quadriceps tendon femoral ligament, MQTFL) and distal (medial patellofemoral ligament, MPFL) fibers. In 20 cadaveric knees, the MPFC footprint on the medial femur was exposed. Images of the medial femur were analyzed using ImageJ software. The length and width of the MPFC footprint were described to the nearest 0.1 mm; the angle of its long axis was described relative to the axis of the femoral shaft (0.1°). The footprint's most proximal and distal margins were described in relation to the adductor tubercle and medial epicondyle. The differences between each were compared using paired t tests. 17 knees from 10 cadavers were included in this study. The MPFC footprint had a length of 11.7 ± 1.8 mm and a width of 1.7 ± 0.4 mm. The long axis of the footprint was at an angle 14.6° ± 16.6° anterior to the axis of the femoral shaft. The most proximal (MQTFL) fibers originated 7.4 ± 3.8 mm anterior and 1.8 ± 4.7 mm distal to the adductor tubercle and 4.1 ± 2.9 mm posterior and 8.4 ± 5.6 mm proximal to the medial epicondyle. The most distal (MPFL) fibers originated 4.9 ± 4.2 mm anterior and 12.7 ± 4.3 mm distal to the adductor tubercle, as well as 7.1 ± 2.4 mm posterior and 0.5 ± 5.6 mm distal to the medial epicondyle. The distal margin of the femoral MPFC footprint was 10.9 ± 1.7 mm distal (p < .001) and 2.6 ± 3.2 mm more posterior (p = .005) than the proximal margin. The femoral footprint of the MPFC has a length almost 7 times greater than its width, with the distal margin being 10.9 mm distal and 2.6 mm posterior to the proximal margin. This differential anatomy within the femoral origin suggests that MPFL and MQTFL reconstruction may require separate positions of femoral fixation to recreate the anatomy of these fibers.


Role of substance P (SP) and calcitonin gene-related peptide (CGRP) in gibbon-ape-leukemia virus (GALV) transduction of CD34+ cells.
Optimization of transduction condition is an important goal to improve gene transduction. Therefore, we aimed to assess the effect of SP and/or CGRP as novel growth/transducing factors on the efficacy of CD34(+) transduction. CD34(+) cells were transduced with Gibbon-Ape-Leukemia virus (GALV), containing Neomycin gene. CD34(+) cells were transduced with GALV presence of SP and/or CGRP. Real Time PCR and colony formation assay (CFU-C) was performed. Viral vectors titration on Hela cells indicated transduction efficiency of 1×10(6)CFU/ml. Real Time PCR of Neo and CFU-C showed stimulatory role of SP on gene transfer 5.9% and 14.84% compared to 3.6% and 12.58% in control group, while opposite role observed for CGRP 0.89% and 7.86%. Both SP and CGRP showed no significant effect in these assays. This study showed including of SP in growth factor cocktail is beneficial for CD34(+) transduction, which could be applied to genetic modification procedures.


Studies on the energy-linked Ca2+ accumulation in pig heart mitochondria - role of Mg2'ons.
Comparative intracellular distribution of Ca2+, Mg2+ and adenine nucleotides has been studied in pig heart by differential centrifugation or fractional extraction and has shown that Mg2+ and ATP are associated mainly with soluble fractions whereas Ca2+ and ADP are more tightly bound to subcellular structures. Ca2+ accumulation and Ca2+ stimulated respiration were studied in pig heart mitochondria under different energetic conditions in the absence or presence of phosphate. Ca2+ concentrations of about 1200 nmoles/mg protein inhibit Ca2+ accumulation, site I substrate oxidation and induce an efflux of mitochondrial Mg2+. These deleterious effects of Ca2+ on respiration occur even in the absence of phosphate or oxidizable substrate; they are completely prevented by ruthenium red only, and partially prevented by the addition of M2+ to the medium. The kinetics of Ca2+ uptake become of the sigmoidal type when Mg2+ is present. This cation strongly inhibits the rate of Ca2+ uptake in the presence of added phosphate and decreases the affinity of Ca2+ for its transport system. In the absence of phosphate, Mg2+ has no effect on Ca2+ uptake. The possible physiological implications of these findings are discussed


A culturally competent intervention of education and care for black women with type 2 diabetes.
This article reports on the development and pilot feasibility testing of a culturally competent intervention of education and care for black women with type 2 diabetes mellitus (T2DM). Using a one group, pretest posttest quasi-experimental design, the intervention was tested with a convenience sample of 25 community black women with T2DM. The conceptual basis, process, and content of the intervention as well as the feasibility and acceptability of study materials and methods are described. Significant improvements from baseline to 3 months were observed in measures of glycemic control, weight, body mass index, and diabetes-related emotional distress. The findings suggest that a culturally sensitive intervention of nurse practitioner diabetes care and education is beneficial for black women with T2DM, resulting in program attendance, kept appointments, improved glycemic control and weight, and decreased diabetes-related emotional distress.


The changing nature of the district nurse patient relationship.
In this article Richard Griffith considers three recent developments in policy and law that have changed the nature of the relationship between district nurses and their patients. The traditional, often paternalistic, professional knows best approach must now give way to a patient focused partnership.


Horizontal transfer of a plasmid possessing mcr-1 marked with a single nucleotide mutation between Escherichia coli isolates from community residents.
The widespread dissemination of phenotypic colistin-resistant (COR) bacteria in the community threatens public health. The horizontal gene transfer of the mobile colistin resistance gene via plasmids is thought to be one of the main mechanisms for dissemination. However, genotypic evidence to prove this in community settings is limited. This study used genome analysis to demonstrate the direct horizontal colistin resistance gene transfer via plasmids in isolates from the community. A total of 19 isolates of COR Escherichia coli from stool specimens of 23 residents from seven households in the Vietnamese community were assessed in this study. The whole-genome sequence data of isolates were acquired using a combination of DNBSEQ short-reads and Nanopore long-read sequencing. Analysis of genomic data was performed using online tools such as Geneious. Analysis of the genomic information of COR E. coli isolates revealed that the isolates from two residents of different households had a similar IncP1 plasmid possessing mcr-1.1, marked with a single nucleotide mutation at the same position. The study provided direct evidence to prove that mcr was horizontally transmitted among bacteria in community residents.


