Novel Th17 Lymphocyte Populations, Th17.1 and PD1+Th17, are Increased in Takayasu Arteritis, and Both Th17 and Th17.1 Sub-Populations Associate with Active Disease.
We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK). We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26-45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK. TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy. Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.


Selective sugar binding to the carbohydrate recognition domains of the rat hepatic and macrophage asialoglycoprotein receptors.
Asialoglycoprotein receptors on the surfaces of both hepatocytes and peritoneal macrophages bind terminal galactose residues of desialylated glycoproteins and mediate endocytosis and eventual degradation of these ligands. The hepatic receptor binds oligosaccharides with terminal N-acetylgalactosamine residues more tightly than ligands with terminal galactose residues, but the macrophage receptor shows no such differential binding affinity. Carbohydrate recognition domains from the macrophage receptor and the major subunit of the hepatic receptor have been expressed in a bacterial system and have been shown to retain the distinct binding selectivities of the receptors from which they derive. Binding of a series of N-acyl derivatives of galactosamine suggests that the 2-substituent of these sugars interacts with the surface of the hepatic receptor with highest affinity binding observed for the N-propionyl derivative. Chimeric sugar-binding domains have been used to identify three regions of the hepatic receptor that are essential for establishing selectivity for N-acetylgalactosamine over galactose. Based on these results and the orientation of N-acetylgalactosamine when bound to an homologous galactose-binding mutant of rat serum mannose-binding protein, a fourth region likely to interact with N-acetylgalactosamine has been identified and probed by site-directed mutagenesis. The results of these studies define a binding pocket for the 2-substituent of N-acetylgalactosamine in the hepatic asialoglycoprotein receptor.


Cellulase and Abscission in the Red Kidney Bean (Phaseolus vulgaris).
Cellulase (beta-1, 4-glucan-glucanohydrolase EC 18.104.22.168) activity in the abscission zone of red kidney bean (Phaseolus vulgaris) was previously shown to exist in at least two different molecular forms. The form of the enzyme which has an isoelectric point of 4.5 is present in both abscising and nonabscising tissue and requires grinding for extraction. Another form of the enzyme which has an isoelectric point of 9.5 is present only in tissue in which the abscission process has been induced. Further, much of this form of cellulase can be removed from the tissue by vacuum infiltration with buffer. Time course studies indicate that while the increase in measurable cellulase activity in tissue which is actively undergoing abscission was due primarily to the appearance of cellulase 9.5, this form of the enzyme cannot be removed by vacuum infiltration until after the breakstrength of the abscission zone has decreased nearly to zero. The intracellular localization of these two forms of cellulase is discussed.


International Tourists' Reactions to a Natural Disaster: Experiences of the 2015 Earthquake in Nepal Among Israeli Travelers.
There is a scarcity of research exploring the experiences of foreign travelers exposed to natural disasters while abroad. This qualitative study explored the experiences of the 2015 earthquake in Nepal among international travelers immediately following the earthquake. In-depth interviews were conducted with 21 Israeli backpackers who were traveling in Nepal at the time of the earthquake. Thematic analysis revealed 4 themes: emotional turmoil, quick recovery, springing into action, and connection to the army. Findings suggest that foreign travelers initially respond with emotional turmoil to the disaster. Then they actively search for ways to effectively cope with the situation by problem solving, creating a community of action and support, and searching their own history for similar circumstances that can provide a sense of competence or clear directions for coping. Implications and limitations of the study, as well as suggestions for future research are discussed.


DEC2 Serves as Potential Tumor Suppressor in Breast Carcinoma.
Identification of new biomarkers can facilitate the development of effective therapeutic strategies in breast cancer (BC). Data from previous studies have revealed that differentiated embryonic chondrocyte gene (DEC) 1 and DEC2 might involve in the progression of various cancer types. We explored the expression profiles and function of DEC1/2 in BC patients in this study. The mRNA expression of DEC1/2 in BC patients and cell lines were taken from the Oncomine and Cancer Cell Line Encyclopedia database. The prognostic impacts of DEC1/2 were mined from the bc-GenExMiner and Kaplan-Meier plotter database. The impact of DEC1/2 genomic alterations on patient survival was calculated by cBioPortal. DEC2 protein expressions were confirmed by Western blotting (WB) in 10 pairs of BC samples. In addition, DEC2 sgRNA was constructed to confirm its affection on cell viability, invasion, and colony formation. The DEC1 and DEC2 mRNA levels are both lower in BC tissues than normal tissues. DEC1/2 expression was high in progesterone receptor (PR) positive BC patients (P = 0.0023), but low in human epidermal growth factor receptor 2 (HER2) positive patients (P < 0.0001). Lower DEC2 mRNA level has significant association with more aggressive pathogenic grade (P < 0.0001) and worse overall survival (OS) of BC patients (P = 5.2 × 10-6). Subgroup analysis showed that low DEC2 level was correlated with worse OS in estrogen receptor (ER) positive BC (P = 0.008). DEC2 (P = 0.00029) alteration was significantly correlated with worse OS in BC patients. WB results also confirmed the lower DEC2 protein levels in BC samples than their paired normal tissues. And, DEC2 silencing by sgRNA resulted in a significant increasing in cell viability, invasion, and colony formation. DEC2 might serve as a tumor suppressor, and its disfunction may involve in the tumorigenesis and indicate bad clinical outcomes in BC patients.


Use of public health nurse competencies to develop a childcare health consultant workforce.
The purpose of this article is to describe the efforts in the state of Georgia to train public health nurse-childcare health consultants (PHN-CCHCs) using the framework of the "Core competencies for public health practice." The goal of the training was twofold: (1) to prepare a statewide cadre of PHNs as the primary workforce for Georgia's emerging childcare health consultation (CCHC) system and (2) to prepare their district nurse directors to lead and support CCHCs. Administrators attended a 2-day workshop followed by access to executive coaching for their management teams. PHNs participated in a three-phase training program, with phases 1 and 3 offered as 3-day workshops with field experiences, and phase 2 offered online and as a practicum. Forty-four administrators and over 85 PHN-CCHCs completed the training. Graduates of the program reported satisfaction with training and reported the use of PHN core competencies in CCHC. Graduates also found enhanced skills in using core competencies to be applicable to a variety of population-based practices. Beyond CCHC being instituted in selected health districts, interest in CCHC has occurred statewide. The PHN-CCHC program enhanced the knowledge and use of core competencies and heightened interest in CCHC statewide.


Route to High Hole Mobility in GaN via Reversal of Crystal-Field Splitting.
A fundamental obstacle toward the realization of GaN p-channel transistors is its low hole mobility. Here we investigate the intrinsic phonon-limited mobility of electrons and holes in wurtzite GaN using the ab initio Boltzmann transport formalism, including all electron-phonon scattering processes and many-body quasiparticle band structures. We predict that the hole mobility can be increased by reversing the sign of the crystal-field splitting in such a way as to lift the split-off hole states above the light and heavy holes. We find that a 2% biaxial tensile strain can increase the hole mobility by 230%, up to a theoretical Hall mobility of 120 cm^{2}/V s at room temperature and 620 cm^{2}/V s at 100 K.


Validation of a novel immunoassay for the detection of synthetic cannabinoids and metabolites in urine specimens.
Synthetic cannabinoid drugs do not cross react on traditional marijuana immunoassay tests, preventing their use in large scale drug screening programs. This paper describes the validation and performance characteristics of two enzyme linked immunosorbent assays designed to detect the use of two common synthetic cannabinoids in urine, JWH-018 and JWH-250. The JWH-018 assay has significant cross-reactivity with several synthetic cannabinoids and their metabolites, whereas the JWH-250 assay has limited cross-reactivity. The assays are calibrated at 5 ng/mL with the 5-OH metabolite of JWH-018 and the 4-OH metabolite of JWH-250. The method was validated with 114 urine samples for JHW-018 and 84 urine samples for JWH-250 and confirmed by using liquid chromatography tandem mass spectrometry, which tests for metabolites of JWH-018, JWH-019, JWH-073, JWH-250 and AM-2201. The accuracy was determined to be 98% with greater than 95% sensitivity and specificity for both assays.


Protection of femoral neck taper in revision of acetabular component.
In hip revision restricted to the acetabular component, the taper of a modular stem is in constant danger of scratching. We used a plastic syringe to protect the taper of the femoral component. A plastic syringe of appropriate size remains well in place and offers a novel and inexpensive protective device for the taper of the femoral component available in every operation room.


