Chronic myeloid leukemia within a year of kidney transplant with elevated alkaline phosphatase correlated with imatinib therapy.
The incidence of certain malignancies is significantly higher after organ transplant. However, there are rare reports of chronic myeloid leukemia in the posttransplant setting. The average reported interval between a transplant and the diagnosis of chronic myeloid leukemia is 44 months (range, 10- 96 mo). We report 2 patients with chronic myeloid leukemia within 1 year of a kidney transplant, which is significantly shorter than those previously reported. Both patients were receiving mycophenolate mofetil and tacrolimus for immunosuppression. They were treated with imatinib for chronic myeloid leukemia, and both patients demonstrated an isolated elevation of serum alkaline phosphatase that was directly correlated with imatinib. Despite a potential interaction between the 2 drugs, blood levels of tacrolimus and imatinib were not elevated during the course of treatment. Isolated elevation of alkaline phosphatase in this particular setting has not been reported previously.


[Phase separation in dipalmitoyl phosphatidylcholine bilayers induced by ionophores and binary electrolytes].
Thermotropic behavior of unsonicated aqueous dispersion of dipalmitoyl phosphatidylcholine (DPPC) has been studied by scanning microcalorimetry and fluorescent probe method. Phase separation in the lipid bilayers was observed for systems containing ionophores (valinomycin, dinactin) and 1 : 1 electrolytes (NaCl, KCl, RbCl, CsCl). The ratio of lipid phases coexisting in the systems appeared to be dependent on the concentration of the electrolytes. Changes in the thermotropic properties of the lipid phase induced by valinomycin were observed when K+ and Rb+ ions-forming complexes with the ionophore were present in the systems. The latter phenomenon was not found for the systems containing dinactin possessing a lower ability for complex formation with the cations.


Adults with Poor Reading Skills, Older Adults, and College Students: the Meanings They Understand During Reading Using a Diffusion Model Analysis.
When a word is read in a text, the aspects of its meanings that are encoded should be those relevant to the text and not those that are irrelevant. We tested whether older adults, college students, and adults with poor literacy skills accomplish contextually relevant encoding. Participants read short stories, which were followed by true/false test sentences. Among these were sentences that matched the relevant meaning of a word in a story and sentences that matched a different meaning. We measured the speed and accuracy of responses to the test sentences and used a decision model to separate the information that a reader encodes from the reader's speed/accuracy tradeoff settings. We found that all three groups encoded meanings as contextually relevant. The findings illustrate how a decision-making model combined with tests of particular comprehension processes can lead to further understanding of reading skills.


Semiclosure wound therapy plus negative pressure wound therapy for an older patient with grade 4 diabetic foot with concomitant vascular occlusion: A case report.
Grade 4 diabetic foot (DF) is a severe infection that causes bone destruction, osteomyelitis, and osteoarticular damage, which, in turn, can lead to serious dry or wet gangrene, or amputation. DF is extremely difficult to treat. A 71-year-old female patient with long-term diabetes complicated with uremia, who undergoes regular hemodialysis 2 to 3 times per week, was admitted with grade 4 DF with Pseudomonas aeruginosa infection, and concomitant vascular occlusion of the lower extremities. The patient had a concurrent nutrition and electrolyte disorder. The patient was diagnosed with type 2 diabetes, grade 4 DF, postamputation of the 2nd toe, vascular occlusion of the lower extremities, atherosclerosis, uremia, hypoproteinemia, and electrolyte disturbances. Treatment with antibiotics and comprehensive measures aimed at improving nutrition and microcirculation, controlling blood glucose, as well as balancing electrolytes were performed to ameliorate the general conditions. Nibbled debridement was used to remove devitalized tissues each time to maintain as much vital cells as possible. Open therapy was used for necrotic tissues, and dressings therapy was used simultaneously for the infected lesion. This combined treatment, involving open therapy with dressing, is referred to as "semiclosure wound therapy." Negative pressure wound therapy (NPWT) was used after a fistula formed. During the treatment procedure, the gangrene 3rd toe was spontaneously shed; the necrotic 1st toe was removed by surgery. The wound gradually healed after 3 months of open therapy combined with dressing. High location amputation was avoided. Semiclosure, which constitutes open therapy combined with the use of dressings, plus NPWT can preserve vital skin cells in the wound and control the aggravation of the infection. It is an effective and novel measure that prevents DF amputation in old patient and promotes wound union.


Recurrent carcinoma of the cervix exclusively in the paraaortic nodes following radiation therapy.
This is a retrospective analysis of 1211 patients with invasive carcinoma of the uterine cervix treated with irradiation alone at the Mallinckrodt Institute of Radiology from 1959 through 1986, of whom 20 developed their first recurrence exclusively in the paraaortic lymph nodes. The incidence of clinically/radiographically detected paraaortic node recurrence by stage at original diagnosis was 1.8% in Stage IB (7/384 patients), 2.3% in Stage IIA (3/128 patients), 1.4% in Stage IIB (5/353 patients), 1.4% in Stage III (4/292 patients), and 5% in Stage IVA (1/20 patients). Forty-five percent of para-aortic node recurrences were observed within the first 12 months after initial diagnosis and 75% within the first 2 years. Sciatic pain, leg edema, and hydronephrosis were identified in most patients. Patients were treated with external irradiation only to the paraaortic lymph nodes. All patients died within 2 years of paraaortic recurrence. Median survival for the entire group was 8.7 months. Median survival was 7.5 months for those failing within 24 months of the original diagnosis compared with 17.8 months for those failing after 24 months from original diagnosis (p = 0.09). Patients who received > 4500 cGy had a median survival of 14.2 months compared with 7.1 months for those treated with < 4500 cGy to the paraaortic recurrence (p = 0.004). Forty-five percent of patients developed mild to moderate nausea during paraaortic irradiation; however, no severe complications from the radiation therapy were noted. Sciatic pain, leg edema, and hydronephrosis commonly occur in patients with paraaortic node recurrence. The presence of these symptoms in a patient with a history of carcinoma of the cervix should initiate an aggressive evaluation.


Editorial: Longitudinal Associations Between Sleep and ADHD Symptoms: ADHD Is a 24-Hour Disorder.
There is a robust literature of predominantly cross-sectional studies demonstrating an association between attention-deficit/hyperactivity disorder (ADHD) and sleep quality in childhood and adolescence, measured by subjective as well as objective measures, dimensional and categorical variables, and controlling for a wide range of confounders such as other disorders.1 Moreover, ADHD symptoms and sleep problems are independently associated with adverse functional outcome and quality of life.2 As a result, these are viewed as common and mutually exacerbating conditions, likely mediated by common neuropathways.3-5.


In vivo CRISPR editing with no detectable genome-wide off-target mutations.
CRISPR-Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1-6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe 'verification of in vivo off-targets' (VIVO), a highly sensitive strategy that can robustly identify the genome-wide off-target effects of CRISPR-Cas nucleases in vivo. We use VIVO and a guide RNA deliberately designed to be promiscuous to show that CRISPR-Cas nucleases can induce substantial off-target mutations in mouse livers in vivo. More importantly, we also use VIVO to show that appropriately designed guide RNAs can direct efficient in vivo editing in mouse livers with no detectable off-target mutations. VIVO provides a general strategy for defining and quantifying the off-target effects of gene-editing nucleases in whole organisms, thereby providing a blueprint to foster the development of therapeutic strategies that use in vivo gene editing.


Regulation of osteosarcoma cell invasion through osteopontin modification by miR-4262.
Osteopontin (OPN) is a phosphorylated glycoprotein that plays a critical role in the invasion of osteosarcoma (OS), the most common primary malignant bone tumor. Since microRNAs (miRNAs) have been well documented as key players in the tumorigenesis, cancer cell growth, and metastases, determination of the involved miRNAs that may regulate OPN-mediated OS cell invasion appears to be one important question in the current understanding and therapeutic strategies for OS. Here, we found that the levels of miR-4262 were significantly decreased and the levels of OPN were significantly increased in OS specimens, compared to the paired adjacent non-tumor tissue. Moreover, miR-4262 and OPN inversely correlated in OS specimens. The 5-year survival of the patients with lower miR-4262 levels in the resected OS was worse than that of patients with high miR-4262 levels. Bioinformatics analyses showed that miR-4262 targeted the 3'-UTR of OPN mRNA to inhibit its translation, which was proved by luciferase reporter assay. Furthermore, miR-4262 overexpression inhibited OPN-mediated cell invasion, while miR-4262 depletion increased OPN-mediated cell invasion in OS cells, in both a transwell cell invasion assay and a scratch wound healing assay. Together, our data suggest that suppression of miR-4262 in OS cells may promote OPN-mediated cancer invasion, highlighting miR-4262 as an intriguing therapeutic target to prevent OS metastases.


A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling.
Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, Amhr2-Cre-YFP/GFP mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM+YFP+ MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM+YFP+ MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM+GFP+ cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM+GFP+ MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.


A Qualitative Study of Decision-making (DM) in Surgery and Cancer Care: an Indian Perspective.
Cancer psychology is a vitally important part of cancer management. Qualitative research is a gateway to exploring this. Weighing the treatment options in terms of quality of life and survival is important. Given the globalization of healthcare seen in the last decade, the exploration of the decision-making process in a developing nation was deemed highly appropriate. The aim is to explore the thoughts of surgical colleagues and care providing clinicians about patient decision-making in cancer care in developing countries, with special reference to India. The secondary objective was to identify factors that may have a role to play in decision-making in India. A prospective qualitative study. The exercise was carried out at Kiran Mazumdhar Shah Cancer Center. The hospital is a tertiary referral center for cancer services in the city of Bangalore, India. A qualitative study by methodology, a focus group discussion was undertaken with the members of the head and neck tumor board. The results showed, in India, decision-making is predominantly led by the clinicians and the patient's family members. A number of factors play an important role in the decision-making process. These include as follows: health outcome measures (quality of life, health-related quality of life), clinician factors (knowledge, skill, expertise, judgment), patient factors (socio-economic, education, cultural), nursing factors, translational research, and resource infrastructure. Important themes and outcomes emerged from the qualitative study. As modern healthcare moves towards a patient-centered care approach, evidence-based patient choice and patient decision-making clearly have a greater role to play, and the cultural and practical issues demonstrated in this article must be considered. The online version contains supplementary material available at 10.1007/s13193-022-01521-x.