The P450 gene CYP749A16 is required for tolerance to the sulfonylurea herbicide trifloxysulfuron sodium in cotton (Gossypium hirsutum L.).
Weed management is critical to global crop production and is complicated by rapidly evolving herbicide resistance in weeds. New sources of herbicide resistance are needed for crop plants so that applied herbicides can be rotated or combined to thwart the evolution of resistant weeds. The diverse family of cytochrome P450 proteins has been suggested to be a source of detoxifying herbicide metabolism in both weed and crop plants, and greater understanding of these genes will offer avenues for crop improvement and novel weed management practices. Here, we report the identification of CYP749A16 (Gh_D10G1401) which is responsible for the natural tolerance exhibited by most cotton, Gossypium hirsutum L., cultivars to the herbicide trifloxysulfuron sodium (TFS, CGA 362622, commercial formulation Envoke). A 1-bp frameshift insertion in the third exon of CYP749A16 results in the loss of tolerance to TFS. The DNA marker designed from this insertion perfectly co-segregated with the phenotype in 2145 F2 progeny of a cross between the sensitive cultivar Paymaster HS26 and tolerant cultivar Stoneville 474, and in 550 recombinant inbred lines of a multi-parent advanced generation inter-cross population. Marker analysis of 382 additional cotton cultivars identified twelve cultivars containing the 1-bp frameshift insertion. The marker genotypes matched perfectly with phenotypes in 188 plants from the selected twelve cultivars. Virus-induced gene silencing of CYP749A16 generated sensitivity in the tolerant cotton cultivar Stoneville 474. CYP749A16 located on chromosome D10 is required for TFS herbicide tolerance in cotton. This finding should add to the repertoire of tools available to farmers and breeders for the advancement of agricultural productivity.


Hierarchical Interconnected NiMoN with Large Specific Surface Area and High Mechanical Strength for Efficient and Stable Alkaline Water/Seawater Hydrogen Evolution.
NiMo-based nanostructures are among the most active hydrogen evolution reaction (HER) catalysts under an alkaline environment due to their strong water dissociation ability. However, these nanostructures are vulnerable to the destructive effects of H2 production, especially at industry-standard current densities. Therefore, developing a strategy to improve their mechanical strength while maintaining or even further increasing the activity of these nanocatalysts is of great interest to both the research and industrial communities. Here, a hierarchical interconnected NiMoN (HW-NiMoN-2h) with a nanorod-nanowire morphology was synthesized based on a rational combination of hydrothermal and water bath processes. HW-NiMoN-2h is found to exhibit excellent HER activity due to the accomodation of abundant active sites on its hierarchical morphology, in which nanowires connect free-standing nanorods, concurrently strengthening its structural stability to withstand H2 production at 1 A cm-2. Seawater is an attractive feedstock for water electrolysis since H2 generation and water desalination can be addressed simultaneously in a single process. The HER performance of HW-NiMoN-2h in alkaline seawater suggests that the presence of Na+ ions interferes with the reation kinetics, thus lowering its activity slightly. However, benefiting from its hierarchical and interconnected characteristics, HW-NiMoN-2h is found to deliver outstanding HER activity of 1 A cm-2 at 130 mV overpotential and to exhibit excellent stability at 1 A cm-2 over 70 h in 1 M KOH seawater.


Is a prosthetic ring required for mitral repair of mitral insufficiency due to posterior leaflet prolapse? Long-term results in 96 patients submitted to repair with no ring.
It is a common statement that every mitral repair should be stabilized by some type of prosthetic mitral ring. In the very specific situation of isolated prolapse of the posterior leaflet (PPL), this statement may be enhanced by the possible anatomically discontinuity of the mitral annulus. This article concerns 96 patients with 'isolated' PPL (IPPL) who were operated upon without ring insertion. Long-term follow-up was obtained in order to ascertain the survival, stability of the repair and the need for reoperation, thus justifying or not the lack of use of a ring. A total of 96 patients, 70 male and 26 female, underwent mitral repair for mitral insufficiency (MI) almost exclusively caused by PPL. Age ranged from 33 to 81 years (mean 60.7+/-11.3). All underwent quadrangular resection of the prolapsed portion and plication of the annulus. In 69 cases local stabilization was achieved by four U stitches, two on each side of the plication, passed through and sutured on some flexible material, 2-3 cm in length. Twenty seven patients had no such local reinforcement. There was one case of early death (1%) caused by refractory hypoxemia in a patient with long lasting pre-operative pulmonary edema. Two patients were lost for follow-up after 2 months. Follow-up was from 0.2 to 14.7 years (mean 4.5), for a total of 422.7 patient-years. There were four late deaths at a mean of 6-year follow-up (0.9-10 years). Actuarial survival was 95.5 and 90.5% at 5 and 8 years, respectively. Event-free for recurrence of significant mitral insufficiency (MI) was 96 and 92% at 5 and 8 years. Event-free of thromboembolic or hemorrhagic events was 84.3 and 72.3% at 5 and 8 years. Event-free from reoperation was 97.8 and 94% at 5 and 8 years. One can conclude that (a) IPPL repair without insertion of a ring is safe and long-lasting (b) the incidence of late death, recurrence of MI, thromboembolic/hemorrhagic events, need for reoperation, is not higher in this subset of patients than in conventional repair (c) such repair might work better and for a longer time, as reaction and sclerosis resulting from ring insertion are avoided (d) minor advantages could be due to an easier surgical procedure, especially through a minimally invasive approach.


Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells.
Although the biological importance of Krüppel-like factor 4 (KLF4) transcription factor in the terminal differentiation of hematopoietic cells to the monocytes has been well established, the underlying mechanisms remain elusive. To clarify the molecular basis of KLF4-mediated monocytic differentiation, we performed detailed genetic studies in acute myeloid leukemia (AML) cells. Here, we report that dihydropyrimidinase like 2 (DPYSL2), also known as CRMP2, is a novel key differentiation mediator downstream of KLF4 in AML cells. Interestingly, we discovered that KLF4-mediated monocytic differentiation is selectively dependent on one specific isoform, DPYSL2A, but not on other DPYSL family genes. Terminal differentiation to the monocytes and proliferation arrest in AML cells induced by genetic or pharmacological upregulation of KLF4 were significantly reversed by short hairpin RNA (shRNA)-mediated selective depletion of DPYSL2A. Chromatin immunoprecipitation assay revealed that KLF4 associates with the proximal gene promoter of DPYSL2A and directly transactivates its expression. Together with the unique expression patterns of KLF4 and DPYSL2 limited to the differentiated monocytes in the hematopoietic system both in human and mouse, the identified KLF4-DPYSL2 axis in leukemia cells may serve as a potential therapeutic target for the development of novel differentiation therapies for patients with AML.