Impact of training modes on fitness and body composition in women with obesity: A systematic review and meta-analysis.
This study aimed to assess the effectiveness of different exercise modalities and determine the optimal exercise prescription for improving cardiorespiratory fitness, body composition, and metabolic health of women with obesity. A systematic review of randomized controlled trials (RCTs) published between January 1988 and October 2020 was conducted. The RCTs were screened using the following inclusion criteria: 1) participants: women aged 18 to 65 years with BMI > 30 kg/m2 and without comorbidities; 2) intervention: exercise; 3) comparison: non-intervention control; and 4) outcomes measures: cardiorespiratory fitness (maximal oxygen consumption), body composition (i.e., body weight, percentage body fat), and/or metabolic measures (i.e., blood pressure, cholesterol). A total of 20 RCTs with a total of 2,062 participants were included. Although the results showed that any form of exercise was more effective than control, improvements in fitness and body composition were modest. Aerobic exercise (vigorous and moderate intensity) appeared most promising for improving fitness and body weight, whereas low-load resistance training resulted in the largest improvements in body fatness. In women living with obesity, aerobic exercise was consistently effective in improving fitness and body composition. Although both resistance training and combined exercise interventions appear promising, more research is needed to evaluate their efficacy and determine an optimal exercise prescription for this population.


Atherosclerosis prevention in youth.
Atherosclerosis-associated circulatory disturbance is one of the most important global issues. In patients with atherosclerosis, eccentric intimal thickening and lipid deposition progress over a long period (at least 20 to 30 years). On the other hand, in patients with atherosclerosis-associated circulatory disturbance represented by myocardial infarction, the direct cause of death is thrombus formation rather than marked stenosis; wall destruction may lead to a fatal outcome. In the future, atherosclerosis susceptibility, that is, intrinsic genes, should be investigated.


[Pathology of spinal tumors].
The Bone Tumor Registry of Westphalia contains data on 7,400 tumors and tumor-like lesions of bone, 135 primary spinal tumors, 187 metastases, 98 plasmacytomas, 4 extranodal manifestations of Hodgkin and non-Hodgkin lymphomas of the vertebral column. The most frequent type of primary tumor is the chordoma (35 cases), followed by osteoblastoma (16 cases), eosinophil granuloma (16), and hemangioma (12 cases). Most of the metastases derive from carcinoma of the breast, bronchial carcinoma, or prostate carcinoma. The present review concentrates on differential diagnosis by means of histological examination, with particular reference to immunohistological methods. In addition, the necessity for complementary assessment of the X-ray findings and histology is emphasized. In particular, the current status of knowledge on the prognosis of primary spinal tumors is presented. In our experience, the preparation of nondecalcified plastic sections has proved especially valuable for diagnostic procedures using punch biopsy specimens.


Co-existing carpal tunnel syndrome in complex regional pain syndrome after hand trauma.
This study highlights the benefits of carpal tunnel release (CTR) in four patients presenting with complex regional pain syndrome (CRPS) after hand surgery who also had carpal tunnel syndrome (CTS) diagnosed clinically and by nerve conduction studies. Three of the patients underwent pre- and postoperative volumetric, circumference, grip strength and range of motion measurements. The Disabilities of the Arm, Shoulder and Hand (DASH) functional outcome measure and pain scores were also used. There was almost complete resolution of CRPS symptoms in all four patients, with notable reductions in oedema and improvements in grip strength and range of motion. There were also improvements in DASH outcome scores and pain scores after CTR.


The HIV-1 nef protein interferes with phosphatidylinositol 3-kinase activation 1.
nef is a human immunodeficiency virus (HIV) gene encoding a 27-kDa myristoylated protein with structural features of a signal transducing molecule, but whose functions are largely unknown. We studied the interactions of Nef with the signal transduction pathways triggered by the platelet-derived growth factor (PDGF) receptor. The association of phosphatidylinositol (PI) 3-kinase with the activated receptor was severely impaired by nef expression. Conversely, PDGF-induced receptor tyrosine phosphorylation, binding to phospholipase C-gamma and to Ras-GAP were not modified. Microtubule-associated protein kinase activation and intracellular calcium influx in response to PDGF were either unaffected or only slightly enhanced. Nef significantly reduced the proliferative response to the growth factor, while the chemotactic response was unchanged. These data show that Nef affects selectively the PI 3-kinase signaling pathway and suggest that this interference results in some of the HIV adverse effects on host cell functions.


Threonine Synthase of Lemna paucicostata Hegelm. 6746.
Threonine synthase (TS) was purified approximately 40-fold from Lemna paucicostata, and some of its properties determined by use of a sensitive and specific assay. During the course of its purification, TS was separated from cystathionine gamma-synthase, establishing the separate identity of these enzymes. Compared to cystathionine gamma-synthase, TS is relatively insensitive to irreversible inhibition by propargylglycine (both in vitro and in vivo) and to gabaculine, vinylglycine, or cysteine in vitro. TS is highly specific for O-phospho-l-homoserine (OPH) and water (hydroxyl ion). Nucleophilic attack by hydroxyl ion is restricted to carbon-3 of OPH and proceeds sterospecifically to form threonine rather than allo-threonine. The K(m) for OPH, determined at saturating S-adenosylmethionine (AdoMet), is 2.2 to 6.9 micromolar, two orders of magnitude less than values reported for TS from other plant tissues. AdoMet markedly stimulates the enzyme in a reversible and cooperative manner, consistent with its proposed role in regulation of methionine biosynthesis. Cysteine (1 millimolar) caused a slight (26%) reversible inhibition of the enzyme. Activities of TS isolated from Lemna were inversely related to the methionine nutrition of the plants. Down-regulation of TS by methionine may help to limit the overproduction of threonine that could result from allosteric stimulation of the enzyme by AdoMet.No evidence was obtained for feedback inhibition, repression, or covalent modification of TS by threonine and/or isoleucine.


Kinetochores, microtubules and the metaphase checkpoint.
A decade ago, kinetochores were generally regarded as rather uninteresting structures that served only to attach mitotic chromosomes to microtubules. In the past few years, however, a number of experiments have belied this view and demonstrated that kinetochores are actively involved in moving chromosomes along the microtubules of the mitotic spindle. Now it appears that in addition to their function in motility, kinetochores act as dynamic and adaptable centres for regulating cell cycle progression through mitosis.


[Pseudoaneurysm of the extracranial vertebral artery; a case report].
Traumatic injury of the vertebral artery is rare and only a few reports have been presented. We treated a case of iatrogenic pseudoaneurysm of the extracranial vertebral artery. A 65-year-old man complained of headache and had a pulsating mass in the soft tissue of the neck which had continued for one month after evacuation of hypertensive cerebellar hemorrhage. The left VAG revealed a large pseudoaneurysm at the third portion of the vertebral artery and the right retrograde VAG revealed agenesis of the vertebral artery. To select the proper treatment was a dilemma. This case was treated by embolization using an occluding spring embolus with direct transcutaneous puncture of pseudoaneurysm. Following this treatment, the mass and associated symptoms resolved without neurological deficit.


Every man his own farrier in Australia: the origins and growth of a veterinary business in colonial New South Wales.
The life and work is told of John Pottie (1832-1908), a Scotsman who graduated from Edinburgh Veterinary College in 1858. A year later, he contracted to provide veterinary care to a consignment of horses bound for Australia. Once there, he founded a firm that has survived to the present day, still marketing products that originated in his own veterinary remedies. John Pottie brought with him a European tradition of livestock care and treatment that was epitomised in Clater's title and book, Every man his own farrier. His career is of interest for several reasons. Firstly it is because he used this tradition to launch a business enterprise in a new and different market in Australia. Secondly, although his training lay in what may be termed the pre-scientific era of the profession's history, he was able to adapt old traditions successfully to the changes that came in the age of Pasteur and Koch. Finally, the manner in which he did this, besides demonstrating his business acumen, also shows how the professional veterinary qualification gained in value in a new age of science.


Long-time follow-up after UPPP for obstructive sleep apnea syndrome. Results of sleep apnea recordings and subjective evaluation 6 months and 2 years after surgery.
Fifty unselected consecutive patients with obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The diagnosis was based on the patient's history and recording of respiration movements (Static Charge Sensitive Bed. SCSB) and oximetry, alone or combined with polysomnography. Renewed SCSB oximetry recordings were used to evaluate the success of the treatment. Six months postoperatively 40% of the patients were classified as non-responders, i.e. their oxygen desaturation indices (ODI) were reduced by less than 50% or were still above 20. The mean body mass index (BMI) was significantly higher in the non-responder group. A second recording with complete data was obtained in 45 patients after an average of 21 months. It was found that 9 patients who had been responders in the first postoperative recording had become non-responders. Only 18 of the patients with complete data could be verified as responders after 2 years. The patients who relapsed showed a significant increase in mean BMI between the first and second postoperative recordings compared to the patients who remained responders. There were no significant differences between responders and non-responders concerning age or preoperative severity of OSAS expressed as ODI, nadir SaO2 and percentage of obstructive periodic breathing. Of the non-responders, 47% in the first postoperative recording and 52% in the second reported complete recovery from excessive daytime sleepiness. This subjective improvement was not correlated to the objective results. The conclusions of this study are thus that one postoperative recording is not enough to estimate the outcome of UPPP and that statements of the patient's subjective recovery alone must not be used for this purpose.