Highlights of the European Society of Musculoskeletal Radiology (ESSR) annual meeting 2008.
Following the 2008 European Society of Musculoskeletal Radiology meeting in Galway, the presented papers and posters were reviewed again. This article highlights those papers that are felt to be of wider interest to the readers of the journal. Work reporting on new innovations and imaging and therapeutic techniques is emphasised in the hope that it will be of use to researchers and those in clinical practice.


Correction: A vessel subtype beneficial for osteogenesis enhanced by strontium-doped sodium titanate nanorods by modulating macrophage polarization.
Correction for 'A vessel subtype beneficial for osteogenesis enhanced by strontium-doped sodium titanate nanorods by modulating macrophage polarization' by Shuo Guo et al., J. Mater. Chem. B, 2020, 8, 6048-6058. DOI: .


Studies on macromomycin, an antitumor protein.
Macromomycin is a protein isolated from the culture filtrate of Streptomyces macromomyceticus. It is an antibiotic and also cytotoxic to a broad spectrum of carcinoma cells, the ID50 for P388 leukemia cells being 1 X 10(-9) M. Macromomycin binds rapidly and tightly to the P388 cell membrane and the eventual death of the cell cannot be reversed by either washing the toxin away or treating the cell with trypsin. The cytotoxicity does not appear to be specific for any phase of the P388 cell cycle. Macromomycin is a single polypeptide, pI 5.38, devoid of methionine and arginine residues and contains 4 cysteine residues joined by two intramolecular disulfide bonds. The cytotoxicity results in inhibition of DNA, RNA, and protein synthesis in P388, the latter inhibition occurring a few hours after the inhibition of nucleic acid synthesis. The antibiotic and antitumor activities are destroyed rapidly by ultraviolet light, which gives a product that differs little in amino acid composition, molecular weight, and antigenic property, but can be separated from the native macromomycin by ion exchange chromatography. It is proposed that macromomycin has an ultraviolet-sensitive prosthetic group upon which much of the biological activity is based.


Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2.
Mesenchymal stem cells (MSCs) show significant therapeutic effects in type 1 diabetes mellitus (T1DM) as regulating the inflammatory processes. However, little is known about the detailed process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild-type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice. We found that Wip1 knockout (Wip1-/-) MSCs had lower therapeutic effects in T1DM mice, and displayed weaker immunosuppressive capability. In vivo distribution analysis results indicated thatWip1-/-MSCs could home to the damaged pancreas and increase the expression of tumor necrosis factor-α (TNF-α), interleukin-17a (IL-17a), interferon-α(IFN-α), IFN-β, and IFN-γ, while decrease the expression of IL-4 and IL-10. Moreover, we confirmedWip1-/-MSCs exhibited weaker immunosuppressive capacity, as evidenced by enhanced expression of bone marrow stromal cell antigen 2(BST2) and IFN-α. In conclusion, these results revealed Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. Our study uncovered that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in MSCs immunoregulation properties.


Role of gastric mucosal blood flow in gastroprotective effect of novel xanthine derivative.
The effect of 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on 40% ethanol-induced gastric lesions and gastric mucosal blood flow was investigated in rats. Gastric mucosal blood flow was measured by the hydrogen gas clearance technique and the test compounds and vehicle were administered intraduodenally. A90 6119 dose-dependently increased gastric mucosal blood flow and decreased gross and histologic gastric mucosal injury induced by 40% ethanol. Both the gastric mucosal blood flow and protective effects of A90 6119 were completely attenuated by pretreatment with indomethacin. The findings demonstrate that A90 6119 protects against ethanol-induced gastric injury, and this effect involves stimulation of endogenous prostaglandin synthesis and an increase in gastric mucosal blood flow.


Quantification of cartilage biomechanical and biochemical properties via T1rho magnetic resonance imaging.
The aim of this study is to develop T1rho as an MR marker of the compositional and functional condition of cartilage. Specifically, we investigate the correlation of changes in cartilage biomechanical and biochemical properties with T1rho relaxation rate in a cytokine-induced model of degeneration. Bovine cartilage explants were cultured with 30 ng/mL of interleukin-1beta to mimic the cartilage degradation of early osteoarthritis. The average rate of T1rho relaxation was calculated from T(1rho) maps acquired on a 4.7 T research scanner. Stress-relaxation biomechanical tests were conducted with a confined compression apparatus to measure uniaxial aggregate modulus (HA) and hydraulic permeability (k0) using linear biphasic theory. Proteoglycan, collagen, and water content were measured via biochemical assays. Average T(1rho) relaxation rate was strongly correlated with proteoglycan content (R2 = 0.926), HA (R2 = 0.828), and log10 k0 (R2 = 0.862). Results of this study demonstrate that T1rho MRI can detect changes in proteoglycan content and biomechanical properties of cartilage in a physiologically relevant model of cartilage degeneration. The T1rho technique can potentially be used to noninvasively and quantitatively assess the biochemical and biomechanical characteristics of articular cartilage in humans during the progression of osteoarthritis.


Impact of meteorological parameters and air pollutants on airborne concentration of Betula pollen and Bet v 1 allergen.
The intensity of birch pollen season is expressed by seasonal pollen integral (SPIn, the sum of the mean daily pollen concentration during the birch pollination period) and the amount of Bet v 1 allergen released per birch pollen grain expressed by pollen allergen potency (PAP). Betula pollen and Bet v 1 allergen were simultaneously measured in the air of Bratislava from 2019 to 2022 by using two Burkard traps (Hirst-type and cyclone) in order to evaluate the causes of the seasonal variation in the SPIn and PAP levels. The highest SPIn (19,975 pollen/m3) was observed in 2022 and the lowest one (1484 pollen/m3) in 2021. The average daily PAP level (4.0 pg Bet v 1/pollen) was highest in 2019 and lowest (2.5 pg Bet v 1/pollen) in 2020. We found that seasonal variation in SPIn was associated mainly with the changes in environmental conditions during the pre-season period, whereas the year-to-year variation in PAP levels was attributed to environmental conditions during both pre- and in-season periods. Our results indicate that rainy weather in June 2020 and cold overcast weather in January‒February 2021 resulted in low SPIn in 2021. On the other hand, dry weather in June 2021 and warm weather in January‒February 2022 resulted in high SPIn in 2022. The low average daily PAP level in 2020 was associated with (1) low levels of gaseous air pollutants in March, when the ripening of pollen takes place; (2) an earlier start of the birch main pollen season (MPS); and (3) dry weather during the MPS. On the other hand, high PAP level in 2019 was associated with higher levels of air pollutants in March and during the MPS.


Improving breast cancer diagnosis with computer-aided diagnosis.
The purpose of this study was to test whether computer-aided diagnosis (CAD) can improve radiologists' performance in breast cancer diagnosis. The computer classification scheme used in this study estimates the likelihood of malignancy for clustered microcalcifications based on eight computer-extracted features obtained from standard-view mammograms. One hundred four histologically verified cases of microcalcifications (46 malignant, 58 benign) in a near-consecutive biopsy series were used in this study. Observer performance was measured on 10 radiologists who read the original standard- and magnification-view mammograms. The computer aid provided a percentage estimate of the likelihood of malignancy. Comparison was made between computer-aided performance and unaided (routine clinical) performance by using receiver operating characteristic (ROC) analysis and by comparing biopsy recommendations. The average ROC curve area (Az) increased from 0.61 without aid to 0.75 with the computer aid (P < .0001). On average, with the computer aid, each observer recommended 6.4 additional biopsies for cases with malignant lesions (P = .0006) and 6.0 fewer biopsies for cases with benign lesions (P = .003). This improvement corresponded to increases in sensitivity (from 73.5% to 87.4%), specificity (from 31.6% to 41.9%), and hypothetical positive biopsy yield (from 46% to 55%). CAD can be used to improve radiologists' performance in breast cancer diagnosis.


Illuminating the path to DNA repair.
Diverse DNA repair pathways correct ranging types of damage and play central roles in genome editing. In this issue of Cell, two publications leverage a new high-throughput screen that links pathway genes with the outcomes of repair, yielding mechanistic insights into the repair process as well as means to shape editing outcomes.


Strength of the relationships between three self-reported dietary intake instruments and serum carotenoids: the Observing Energy and Protein Nutrition (OPEN) Study.
To assess the strength of the relationships between serum carotenoids and three self-reported dietary intake instruments often used to characterize carotenoid intake in studies of diet and disease. Participants completed a Diet History Questionnaire (DHQ), two 24 h dietary recalls (24HR), a fruit and vegetable screener and a fasting blood draw. We derived dietary intake estimates of α-carotene, β-carotene, cryptoxanthin, lutein, zeaxanthin and lycopene from each diet instrument and calculated sex-specific multivariate correlations between dietary intake estimates and their corresponding serum values. Montgomery County, Maryland, USA. Four hundred and seventy women and men aged 40-69 years in the National Cancer Institute's Observing Protein and Energy Nutrition (OPEN) Study. Serum carotenoids correlated more strongly with the DHQ (r = 0·34-0·54 for women; r = 0·38-0·56 for men) than with the average of two recalls (r = 0·26-0·47 for women; r = 0·26-0·40 for men) with the exception of zeaxanthin, for which the correlations using recalls were higher. With adjustment for within-person variation, correlations between serum carotenoids and recalls were greatly improved (r = 0·38-0·83 for women; r = 0·42-0·74 for men). In most cases, correlations between serum carotenoids and the fruit and vegetable screener resembled serum-DHQ correlations. Evidence from the study provides support for the use of the DHQ, a fruit and vegetable screener and deattenuated recalls for estimating carotenoid status in studies without serum measures, and draws attention to the importance of adjusting for intra-individual variability when using recalls to estimate carotenoid values.


Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice.
Caesalpinia pyramidalis Tul. (Fabaceae) is an endemic tree of the Northeast region of Brazil, mainly in the Caatinga region. More commonly, inner bark or flowers are traditionally used to treat many painful and inflammatory processes. A common use of this plant is made by macerating a handful of its stem bark in a liter of wine or sugarcane brandy. It is drunk against stomachache, dysenteries, and diarrheas. The ethanol extract of Caesalpinia pyramidalis inner bark was used in mice via oral route, at the doses of 10, 30, and 100mg/kg, in behavioral models of nociception and investigates some of the mechanisms underlying this effect. The ethanol extract (30 and 100mg/kg, P<0.001), given orally, produced dose dependent inhibition of acetic acid-induced visceral pain. The ethanol extract also caused significant and dose-dependent inhibition of capsaicin-(100mg/kg, P<0.001) and glutamate-(10, 30, and 100mg/kg, P<0.01) induced pain. The antinociception caused by the ethanol extract (30mg/kg) in the abdominal constriction test was significantly attenuated (P<0.001) by intraperitoneal treatment of mice with l-arginine (600mg/kg). Collectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis produced dose-related antinociception in several models of pain through mechanisms that involved both glutamatergic system and/or the l-arginine-nitric oxide pathway, supporting the folkloric usage of the plant to treat various painful processes.


Clinical study of hemospermia.
Sixty-five cases of hemospermia seen over a ten-year period were reviewed. No specific etiology was disclosed, although renal tuberculosis was seen in 11 per cent of cases, indicating that hemospermia is a self-limiting and benign condition which does not require full urologic investigation.


Renal artery spasm: a cause of acute renal failure following abdominal surgery for neuroblastoma.
Interruption of arterial blood supply to the kidney results in acute renal failure (ARF). We describe a case of ARF caused by renal artery spasm following resection of a large abdominal neuroblastoma, combined with paraaortic lymph node dissection and ipsilateral nephrectomy. The blood flow was reestablished by administration of local anesthetics (lidocaine) into the obliterated renal artery through the angiographic catheter. An urgent angiography was of value for the early diagnosis and treatment of this lesion.


Competence of alpha spectrometry analysis algorithms used to resolve the 241Am and 243Am alpha peak overlap.
Five alpha spectrometry analysis algorithms were evaluated for their ability to resolve the 241Am and 243Am peak overlap present under typical low-level counting conditions. The major factors affecting the performance of the algorithms were identified using design-of-experiment combined with statistical analysis of the results. The study showed that the accuracy of the 241Am/243Am ratios calculated by the algorithms depends greatly on the degree of peak deformation and tailing. Despite the improved data quality obtained using an algorithm that may include peak addition and tail estimation, the accurate determination of 241Am by alpha spectrometry relies primarily on reduction of peak overlap rather than on algorithm selection.


[An analysis of the prevalence of clinical refraction (based on data from the reciprocal dispensary care of students at the I. M. Sechenov Moscow Medical Academy)].
Results of mutual check-ups of 5-year students of therapeutic and medical prophylactic faculties of I. M. Sechenov Moscow Medical Academy in 1991-1994 are analyzed. A total of 584 case histories of students are reviewed. The data demonstrated correlation of many signs in the sample and statistical data of ophthalmological publications on refraction. Conclusions about errors in prescription and use of eyeglasses are made. Violation of visual loading regimen by these students are detected.


Design and in vitro assessment of L-lactic acid-based copolymers as prodrug and carrier for intravitreal sustained L-lactate release to reverse retinal arteriolar occlusions.
Ophthalmic conditions in which the retinal vasculature is obstructed generally lead to vision loss. Administration of the vasodilator L-lactate might offer a treatment strategy by restoring the blood flow, but unfortunately its effect after single intravitreal injection is short-lived. This study describes a concept in which the sustained release of L-lactic acid from a biodegradable copolymer system is investigated. The 50:50 (n/n) copolymer system, composed of L-lactic acid and L,D-2-hydroxyoctanoic acid, is a viscous injectable that will form an intravitreal drug depot. Hydrolysis of the copolymer will automatically lead to the release of L-lactic acid, which will convert to L-lactate at physiological pH, thereby providing a carrier and pro-drug in one. In vitro and ex vivo release studies demonstrate an L-lactic acid release over several weeks. Biocompatibility of the co-polymer and its degradation products is shown on a human retinal pigment epithelial cell line and on ex vivo retinal tissues. A low molecular weight copolymer (1200 g/mol) with low polydispersity has promising properties with a constant release profile, good biocompatibility and injectability.


Impact of complications after surgery for colorectal liver metastasis on patient survival.
In some patients with colorectal liver metastases it is not clear whether liver resection or isolated liver perfusion is the best treatment option. For instance, the risk of complications after surgery may be so substantial and affect subsequent survival. Aim of the present study is to compare complication occurrence and its effect on survival after liver resection and perfusion. Patient records of all 225 patients with colorectal liver metastases treated with liver resection (n = 121) or liver perfusion (n = 104) in the period 1997-2006 were reviewed for complications during the initial hospitalisation until 30 d after discharge, and to assess patient survival until the last hospital visit. Median duration of follow-up was 38 mo for overall survival and 22 mo for survival after surgery. Complications occurred less often in patients undergoing resection than perfusion (29.8% versus 49.0%, X(2) = 8.77, P < 0.01). Postoperative mortality rates were similar in both groups (4.1% and 4.8%, respectively). As expected, long term survival after liver surgery was better in the resection group: at 3 y, 60% of patients survived in the resection group, compared with 22% after liver perfusion (log rank X(2) = 35.29 P < 0.001). However, liver resection patients with postoperative complications, had similar survival as perfusion patients without complications (log rank X(2) = 2.45, p = 0.12). This remained after adjustment for differences between the patient groups at time of surgery. Liver resection has superior long-term survival, but survival is significantly reduced by the occurrence of post-surgical complications. When complications occur after liver resection, survival is comparable to patients who underwent uncomplicated liver perfusion.


Psychotropic drug tenoten activates mitogen-activated MAP/ERK kinase regulatory cascade controlling the neuroprotective effects.
For evaluation of the molecular mechanisms underlying the effects of tenoten, a preparation based on ultralow-dose antibodies to S100 proteins and intended for the therapy of anxious and depressive disorders, we studied its influence on mitogen-activated ERK kinase cascade in Helix lucorum subpharyngeal ganglion complex. Western blot analysis showed that incubation of the ganglion preparation with tenoten resulted in significant activation of mitogen-activated ERK kinases, which was reduced by PD98059 (blocker of upstream protein kinase). This attests to a specific effect of the drug on mitogen-activated ERK kinase cascade. It is hypothesized that the therapeutic efficiency of tenoten is realed to activation of mitogen-activated ERK kinase cascade.


Interpersonal and temporal variability of urinary cotinine in elderly subjects.
Although a single measurement of urinary cotinine is often used for biological monitoring, the validity of this measurement for estimating long-term exposure has not been well evaluated. The purpose of this study was to determine the efficacy of using a single measurement per person to estimate long-term smoking exposure in an elderly population. Analysis was conducted using a cohort of elderly subjects for whom multiple urinary cotinine measurements had been collected over eight weeks. The mixed-effects model of urinary cotinine indicated that interpersonal variability was greater than temporal variability. The efficacy of using single measurements to track the mean long-term exposure of a population is supported by the relatively consistent population averages. The classification of high and low exposure groups using a single measurement or using eight measurements produced similar group distributions. When using cut-off levels of 20 and 100 μg cotinine/g creatinine, 9.3% and 5.6% of individual exposures were misclassified, respectively, when using a single measurement. Urinary cotinine can be a useful biomarker for characterizing exposure to tobacco smoke. Although the incidence of misclassification decreased with an increase in the number of measurements, a single measurement of the urinary cotinine level may accurately represent long-term exposure to tobacco smoke.


Social learning theory and cognitive behavioral models of body dysmorphic disorder.
Contemporary cognitive behavioral models of body dysmorphic disorder are reviewed, whereby the first by Neziroglu and colleagues emphasizes conditioning processes and relational frame theory and the latter by Veale emphasizes information processing. A brief review of the existing cognitive behavioral therapy research follows the presentation of the models. The majority of publications on BDD continue to deal with phenomenology and epidemiology, and much more research on cognitive behavioral treatment is needed. Treatment research should be geared towards testing elements of the models explicated in this article, and randomized controlled trials are greatly needed.


Quality of life burden on United States infants and caregivers due to lower respiratory tract infection and adjusting for selective testing: Pilot prospective observational study.
Policymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV-LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing. The study enrolled infants <1 year with a clinically diagnosed LRTI encounter between January and May 2021. Using an established 0-100 scale, the 36 infants' and caregivers' QoL at enrollment and quality-adjusted life year losses per 1000 LRTI episodes (quality-adjusted life years [QALYs]/1000) were validated and analyzed. Regression analyses examined predictors of RSV-testing and RSV-positivity, creating modeled positives. Mean QoL at enrollment in outpatient (n = 11) LRTI-tested infants (66.4) was lower than that in not-tested LRTI infants (79.6, p = 0.096). For outpatient LRTI infants (n = 23), median QALYs/1000 losses were 9.8 and 0.25 for their caregivers. RSV-positive outpatient LRTI infants (n = 6) had significantly milder QALYs/1000 losses (7.0) than other LRTI-tested infants (n = 5)(21.8, p = 0.030). Visits earlier in the year were more likely to be RSV-positive than later visits (p = 0.023). Modeled RSV-positivity (51.9%) was lower than the observed rate (55.0%). Infants' and caregivers' QALYs/1000 loss were positively correlated (rho = 0.34, p = 0.046), indicating that infants perceived as sicker imposed greater burdens on caregivers. The overall median QALYs/1000 losses for LRTI (9.0) and RSV-LRTI (5.6) in US infants are substantial, with additional losses for their caregivers (0.25 and 0.20, respectively). These losses extend equally to outpatient episodes. This study is the first reporting QALY losses for infants with LRTI born at term or presenting in nonhospitalized settings, and their caregivers.