Endogenous protease-dependent replication of human influenza viruses in two MDCK cell lines.
Multi-cycle replication and plaque formation of influenza A and B viruses and cleavage activation of their hemagglutinin (HA) by an endogenous protease(s) were examined in two MDCK cell lines, MDCK(-) and MDCK(+). No exogenous trypsin was required for multi-cycle replication and plaque formation of all the influenza A viruses tested in the MDCK(+) cell, while those of the viruses in the MDCK(-) cell were completely trypsin-dependent. In both cell lines, on the other hand, influenza B viruses grew well in the absence of trypsin. The capability of multiple replication and plaque formation of the influenza viruses correlated with cleavage of the HA precursor (HA0) to HA1 and HA2, indicating that both cell lines express an HA activating endoprotease(s); that of the MDCK(+) cell activates the HA of influenza A and B viruses, and that of the MDCK(-) cell does only the HA of influenza B virus. Furthermore, the protease of the MDCK(+) cell was strongly suggested to be present on the cell surface and a serine protease. The MDCK(+) cell would be useful for isolation of influenza viruses from clinical specimens and for screening of protease inhibitors for anti-influenza virus drugs.


Sub-chronic oral toxicity assessment (90 days) of ethanolic fraction of leaves of Neurocalyx calycinus (R. Br. ex Benn.) Rob. in rodents: A lesser known ethnomedicinal plant from the Cholanaickan tribal community, India.
The objective of the present study was to evaluate the safety of long term consumption of ethanolic fraction of Neurocalyx calycinus leaves (NCEF) in rodents. The NCEF was subjected to detect the presence of various phytoconstituents. In acute oral toxicity study, graded doses of NCEF was administered in mice and were observed up to 14 days. In sub-chronic oral toxicity study, NCEF was administered to Wistar rats at doses of 50, 500 and 1000 mg/kg b.w. per day for 90 days and after that, observed up to 28 days. NCEF showed the presence of alkaloids, steroids, phenolics and glycosides. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the highest dose level (6400 mg/kg b.w.). In sub-chronic oral toxicity study, there were no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical, hepatic oxidative stress marker analysis and urine analysis revealed the non-adverse effects of prolonged oral consumption of NCEF. The histopathologic examination did not show any differences in vital organs. Based on our findings, NCEF, at dosage levels up to 1000 mg/kg b.w., is non-toxic and safe for long term oral consumption.


The perception of sub-clinical personality disorders by employers, employees and co-workers.
This study set out to determine people's perceptions of different dark-side personality types in the workplace. A total of 240 adults with at least one year's work experience rated vignettes describing job candidates with sub-clinical PDs. PDs were grouped into (Hogan and Hogan's 1997) personality clusters 'Moving Away from', 'Moving Against' and 'Moving Toward' others. PDs in the Moving Toward cluster were rated as the most desirable employees. Participants were least willing to work with or for PDs in the Moving Against cluster. Moving Against candidates were perceived as less successful than Moving Towards candidates, suggesting that people believe the costs of working with people with many PDs (e.g. psychopathy and narcissism) outweigh any benefits there may be. Implications and limitations are noted.


Endometrial adenocarcinoma encountered at the time of hysteroscopic endometrial ablation.
To determine the diagnostic accuracy and possible role of treatment of hysteroscopic endometrial resection in women with abnormal uterine bleeding (AUB) diagnosed with endometrial adenocarcinoma. Retrospective analysis (Canadian Task Force classification II-2). University-affiliated center. Thirteen women with AUB and eight with postmenopausal bleeding. Preablation endometrial office biopsy and hysteroscopic evaluation. Preablation endometrial biopsy was inadequate, inconclusive, or difficult to obtain in these women, and endometrial cancer was found at the time of resectoscopic surgery. Total endomyometrial resection including the tubal ostia was completed in eight women (group 1) and partial resection in five (group 2). Endometrial adenocarcinoma was confirmed histologically in all patients. A small focus of cancer was found in only two women in group 1 after total resection; in one the procedure was performed 9 years earlier and in the other it was completed hastily after absorption of 800 ml of 1.5% glycine irrigation solution. In women in group 2 malignancy was highly suspected and total resection was considered unwise. All patients were alive and well 0.5 to 9 years after hysterectomy, with no evidence of recurrent cancer.


Experimental hypertension and catecholamine distribution in the rat brain.
Hypertension was induced in rats (Hebrew University strain) by three different procedures: (1) deoxycorticosterone acetate (DOCA)--salt treatment; (2) unilateral renal artery clip or (3) chronic salt-loading. Noradrenaline (NA) and dopamine (DA) distribution in different brain areas was assayed following induction of hypertension. NA content increased significantly in various areas: the increase of NA in the pons-medulla was common to all procedures inducing hypertension. NA content increased also in the mesencephalon, the hypothalamus and the rest of the forebrain (DOCA--salt hypertension), in the mesencephalon, the hypothalamus and the cortex (in renal clip hypertension). No significant changes in DA content were observed in any region of the brain following induction of hypertension by the three different methods. In two substrains, selected from the Hebrew University strain, for their respective sensitivity (H) or immunity (N) to hypertension induced by DOCA--salt treatment, there were no significant increases in NA or DA in any part of the brain following DOCA--salt treatment. Comparison of NA concentrations in these strains showed that NA was significantly higher in the pons-medulla of the untreated N strain rats than in the medulla of untreated H strain or in untreated rats of the original strain (Hebrew University). A model is presented suggesting that central NA-containing neurons plays a major role in controlling hypertension.


Cost-effectiveness of endoscopic endonasal vs transcranial approaches for olfactory groove meningioma.
Endoscopic endonasal approaches (EEAs) have been adopted as an alternative to standard transcranial approaches for olfactory groove meningiomas (OGMs). However, the relative cost-effectiveness remains controversial. Cost-utility analysis from a societal perspective comparing EEA vs transcranial approaches for OGM was used in this study. Surgical treatment was modeled using decision analysis, and a Markov model was adopted over a 20-year horizon. Parameters were obtained from literature review. Costs were expressed in 2017 Canadian dollars. In the base case, EEA was cost-effective compared with transcranial surgery with an incremental cost-effectiveness ratio of $33 523 ($30 475 USD)/QALY. There was a 55% likelihood that EEA was cost-effective at a willingness-to-pay of $50 000/QALY. EEA remained cost-effective at a cerebrospinal fluid leak rate below 60%, gross total resection rate above 25%, and base cost less than $66 174 ($60 158 USD). EEA may be a cost-effective alternative to transcranial approaches for selected OGM.