Humoral and cellular immunity rates in chemical plant workers employed in the production of liquid pesticides.
In order to assess the immunological system of the chemical plant workers certain rates of cellular and humoral immunity were estimated. The study group was composed of 19 males employed in the production of liquid pesticides, and 18 females performing ancillary jobs and handling closed containers. They were alternatively exposed to phosphoroorganic compounds and pyrethroides, and to chlorinated hydrocarbons, carbamates, nitrophenols and organic solvents, however exposure to the latter was lower. Chronic bronchitis was observed in 7 (37%) males and 4 (22%) females. Serum concentrations of immunoglobulins G, A and M, complement protein Cs, and circulating immune complexes were estimated. The peripheral blood leukocyte count and percentage, the granulocyte adherence and phagocytic activity, spontaneous NBT-dye reduction as well as cytochemical reactions to alkaline and acid phosphatase, beta-glucuronidase, myeloperoxidase and catalase of neutrophils were evaluated; the lymphocyte subpopulations CD3, CD4, CD8, CD16 were also estimated. As compared to controls, a significantly increased serum IgG concentration was found, together with elevated IgM in males and IgA in females. The leukocyte count in males was significantly higher. A considerable decrease in the percentage of neutrophils was accompanied by a significantly greater spontaneous NBT-dye reduction in both groups. Neutrophil adherence impairment was observed in males. Cytochemical reactions to beta-glucuronidase and catalase in both sexes, to alkaline and acid phosphatase in females, and to myeloperoxidases in males were significantly lowered, whereas the reaction to acid phosphatase in males was significantly enhanced. The percentages of lymphocytes CD3, CD4 and the CD4/CD8 ratio were significantly decreased.


Print-and-peel fabricated passive micromixers.
Advection driven mixing is essential for microfluidics and poses challenges to the design of microdevices. Force transducers or complex channel configurations provide means for, respectively, active or passive disrupting of laminar flows and for homogenizing the composing fluids. Print-and-peel (PAP) is a nonlithographic fabrication technique that involves direct printing of masters for molding polymer components of microdevices. PAP, hence, allows for facile and expedient preparation of microfluidic devices, without requiring access to specialized microfabrication facilities. We utilized PAP for fabrication of microfluidic devices capable of turning, expanding, and contracting microflows. We examined the mixing capabilities of these devices under flow conditions of small Reynolds numbers (0.2-20) and large Peclet numbers (260-26 000), under which advection is the dominant mode of mass transfer. We focused on mixing channels with arched shapes and examined the dependence of the mixing performance on the turns and the expansions along the direction of the microflows. Three-dimensional expansion and contraction, along with an increase in the modes of twisting of the laminar currents, improved the quality of mixing. The simplicity in the described fabrication of the investigated passive micromixers makes PAP an attractive alternative for expedient device prototyping.


[Palliative Care for Non-cancer Patients].
Although palliative care has been developed and implemented as care for cancer pain, it is holistic care for suffering that includes physical, psychosocial and spiritual pain of life-threatening illness. It turned out that non-cancer patients in the end-stage are also suffering from various pain that should be treated as cancer patients. Trajectories of illness in non-cancer patients are with more gradual decline than those of cancer patients with steady progression and it is often difficult to make decision about end-of-life. The purpose of advance care planning was originally to help describe legal documents. This process is proved to contribute to improving QOL of patients and their families to discuss preference, hope, economic problems, spiritual question as well as medical treatment In Japan guideline of decision making process in end-of-life stage has been established. A program of communication training in end-of-life discussion has been made. Under current situation some comments on the role of anesthesiologists are also mentioned.


Bradycardia-dependent early afterdepolarizations in a patient with QTU prolongation and torsade de pointes in association with marked bradycardia and hypokalemia.
Endocardial monophasic action potentials (MAPs) were recorded at the right ventricular apex in a patient with QTU prolongation and torsade de pointes (TdP) in association with marked bradycardia and hypokalemia. There was a distinct hump on phase 3 repolarization of the MAPs characteristic of early afterdepolarizations (EADs), which was associated with marked prolongation of the QTU interval on the surface electrocardiogram. EAD amplitude was bradycardia dependent, and there was a strong correlation (r = 0.91) between the preceding RR interval and the amplitude of the EAD (percent of MAP amplitude). Intravenous administration of lidocaine or right ventricular pacing suppressed the ventricular premature complexes and TdP in association with the suppression of the EADs on the MAPs. Furthermore, these EADs were not recorded on the MAPs 1 month later when the QTU prolongation and TdP had disappeared. These findings suggest that the TU abnormality and QTU prolongation responsible for TdP were due to bradycardia-dependent EADs.


Use of a quality improvement tool, the prioritization matrix, to identify and prioritize triage software algorithm enhancement.
Complex decision support software can require significant effort in maintenance and enhancement. A quality improvement tool, the prioritization matrix, was successfully used to guide software enhancement of algorithms in a symptom assessment call center.


Malignant pleural mesothelioma after radiation therapy for breast cancer. A report of two additional patients.
Malignant pleural mesotheliomas (MPMs) are rare tumors that usually have a fatal outcome. The association of these tumors with asbestos exposure is well established. Induction of malignant mesothelioma by nonasbestos-related causes also has been reported in the literature, although the number of documented cases is extremely small. Two additional patients with malignant pleural mesothelioma many years after radiotherapy for breast cancer are reported. The observations as reported in the literature on the involvement of radiation in the development of MPMs are reviewed and compared with the authors' clinical experience. In a retrospective random review, 1000 patients who received thoracic irradiation at M. D. Anderson Cancer Center were studied for histologic and radiographic evidence of MPM. The selection criteria included the development of a unilateral pleural effusion years after successful treatment with thoracic irradiation for a proven malignancy. Patients with a history compatible with asbestos exposure were excluded from the review. There have been only three previous cases of documented MPM associated with thoracic irradiation reported in the English literature. A review of the experience at our institution has demonstrated three patients with radiation-induced MPM. One patient has been reported elsewhere. Details of the other two patients are discussed in this paper. Nonasbestos-related causes of MPMs are rare. The additional two patients lend added support to the association between thoracic irradiation and the development of MPM. The development of a unilateral pleural effusion occurring years after successful treatment of a proven malignancy with thoracic irradiation should alert the clinician to the possibility of MPM.


The social organism: congresses, parties, and committees.
We propose that what makes an organism is nearly complete cooperation, with strong control of intraorganism conflicts, and no affiliations above the level of the organism as unified as those at the organism level. Organisms can be made up of like units, which we call fraternal organisms, or different units, making them egalitarian organisms. Previous definitions have concentrated on the factors that favor high cooperation and low conflict, or on the adapted outcomes of organismality. Our approach brings these definitions together, conceptually unifying our understanding of organismality. Although the organism is a concerted cluster of adaptations, nearly all directed toward the same end, some conflict may remain. To understand such conflict, we extend Leigh's metaphor of the parliament of genes to include parties with different interests and committees that work on particular tasks.


KCNQ1OT1: An Oncogenic Long Noncoding RNA.
Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.


Elevated serum antimelanocyte antibody level in cerebriform intradermal nevus with vitiligo.
We describe a rare, but typical case of cerebriform intradermal nevus associated with vitiligo. A 45-year-old man had a patch of alopecia over his vertex scalp for 15 years. The microscopic findings of the biopsy revealed a typical deep-seated intradermal nevus and neuroid differentiation with a few pigments. Three hypopigmented patches developed on the forehead, cheek and index finger five years after the scalp lesion, with loss of both melanocytes and melanins. In addition, no dopa reactions were present. Compared to normal controls, the serum anti-melanocyte antibody level in the patient was elevated as determined by cellular enzyme-linked immunosorbent assay (cellular ELISA). This is the first reported case with elevation of serum antimelanocyte antibody level of cerebriform intradermal nevus with vitiligo. This antibody's presence may be related to the occurrence of the vitiligo in patient with cerebriform intradermal nevus.


Risk Assessment for Salmonellosis in Chicken in South Korea: The Effect of Salmonella Concentration in Chicken at Retail.
Salmonellosis caused by chicken consumption has been a critical issue in food safety worldwide, including in Korea. The probability of illness from consumption of chicken was simulated in study, based on the recipe of Dakgalbi, a commonly eaten chicken dish in Korea. Additionally, the processing stage at slaughterhouses to decrease Salmonella concentration in broilers was modeled to explore its effect on the likelihood of illness. A Monte Carlo simulation model was created using @RISK. Prevalence of Salmonella in chickens at the retail stage was found to be predominantly important in determining the probability of illness. Other than the prevalence, cooking temperature was found to have the largest impact on the probability of illness. The results also demonstrated that, although chlorination is a powerful tool for decreasing the Salmonella concentration in chicken, this effect did not last long and was negated by the following stages. This study analyzes the effects of variables of the retail-to-table pathway on the likelihood of salmonellosis in broiler consumption, and also evaluates the processing step used to decrease the contamination level of Salmonella in broilers at slaughterhouses. According to the results, we suggest that methods to decrease the contamination level of Salmonella such as chlorination had little effect on decreasing the probability of illness. Overall, these results suggest that preventing contamination of broiler with Salmonella must be a top priority and that methods to reduce the concentration of Salmonella in broilers at slaughterhouses hardly contribute to safe consumption of Salmonella-contaminated chicken.