Metabolic and cognitive changes in hereditary ataxia.
Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were studied with [18F]-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance imaging (MRI), cognitive testing and scored neurological examination, and compared with normal controls. The neurological examination, MRI and cognitive tests showed no significant differences between at risk and normal control subjects. Mild cognitive deficits were seen in affected subjects; the degree of cognitive change appeared to relate to the severity of the illness. MRI demonstrated cerebellar and brainstem atrophy in all affected subjects. PET studies showed higher global metabolic rates (mean [SD]) in at risk subjects (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g). Normalized (region/global average) regional metabolic rates were reduced in cerebellar hemispheres and vermis, and in frontal and prefrontal areas of affected subjects in comparison to at risk and normal control subjects. These findings indicate that functional changes in some forms of autosomal dominant hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to involve other parts of the neuraxis.


Exploring the cause of oseltamivir resistance against mutant H274Y neuraminidase by molecular simulation approach.
Oseltamivir (Tamiflu) is the preferred anti-viral drug employed to fight the flu virus in infected individuals. The principal target for this drug is a virus surface glycoprotein, neuraminidase (NA), which facilitates the release of nascent virus and thus spreads infections. Until recently, only a low prevalence of neuraminidase inhibitors (NAIs) resistance (<1%) had been detected in circulating viruses. However, there have been reports of significant numbers of A (H1N1) influenza strains with a H274Y neuraminidase mutation that was highly resistant to the NAI, oseltamivir. In this study, we highlight the effect of point mutation-induced oseltamivir resistance in H1N1 subtype neuraminidases by molecular docking and molecular dynamics simulation approach. Our results suggested that wild-type NA could be more indispensable for the oseltamivir binding, as characterized by minimum number of H-bonds, high flexibility and largest binding affinity than mutant-type NA. This study throws light on the possible effects of drug-resistant mutations on the large functionally important collective motions in biological systems.


On investigating the statistical properties of the populous path algorithm by computer simulation. Counterconclusions to those of Tateno and Nei.
Goodman et al.'s (1974) populous path algorithm for estimating hidden mutational change in protein evolution is designed to be used as an adjunct to the maximum parsimony method. When the algorithm is so used, the augmented maximum parsimony distances, far from being overestimates, are underestimates of the actual number of nucleotide substitutions which occur in Tateno and Nei's (1978) computer simulation by the Poisson process model, even when the simulation is carried out at two and a half times the sequence density. Although underestimates, our evidence shows that they are nevertheless more accurate than estimates obtained by a Poisson correction. In the maximum parsimony reconstruction, there is a bias towards overrepresenting the number of shared nucleotide identities between adjacent ancestral and descendant nodal sequences with the bias being stronger in those portions of the evolutionary tree sparser in sequence data. Because of this particular property of maximum parsimony reconstructed sequences, the conclusions of Tateno and Nei concerning the statistical properties of the populous path algorithm are invalid. We conclude that estimates of protein evolutionary rates by the maximum parsimony--populous path approach will become more accurate rather than less as larger numbers of closely related species are included in the analysis.


[Cut a long story too short: Challenges in clinical research].
Clinical research reflects a mandatory prerequisite to translate basic research into clinical practice. While a lack of available qualified doctors to fill positions in hospitals as well as in the ambulant sector has prompted political decisions to counteract, Germany has witnessed an insidious deterioration of clinical research over time and compared to other industrialized countries. Measures to prevent an increasing loss of academic profile have to tackle all aspects from undergraduate to postgraduate training to attract highly skilled doctors in sustainable structures to reflourish academic medicine. Cornerstones to achieve these goals involve establishing of structured graduate programs, acknowledgment of time spend in clinical research in residency programs, extra occupational opportunities to achieve dual qualification (e. g. Master programs in clinical research) as well as independent positions with inherent carrier perspectives in academic medicine for doctors interested in clinical and translational research.


[Angular and sliding stable internal fixation of proximal humerus fractures using the "Varion" intramedullary nail].
Intramedullary angular and sliding stable interlocking nails are attracting increasing attention in the treatment of fractures of the proximal humerus. This prospective study evaluates the clinical and radiological outcome of the "Varion" nail osteosynthesis system. Additionally we analysed the impact of the postoperative head-shaft angle on the functional outcome. We examined 61 patients who were treated with a Varion nail and were re-evaluated after an average follow-up period of 7.1 months. We assessed the pre-trauma DASH score and the Constant score of the non-injured side. We also measured the postoperative radiographic head-shaft angle. At the follow-up exam we determined the DASH and Constant scores of the treated extremity and made control radiographs. We were able to re-evaluate 54 patients. The DASH score at follow-up averaged 19.3 and the mean postoperative Constant score reached 67.4 points and thus 81.1 % of the score of the non-injured side. The average pain level was 1.3 on the VAS. A high patient satisfaction was obtained. There was a significant correlation between the complexity of the fracture and the clinical outcome. The best functional result was seen when the postoperative head-shaft angle was between 140 and 151°. There were 7 cases of postoperative complications, in 5 of these cases minor revision surgeries were carried out. The "Varion nail" provides safe and effective treatment of even complicated proximal humerus fractures with good clinical and functional results. The optimum angle between head and shaft axis lies between 141 and 150°.


Sonographic biometry in obstructive uropathy of children: preoperative diagnosis and postoperative monitoring.
Renal sonography was performed in 92 children with obstructive uropathy or vesicoureteral reflux preoperatively and at follow-up. Renal volume and the anteroposterior diameter of the renal pelvis proved to be the most reliable morphometric criteria for objective sonographic staging and follow-up of urinary tract obstruction. If transient obstruction occurred after uncomplicated antireflux ureterovesico-plasties (n = 41), it lasted at most 4 weeks. Kidneys with transient postoperative ureterovesical junction obstruction (n = 21) reverted to normal sonographic pattern within 4 weeks following ureteral reimplantation. In cases of ureteropelvic junction obstruction (n = 30), it took up to 6 months for the majority of kidneys to present almost normal sonographic findings. Sonographic biometry and the knowledge about the uncomplicated postoperative course render postsurgical monitoring easier and more reliable.


Atrial coronary hyperemia and ischemia in response to variations in atrial pressure in dogs.
We altered the mechanical activity of the atrial myocardium in open-chest dogs and measured changes in coronary blood flow distribution, using the radioactive microsphere technique. When left and right atrial pressures were decreased to 2 mm Hg by hypovolemia, atrial coronary blood flow fell to values nearly 50% below baseline. Acute left atrial hypertension was induced by creating mitral valvular incompetence. Progressive increases in left atrial pressure from 8 to 12 to 20 mm Hg caused increases in left atrial coronary blood flow from 47 to 54 to 75 ml/100 gm X min (mean values). Severe left atrial hypertension (32 mm Hg) caused a fall in left atrial blood flow to 30 ml/100 gm X min. The P wave in lead II of the ECG widened by a mean value of 18 msec, suggesting ischemic impairment of left atrial depolarization.


Tris(1H-benzimidazol-2-ylmeth-yl)amine methanol tris-olvate.
The structure of the tertiary amine tris-(1H-benzimidazol-2-ylmeth-yl)amine (C24H21N7, abbreviated ntb) has been previously reported twice as solvates, namely the monohydrate and the aceto-nitrile-methanol-water (1/0.5/1.5) solvate, both with the tripodal conformation formed via multiple hydrogen bonds. Now, we report the tri-methanol adduct, ntb·3CH3OH, where the amine has the stair conformation featuring one benzimidazole group oriented in the opposite direction from the other two. The asymmetric unit contains one-half amine, completed through the mirror plane m in space group Pmn21 to form the ntb mol-ecule, with the H atom for each imidazole moiety equally disordered between both N sites available in the imidazole ring. The asymmetric unit also contains one and a half methanol mol-ecules, one being placed in general position with the hy-droxy H atom disordered over two sites with occupancy ratio 1:1, while the other lies on the m mirror plane, and has thus its hy-droxy H atom disordered by symmetry. As in the previously reported solvates, all imine and amine groups of the ntb mol-ecules and the methanol mol-ecules are involved in N-H⋯O and O-H⋯N hydrogen bonds. In the title compound, however, the involved H atom is systematically a disordered H atom provided by an imidazole group or a methanol mol-ecule.


Differential behavioral effects of the neuroactive steroid allopregnanolone on neonatal rats prenatally exposed to alcohol.
The effects of prenatal alcohol exposure on the behavioral response to the neuroactive steroid allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) were investigated in neonatal rats. Two behaviors were assessed: retention of an odor conditioning task and production of ultrasonic vocalizations after brief maternal separation. Subjects from one of the three prenatal conditions (lab chow, alcohol, or pair-fed) received either no injection or an ICV injection of vehicle or one of three doses (1.25-5.0 micrograms) of allopregnanolone either 20 min prior to or immediately after training in an appetitive odor association paradigm. Retention was assessed 1 h later in a two-choice odor preference chamber. Posttraining injections of allopregnanolone caused a dose-dependent impairment in retention in the odor task, but there was no differential sensitivity to allopregnanolone in the alcohol-exposed offspring. All pretraining injections, including the vehicle, resulted in impairments in retention on the task, suggesting an impairment due to stress but not due to allopregnanolone. Allopregnanolone also reduced ultrasonic vocalizations after brief maternal separation in all subjects in a second experiment, but alcohol-exposed offspring displayed a dose-dependent shift to the right in their anxiolytic response to this neurosteroid. This decreased sensitivity suggests that prenatal alcohol exposure may cause a decrease in the density or affinity of the GABA receptors involved in stress response, but not cognitive processes, at this age.