Extensive FE-SEM/EDS, HR-TEM/EDS and ToF-SIMS studies of micron- to nano-particles in anthracite fly ash.
The generation of anthropogenic carbonaceous matter and mixed crystalline/amorphous mineral ultrafine/nano-particles in the 1 to 100 nm size range by worldwide coal power plants represents serious environmental problems due to their potential hazards. Coal fly ash (CFA) that resulted from anthracite combustion in a Portuguese thermal power plant was studied in this work. The physico-chemical characterization of ultrafine/nano-particles present in the CFA samples and their interaction with environment are the aim of this study. The methodologies applied for this work were field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray spectroscopy (EDS), high-resolution transmission electron microscopy with energy dispersive X-ray spectroscopy (HR-TEM/EDS) and time of flight secondary ion mass spectrometry (ToF-SIMS). Some hazardous volatile elements, C, N, S and Hg contents were also determined in the studied samples. Generally, the CFA samples comprise carbonaceous, glassy and metallic solid spheres with some containing mixed amorphous/crystalline phases. The EDS analysis coupled with the FE-SEM and HR-TEM observations of the fly ash particles with 100 to 0.1 nm demonstrates that these materials contain a small but significant proportion of encapsulated HVEs. In addition, the presence of abundant multi-walled carbon nanotubes (MWCNTs) and amorphous carbon particles, both containing hazardous volatile elements (HVEs), was also evidenced by the FE-SEM/EDS and HR-TEM/EDS analysis. A wide range of organic and inorganic compounds was determined by chemical maps obtained in ToF-SIMS analysis.


Determination of fluoxetine and norfluoxetine in human plasma by high-pressure liquid chromatography with fluorescence detection.
Fluoxetine is an atypical antidepressant drug, which selectively inhibits the neuronal reuptake of serotonin, and is widely used in the treatment of depressive disorders. The aim of this research is the development of an HPLC method with fluorescence detection for the monitoring of fluoxetine plasma levels. The determination requires no more than 250 microl of plasma, which undergo solid phase extraction (SPE), then are injected in the HPLC. For the analytical separation a reversed phase C8 column (150 x 4.6 mm I.D.) was used, while the mobile phase was a mixture of acetonitrile and water containing perchloric acid and tetramethylammonium perchlorate (flow rate: 1 ml min(-1)). The very low levels of analytes in plasma required the employment of a fluorescence detector (lambda(exc) = 230 nm, lambda(em)=290 nm), which also granted a good selectivity. Fluoxetine is revealed as a single peak at a retention time of 9.7 min, while norfluoxetine, the main metabolite of fluoxetine, is revealed at a retention time of 8.1 min. Linearity was obtained over the concentration range 8-200 ng ml(-1) for both substances. The method seems suitable, in accuracy and precision, for the determination of fluoxetine plasma levels of patients; furthermore, it is rapid and sensitive.


Mechanisms of augmented field potential responses in the rat olfactory bulb.
Olfactory bulb field potential and single unit responses to paired pulse stimulation of the lateral olfactory tract were observed in the rat. In agreement with previous reports, surgical levels of barbiturate anesthesia prolonged the period of diminution of the field potential responses to the test pulse relative to the effect seen under light anesthesia. Very deep barbiturate anesthesia (sufficient to depress the EEG) led to decreased responses to the primary pulse but augmented responses to the test pulse. Urethane and ether anesthesia produced augmented test responses without severely depressing the EEG and without producing a period of diminished test responses. Single unit recordings failed to show external plexiform layer units excited at the time of maximal augmentation of the field potential. Simultaneous single unit and field potential recordings showed that prolonged diminution of the field potential response was associated with prolonged suppression of unit responses to the test pulse, while augmented field potential responses were associated with decreased suppression of unit responses to the test pulse. These observations are most easily explained by the assumption of temporal facilitation in the synaptic output of mitral and tufted cells. This facilitation is masked by feedback inhibition under some conditions, particularly under barbiturate anesthesia.


Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse.
In order to investigate the cytogenetic patterns in relapsed acute myelogenous leukemia (AML), a clinical and cytogenetic follow-up of patients newly diagnosed for the Fourth International Workshop on Chromosomes in Leukemia (4IWCL) was evaluated at the 6IWCL. Information was received on 103 patients in relapse who were then classified into seven groups according to the diagnostic karyotype. These groups were: normal, t(8;21), t(15;17), +8, a single specific abnormality either numerical or structural other than those already listed, a single nonrandom or miscellaneous abnormality again either numerical or structural, and complex abnormalities. The patient's age, diagnostic FAB type, the number of relapses, the total survival time, and the karyotype in relapse were considered in each of these cytogenetic groups. The remission and survival rates were comparable in all groups except the +8 group, where patients relapsed earlier and had a shorter survival time. Multiple relapses occurred most frequently in the t(8;21) group, whereas none of the patients with t(15;17) relapsed more than once, although the total survival time was similar to the two groups. Thirty-nine percent of the patients relapsed with the same karyotype as at diagnosis. A more complex karyotype showing evolution was found in 53%, and 8% showed either a less-complicated karyotype or appeared to have reverted to normal. Numerical abnormalities in relapse frequently involved trisomy of chromosomes 8 and/or 21. There was a nonrandom development of 9q- with relapse in patients with t(8;21). A pericentric inversion of chromosome 4, and abnormality infrequently reported at diagnosis, was found in relapse in association with t(15;17), t(8;21), and +8 karyotypes. Changes considered to be typically secondary in nature involving 5q, 7q, and 12p were seen in only seven cases. Twenty-one patients who had an apparently normal karyotype at diagnosis remained normal in relapse, indicating that absence of clonal chromosome abnormality is a real observation in AML rather than a failure of detection.


Neonatal hepatitis with obstructive jaundice in an SZ heterozygous alpha 1-antitrypsin-deficient boy and destructive lung disease in his SZ mother. A review of the literature.
SZ-Alpha 1-antitrypsin deficiency, leading to severe transient neonatal cholestasis with mild hepatitis is rare. In our patient, intrahepatic bile duct hypoplasia was suspected. Since cholecystography and hepatic scintigraphy failed to reveal intrahepatic bile ducts, a diagnostic surgical liver biopsy was performed. Typical intrahepatocytic PAS-positive granules and a low serum alpha 1-antitrypsin concentration allowed a correct diagnosis of the SZ phenotype. The administration of an elementary diet quickly improved the clinical condition of our patient. Follow-up studies of this case and others will allow a better establishment of prognostic criteria and help in genetic counselling.