Prevalence of Toxoplasma gondii in slaughtered pigs in the state of Pernambuco, Brazil.
The object of this study was to investigate Toxoplasma gondii antibodies and parasite DNA in pigs in the state of Pernambuco, Brazil. Blood samples were collected from 305 slaughtered pigs in 11 municipalities, and their sera were tested for T. gondii antibodies using the indirect fluorescent antibody test (IFAT, cutoff 1:64); 38 (12.5%) samples were positive. Attempts were made to detect T. gondii DNA in the heart tissue of seropositive pigs using the B 1 gene and PCR; 21 (55.2%) of the 38 hearts were positive. This is the first detection of T. gondii DNA in tissues of serologically positive swine in the State of Pernambuco, Brazil.


Detection of beta-2 transferrin in otorrhea and rhinorrhea in a routine clinical laboratory setting.
A simple, straightforward, and rapid method for the detection of beta-2 transferrin in otorrhea and rhinorrhea that can be used in a routine clinical laboratory is described. The beta-2 transferrin was detected by agarose gel electrophoresis of the fluid on Beckman Paragon equipment, followed by pressure transfer to a nitrocellulose membrane and then incubation with enzyme-labeled antitransferrin antibody and substrate. The procedure was fast (3.5 h) and sensitive (detected as little as 1 microgram/ml) and required only 3 microliters of fluid. Beta-2 transferrin was detected in cerebrospinal fluid diluted up to eightfold. No special training or expertise was needed, and all equipment and procedures used are commonly available in a routine clinical laboratory.


Psychophysiological assessment of expressed emotion in schizophrenia. A case example.
Previous research has demonstrated a different psychophysiological response of schizophrenic patients depending on whether their key relative was rated high or low on Expressed Emotion (EE). A case assessment is described in which a young man suffering from schizophrenia, who lived with both a high EE and a low EE parent, was tested psychophysiologically in their presence using an ABAC design. The patient demonstrated a significantly higher amount of spontaneous activity in skin conductance level when the high EE parent was present. The high EE parent also demonstrated a greater perceived inability to cope, and a higher level of personal distress.


Sensorimotor Control in Dystonia.
This is an overview of the sensorimotor impairments in dystonia, a syndrome characterized by sustained or intermittent aberrant movement patterns leading to abnormal movements and/or postures with or without a tremulous component. Dystonia can affect the entire body or specific body regions and results from a plethora of etiologies, including subtle changes in gray and white matter in several brain regions. Research over the last 25 years addressing topics of sensorimotor control has shown functional sensorimotor impairments related to sensorimotor integration, timing, oculomotor and head control, as well as upper and lower limb control. In the context of efforts to update the classification of dystonia, sensorimotor research is highly relevant for a better understanding of the underlying pathology, and potential mechanisms contributing to global and regional dysfunction within the central nervous system. This overview of relevant research regarding sensorimotor control in humans with idiopathic dystonia attempts to frame the dysfunction with respect to what is known regarding motor control in patients and healthy individuals. We also highlight promising avenues for the future study of neuromotor control that may help to further elucidate dystonia etiology, pathology, and functional characteristics.


[Implication of non-perforating deep sclerectomy with amniotic membrane implantation for primary open-angle glaucoma].
To evaluate the efficacy of non-perforating deep sclerectomy (NPDS) with amniotic membrane implantation for primary open-angle glaucoma (POAG). Fourteen cases (23 eyes) of POAG underwent NPDS with amniotic membrane implantation. NPDS was performed with a fornix-based conjunctival flap using 0. 04% mitomycin C(MMC) under the scleral flap for 4 minutes. A 6 mm x 9 mm amniotic membrane was then placed under the scleral flap and sutured using 10-0 nylon. One month postoperatively, the intraocular pressure (IOP) was less or equal to 21 mmHg in 23 eyes, with a total success rate of 100%. After 3 months of follow-up for 20 eyes, the completely success rate was 90%, and the partly success rate was 100%. After 6 months of follow-up for 11 eyes, the completely success rate was 72.7%, the partly success rate was 100%, and the visual acuity had no significance between the pre-operation and post-operation. After 12 months of follow-up for 6 eyes, the success rate was 66. 7%. A good bleb formation was seen in the eyes and the IOP was controlled successfully. No serious complication was found in all eyes. Amniotic membrane is an effective and safe implantation material for NPDS.


Lumbar Canal Stenosis Caused by Spondylolisthesis and Intraspinal Canal Calcifications Associated with Psoriatic Arthritis: A Case Report.
Soft tissue calcifications are common findings in patients with various diseases, such as malignant tumors, collagen diseases, trauma, and chronic kidney disease. The majority of these lesions are not clinically significant; however, they can cause specific disorders within a limited space, such as the spinal canal. Here, we report the case of a patient undergoing fusion surgery for lumbar canal stenosis due to degenerative spondylolisthesis and multiple intraspinal canal calcifications associated with psoriatic arthritis (PsA). A 55-year-old female patient presented with pain in the left leg and intermittent claudication for 1 month. One year ago, she was diagnosed with PsA and received outpatient treatment, including biological medication, at the Division of Rheumatology, Department of Internal Medicine of our institution. She was referred to our department, and radiological examination revealed lumbar canal stenosis caused by spondylolisthesis and multiple calcifications in the lumbar spinal canal. We performed posterior lumbar interbody fusion (PLIF) with percutaneous pedicle screw fixation concomitant with removal of the calcifications. The postoperative course was uneventful, and her neurological symptoms improved. Although several prior case reports have noted intraspinal canal calcifications due to collagen disease or chronic kidney disease, calcifications associated with PsA are rare. We discuss the diagnosis of PsA and its relationship with intraspinal canal calcifications by reviewing the previous relevant literature.


Potential use of hematopoietic stem cells after radiation injury.
Bone marrow transplantation has been used for several years in the treatment of hematopoietic system malfunction. However, this particular therapy option has had minimal benefit when the hematopoietic system failure results from radiation exposure, such as that after the Chernobyl accident. In the last ten years, there has been considerable progress in the development of methods to encourage stem cell repopulation with the application of hematopoietic growth factors, and to reconstitute the hematopoietic system with stem cells extracted from the peripheral blood. Problems with allogeneic bone marrow or peripheral blood stem cell transplantation as a therapy option include graft-versus-host disease and a shortage of human leukocyte antigen (HLA)-matched donors. These problems can be overcome if an autologous bone marrow or peripheral blood transplant is performed, but this is not always practical. Another approach to combat these difficulties is the use of umbilical cord blood as a source of donor cells, since placental blood is rich in stem cells and less prone to lead to graft-versus-host disease than mature blood.


Is rheumatoid arthritis in Indians associated with HLA antigens sharing a DR beta 1 epitope?
HLA class II antigens were identified in a group of 44 patients with rheumatoid arthritis (RA) originating largely from the north or northeast of the Indian subcontinent and resident now in east London. Compared with 67 locally typed east London Asian controls, the prevalence of three HLA-DR antigens was raised in the patients: DR1 18.2% v 6.0% chi 2 = 3.99, DR4 20.5% v 11.9% chi 2 = 1.48, and DRw10 27.3% v 8.9% chi 2 = 6.56. These differences were also found when the patients with RA were compared with a larger control group of 110 northern Indians: DR1 18.2% v 7.2% chi 2 = 4.02, DR4 20.5% v 7.2% chi 2 = 5.56, and DRw10 27.3% v 8.1% chi 2 = 9.7. Twenty five (57%) of the patients expressed at least one of these antigens. All patients were also characterised for HLA-Dw types by mixed lymphocyte culture typing. The prevalence of the HLA-DR4 associated Dw types in the patients was: Dw4 2.3%, Dw10 0%, Dw14 11.4%, and Dw15 6.8%. The DR beta 1 chains of DR1 and DRw10 together with the Dw types of DR4 other than Dw10 share amino acid residues in a region of the third hypervariable region considered to be critical in antigen presentation. It is concluded that RA in Indians is associated with these HLA antigens, and data from this study support the hypothesis of a cross reactive epitope common to HLA specificities associated with RA.