Neuralgic amyotrophy is not the most common neurologic disorder of the shoulder: a 78-month prospective study of 60 neurologic shoulder patients in a specialist shoulder clinic.
Neuralgic amyotrophy (NA) was first described in 1948. Traditional literature describes a painful attack with sudden onset, followed by paresis, with varied outcomes. Recent studies have suggested NA is currently underdiagnosed. However, a large number of studies detailing NA originate from a small group of sources. Our study compared the onset, diagnosis, investigation, and treatment of all neurologic shoulder conditions to provide comparable data for these studies. Data were collected from 60 patients (81.6% male; median age, 41.5 years) during a 78-month period. Patients with a diagnosis of a neurologic disorder of the shoulder with confirmatory electromyogram (EMG) studies were included. NA was diagnosed in 18 patients before the EMG investigation. Of the clinically diagnosed NA patients, only 5 (27.8%) had EMG findings supportive of NA. A further 5 patients with a clinical diagnosis other than NA were diagnosed with NA after EMG findings. Overall, 10 patients (16.6%) in our study were diagnosed with NA after EMG studies. Only 4 (40.0%) reported a sudden onset attack associated with NA. Supraspinatus and infraspinatus were involved in 9 patients (90.0%), suggesting a predictable distribution of muscle involvement. These results suggest that NA is overdiagnosed and does not warrant the increased attention suggested by recent articles. The current study also highlights a necessity to perform EMG investigations in all cases of suspected NA because the accuracy of the clinical assessment is poor.


Increasing vaccine coverage through new delivery systems: a Sudan approach.
Public education, community mobilization, and health education raise the awareness of mothers and families and provide them with the network to see that their children are immunized. In Sudan a birth registration and follow-up system was developed to ensure the full immunization of all newborn children. Three different systems are under investigation in health centers in the Khartoum region to increase the number of children one year of age who are fully immunized. A simple continuous system for health education and the availability of health facilities appear to be important elements in increasing vaccination coverage.


Structure-function relationships in serine protease-bovine pancreatic trypsin inhibitor interaction.
We report our progress in understanding the structure-function relationships for the interaction between BPTI and serine proteases. We focused on extensive mutagenesis of four crucial positions from the protease binding loop of BPTI. Selected variants were characterized by determination of association constants, stability parameters and structures of protease-inhibitor complexes.


Correction: Genome Wide Association Study Identifies New Loci Associated with Undesired Coat Color Phenotypes in Saanen Goats.
[This corrects the article DOI: 10.1371/journal.pone.0152426.].


Temperature dependence of binding of a fluorescent hypoxia probe.
The rate of binding of a fluorescent probe for hypoxia, AF-2, is dependent upon cell temperature as well as oxygenation. Aerobic cells bind AF-2 about 5 times less rapidly at 37 degrees C than at 45 degrees C. Below 42 degrees C, the rate of AF-2 binding by aerobic cells increases by a factor of about two for each 10 degrees C, but above 42 degrees C, the rate increases 10-fold for each additional 10 degrees C. However, for cells incubated under nitrogen, these biphasic kinetics were not observed, and the rate of metabolism and binding increased only two-fold per 10 degrees C from 28 degrees to 45 degrees C. These differences in binding kinetics cannot be explained by a decrease in the rate of auto-oxidation of the nitro anion radical, but might involve differences in the available reducing equivalents in cells heated under air or nitrogen. The possibility of using fluorescent probes to measure temperatures of individual tumor cells during hyperthermic treatment is discussed.


Mice lacking the melanin-concentrating hormone receptor-1 exhibit an atypical psychomotor susceptibility to cocaine and no conditioned cocaine response.
The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem functioning [Smith DG, Tzavara ET, Shaw J, Luecke S, Wade M, Davis R, et al. Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor deficient mice. J Neurosci 2005;25:914-22]. On a first free-drug session, MCHR1-deficient mice exhibited significantly higher levels of locomotor activity elicited by the novelty of the test chambers than their wild-type counterparts. On the following day session, a first injection of 6 or 12 mg/kg cocaine induced comparable dose-related psychomotor activations in both genotypes, without significant difference in the relative increase in locomotion. Over the following eight once-daily test sessions, the slight psychomotor increase induced by 6 mg/kg was equivalent in both genotypes and constant over the sessions. At 12 mg/kg, cocaine induced a clear-cut incremental responsiveness to cocaine in both genotypes on the three first sessions; on the following sessions, only the wild-types displayed an incremental responsiveness until the last session, a sensitized effect that was confirmed for the wild-types but not for the knockouts on a subsequent sensitization test (cocaine challenge). Finally, the knockouts did not exhibit any sign of cocaine-conditioning (saline challenge), contrarily to the wild-types. It is speculated that MCHR1 may contribute to the neurobiological mechanisms of conditioned cocaine-induced psychomotor effects, possibly to those underpinning sensitization, and to a lesser extent to those sub-serving acute pharmacological cocaine action.


Cre-loxP System-Based Mouse Model for Investigating Graves' Disease and Associated Orbitopathy.
Background: Graves' disease (GD), one of the most common forms of autoimmune thyroid disorders, is characterized by hyperthyroidism caused by antibodies (Abs) against the extracellular A-subunit of the thyrotropin receptor (TSHR). Various approaches have been used to create mouse models of GD, including transfected fibroblasts and immunization with plasmids or adenoviruses expressing human TSHR A-subunit (hTSHR A-subunit). These models, however, require repeated immunization and produce inconsistent results. In this study, we established a novel Cre-loxP system-based mouse model that is able to generate the hTSHR A-subunit, mimicking human GD, and characterized the histological changes in Graves' orbitopathy (GO) progression after a single injection. Materials and Methods: A Cre-loxP system-based mouse model was constructed by inserting the CAG-loxP-STOP-loxP-hTSHR A-subunit cassette into the Rosa26 locus of the mouse genome. Conditional expression of the hTSHR A-subunit was successfully achieved by intramuscular injection of the transactivator of transcription-Cre recombinase (GD mice). Blood tests for anti-TSHR Abs and the total thyroxine (T4) level were performed. Magnetic resonance imaging (MRI) was used to monitor morphological changes in the eyes. A histological examination of the thyroid gland and retrobulbar tissues was performed to observe pathological changes. Results: Twenty-four (8 control and 16 GD) mice were investigated. All GD mice exhibited higher levels of TSHR Abs compared with the control group. Moreover, more than 80% of the mouse models showed elevated T4 levels accompanied by thyroid goiter. MRI analysis revealed an increased volume of retrobulbar tissue, while immunohistochemical staining of orbital tissues exhibited macrophage infiltration and muscle fibrosis in the GD mice, contrasting with the control group. Conclusions: Our novel mouse model for GD, which showed the histological features of GO, was successfully established using the Cre-loxP system. This animal model offers improved insights and contributes to advancing methodological developments for GD and GO.


Ultrasound diagnostics as a method of investigation of plastic induration of the penis.
Using the ultrasound technique of visualization (grey-scale technique) and a method of 'water bath', the authors obtained echograms of plastic indurations of the penis. The echograms can be immediately photographed and interpreted. By their quick, painless and simple performance, without contrast medium and hazardous irradiation, the authors gain an advantage over some other diagnostic methods.


Synthesis, penetrability and intracellular targeting of fluorescein-tagged peptoids and peptide-peptoid hybrids.
The search for novel, generally applicable and highly efficient delivery tools is a major activity in the biotechnology arena. Using highly optimized microwave based solid-phase chemistry a series of fluorescein-labelled cationic peptoid conjugates were synthesized within 24h and cellular uptake into HeLa, L929 and K562 cells examined via flow cytometry. As expected, analysis revealed that longer oligomers achieved greater cellular penetration (7e (9 mer)>7d (7 mer)>7c (5 mer)>7b (3 mer)>7a (1 mer)) with the nonamer 7e proving to be a remarkable vehicle for all the cell lines, showing excellent penetrability into K562 and L929 cells and extraordinary cell delivery into HeLa cells. Confocal microscopy showed that the hybrid peptoid-nuclear localizing sequence (PKKKRKV from the simian virus 40 large T antigen) resulted in very high levels of nuclei delivery after 3h, opening up a range of applications such as nuclei staining of living cells with non-DNA-intercalating fluorescent probes.


Thrombolytic therapy for catheter-related thrombosis.
Thrombosis of the central venous system (CVT) occurs in 20% to 30% of patients with indwelling catheters. This complication is usually treated with anticoagulation, extremity elevation, and catheter removal. Thirty-eight patients with CVT at our institution were treated with thrombolytic therapy to rapidly resolve symptoms and avoid removal of the catheters. Complete clot lysis occurred in 36 of 38 patients (95%) within 1 to 5 days (mean: 2.4 days). Symptoms resolved with clot resolution. Thrombolytic therapy detected stenoses in 22 patients. Angioplasty was successful in 64% of these patients. Five catheters were removed. Complications occurred in six patients: nonfatal pulmonary embolus, three bleeding episodes, pain with infusion of urokinase, and an episode of septic phlebitis. This experience suggests that thrombolytic therapy is safe, rapidly resolves symptoms of thrombosis, uncovers anatomic abnormalities amenable to angioplasty, and allows central venous catheters to remain in place despite central venous thrombosis.


4D Brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds.
What's known on the subject? and What does the study add? There are a number of techniques used successfully to perform brachytherapy, including 2-stage procedures and realtime techniques using loose seeds. This study demonstrates a one-stage realtime brachytherapy technique using stranded seeds with improved time efficiency and clinical outcome: 4D Brachytherapy. This paper reviews the development of a new one-stage prostate brachytherapy technique (4D Brachytherapy) using a combination of stranded and loose seeds. This novel technique utilizes a nomogram constructed from over 1000 procedures to calculate the seed requirement in advance of the implant. This allows stranded seeds to be pre-ordered and loaded prior to the procedure rather than per-operatively, resulting in a more efficient use of operating room time. The use of both stranded and loose seeds may reduce the risk of migration from peripherally placed seeds via the venous plexus, whilst maintaining the flexibility to optimize the dose within the prostate and especially at the apex of the gland. Prospectively collected data show significantly improved dosimetry: median D(90) 143 and 153 Gy (P < 0.005) and median V(100) 88% and 93% (P < 0.005) for the Seattle technique and 4D Brachytherapy implant technique, respectively. Also there was a reduced short-term urinary morbidity as assessed by the change in International Prostate Symptom Score (IPSS) at 3 months and 1 year compared with the Seattle technique. Mean (sd) change in IPSS from baseline at 1 year was 2.73 (5.92) and 0.97 (5.10) for the Seattle and 4D Brachytherapy series, respectively (P < 0.049).