On simplicity and complexity in the brave new world of large-scale neuroscience.
Technological advances have dramatically expanded our ability to probe multi-neuronal dynamics and connectivity in the brain. However, our ability to extract a simple conceptual understanding from complex data is increasingly hampered by the lack of theoretically principled data analytic procedures, as well as theoretical frameworks for how circuit connectivity and dynamics can conspire to generate emergent behavioral and cognitive functions. We review and outline potential avenues for progress, including new theories of high dimensional data analysis, the need to analyze complex artificial networks, and methods for analyzing entire spaces of circuit models, rather than one model at a time. Such interplay between experiments, data analysis and theory will be indispensable in catalyzing conceptual advances in the age of large-scale neuroscience.


Influenza virus hemagglutinin stimulates the protein kinase C activity of human polymorphonuclear leucocytes.
Human polymorphonuclear leukocytes (PMNL) incubated with influenza virus, A/USSR/90/77 (H1N1) or its hemagglutinin produced a significant increase in their PKC activity when compared with untreated PMNL. The activated kinase translocated from cytosol to cellular membrane. The calcium-dependent enzyme activity was inhibited by a specific inhibitor suggesting that alpha and/or beta isoforms of PKC were involved.


Tranexamic acid and reduction of blood transfusion in lower limb trauma surgery: a randomized controlled study.
Post-operative blood loss in lower limb trauma fractures increases morbidity. Very few studies have evaluated the efficacy of Tranexamic Acid (TXA) in reducing blood loss and the consequent requirement of blood transfusion in the Indian population. This was a randomized controlled study of 100 patients with lower limb trauma. Fifty patients were given 1 g of TXA before surgery, and 50 patients were not given TXA. The requirement of blood transfusion, fall in Hb, the number of days admitted in the hospital after surgery were recorded, and evidence of deep vein thrombosis (DVT) was monitored. Baseline demographics between the groups were comparable. The required blood transfusion and fall in Hb in patients receiving intra-operative TXA were significantly lower than those not given TXA (p < 0.0001). There was no significant difference in the length of hospital stay between the two groups (p = 0.6). There was no significant difference in the incidence of DVT in both groups. TXA helps reduce the morbidity of trauma patients by reducing the requirement for blood transfusion. Its use is safe in lower limb trauma surgery and lowers the cost of therapy to the patient.


Replication of DNA Containing Mirror-Image Thymidine in E. coli Cells.
DNA damage can occur naturally or through environmental factors, leading to mutations in DNA replication and genomic instability in cells. Normally, natural d-nucleotides were selected by DNA polymerases. The template l-thymidine (l-T) has been shown to be bypassed by several types of DNA polymerases. However, DNA replication fidelity of nucleotide incorporation opposite l-thymidine in vivo remains unknown. Here, we constructed plasmids containing a restriction enzyme (PstI) recognition site in which the l-T lesion was site-specifically located within the PstI recognition sequence (CTGCAG). Further, we assessed the efficiencies of nucleotide incorporation opposite the l-T site and l-T lesion bypass replication in vitro and in vivo. We found that recombinants containing the l-T lesion site inhibited DNA replication. In addition, A was incorporated opposite the l-T lesion by routine PCR assay, whereas preference for nucleotide incorporation opposite the l-T site was A (13%), T (22%), C (46%), and G (19%), and no nucleotide insertion and deletions were detected in E. coli cells. In particular, a novel restriction enzyme-mediated method for detection of the mutagenic properties of DNA lesion was established, which allows us to readily detect restriction-digestion of the l-T-bearing plasmids. The study provided significant insight into how mirror-image nucleosides perturb the fidelity of DNA replication in vivo and whether they elicit mutagenic effects, which may help to understand both how DNA damage interferes with the flow of genetic information during DNA replication and development of diseases caused by gene mutation.


Surgeon's clinical valuation and accuracy of ultrasound in the diagnosis of acute appendicitis: A comparison with intraoperative evaluation. Five years experience.
Acute appendicitis is the most common cause of acute abdomen in adolescents, with an overall incidence of 7%. Two such tools are used to diagnose acute appendicitis: ultrasound and Computer Tomography imaging. End point of this study was to verify the accuracy of ultrasound imaging in the diagnosis of acute appendicitis with respect to intraoperative observations and the respective clinical and laboratory findings in young and in the elderly. We considered all the appendectomies for acute appendicitis performed between 1 January 2010 and 1 January 2015. We evaluated clinical symptoms, laboratory findings, ultrasound findings, intraoperative signs, and anatomical and pathological findings. In the study we compared the ultrasound and intraoperative findings and then compared these with the respective clinical and laboratory data. In a comparison of diagnostic accuracy, the difference between clinical and ultrasound examinations was not significant. The differences between the diagnostic accuracy of clinical and laboratory findings and between ultrasound and laboratory investigations were statistically significant. We defined white blood cells and C protein levels as non-diagnostic of the type of acute inflammation but rather as indicators of the severity of the inflammatory process. We also agree with the authors who proposed the incorporation of ultrasonography into routine practice in the diagnosis of acute appendicitis, but only and exclusively to support other diagnostic procedures and preferably within emergency departments. A thorough clinical examination of patients with suspected acute appendicitis is still the best diagnostic procedure available to us.


Normal human bone marrow cultures in vitro: cellular composition and maturation of the granulocytic colonies.
The analysis of single haemopoietic colonies grown in methylcellulose and in agar was performed at intervals by a cytocentrifugation method. Correlation was established between morphology of the whole colonies and their cellular content. Three main cell lines predominated: neutrophils, macrophages, eosinophils; a few colonies contained a pure population of basophil-like granulocytes. Development was followed from myeloblasts to polymorphs, both being present in most of the colonies. Cumulated results showed that (1) the proliferating compartment remained quite large till day 14, with 58% of cells in S phase, and rapidly decreased after day 16, and that (2) the polymorphs rapidly disappeared from the culture medium. Differentiation proceeded at different rates from one colony to the other, thus suggesting heterogeneity between colony forming cells (CFC). Neutrophil colonies appeared and lysed more rapidly than did eosinophil colonies. Macrophages arose from large immature cells with many promyelocyte features; such cells were present in mixed colonies, containing both neutrophils and macrophages. It is very likely that granulopoiesis results from the development of distinct committed CFC. This work was carried out using normal human bone marrow and may be a useful tool for studying pathological material in the future.