The effect of nearby bubbles on array gain.
The coherent processing of signals from multiple hydrophones in an array offers improvements in angular resolution and signal-to-noise ratio. When the array is steered in a particular direction, the signals arriving from that direction are added in phase, and any signals arriving from other directions are not. Array gain (AG) is a measure of how much the signal arriving from the steering direction is amplified relative to signals arriving from all other directions. The subject of this paper is the manner in which the AG of an acoustic array operating in water that contains air bubbles is affected by scattering from nearby bubbles. The effects of bubbles on acoustic attenuation and dispersion are considered separately from their effects on AG. Acoustic measurements made in bubbly water using the AB Wood tank at the Institute of Sound and Vibration Research, University of Southampton, in June 2008 show that as bubble density increases, relative phase shifts in individual hydrophone signals increase and signal correlation among the hydrophones is reduced. A theory and numerical simulation linking bubble density at the hydrophone to the AG is in good agreement with the measurements up to the point where multiple scattering becomes important.


BRCA1 functions as a breast stem cell regulator.
BRCA1 is an important susceptibility gene for breast cancer, which confers substantial lifetime risks of breast cancer, particularly in the pre-menopausal age group. Typically, carriers of BRCA1 mutations develop breast tumours that grow rapidly and are high grade and oestrogen receptor negative. They also possess a basal epithelial phenotype, as defined by cytokeratin expression, that is not present in most breast cancers. It has recently been proposed that the adult breast stem cell expresses only basal keratins. Others have indicated a CD44 positive, CD24 negative phenotype for breast cancer stem cells. In this paper, I argue that the biology of human BRCA1 and its rodent homologues and the clinicopathological features of breast cancer related to BRCA1 support the notion that one of the key functions of BRCA1 is to act as a stem cell regulator. This has implications for the management of carriers of mutations of BRCA1, in part because support for the role of BRCA1 as a stem cell regulator would emphasise the distinct nature of breast cancer related to BRCA1.


Snakebite Envenoming - A Combined Density Equalizing Mapping and Scientometric Analysis of the Publication History.
Estimates suggest that more than 25,000 to 125,000 people die annually from snakebite envenomation worldwide. In contrast to this major disease burden, thorough bibliometric studies do not exist so far that illustrate the overall research activity over a long time span. Therefore, the NewQIS-platform conducted an analysis on snakebite envenoming using the Thomson Reuters database Web of Science. To determine and assess changes regarding the scientific activities and to specifically address the more recent situation we analyzed two time intervals (t). During the first time interval from 1900 to 2007 (t1) 13,015 publications (p) were identified. In the following period (2008-2016 = t2) 4,982 publications were identified by the same search strategy. They originate from 114 (t1) respectively 121 countries (t2), with the USA (p = 3518), Brazil (p = 1100) and Japan (p = 961) being most productive in the first period, and the USA (p = 1087), Brazil (p = 991) and China (p = 378) in the second period, respectively. Setting the publication numbers in relation to GDP/capita, Brazil leads with 92 publications per 10,000 Int$GDP/capita, followed by India with 79 publications per 10000 Int$GDP/capita (t1). Comparing the country's publication activity with the Human Development Index level indicates that the majority of the publications is published by highly developed countries. When calculating the average citation rates (citations per published item = CR) mainly European countries show the highest ranks: From 1900-2007 Sweden ranks first with a CR = 27, followed by the Netherlands (CR = 24.8), Switzerland (CR = 23), Spain, Austria and the USA (CR = 22). From 2008 to 2016 the highest rate achieves Switzerland with a value of 24.6, followed by Belgium (CR = 18.1), Spain (CR = 16.7), Costa Rica (CR = 14.9) and Netherlands (CR = 14). Compared with this, the USA was placed at rank 13 (CR = 9,5). In summary, the present study represents the first density-equalizing map projection and in-depth scientometric analysis of the global research output on snakebites and its venoms. So it draws a sketch of the worldwide publication architecture and indicates that countries with a high incidence of snakebites and a low economical level still need to be empowered in carrying out research in this area.


Waldenstrom's macroglobulinemia presenting with spinal cord compression: a case report.
Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma characterized by a wide range of clinical presentations related to direct tumor infiltration and the production of IgM. Most commonly it presents with cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity syndrome. We report a case of WM in an 81-year-old man who initially presented with severe back pain. The patient had no peripheral lymphadenopathy or hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine revealed an epidural mass causing spinal cord compression at T9. Surgical decompression was performed and pathological analysis of the mass revealed a lymphoproliferative B-cell process. The diagnosis of WM was established after cytomorphologic and immunohistochemical analysis of the patient's bone marrow revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow infiltrate along with an elevated serum IgM level. The patient responded both clinically and serologically to local radiotherapy. This case is unusual because the patient lacked all common clinical features of WM. This is the first reported case of epidural spinal cord compression as the initial manifestation of WM, adding to the spectrum of clinical presentations seen in this disease.


Reconfiguring the AR-TIF2 Protein-Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen.
The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein-protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins. We reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in U-2 OS cells would behave differently in the CaP cell background. Although we did not observe any significant differences in the compound responses between the assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay would be more amenable to screening, because both the virus and cell culture demands are lower. We implemented a testing paradigm of counter-screens and secondary hit characterization assays that allowed us to identify and deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional activation (AR-TA) through antagonism of AR ligand binding or by non-specifically blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor molecules act distally to AR ligand binding, they have the potential to modulate AR-TA in a cell-specific manner that is distinct from existing anti-androgen drugs, and to overcome the development of resistance to AR antagonism. We anticipate that the application of this testing paradigm to characterize the hits from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed into novel therapeutics for CaP and CRPC.


Cycloxaprid insecticide: nicotinic acetylcholine receptor binding site and metabolism.
Cycloxaprid (CYC) is a novel neonicotinoid prepared from the (nitromethylene)imidazole (NMI) analogue of imidacloprid. In this study we consider whether CYC is active per se or only as a proinsecticide for NMI. The IC50 values (nM) for displacing [(3)H]NMI binding are 43-49 for CYC and 2.3-3.2 for NMI in house fly and honeybee head membranes and 302 and 7.2, respectively, in mouse brain membranes, potency relationships interpreted as partial conversion of some CYC to NMI under the assay conditions. The 6-8-fold difference in toxicity of injected CYC and NMI to house flies is consistent with their relative potencies as in vivo nicotinic acetylcholine receptor (nAChR) inhibitors in brain measured with [(3)H]NMI binding assays. CYC metabolism in mice largely involves cytochrome P450 pathways without NMI as a major intermediate. Metabolites of CYC tentatively assigned are five monohydroxy derivatives and one each of dihydroxy, nitroso, and amino modifications. CYC appears be a proinsecticide, serving as a slow-release reservoir for NMI with selective activity for insect versus mammalian nAChRs.


[Diagnosis and treatment for 2 cases of tuberous sclerosis complex with pulmonary lymphangioleiomyomatosis].
To improve the diagnosis and treatment for tuberous sclerosis complex (TSC) with pulmonary lymphangioleiomyomatosis, a retrospective analysis was performed based on the clinical data of 2 patients with such disease. Both of them have typical thin-walled cystic lesion throughout the lung field, renal angioleiomyolipoma, and various degrees of skin lesions. Central nervous system is involved in one patient. Lesions in the lung and kidney in one patient were improved significantly after 5 months of rapamycin treatment. The clinical phenotypes were diverse in TSC patients. The CT imaging showed typical characteristics when the lung was invaded by the tumor. When a patient was diagnosed as pulmonary lymphangioleiomyomatosis, we should pay attention to the clinical screening of TSC. Rapamycin is an effective and safe treatment for this disease.


Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.
Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden. In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007-2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors). In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population. Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.


Primary retroperitoneal extraovarian granulosa cell tumor.
Extraovarian granulosa cell tumors (GCTs) develop from ectopic gonadal tissue situated along the embryonal route of the genital ridge. Primary retroperitoneal tumors are extremely rare, with an incidence of 02% -06% and 80-85% probability of malignancy. Only eight such case reports have been published previously. We herein, report a rare case of extraovarian retroperitoneal GCT in a 55-year-old woman who presented with intermittent left lumbar region pain of one-year duration. She had a history of hysterectomy and bilateral salpingo-oophorectomy 8 years ago for uterine leiomyoma. Laparotomy revealed a retroperitoneal mass measuring 8cm x 10cm x 20cm in size, solid cystic with areas of necrosis and hemorrhage. The gross features, classical histopathology, and positive immunostaining of the retroperitoneal mass with inhibin, calretinin, PR, WT1 and immunonegativity for EMA were characteristic of adult-type GCT. Excluding any previous history of primary ovarian GCT in this patient, a de-novo retroperitoneal diagnosis was established.