MiR-30a-5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways.
Hydatidiform moles are gestational trophoblastic disease. They are abnormal proliferations of trophoblast cells that have the potential to become cancerous. miR-miR30a-5p is a tumour suppressor that participates in the development of numerous diseases. However, the role of miR-30a in hydatidiform moles and the mechanisms underlying its effects are presently unclear. This study explored the levels of miR-30a and B3GNT5 expression in human hydatidiform mole tissue. The results showed that miR-30a and B3GNT5 were differentially expressed in normal placenta and hydatidiform mole, and miR-30a decreased cell proliferation, invasion and migration in trophoblast cell lines. Upon further examination, it was confirmed that miR-30a directly targeted the 3'untranslated region of B3GNT5 using a dual-luciferase assay. The results of the present study also revealed that miR-30a reduced the proliferation, invasion and migration ability in JAR and BeWo cells by regulating B3GNT5, which may inactivate the ERK and AKT signalling pathways. This study demonstrated that miR-30a was a novel target B3GNT5 that serves an important role in the development of hydatidiform moles, suggesting that miR-30a may serve as a novel potential biomarker or useful diagnostic and therapeutic tool for hydatidiform moles in clinical settings.


The role of P2X7 receptor in infection and metabolism: Based on inflammation and immunity.
The P2X7 receptor (P2X7R) is a ligand-gated receptor belonging to the P2 receptor family. It is distributed in various tissues of the human body and is involved in regulating the physiological functions of tissues and cells to affect the occurrence and development of diseases. Unlike all other P2 receptors, the P2X7 receptor is mainly expressed in immune cells and can be activated not only by extracellular nucleotides but also by non-nucleotide substances which act as positive allosteric modulators. In this review, we comprehensively describe the role of the P2X7 receptor in infection and metabolism based on its role as an important regulator of inflammation and immunity, and briefly introduce the structure and general function of the P2X7 receptor. These provide a clear knowledge framework for the study of the P2X7 receptor in human health. Targeting the P2X7 receptor may be an effective method for the treatment of inflammatory and immune diseases. And its role in microbial infection and metabolism may be the main direction for in-depth research on the P2X7 receptor in the future.


Identification in histological sections of species origin of cells from mouse, rat and human.
A simple method for identifying the species of origin of mammalian cells in tissue sections using Hoechst dye #33258 is described. This rapid procedure involves staining fresh frozen or formalin fixed paraffin sections with 4 micrograms/ml of Hoechst #33258 for one minute at room temperature; following one to five minutes of washing in running tap water, the slides are coverslipped using McIlvaine's buffer (pH 5.5) and sealed with clear lacquer. Sections examined by fluorescence microscopy indicate that mouse cells contain several small discrete intranuclear fluorescent bodies, which are absent in cells from either rat or human. This simple technique should be useful in studying developmental phenomena in chimeric organs.


Potential use of FDG-PET scan after induction chemotherapy in surgically staged IIIa-N2 non-small-cell lung cancer: a prospective pilot study. The Leuven Lung Cancer Group.
Clearance of viable tumour cells in mediastinal lymph nodes (MLN) by induction chemotherapy (IC)--so-called MLN downstaging--is an important aspect of combined-modality treatment of N2-NSCLC. Reassessment of MLN after IC by CT is far from accurate, while re-mediastinoscopy is often technically difficult. Based on our previous results with FDG-PET in the initial staging of N2 disease, we investigated whether PET after IC could be helpful in predicting MLN downstaging and therapeutic outcome. Patients underwent a first PET before IC. After three cycles of platinum-based IC, a second PET was performed before locoregional therapy, either surgery or radiotherapy. PET results were correlated with pathology of the MLN when available, and with survival. Fifteen surgically staged N2-NSCLC patients were prospectively included. Locoregional therapy after IC consisted of surgery in nine and radiotherapy in six. Correlation with pathology of the nine resection specimens revealed that the accuracy of PET in predicting MLN downstaging was 100% (six true negatives; three true positives), whereas for CT it was only 67% (two false pos; one false neg). Reassessment with PET after IC was correlated with the outcome after the entire combined modality treatment. Survival was significantly better in patients with mediastinal clearance (P = 0.01) or with a greater than 50% decrease in the Standardised Uptake Value (SUV) of the primary tumour (P = 0.03) after IC. Mediastinal PET after IC accurately assesses pathologic MLN downstaging in N2-NSCLC. The data suggest a possible correlation of early survival with mediastinal clearance and an important decrease of SUV in the primary tumour. Confirmation of these preliminary findings would establish PET as a useful non-invasive tool to select patients for intensive locoregional treatment after IC.


Learning from others' mistakes in capuchin monkeys (Cebus apella).
We investigated whether tufted capuchin monkeys (Cebus apella) learn from others' mistakes. We prepared three kinds of transparent containers having the same appearance: one that could be opened by the lid, one that could be opened from the bottom, and one that could be opened either way. Using each of the first two one-way-open type containers, the monkeys were trained to copy the human demonstrator's action to open the container and obtain a piece of sweet potato contained therein. After this training, the demonstrator showed the monkeys an action that would open or fail to open the third, two-way-open type container. None of the monkeys reliably opened the container by spontaneously compensating for the demonstrator's failure (Experiment 1). In Experiment 2, the same subjects were trained to correct their own mistakes immediately after failure, before we introduced the same test as in Experiment 1. This experience did not result in subjects using the demonstrator's failure to produce a successful action. In Experiment 3, we placed two monkeys face to face. In this situation, the second monkey was presented with the container after the first monkey failed to open it. As a result, two capuchin monkeys capitalized on the partner's failure to correctly guide his/her behavior. Thus, the monkeys monitored not only the outcome of the others' action, but also that action per se. This result suggests that not only humans and apes, but also monkeys may understand the meaning of others' actions in social learning.


Myocardial metabolism of 123I-BMIPP in patients with hypertrophic cardiomyopathy: assessment by radial long-axis SPET.
To elucidate the metabolism of free fatty acid in the myocardium of hypertrophic cardiomyopathy (HCM), SPET was performed with 123I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP), an analogue of free fatty acid, and with 201Tl in nine patients with HCM and eight healthy volunteers who acted as controls. For quantitative analysis of the apical area, a radial long-axis tomogram was reconstructed every 6 degrees after short-axis tomography. The relative regional uptake (RRU, %) in each segment was obtained by normalizing to the maximal value among all segments. The 3-h washout rate was calculated both for BMIPP and for 201Tl. The ratio of the RRU of BMIPP to that of 201Tl was significantly lower in the apical and antero-septal regions compared with other walls (P < 0.01) in the patients with HCM, whereas uptake of both BMIPP and 201Tl in the controls was homogeneous and there was a significant correlation between them. The coefficient of variation (CV) in all segments in the HCM patients was significantly higher (P < 0.01) than that of the controls both BMIPP and 201Tl, indicating inhomogeneous uptake of BMIPP in the HCM patients. The washout rate of BMIPP over 3 h was significantly higher in the patients with HCM (mean +/- S.D. 26.3 +/- 7.3%) than the controls (18.3 +/- 7.5%, P < 0.05). The ratio of segmental washout rate of BMIPP to that of 201Tl in the HCM patients was increased, especially in the septum and apex.(ABSTRACT TRUNCATED AT 250 WORDS)


Hydrogen peroxide predisposes neonatal rat ventricular myocytes to Fas-mediated apoptosis.
Neonatal rat ventricular myocytes (NRVM) grown in normoxic environment are not susceptible to Fas-induced apoptosis. In the present work, we tested the hypothesis that free radical injury represented by transient exposure to H2O2 sensitizes NRVM to Fas-mediated apoptosis. NRVM were treated with H2O2 (0.5 mM) for 2-4 h and thereafter exposed for 7 h to recombinant Fas ligand (rFasL, 10 ng/ml) plus an enhancing antibody (1 microg/ml). Apoptotic cardiomyocytes were counted and apoptosis-related proteins were measured by Western blot. H2O2 alone induced apoptosis (9.4+/-1.0%) that was preceded by activation of caspases-8 and -3, and PARP degradation. Incubation of NRVM with H2O2, followed by exposure to rFasL, increased the apoptotic index to 13.8+/-2.0%, but did not change caspase-8 or PARP activation. To investigate the mechanism underlying the sensitizing affect of H2O2 towards Fas-induced apoptosis, we studied the effects of H2O2 on the expression of key apoptosis signaling proteins. Incubation with H2O2 for 2-4 h decreased Fas expression and the expression of the Fas-related antiapoptotic proteins FLIP(L) and ARC, and increased the expression of the antiapoptotic proteins bcl-2 and xIAP. FADD expression was unchanged. Next, we tested the effect of H2O2 on the apoptosis-inducing, Fas-dependent Daxx-ASK-1-JUN kinase pathway. H2O2 dramatically increased ASK-1 expression and JUN kinase activation, but did not effect Daxx expression. Based on these findings we concluded that H2O2 sensitizes NRVM to Fas-mediated apoptosis by activating the Daxx-ASK-1-JUN kinase pathway, and by shifting the balance between proapoptotic and antiapoptotic proteins towards the former.


Central airway obstruction from lymphomatoid granulomatosis treated with an endobronchial stent.
Lymphomatoid granulomatosis (LG) is an extremely rare disease and is an unusual cause of central airway obstruction (CAO) with no standard of treatment in these conditions. LG is characterized by angioinvasion and angioinfiltration along with lymphohistiocytic cells. We present a 21-year-old female with LG who developed endobronchial lesions causing malignant CAO and acute hypoxic respiratory failure. She was treated with argon plasma coagulation, as well as a self-expandable metallic stent in the left main bronchus. Her stent was removed 4 months later after chemotherapy. Endobronchial stenting may be a useful bridge in patients who are undergoing more definitive treatment.