Two new bioactive oleanane triterpene glycosides from Terminalia arjuna.
Two new oleanane-type triterpene glycosides designated as Termiarjunoside I and Termiarjunoside II were isolated from stem bark of Terminalia arjuna (Combretaceae) and characterized as olean-1alpha,3beta,9alpha,22alpha-tetraol-12-en-28-oic acid-3beta-D-glucopyranoside (1) and olean-3alpha,5alpha,25-triol-12-en-23,28-dioic acid-3alpha-D-glucopyranoside (2) based on chemical and spectral data evidences. Both compounds 1 and 2 potently suppressed the release of nitric oxide and superoxide from macrophages and also inhibited aggregation of platelets.


Accessible Personal Ultrasound Training Simulator.
Ultrasound simulators are increasingly used for teaching and training purposes, but development has been limited by the need for dedicated and often expensive hardware. The objective of this study was to develop and deploy an accessible and very low-cost personal ultrasound training simulator and obtain trainee feedback. An ultrasound simulator software program that uses a smartphone as a "mock-probe" and a laptop computer as a "mock ultrasound machine" was created. Spatial positional data is acquired from the smartphone's inbuilt accelerometer and gyroscope and transmitted to the laptop computer for processing and display of simulated ultrasound images in real time by the software program. After obtaining institutional review board approval and informed consent, all first-year radiology residents at our institution were provided access to the simulator program during the "bootcamp" introductory conference series, and a written survey was conducted to obtain feedback. A personal ultrasound training simulator software program (Persimus) that reliably performs motion sensing along 2 axes and displays simulated ultrasound images was developed. Nine of 12 (75%) first-year residents at our institution participated in the written survey. Residents' scored values were 8.44 ± 1.33 and 8.44 ± 1.33 (mean + standard deviation) for perceived utility and overall impression and satisfaction, respectively, of the simulator on the Likert scale (1-10, with 10 being the highest score). Personal ultrasound simulators are technically feasible. These are well received by first-year radiology residents and perceived as useful to their education.


GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.
Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-β (TGFβ1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFβ1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.


Photograph-based ergonomic evaluations using the Rapid Office Strain Assessment (ROSA).
The Rapid Office Strain Assessment (ROSA) was developed to assess musculoskeletal disorder (MSD) risk factors for computer workstations. This study examined the validity and reliability of remotely conducted, photo-based assessments using ROSA. Twenty-three office workstations were assessed on-site by an ergonomist, and 5 photos were obtained. Photo-based assessments were conducted by three ergonomists. The sensitivity and specificity of the photo-based assessors' ability to correctly classify workstations was 79% and 55%, respectively. The moderate specificity associated with false positive errors committed by the assessors could lead to unnecessary costs to the employer. Error between on-site and photo-based final scores was a considerable ∼2 points on the 10-point ROSA scale (RMSE = 2.3), with a moderate relationship (ρ = 0.33). Interrater reliability ranged from fairly good to excellent (ICC = 0.667-0.856) and was comparable to previous results. Sources of error include the parallax effect, poor estimations of small joint (e.g. hand/wrist) angles, and boundary errors in postural binning. While this method demonstrated potential validity, further improvements should be made with respect to photo-collection and other protocols for remotely-based ROSA assessments.


Multicenter outcomes of robotic reconstruction during the early learning curve for minimally-invasive pancreaticoduodenectomy.
Perceived excess morbidity during the early learning curve of minimally-invasive pancreaticoduodenectomy (MIPD) has limited widespread adoption. It was hypothesized that robot-assisted reconstruction (RA) after MIPD allows anastomotic outcomes equivalent to open pancreaticoduodenectomy (PD). Intent to treat analysis of centrally audited data accrued during early adoption of RA-MIPD at five centers. CUSUM analysis of operating times at each center identified 92 RA-MIPD during the early learning curve. Mean age was 65 ± 12 years with body mass index 25.8 ± 5.0. Surgical indications included malignant (60%) and premalignant (38%) lesions. Median operating time was 504 min (interquartile range 133) with 242 ml median estimated blood loss (IQR 398) and twelve (13%) conversions to open PD. Major complication rate (Clavien-Dindo III/IV) was 24% with 2 (2.2%) deaths and ten (10.9%) reoperations. Nine (9.9%) clinically significant pancreatic fistulae were observed (4 grade B; 5 grade C). Margin negative resection rate for malignancy was 90% (75% for PDA) with mean harvest of 16 ± 8 lymph nodes. These multicenter data during the early learning curve for RA-MIPD do not demonstrate excess anastomotic morbidity compared to open. Further studies are required to determine whether surgeon proficiency and evolving technique improve anastomotic outcomes compared to open.


Evaluation of adiponectin gene expression in the abdominal adipose tissue of broiler chickens: feed restriction, dietary energy, and protein influences adiponectin messenger ribonucleic acid expression.
We studied the effects of feed restriction and different energy and protein contents of the diet on BW, abdominal adipose tissue percentage, and adiponectin gene expression in abdominal adipose tissue in broiler chickens. Two experiments were conducted to determine whether feed restriction and dietary energy and protein levels alter adiponectin mRNA abundance in broiler chicks. Body weight and abdominal adipose tissue percentage were recorded and abdominal adipose tissue samples were collected at sampling days. Adiponectin mRNA expression in abdominal adipose tissue was quantitated using real-time quantitative PCR. We found that BW, abdominal adipose tissue percentage, and adiponectin gene expression were decreased in restricted chicks compared with those fed ad libitum at 32 d of age, but feed restriction had no effect on abdominal adipose tissue percentage and adiponectin gene expression at 49 d of age (experiment 1). Body weight was increased significantly in broilers fed on low-energy diets compared with those fed high-energy diets in experiment 1. Also, increasing levels of dietary protein increased BW in broiler chicks in experiment 2. A positive response in adiponectin gene expression and abdominal adipose tissue percentage was achieved by decreasing protein level in the diet of chicks at 32 d of age, but dietary protein had no effect on adiponectin gene expression at 49 d of age (experiment 1). Also, in experiment 2, abdominal adipose tissue percentage increased as dietary protein with fixed level of energy decreased in broiler chickens at 42 and 56 d of age. In experiment 1, increasing dietary energy levels increased adiponectin gene expression and abdominal adipose tissue percentage in chicks at 32 d of age. Also, we showed that dietary energy had an effect on abdominal adipose tissue percentage at 49 d of age. In experiment 2, a high-energy diet with a fixed level of protein increased abdominal adipose tissue percentage in chicks at 42 and 56 d of age. Dietary energy and protein levels had no significant effect on adiponectin gene expression in abdominal adipose tissue in broilers.