Compression Performance and Deformation Behavior of 3D-Printed PLA-Based Lattice Structures.
The aim of this study is to fabricate biodegradable PLA-based composite filaments for 3D printing to manufacture bear-loading lattice structures. First, CaCO3 and TCP as inorganic fillers were incorporated into a PLA matrix to fabricate a series of composite filaments. The material compositions, mechanical properties, and rheology behavior of the PLA/CaCO3 and PLA/TCP filaments were evaluated. Then, two lattice structures, cubic and Triply Periodic Minimal Surfaces-Diamond (TPMS-D), were geometrically designed and 3D-printed into fine samples. The axial compression results indicated that the addition of CaCO3 and TCP effectively enhances the compressive modulus and strength of lattice structures. In particular, the TPMS-D structure showed superior load-carrying capacity and specific energy absorption compared to those of its cubic counterparts. Furthermore, the deformation behavior of these two lattice structures was examined by image recording during compression and computed tomography (CT) scanning of samples after compression. It was observed that pore structure could be well held in TPMS-D, while that in cubic structure was destroyed due to the fracture of vertical struts. Therefore, this paper highlights promising 3D-printed biodegradable lattice structures with excellent energy-absorption capacity and high structural stability.


Boundary slip study on hydrophilic, hydrophobic, and superhydrophobic surfaces with dynamic atomic force microscopy.
Slip length has been measured using the dynamic atomic force microscopy (AFM) method. Unlike the contact AFM method, the sample surface approaches an oscillating sphere with a very low velocity in the dynamic AFM method. During this process, the amplitude and phase shift data are recorded to calculate the hydrodynamic damping coefficient, which is then used to obtain slip length. In this study, a glass sphere with a large radius was glued to the end of an AFM cantilever to measure the slip length on rough surfaces. Experimental results for hydrophilic, hydrophobic, and superhydrophobic surfaces show that the hydrodynamic damping coefficient decreases from the hydrophilic surface to the hydrophobic surface and from the hydrophobic one to the superhydrophobic one. The slip lengths obtained on the hydrophobic and superhydrophobic surfaces are 43 and 236 nm, respectively, which indicates increasing boundary slip from the hydrophobic surface to the superhydrophobic one.


Evidence for the presence of kinetin in DNA and cell extracts.
In contrast to the current view that kinetin (N6-furfuryladenine) is an unnatural and synthetic compound, we have detected it in commercially available DNA, in freshly extracted cellular DNA from human cells and in plant cell extracts by two independent methods. First, we discovered that N6-furfuryladenine has electrochemical properties that can be applied for monitoring this modified base by a HPLC/UV/EC method. Second, we have confirmed electrochemical assignments by mass-spectrometric analysis. A pathway of kinetin formation is proposed in which the formation of furfural by oxidative damage of the deoxyribose moiety of DNA is followed by its reaction with adenine residues to form N6-furfuryladenine. Since this modification can lead to mutations, the odd DNA base has to be removed by repair enzymes.


Neurocognitive measures in the assessment of vestibular disturbance in patients with brain injury.
Problems with balance and dizziness are one of the most common complaints of individuals who have experienced a brain injury and are reported in up to 90% of cases. Despite the ubiquity of vestibular disturbance in this population, there remains a dearth of research on the interaction between physiological and cognitive systems responsible for maintaining balance. The purpose of this article is to review studies on the interaction of physiological and cognitive processes required to maintain balance that may aide assessment and recovery of balance disturbance in patients with brain injury. This article provides a review of research on the role of higher order cognitive processes in maintaining balance and rational for further inclusion of neurocognitive measures in the assessment of vestibular disturbance. Greater inclusion of neurocognitive measures in assessment of vestibular disturbance provides a method of assessment containing increased ecological validity compared to traditional assessments, better prepares patients for discharge, and may reduce the incidence of future injury.


Rutin increases alpha-tubulin acetylation via histone deacetylase 6 inhibition.
Microtubules are dynamic cytoskeletal filaments composed of alpha- (α) and beta (β)-tubulin proteins. α-tubulin proteins are posttranslationally acetylated, and loss of acetylation is associated with axonal transport defects, a common alteration contributing to the pathomechanisms of several neurodegenerative diseases. Restoring α-tubulin acetylation by pharmacological inhibition of HDAC6, a primary α-tubulin deacetylase, can rescue impaired transport. Therefore, HDAC6 is considered a promising therapeutic target for neurodegenerative diseases, but currently, there is no clinically approved inhibitor for this purpose. In this study, using drug repurposing strategy, we aimed to identify compounds possessing HDAC6 inhibition activity and inducing α-tubulin acetylation. We systematically analyzed the FDA-approved library by utilizing virtual screening and consensus scoring approaches. Inhibition activities of promising compounds were tested using in vitro assays. Motor neuron-like NSC34 cells were treated with the candidate compounds, and α-tubulin acetylation levels were determined by Western blot. Our results demonstrated that rutin, a natural flavonoid, inhibits cellular HDAC6 activity without inducing any toxicity, and it significantly increases α-tubulin acetylation level in motor neuron-like cells.


Stapled closed technique for laryngectomy and pharyngeal repair.
Total laryngectomy is a recognised treatment for advanced laryngeal carcinoma. Traditionally, pharyngeal repair is performed with layered sutures. We describe our experience with a technique of closed pharyngoplasty using a linear stapler device. Ten total laryngectomies were performed from July 2002 to July 2004, using an Ethicon TLC 75 linear stapler for pharyngeal closure. Data collected included age, sex, staging, endoscopic assessment, surgical margins and post-operative course (including complications and swallowing). Patients comprised eight men and two women. The mean age was 55.4 years. Six patients had stage T4 endolaryngeal carcinoma and four had stage T3. Four patients underwent pre-operative radiotherapy. Clear surgical margins were achieved in all patients. One patient developed a pharyngocutaneous fistula. Patients resumed oral intake at 48 hours, or at 72 hours if they had undergone pre-operative radiotherapy. Patients' mean hospital stay was seven days. This stapled closed technique for pharyngoplasty is efficient and eliminates the risk of wound contamination, thus theoretically reducing the risk of tumour seeding. In addition, we were able to commence patients on oral fluids at a mean of 48 hours after surgery. The mean hospital stay was seven days. We recommend this technique as an alternative for repairing the pharynx in patients undergoing total laryngectomy for endolaryngeal carcinoma.


Insulin-producing cells derived from rat bone marrow and their autologous transplantation in the duodenal wall for treating diabetes.
Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM.


[A study of CD23 expression and regulation in the patients with asthma].
To study the pathogenesis of asthma, we examined the CD23 expression on peripheral blood mononuclear cells (PBMC) from 25 healthy donors and 28 asthmatic patients with APAAP test. The results demonstrated that CD23 antigen expressed strongly on PBMC from patients and their PBMC correlated positively with their IgE level (r = 0.78 P < 0.01). We investigated the regulation of CD23 expression by IL-4 and IFN-gamma in vitro, the results demonstrated that IFN-gamma could inhibit spontaneous and IL-4 induced expression of CD23. It was suggested that the analysis of the percentage of positive CD23 expression is useful for making diagnosis and assessing severity of asthma and is of significance in elucidating the pathogenesis of the asthma.


Neural correlates of moral and non-moral emotion in female psychopathy.
This study presents the first neuroimaging investigation of female psychopathy in an incarcerated population. Prior studies have found that male psychopathy is associated with reduced limbic and paralimbic activation when processing emotional stimuli and making moral judgments. The goal of this study was to investigate whether these findings extend to female psychopathy. During fMRI scanning, 157 incarcerated and 46 non-incarcerated female participants viewed unpleasant pictures, half which depicted moral transgressions, and neutral pictures. Participants rated each picture on moral transgression severity. Psychopathy was assessed using the Psychopathy Checklist-Revised (PCL-R) in all incarcerated participants. Non-incarcerated participants were included as a control group to derive brain regions of interest associated with viewing unpleasant vs. neutral pictures (emotion contrast), and unpleasant pictures depicting moral transgressions vs. unpleasant pictures without moral transgressions (moral contrast). Regression analyses in the incarcerated group examined the association between PCL-R scores and brain activation in the emotion and moral contrasts. Results of the emotion contrast revealed a negative correlation between PCL-R scores and activation in the right amygdala and rostral anterior cingulate. Results of the moral contrast revealed a negative correlation between PCL-R scores and activation in the right temporo-parietal junction. These results indicate that female psychopathy, like male psychopathy, is characterized by reduced limbic activation during emotion processing. In contrast, reduced temporo-parietal activation to moral transgressions has been less observed in male psychopathy. These results extend prior findings in male psychopathy to female psychopathy, and reveal aberrant neural responses to morally-salient stimuli that may be unique to female psychopathy.