Assessment of factors associated with surgical difficulty during removal of impacted maxillary third molars.
Estimating the difficulty of removing third molars is a common dilemma. However, the estimation of the difficulty associated with maxillary third molar surgery has not yet been defined. The aim of the present study was to determine the degree of difficulty and identify predictor variables associated with the occurrence of difficulty in the removal of impacted maxillary third molars. A prospective cohort study was carried out involving patients who underwent at least 1 surgical removal of an impacted maxillary third molar at the Oral and Maxillofacial Surgery Unit, University of Pernambuco (Pernambuco, Brazil). Predictor variables indicative of surgical difficulty were classified by their demographic, clinical, and radiographic aspects. Degree of surgical difficulty was categorized as low, moderate, or high based on the surgical technique used. Descriptive and bivariate statistics were computed. In total, 106 patients fulfilled the eligibility criteria and 204 surgeries were performed. Patients' mean age was 22.8 ± 2.2 years and the proportion of women to men was 3:1. Approximately 20% of patients were overweight. Surgical difficulty was generally low and 5 variables were significantly associated with the occurrence of a high degree of surgical difficulty. Surgical difficulty during the removal of impacted maxillary third molars is generally low. However, for cases with a high degree of difficulty, identification of predictor variables may be useful for students and inexperienced clinicians to consider the decision not to execute the procedure, thus avoiding complications that often require complex management.


NeuroScholar's electronic laboratory notebook and its application to neuroendocrinology.
Scientists continually relate information from the published literature to their current research. The challenge of this essential and time-consuming activity increases as the body of scientific literature continues to grow. In an attempt to lessen the challenge, we have developed an Electronic Laboratory Notebook (ELN) application. Our ELN functions as a component of another application we have developed, an open-source knowledge management system for the neuroscientific literature called NeuroScholar (http://www. neuroscholar. org/). Scanned notebook pages, images, and data files are entered into the ELN, where they can be annotated, organized, and linked to similarly annotated excerpts from the published literature within Neuroscholar. Associations between these knowledge constructs are created within a dynamic node-and-edge user interface. To produce an interactive, adaptable knowledge base. We demonstrate the ELN's utility by using it to organize data and literature related to our studies of the neuroendocrine hypothalamic paraventricular nucleus (PVH). We also discuss how the ELN could be applied to model other neuroendocrine systems; as an example we look at the role of PVH stressor-responsive neurons in the context of their involvement in the suppression of reproductive function. We present this application to the community as open-source software and invite contributions to its development.


Uterine Fibroid in a 16-Year-Old Adolescent Managed with a Fertility-Sparing Approach: A Case Report and Review of the Literature.
Uterine fibroids are the most common benign tumor of the uterus in adult women. However, it is exceedingly rare in adolescents. A 16-year-old girl presented with severe anemia and abnormal uterine bleeding. MRI of the pelvis demonstrated a 9-cm mass within the uterus concerning for leiomyoma or leiomyosarcoma. A fertility preserving myomectomy led to the final diagnosis of a benign uterine fibroid. Despite the rare incidence of leiomyomas in adolescents, it is imperative that it is included in the differential diagnosis when young women present with abnormal uterine bleeding. A less common diagnosis to consider is leiomyosarcoma; however, this is histologically diagnosed. Thus, a fertility-preserving myomectomy permits for a diagnostic opportunity to rule out a potential malignancy.


Two different types of intervening sequences in the glucoamylase gene from Aspergillus niger.
One single glucoamylase gene could be identified in the chromosomal DNA of Aspergillus niger by Southern blot analysis. This glucoamylase gene was isolated from a genomic library of A. niger DNA. The glucoamylase gene is situated on a 2.5-kb EcoRI-EcoRV fragment and contains five intervening sequences in the coding region. One 169-bp intron is involved in differential mRNA processing leading to the two different glucoamylase enzymes G1 and G2; the other four introns are all very small ranging from 55 to 75 bp in length. One intron has a significant homology to the coding region which immediately follows, and it contains the internal conserved sequence TACTAAC, which is also found in yeast chromosomal gene introns, and is thought to participate in mRNA splicing. Two transcription initiation sites and a typical eukaryotic promoter region with TATAAT and CAAT boxes are located upstream from the gene.


Increased histone mRNA levels during inhibition of protein synthesis.
Inhibition of protein synthesis by cycloheximide or puromycin specifically increases the amount of translatable histone mRNA in exponentially growing and in synchronous G1 HeLa cells by 5-fold in 3 hours. In this case histone gene expression is uncoupled from DNA replication. We conclude that the level of histone mRNA is regulated by a labile protein and is only indirectly dependent on DNA synthesis.


Analysis of Yersinia pestis gene expression in the flea vector.
Yersinia pestis is the causative agent of plague. Unlike the other pathogenic Yersinia species, Y. pestis has evolved an arthropod-borne route of transmission, alternately infecting flea and mammalian hosts. Distinct subsets of genes are hypothesized to be differentially expressed during infection of the arthropod vector and mammalian host. Genes crucial for mammalian infection are referred to as virulence factors whilst genes playing a role in the flea vector are termed transmission factors. This article serves as a review of known factors involved in flea-borne transmission and introduces an 'in vivo' microarray approach to elucidating the genetic basis of Y. pestis infection of- and transmission by the flea.


Inflammatory Th17 responses to infection with Mycobacterium avium subspecies paratuberculosis (MAP) in cattle and their potential role in development of Johne's disease.
Chronic intestinal inflammation typically associated with late stage Johne's disease (JD) in cattle occurs despite a lack of significant expression of the typical proinflammatory cytokines IFNγ and TNFα derived from Th1- like T cells. In contrast, these cytokines appear to be relatively abundant during early infections with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of JD in cattle. The roles of non-classical immune responses, such as those associated with Th17 cells, in response to MAP infection and development of clinical JD are less clear. In this review, we examine literature suggesting that Mycobacterial infections, including Mycobacterium tuberculosis, Mycobacterium bovis, and MAP, are all associated with expression of Th17 promoting cytokines (IL-23, IL-22, IL-17a). We discuss the possibility that Th17 associated cytokines, particularly IL-23, may act as contributing factors in development and maintenance of inflammation characteristic of clinical JD. An as yet relatively unexplored source of chronic inflammation due to over expression of IL-1α and IL-1β is also presented. We further discuss the fact that, as with the typical Th1-like cytokines IFNγ and TNFα , IL-17a is not significantly expressed in CD4+ T cells from cows with clinical JD, possibly due to T cell exhaustion. Finally, we present the notion that the Th17 driving cytokine IL-23 expressed by infected macrophages and associated epithelial cells may contribute to chronic inflammation during later stages of JD.


Two-day cefamandole versus five-day cephazolin prophylaxis in 965 total hip replacements. Report of a multicentre double blind randomised trial.
The aim of this trial was to compare a 5-day course of cephazolin with a regimen of 2 days of cefamandole in 965 total hip replacements (488 in the cefamandole group and 477 in the cephazolin group). The effect of the prophylactic antibiotic on the bacterial colonization of drains (mean duration of drainage: 3.2 +/- 0.3 days) and on the susceptibility of colonizing organisms was assessed. No significant difference was observed in the percentage of infected drains between the two groups. The cefamandole group had a lower rate of Gram-negative organisms (23% versus 44%, p less than 0.01). The rate of deep infections within one year after operation was 0.7% in the cefamandole group versus 0.5% in the cephazolin group, and the difference is not significant. Cefamandole given for two days appears to be an effective prophylaxis against sepsis in total hip replacements.


Detection of an HLA-A*30 variant, HLA-A*30:114, in a Taiwanese individual.
One nucleotide substitution in codon 219 of HLA-A*30:01:01:01 results in a novel allele, HLA-A*30:114.


An evaluation of studies concerning reproduction after first trimester induced abortion.
This report gives an estimate of the United States population at risk of fertility complications after legally induced abortion. It also includes a review of the published literature concerning long-term effects of abortion, such as secondary infertility, ectopic pregnancy, and adverse pregnancy complications.


Transcription Factor Forkhead Box P (Foxp) 1 Reduces Brain Damage During Cerebral Ischemia-Reperfusion Injury in Mice Through FUN14 Domain-containing Protein 1.
Mitophagy plays a significant role in modulating the activation of pyrin domain-containing protein 3 (NLRP3) inflammasome, which is a major contributor to the inflammatory response that exacerbates cerebral ischemia-reperfusion (I/R) injury. Despite this, the transcriptional regulation mechanism that governs mitophagy remains unclear. This study sought to explore the potential mechanism of Forkhead Box P1 (Foxp1) and its impact on cerebral I/R injury. We investigated the potential neuroprotective role of Foxp1 in cerebral I/R injury by the middle cerebral artery occlusion (MCAO) mouse model. Additionally, we assessed whether FUN14 domain-containing protein 1 (FUNDC1) could rescue the protective effect of Foxp1. Our results showed that overexpression of Foxp1 prevented brain damage during cerebral I/R injury and promoted NLRP3 inflammasome activation, whereas knockdown of Foxp1 had the opposite effect. Notably, Foxp1 overexpression directly promotes FUNDC1 expression, enhanced mitophagy activation, and inhibited the inflammatory response mediated by the NLRP3 inflammasome. Furthermore, we confirmed through chromatin immunoprecipitation (ChIP) and luciferase reporter assays that FUNDC1 is a direct target gene of Foxp1 downstream. Furthermore, the knockdown of FUNDC1 reversed the increased activation of mitophagy and suppressed NLRP3 inflammasome activation induced by Foxp1 overexpression. Collectively, our findings suggest that Foxp1 inhibits NLRP3 inflammasome activation through FUNDC1 to reduce cerebral I/R injury.


[PET-MR in patients with glioblastoma multiforme].
Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. In recent years newer therapeutic approaches have been developed. To allow for an optimized treatment planning it is important to precisely delineate necrotic tissue, edema and vital tumor tissue and to identify the most aggressive parts of the GBM. The magnetic resonance (MR) portion of an MR-positron emission tomography (PET) examination in patients with GBM should consist of both structural and functional sequences including diffusion-weighted and perfusion sequences. The use of (18)F-fluorodeoxyglucose ((18)F-FDG) is limited in patients with gliomas as glucose metabolism is already physiologically high in parts of the brain but (18)F-FDG is nevertheless a commonly used radiopharmaceutical for neuro-oncological questions. (18)F-fluorothymidine reflects the cellular activity of thymidine kinase 1 and correlates with the expression of KI-67 as an index of mitotic activity. The nitroimidazole derivatives (18)F-fluoromisonidazole and (18)F-fluoroazomycin arabinoside ((18)F-FAZA) allow the detection of hypoxic areas within the tumor. In recent years amino acid tracers, such as (18)F-fluoroethyltyrosine are increasingly being used in the diagnosis of gliomas. The simultaneous PET-MR image acquisition allows new approaches, e.g. motion correction by the simultaneous acquisition of MR data with a high temporal resolution and an improved quantification of the PET signal by integrating the results of functional MR sequences. Moreover, the simultaneous acquisition of these two time-consuming methods leads to reduced imaging times for this, often severely ill patient group.