Family practitioners' diagnostic decision-making processes regarding patients with respiratory tract infections: an observational study.
The influence of patient characteristics on family practitioners' (FPs') diagnostic decision making has mainly been investigated using indirect methods such as vignettes or questionnaires. Direct observation-borrowed from social and cultural anthropology-may be an alternative method for describing FPs' real-life behavior and may help in gaining insight into how FPs diagnose respiratory tract infections, which are frequent in primary care. To clarify FPs' diagnostic processes when treating patients suffering from symptoms of respiratory tract infection. This direct observation study was performed in 30 family practices using a checklist for patient complaints, history taking, physical examination, and diagnoses. The influence of patients' symptoms and complaints on the FPs' physical examination and diagnosis was calculated by logistic regression analyses. Dummy variables based on combinations of symptoms and complaints were constructed and tested against saturated (full) and backward regression models. In total, 273 patients (median age 37 years, 51% women) were included. The median number of symptoms described was 4 per patient, and most information was provided at the patients' own initiative. Multiple logistic regression analysis showed a strong association between patients' complaints and the physical examination. Frequent diagnoses were upper respiratory tract infection (URTI)/common cold (43%), bronchitis (26%), sinusitis (12%), and tonsillitis (11%). There were no significant statistical differences between "simple heuristic'' models and saturated regression models in the diagnoses of bronchitis, sinusitis, and tonsillitis, indicating that simple heuristics are probably used by the FPs, whereas "URTI/common cold'' was better explained by the full model. FPs tended to make their diagnosis based on a few patient symptoms and a limited physical examination. Simple heuristic models were almost as powerful in explaining most diagnoses as saturated models. Direct observation allowed for the study of decision making under real conditions, yielding both quantitative data and "qualitative'' information about the FPs' performance. It is important for investigators to be aware of the specific disadvantages of the method (e.g., a possible observer effect).


Cultural meanings of tuberculosis in Aceh Province, Sumatra.
This paper shows how disease transmission and particularly what biomedicine calls tuberculosis are interpreted in the non-Western context of Aceh Province, Sumatra, Indonesia. It tries also to focus on factors influencing perceptions and health-seeking behaviors. Results show that what biomedicine calls TB is represented by a semantic network of illnesses. Parts of this network are clearly identified as transmissible while others are related to specific phenomena affecting the individual, such as terbuk (poisoning) or trouk (fatigue produced by hard work), and are not considered contagious. Forms of transmission are interpreted mostly through empirical and analogic categories. TB is attributed to four different aspects: (a) biomedical categories such as germ theory; (b) socio-economic conditions; (c) transgression of social rules; and (d) poisoning and the influences of supernatural powers. Health-seeking behaviors are related to the perceived causes of the disease, economic factors, and the accessibility of health services.


Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.
Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, the actin-related protein 2/3 complex (Arp2/3), we report here a molecular mechanism that unexpectedly reveals the inter-relationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons and striatal hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this antipsychotic-responsive locomotion can be mimicked in wild-type mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.


Synthesis of superhydrophobic surfaces with Wenzel and Cassie-Baxter state: experimental evidence and theoretical insight.
We demonstrate surfactant- and template-free synthesis of superhydrophobic thin films by controlling surface morphology. The surface morphology evolution process was determined from time-dependent studies. The relationships between the water contact angle, sliding angle, water droplet size, and surface microstructures were investigated. It is found that structural parameters play an important role in determining the adhesion of a droplet on superhydrophobic surfaces and the liquid-solid adhesion can be effectively manipulated through tailoring the morphology or the size of the microstructures on the surface. We provide a theoretical explanation for the Cassie-Baxter state (water rolls) and the Wenzel state (sticky surface, water adheres) with droplet size on different microstructure surfaces. The new theoretical insight provided in this study matches well with experimental results.


Observations on clinical efficacy of albendazole emulsion in 264 cases of hepatic cystic echinococcosis.
Two regimens of albendazole emulsion (AbzE), a novel formulation, were used in the treatment of 264 cases of hepatic cystic echinococcosis. AbzE 10 mg/kg per day (calculated by albendazole base) was administered orally to 71 cases for 6 months to over 1 year. Imaging evaluation at the end of courses showed overall efficacy in 97.2%, (cure rate 60.6%, and inefficacy rate 2.8%); The follow-up study on 62 cases 3-4 years post therapeutic courses showed overall efficacy in 92.0% (cure rate 83.9%, ineffective rate 1.5% and recurrence rate 6.5%); Abz 12.5 mg/kg per day was administered orally to 193 cases for 3 months to over 1 year, resulting in an overall efficacy of 97.9%, (cure rate 75.1% and inefficacy rate 2.1%). The follow-up study in 139 cases 2-4 years post treatment demonstrated efficacy in 89.2%, (cure rate 84.2% and recurrence rate 10.8%); Mild reversible adverse reactions were observed in 14.4% of the patients. Retreatment of recurrent hydatidosis patients with AbzE provided promising results. AbzE is considered to be superior to the albendazole tablet or capsule formulations currently used in treatment of liver cystic hydatid disease.


Epidemiology and Prevention of Prostate Cancer.
Worldwide, prostate cancer (PCa) represents the second most common solid tumor in men. To assess the geographical distribution of PCa, epidemiological differences, and the most relevant risk factors for the disease. Estimated incidence, mortality, and prevalence of PCa for the year 2020 in 185 countries were derived from the IARC GLOBOCAN database. A review of English-language articles published between 2010 and 2020 was conducted using MEDLINE, EMBASE, and Scopus to identify risk factors for PCa. In the year 2020, there were over 1414000 estimated new cases of PCa worldwide, with an age-standardized rate (ASR) incidence of 31 per 100000 (lifetime cumulative risk: 3.9%). Northern Europe has the highest all-age incidence ASR (83), while the lowest ASR was in South-Central Asia (6.3). In the year 2020, there were over 375000 estimated deaths worldwide, and the overall mortality ASR was 7.7 per 100000, with the highest ASR in the Caribbean (28) and the lowest in South-Central Asia (3.1). Family history, hereditary syndromes, and race are the strongest risk factors for PCa. Metabolic syndrome was associated with the risk of developing PCa, high-grade disease, and adverse pathology. Diabetes and exposure to ultraviolet rays were found to be inversely associated to PCa incidence. Cigarette smoking and obesity may increase PCa-specific mortality, while regular physical activity may reduce disease progression. Although 5-alpha reductase inhibitors are known to be associated with a reduced incidence of PCa, available studies failed to show an effect on overall mortality. Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality. Prostate cancer (PCa) rates vary profoundly worldwide, with incidence and mortality rates being highest in Northern Europe and Caribbean, respectively. South-Central Asia has the lowest epidemiological burden. Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease itself, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.