Vacations to sunny destinations, sunburn, and intention to tan: a cross-sectional study in Denmark, 2007-2009.
Denmark has experienced an increase in melanoma incidence since the 1960s. Exposure to ultraviolet radiation is the main preventable cause of this cancer. We examined current travel to, and sun-related behaviour of Danes at, sunny destinations in relation to their risk for sunburn. A population-based sample of 11,158 respondents aged 15-59 years completed three questionnaires in 2007-2009 that included items on exposure to ultraviolet radiation. Using logistic regression analysis we examined the relations between sunny vacations, sun-related behaviour, demographic factors and risk for sunburn. During 2007-2009, 44.8-45.8% of the respondents travelled to a sunny destination at least once a year; 24% became sunburnt, and 69% tanned intentionally. The odds ratio for sunburn in general for people who went on a sunny vacation as compared with those who did not was 1.6 (1.5-1.7). Sunscreen use (1.9; 1.4-2.6) and intentional tanning (3.4; 2.8-4.1) were positively associated with sunburn on vacation. Taking a vacation in a sunny place is a risk factor for sunburn, especially for young people. The recommendation for sunscreen use should be re-evaluated, as intention to tan is the most important factor in sunburn on vacation and should be targeted more strategically.


A TLC-Direct Bioautography Method for Detection of Antiurolithiatic Metabolites.
Hyperoxaluria is major urinary disorder troubling largest population throughout the world predominantly involving calcium oxalate (CaOx) crystals. Ancient Ayurvedic system of medicine in India claims better option in treatment of urolithiasis. A plant from "Pashanbheda" group is Phyllanthus niruri L., possessing antiurolithiatic activity, needed to be screened and validated. In the present study, a rapid, easy and efficient method for CaOx crystal inhibition in the agar gel system analogous to antimicrobial well diffusion assay is proposed. A novel thin-layer chromatography (TLC)-direct bioautography method was also proposed to detect the antilithiatic metabolites. It helps to localize the active metabolites in P. niruri, further the partial structure elucidation was characterized by High Resolution Liquid Chromatography by mass spectroscopy (LC-HRMS) analysis. The agar well diffusion method shows 50% inhibitory concentration (IC50) value at 228.55 and 493.529 mg/mL for tri-sodium citrate and P. niruri extract, respectively. The lowest concentration showing visible crystal inhibition (minimum inhibitory concentration, MIC) in both samples was found to be 20 mg/mL. In this study, a unique agar gel well diffusion and TLC-direct bioautography method successfully screened, detected and confirmed CaOx crystal inhibitory metabolites from P. niruri. The tuberonic acid was detected in bioactive fraction of P. niruri by LC-HRMS characterization.


Structural studies of Escherichia coli UDP-N-acetylmuramate:L-alanine ligase.
Uridine diphosphate N-acetylmuramate:L-alanine ligase (EC 188.8.131.52, UNAM:L-Ala ligase or MurC gene product) adds the first amino acid to the sugar moiety of the peptidoglycan precursor, catalyzing one of the essential steps in cell wall biosynthesis for both gram-positive and gram-negative bacteria. Here, we report our studies on the secondary and quaternary structures of UNAM:L-Ala ligase from Escherichia coli. The molecular weight of the purified recombinant enzyme determined by electrospray ionization mass spectrometry agreed well with the molecular weight deduced from the DNA sequence. Through sedimentation equilibrium analysis, we show that the enzyme exists in equilibrium between monomeric and dimeric forms and that the dissociation constant of the dimer, Kd, was determined to be 1.1 +/- 0.4 microM at 37 degrees C and 0.58 +/- 0.30 microM at 4 degrees C. A very similar Kd value was also obtained at 37 degrees C by gel filtration chromatography. The secondary structure of the enzyme was characterized by circular dichroism spectroscopy. No change in the secondary structure was observed between the monomeric and dimeric forms of the enzyme. The activity assays at enzyme concentrations both below and above the determined Kd value lead to the conclusion that the enzyme is active both as dimers and as monomers and that the specific activity is independent of the oligomerization state.


A Pilot Intervention Targeting Dietary Intake in School Cafeterias.
This study assessed fruit and vegetable (F&V) waste during school meals in two public elementary schools, and investigated the impact of a tasting intervention implemented in one of these schools. F&V waste was evaluated before (baseline), immediately after (post-testing), and six weeks following (follow-up), the tasting intervention. The modal outcome at each assessment was that children ate all of the served F&Vs. During tastings, most children attempted and liked the offered F&Vs. No differences between schools in F&V waste were evident at post-testing; at follow-up, the intervention school had significantly less F&V waste than the control school. Generally, students were consuming the F&Vs served. Policy impact might be enhanced via a low-intensity tasting intervention.


Expression and characterization of the heme-binding domain of Chlorella nitrate reductase.
A recombinant protein corresponding to the putative heme-binding domain of assimilatory NADH:nitrate reductase from Chlorella vulgaris has been expressed and purified from transformed Escherichia coli BL21 cells. The recombinant protein, exhibited a subunit molecular mass of approximately 10 kDa with a N-terminal sequence beginning with the residues PAGA in agreement with that predicted by cDNA analysis. The UV-visible spectrum of the protein confirmed the incorporation of heme with maxima at 413 nm and 423, 528, and 557 nm for the oxidized and reduced forms, respectively. Circular dichroism spectra indicated the environment of the heme chromophore was very similar to that of the native enzyme. Potentiometric titrations of the recombinant heme domain yielded a midpoint potential of +16 mV (n = 1, pH 7), substantially higher than the values of -160 mV obtained for the native enzyme and -28 mV obtained for a previously expressed recombinant heme domain that contained part of the Mo-pterin domain. These results indicate that portions of the amino acid sequence that are involved in the formation of the Mo-pterin domain of Chlorella nitrate reductase influence the redox potential of the heme prosthetic group.


Grafting of a novel gold(III) complex on nanoporous MCM-41 and evaluation of its toxicity in Saccharomyces cerevisiae.
The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl(3)@PF-MCM- 41 (AuCl(3) grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6- trimethylpyridine)Au(III) and AuCl(3)@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl(3)@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum.


Impact of environmental changes on the reproductive biology in Pyrostegia venusta Presl.
Local environment (temperature and relative humidity) affects reproductive biology in Pyrostegia venusta (Bignoniaceae) growing at Agra and Mysore. At Agra, the species flowers profusely during December to March, but fails to bear fruits. At Mysore, on the other hand it flowers during November to February and produces well developed fruits with winged seeds. This species, growing at two places, exhibited differences in their pollen fertility and in vivo pollen germination. Pollen fertility at Agra and Mysore was 27.55 and 80-90%, respectively The in vivo pollen germination on stigmatic surface was only 3-4% at Agra, but 85-95% at Mysore. The flowers at Agra also exhibited heterostyly and increased number of stamens and stigmatic lobes. The significantly low and wide ranged temperature (4.5-33.8 degrees C) and between 23-98% RH during the flowering period at Agra could be the cause for reduced in pollen fertility floral polymorphism and inhibition of pollen germination on the stigmatic surface and fruitlessness. At Mysore, where temperature ranges between 20.2-33.5 degrees C and RH varies from 33-75% profuse fruiting takes place. The study shows a direct control of environment over the process of reproduction.


Visualising the activity of the cystine-glutamate antiporter in glial cells using antibodies to aminoadipic acid, a selectively transported substrate.
The cystine-glutamate antiporter is a transport system that facilitates the uptake of cystine, concomitant with the release of glutamate. The cystine accumulated by this transporter is generally considered for use in the formation of the cysteine-containing antioxidant glutathione, which is abundant in many glial cells. This study used the simple strategy of generating an antibody to aminoadipic acid, a selective substrate for the cystine-glutamate antiporter. Stereospecific accumulation of aminoadipic acid into specific cell types in rat brain slice preparations was detected immunocytochemically. Strong accumulation was detected in astroglial cells in all brain regions studied including those in white matter tracts. Strong accumulation into radial glial cells, including the retinal Müller cells and the Bergmann glial cells was also observed. Glial accumulation was observed not only in cells within the blood brain barrier, but also outside such; anterior pituitary folliculostellate cell and intermediate lobe pituitary glial cells exhibited strong accumulation of aminoadipic acid. Interestingly, some glial cells such as the posterior pituitary glial cells (pituicytes) exhibited very little if any accumulation of aminoadipic acid. Within the brain labelling was not uniform. Particularly strong labelling was noted in some regions, such as the glial cells surrounding the CA1 pyramidal cells. By contrast, neurons never exhibited uptake of aminoadipic acid. Because cystine uptake is associated with glutamate release, it is suggested that this antiporter might contribute to release of glutamate from glial cells under some pathophysiological conditions.


Cadmium activates a mitogen-activated protein kinase gene and MBP kinases in rice.
Mitogen-activated protein kinase (MAPK) pathways are modules involved in the transduction of extracellular signals to intracellular targets in all eukaryotes. In plants, it has been evidenced that MAPKs play a role in the signaling of biotic and abiotic stresses, plant hormones, and cell cycle cues. However, the effect of heavy metals on plant MAPKs has not been well examined. The Northern blot analysis of OsMAPK mRNA levels has shown that only OsMAPK2, but not OsMAPK3 and OsMAPK4, expressed in suspension-cultured cells in response to 100-400 microM Cd treatments. The OsMAPK2 transcripts increased within 12 h upon 400 microM Cd treatment. In addition, we found that 42- and 50-kDa MBP kinases were significantly activated by Cd treatment in rice suspension-cultured cells. And 40-, 42-, 50- and 64-kDa MBP kinases were activated in rice roots. Furthermore, GSH inhibits Cd-induced 40-kDa MBP kinase activation. By immunoblot analysis and immunoprecipitation followed by in-gel kinase assay, we confirmed that Cd-activated 42-kDa MBP kinase is a MAP kinase. Our results suggest that a MAP kinase cascade may function in the Cd-signalling pathway in rice.