Association of plasma viscosity and carotid thickening in a French working cohort.
Plasma viscosity and intima-media thickness (IMT) are frequently associated with cardiovascular disease and its risk factors. We evaluated the association of rheologic and vascular factors in asymptomatic subjects. Plasma viscosity (coaxial cylinder viscometry) and both preintrusive and intrusive atherosclerosis in the carotid arteries (ultrasonography) were investigated in 246 men and 337 women aged 17 to 65 years from the AXA study, a prospective cohort of healthy workers. Plasma viscosity was positively related to age-adjusted mean bifurcation carotid artery IMT (P < .01 for men; P < .04 for women) and maximum carotid artery IMT (P < .01 for men; P < .02 for women), but not to mean common carotid artery IMT. Multivariate adjustment affected these relations to a greater extent in men than in women. The odds ratio (range) of having intrusive atherosclerosis in relation to 1 SD greater plasma viscosity was 2.27 (1.52 -3.38) in men and 1.63 (1.17-2.26) in women. Adjustment of age, waist-to-hip ratio, smoking, hypercholesterolemia, hypertension, diabetes, and fibrinogen had very little effect on the magnitude of these odds ratios. Thus, plasma viscosity was associated with carotid thickening, suggesting that rheologic factors are involved in the subclinical phase of atherosclerosis.


Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization.
Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension. The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg. The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.


Estimating and evaluating the rice cluster distribution uniformity with UAV-based images.
The uniformity of the rice cluster distribution in the field affects population quality and the precise management of pesticides and fertilizers. However, there is no appropriate technical system for estimating and evaluating the uniformity at present. For that reason, a method based on unmanned aerial vehicle (UAV images) is proposed to estimate and evaluate the uniformity in this present study. This method includes rice cluster recognition and location determination based on the RGB color characteristics of the seedlings of aerial images, region segmentation considering the rice clusters based on Voronoi Diagram, and uniformity index definition for evaluating the rice cluster distribution based on the variation coefficient. The results indicate the rice cluster recognition attains a high precision, with the precision, accuracy, recall, and F1-score of rice cluster recognition reaching > 95%, 97%, 97%, 95%, and 96%, respectively. The rice cluster location error is small and obeys the gamma (3.00, 0.54) distribution (mean error, 1.62 cm). The uniformity index is reasonable for evaluating the rice cluster distribution verified via simulation. As a whole process, the estimating method is sufficiently high accuracy with relative error less than 0.01% over the manual labeling method. Therefore, this method based on UAV images is feasible, convenient, technologically advanced, inexpensive, and highly precision for the estimation and evaluation of the rice cluster distribution uniformity. However, the evaluation application indicates that there is much room for improvement in terms of the uniformity of mechanized paddy field transplanting in South China.


Treatment of temporomandibular myofascial pain with deep dry needling.
The present study was designed to evaluate the usefulness of deep dry needling in the treatment of temporomandibular myofascial pain. We selected 36 patients with myofascial pain located in the external pterygoid muscle (30 women/6 men, mean age=27 years with SD±6.5). We studied differences in pain with a visual analog scale and range of mandibular movements before and after intervention. We found a statistically significant relationship (p<0.01) between therapeutic intervention and the improvement of pain and jaw movements, which continued up to 6 months after treatment. Pain reduction was greater the higher was the intensity of pain at baseline. Although further studies are needed, our findings suggest that deep dry needling in the trigger point in the external pterygoid muscle can be effective in the management of patients with myofascial pain located in that muscle.


Ca2+ mobilization mediated by transient receptor potential canonical 3 is associated with thrombin-induced morphological changes in 1321N1 human astrocytoma cells.
Activated astrocytes show various patterns of Ca(2+) mobilization under pathological conditions. In the present study we revealed a novel function of astrocytic Ca(2+) dynamics through investigation of thrombin-induced unique Ca(2+) entry. Using 1321N1 human astrocytoma cells, which have been shown to be a good model for detecting morphological dynamics, we observed rapid retraction of bipolar protrusions that were reversibly evoked by 0.03-3 U/mL thrombin. Morphological changes were predominantly dependent on a specific thrombin receptor subtype, proteinase-activated receptor 1 (PAR-1). In parallel, Fura-2 imaging of intracellular Ca(2+) concentration ([Ca(2+)](i)) showed that thrombin induced heterogeneous Ca(2+) responses with asynchronous repetitive peaks. These oscillations were found to be a result of repetitive Ca(2+) release from intracellular stores, followed by refilling of Ca(2+) from the extracellular region without a direct [Ca(2+)](i) increase. Pharmacological manipulation with BAPTA-AM, cyclopiazonic acid, and 2-aminoethoxydiphenyl borate indicated that Ca(2+) mobilization was involved in thrombin-induced morphological changes. We further addressed the role of Ca(2+) entry using small interfering RNA (siRNA) for transient receptor potential canonical 3 (TRPC3). As a result, both thrombin-induced morphological changes and oscillatory Ca(2+) responses were significantly attenuated in siRNA-transfected cells. Inhibition of TRPC3 with pyrazole-3 also provided support for the contribution of Ca(2+) influx. Moreover, TRPC3-mediated Ca(2+) dynamics regulated thrombin-induced phosphorylation of myosin light chain 2. These results suggest a novel function of astrocytic Ca(2+) dynamics, including Ca(2+) entry, in the pathophysiological effects of PAR-1-mediated astrocytic activation. TRPC3 forms a functional Ca(2+) channel and might modulate astrocytic activation in response to brain hemorrhaging.


Comparison of the status epilepticus severity score and the epidemiology-based mortality score in predicting 30-day mortality and status epilepticus cessation.
To evaluate the role of the Status Epilepticus Severity Score (STESS) and the Epidemiology-based Mortality score (EMSE) in predicting 30-day mortality and SE (Status epilepticus) cessation, and their prognostic performance in subgroups of patients with specific characteristics. We reviewed consecutive episodes of SE occurring in patients aged ≥14 years at Baggiovara Civil Hospital (Modena, Italy) from 2013 to 2021. We evaluated the predictive accuracy of EMSE and STESS for 30-day mortality and SE cessation through stepwise regression binary logistic models adjusted for possible univariate clinical confounders. Seven hundred and eleven patients were enrolled. The mean value of STESS was 3.2 (SD 1.7) and of EMSE was 80.1 (SD 52.6). Within 30 days of the onset of SE, 28.4% of patients (202/711) died. EMSE had higher discriminatory ability for 30-day mortality compared with STESS (AUROC: 0.799; 95% CI: 0.765-0.832 versus 0.727; 95% CI: 0.686-0.766, respectively; p = 0.014). SE cessation within 1 h for convulsive SE and within 12 h for nonconvulsive SE was achieved in 35.3% (251/711) of patients. No significant difference was found between EMSE and STESS in discriminatory ability for SE cessation (AUROC: 0.516; 95% CI: 0.488-0.561 and 0.518; 95% CI: 0.473-0.563, respectively; p = 0.929). EMSE was superior to STESS in predicting 30-day mortality in patients with specific characteristics. No difference between the two scores was found in predicting SE cessation in subgroups of patients with specific characteristics. EMSE seems superior to STESS in predicting 30-day mortality, particularly in specific patient categories. Conversely, there is no difference in the ability of these scores in predicting SE cessation, which is overall rather low.


Relation between volume swallowed and velocity of the bolus ejected from the pharynx into the esophagus.
The velocity of the front face of a liquid saline bolus ejected from the pharynx into the esophagus was measured by recording changes of luminal electrical impedance with three sets of electrodes in 9 subjects. At a site 26 cm from the incisors, the mean velocity of the front face of the bolus increased from 10 to 70 cm sec-1 as the volume swallowed was raised from 5 to 30 ml. The velocity of the front face of the bolus was greater 26 cm from the incisors than it was 32 cm from the incisors.


[Correlation between nutrient levels of vitamin A and zinc and HOX C4 gene expression in mice embryos].
Correlation between nutrient levels of vitamin A and zinc and HOX C4 (3.5) gene expression in mice embryos was studied. The Kunming female mice were divided three groups: deficient group (DG) fed with fodder deficient of vitamin A and zinc, replenished group (RG) fed with fodder deficient of vitamin A and zinc until the 7th day after conception and then fed with fodder rich in vitamin A and zinc, and normal group (NG), fed with normal fodder. After obvious symptoms of vitamin A and zinc deficiency appeared, the mice were mated. On the 12th day after conception, pregnant mice were killed and their levels of vitamin A and zinc were determined and the content of mRNA of HOX C4 (3.5) were determined for the embryos with situ hybridization. The level of vitamin A was 0.44 mumol/L, 1.03 mumol/L and 1.40 mumol/L, respectively and that of zinc 124.3 mg/kg, 152.1 mg/kg and 193.8 mg/kg in DG, RG and NG, respectively. The mRNA of HOX C4 (3.5) gene expression in mouse embryos increased significantly in DG, RG and NG (P < 0.05). Levels of vitamin A and zinc in the body of pregnant mice positively correlated significantly with their HOX C4 (3.5) gene expression, with coefficients of correlation of 0.78 to 0.99.


Design, implementation, and preliminary results of an Emergency Medical Technician-Intermediate training program on an Air Force installation.
Design and implementation of an Emergency Medical Technician-Intermediate program based on Air Force medical technician training is discussed. Criteria for candidate selection is given and course content is outlined. Ambulance use by the population as well as response times and success rates for field cardiac arrest for a 2-year period are discussed. Recommendations for future development are given.