Anti-inflammatory mechanism of electroacupuncture involves the modulation of multiple systems, levels and targets and is not limited to "driving the vagus-adrenal axis".
In October 2021, an international collaborative study on the use of electroacupuncture (EA) to treat inflammation was published in the journal Nature by Dr. Qiufu Ma's team. Based on the results of EA on inflammation in the mouse model of lipopolysaccharide inflammatory storm, the study showed that the distal effect of acupuncture can be achieved by "driving the vagus-adrenal axis (through the adrenal medulla, by releasing catecholamines)." PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia but not the abdominal fascia, are crucial for driving this axis. The study suggests the existence of specificity distribution of acupoints, that different EA stimulation intensities or different needle penetration depths have different therapeutic effects, that photosensitive stimulation may be a substitute for needle acupuncture, and that massage, stretching and body movements may also activate PROKR2Cre-markable dorsal root ganglion sensory neurons and elicit anti-inflammatory effects. However, results of some other studies are contrary to the conclusions of Ma's team. For examples: low-intensity EA at GB30 point significantly reduced the inflammation in the rat model of persistent inflammation, which is more relevant to the real daily acupuncture practice, and this effect was partly related to the adrenal cortex and associated with the stimulation of corticosterone and adrenocorticotropic hormone; manual acupuncture (similar to the low-intensity EA) at KI3, Zhichuan point (an extra point), etc. was effective in a severe COVID-19 patient with sepsis; stimulating ST25 with low-intensity EA or manual acupuncture was effective against gastrointestinal inflammations; the above mentioned points are not in an area enriched with PROKR2Cre-marked sensory nerve endings. Evidence shows that the mechanism of EA against inflammation includes modulating multi-systems, multi-levels and multi-targets, which does not limit to "driving the vagus-adrenal axis." Please cite this article as: Fan AY. Anti-inflammatory mechanism of electroacupuncture involves the modulation of multiple systems, levels and targets and is not limited to "driving the vagus-adrenal axis." J Integr Med. 2023; 21(4):320-323.


Yeast cell debris and protein partitioning in the poly(ethylene glycol)-poly(vinyl alcohol) biphasic system.
Yeast cells, cell debris and protein partitioning have been investigated in the poly(ethylene glycol) (PEG) 8000/poly(vinyl alcohol) (PVA) 10,000 system. Cells and cell debris partition into the lower (PVA) phase over the pH range 4.8-7.5, and with up to 0.37 M KCl at pH 5.9. Protein partitioning is more pH-dependent in the PEG/PVA system than in the PEG/dextran system, and a significant fraction of the total protein is found at the interface at lower pH values. Significant, rapid purification of overproduced pyruvate kinase in a PEG/PVA system containing Blue Sepharose CL-6B particles is demonstrated.


Formulation and efficacy of ECO/pRHO-ABCA4-SV40 nanoparticles for nonviral gene therapy of Stargardt disease in a mouse model.
It is still a challenge to develop gene replacement therapy for retinal disorders caused by mutations in large genes, such as Stargardt disease (STGD). STGD is caused by mutations in ABCA4 gene. Previously, we have developed an effective non-viral gene therapy using self-assembled nanoparticles of a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid containing rhodopsin promoter (pRHO-ABCA4). In this study, we modified the ABCA4 plasmid with simian virus 40 enhancer (SV40, pRHO-ABCA4-SV40) for enhanced gene expression. We also prepared and assessed the formulations of ECO/pDNA nanoparticles using sucrose or sorbitol as a stablilizer to develop consistent and stable formulations. Results demonstrated that ECO formed stable nanoparticles with pRHO-ABCA4-SV40 in the presence of sucrose, but not with sorbitol. The transfection efficiency in vitro increased significantly after introduction of SV40 enhancer for plasmid pCMV-ABCA4-SV40 with a CMV promoter. Sucrose didn't affect the transfection efficiency, while sorbitol resulted in a fluctuation of the in vitro transfection efficiency. Subretinal gene therapy in Abca4-/- mice using ECO/pRHO-ABCA4 and ECO/pRHO-ABCA4-SV40 nanoparticles induced 36% and 29% reduction in A2E accumulation respectively. Therefore, the ECO/pABCA4 based nanoparticles are promising for non-viral gene therapy for Stargardt disease and can be expended for applications in a variety of visual dystrophies with mutated large genes.


Clinical characteristics of patients with bipolar disorder and premorbid traumatic brain injury: a cross-sectional study.
About one in ten diagnosed with bipolar disorder (BD) has experienced a premorbid traumatic brain injury (TBI), while not fulfilling the criteria of bipolar and related disorder due to another medical condition (BD due to TBI). We investigated whether these patients have similar clinical characteristics as previously described in BD due to TBI (i.e. more aggression and irritability and an increased hypomania/mania:depression ratio) and other distinct clinical characteristics. Five hundred five patients diagnosed with BD type I, type II, or not otherwise specified, or cyclothymia were interviewed about family, medical, and psychiatric history, and assessed with the Young Mania Rating Scale (YMRS) and the Inventory of Depressive Symptoms Clinician Rated 30 (IDS-C30). Principal component analyses of YMRS and IDS-C30 were conducted. Bivariate analyses and logistic regression analyses were used to compare clinical characteristics between patients with (n = 37) and without (n = 468) premorbid TBI. Premorbid TBI was associated with a higher YMRS disruptive component score (OR 1.7, 95% CI 1.1-2.4, p = 0.0077) and more comorbid migraine (OR 4.6, 95% CI 1.9-11, p = 0.00090) independently of several possible confounders. Items on disruptive/aggressive behaviour and irritability had the highest loadings on the YMRS disruptive component. Premorbid TBI was not associated with an increased hypomania/mania:depression ratio. Disruptive symptoms and comorbid migraine characterize BD with premorbid TBI. Further studies should examine whether the partial phenomenological overlap with BD due to TBI could be explained by a continuum of pathophysiological effects of TBI across the diagnostic dichotomy. Trial registration ClinicalTrials.gov: NCT00201526. Registered September 2005 (retrospectively registered).