Kocuria rosea, kocuria kristinae, leuconostoc mesenteroides as caries-causing representatives of oral microflora.
Recently, opportunistic microflora are increasingly known to be involved in the development of pathological processes in various systems and organs. This situation promotes interest in their detailed study as causative agents of bacterial infections. To study the microbial species residing in carious cavities in acute profound caries. The study involved 14 people with a diagnosis of acute profound caries. Microbiological methods included determining species of microorganisms' cultures from carious cavities in acute profound caries. Final identification was carried out by automatic bacteriological analyzer Vitec-2compact bioMérieux. Among the bacteria isolated, Kocuria rosae, Kocuria kristinae, and Leuconostoc mesenteroides are the focus of the authors' attention due to their identification rate in the patients. These microbial species are little studied due to the lack of data on their cariogenic associations.The meticulous study of the microorganisms, isolated from carious cavities in patients with acute profound caries by automatic bacteriological analyzer Vitec-2 Systems bioMérieux, and findings on their biochemical properties allow us to conclude that Kocuria rosae, Kocuria kristinae, and Leuconostoc mesenteroides are among the microorganisms making up the microflora of carious cavities under acute profound caries and are involved in the development of the caries process.


Sertraline: new indication. May help children with obsessive-compulsive disorder.
(1) The choice of treatment for children with obsessive-compulsive disorder is difficult. Behaviour therapy and antidepressants have not been assessed adequately in this setting, and their efficacy seems limited. Clomipramine was the first antidepressant to show a degree of efficacy. (2) Sertraline is the first drug to be licensed in France for children aged from 6 to 17 years with obsessive-compulsive disorder. (3) According to our literature search, the evaluation file on sertraline in this indication mainly contains data from a double-blind placebo-controlled trial involving 187 children. After 3 months of treatment, sertraline was significantly more effective than placebo, although most children remained symptomatic. Direct comparison is lacking, but sertraline seems as effective as clomipramine. (4) However, 13% of children receiving sertraline left this trial because of adverse events (3% on placebo; p = 0.02). The short-term safety profile of sertraline in children is the same as in adults, i.e. mainly nausea, agitation, headache, insomnia and tremor. (5) We have no data on the effects of prolonged sertraline therapy in children, particularly on neuropsychological development. (6) The first-line treatment of obsessive-compulsive disorder is behaviour therapy. Sertraline, like clomipramine, is an option when behaviour therapy fails or is unfeasible. The choice between sertraline and clomipramine should be discussed case by case, according to their safety profiles; however, we have more experience with clomipramine, which should therefore be preferred over sertraline.


Ultrasonography in the diagnosis of Hashimoto's thyroiditis.
Hashimoto's thyroiditis is a type of autoimmune thyroid disease with an increasing prevalence in past decades. Its diagnosisis mostly based on ultrasonography. Ultrasonography is a useful and essential tool to make this diagnosis based on the characteristics of the disease. In the differential diagnosis of thyroid nodules, ultrasound-guided fine-needle biopsy is an effective method to distinguish Hashimoto's thyroiditis from other thyroid disorders. One exciting and recent advance is that non-invasive ultrasound-based methods have supplemented fine-needle aspiration to diagnose Hashimoto's thyroiditis under more complex conditions. In this review, we discuss the recent advantages of ultrasonography in the diagnosis of Hashimoto's thyroiditis.


Sexual homicide: a spatial analysis of 25 years of deaths in Los Angeles.
Although it has been frequently studied over the last 100 years, empirical studies of sexual homicide are lacking. The majority of the existing studies have been descriptive in nature. In this study, we consider the spatial geometry of sexual homicide and the impact of time and distance on case solvability. An analysis of sexual homicides (n = 197) from 1980 to 2004 for Los Angeles County was conducted. Offender and victim journey to encounter site, journey to body disposal site, and journey-after-crime trips were examined. Descriptive and bivariate analyses were performed to examine victim, offender and case characteristics. Using logistic regression models both time factors and offense geometries were found to be significant predictors in case solvability. Simpler geometries are significantly more likely to be solved than cases with complex geometries and the longer a case remains unsolved the less likely it is that it will be closed. The results provide support for some of the findings from earlier descriptive studies and extend our understanding of the spatial geometry of sexual homicide.


Common injuries related to weightlifting: MR imaging perspective.
Weightlifting has evolved to become a ubiquitous form of exercise. Resistance training has been shown to have beneficial effects on both muscle and osseous maintenance and development. Competitive weightlifting sports continue to enjoy tremendous popularity, with participants striving to establish new standards in performance and more demanding personal goals. Thus, it is not surprising that we have also seen an increase in injuries related to weightlifting. Many of these injuries are radiographically occult and are best suited for evaluation by magnetic resonance (MR) imaging because many involve the soft tissues. In this article, we discuss some of the factors that contribute to these injuries and address the mechanisms of injury and the MR imaging manifestations of the more common injuries.


In vitro studies with R 51,211 (itraconazole).
The in vitro activity of R 51,211 (itraconazole, accepted generic name; Janssen Pharmaceutica, Beerse, Belgium), a new orally active triazole, was compared with those of two existing orally active azoles, ketoconazole and BAY n 7133, and a topical agent, Ro 14-4767/002. An agar dilution procedure (Kimmig agar) was performed with 148 isolates of pathogenic fungi. Incubation was at 30 degrees C from 48 h to 7 days. R 51,211 was dissolved in 0.2 N HCl in absolute ethanol, ketoconazole was dissolved in 0.2 N HCl alone, BAY n 7133 was dissolved in absolute ethanol, and Ro 14-4767/002 was dissolved in dimethyl sulfoxide. R 51,211 and Ro 14-4767/002 were the most active drugs against isolates of Histoplasma capsulatum, and R 51,211 showed the greatest activity in vitro against isolates of Blastomyces dermatitidis and Cryptococcus neoformans. Ro 14-4767/002 was the most active drug against 30 isolates of dermatophytes, followed by R 51,211, ketoconazole, and BAY n 7133. R 51,211 showed the best activity in vitro against 19 isolates of Aspergillus fumigatus and Aspergillus flavus, as well as 19 isolates of dematiaceous fungi. All four drugs had 90% MICs of greater than or equal to 16 micrograms/ml when tested with isolates of zygomycetous fungi.


Subcellular Journey of Rare Cold Inducible 2 Protein in Plant Under Stressful Condition.
Rare cold inducible 2 (RCI2) proteins are small hydrophobic membrane proteins in plants, and it has been widely reported that RCI2 expressions are dramatically induced by salt, cold, and drought stresses in many species. The RCI2 proteins have been shown to regulate plasma membrane (PM) potential and enhance abiotic stress tolerance when over-expressed in plants. RCI2 protein structures contain two transmembrane domains that are thought to be PM intrinsic proteins and have been observed at the PM and endomembranes. However, cellular trafficking of RCI2s are not fully understood. In this review, we discussed (i) general properties of RCI2s characterized in many species, (ii) the uses of RCI2s as a tracer in live cell imaging analyses and when they are fused to fluorescence proteins during investigations into vesicle trafficking, and (iii) RCI2 functionalities such as their involvement in rapid diffusion, endocytosis, and protein interactions. Consequently, the connection between physiological characteristics of RCI2s and traffic of RCI2s interacting membrane proteins might be helpful to understand role of RCI2s contributing abiotic stresses tolerance.


RELATIONSHIP OF ADIPONECTIN LEVEL WITH LIPID PROFILE IN TYPE-2 DIABETIC MEN WITH CORONARY HEART DISEASE.
Cerebro-vascular disease is a commonest long term complication of type-2 diabetes mellitus. The study was done to determine concentration of serum adiponectin and lipid profile in type-2 diabetic men with coronary heart disease (CHD) in the region of Khyber Pakhtunkhwa (KPK), and to find possible relationship between them. This was a cross-sectional study comprising of randomly selected thirty six healthy adult males and thirty six type-2 diabetic males with coronary heart disease. Their fasting blood samples were analysed for serum adiponectin, fasting blood glucose, glycosylated haemoglobin and lipid profile which included total cholesterol (T-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The relationship of adiponectin with other variables in type-2 diabetic men with coronary heart disease was determined with Pearson correlations coefficient (r). Type-2 diabetic males with coronary heart disease when compared to healthy males showed significantly low levels of serum adiponectin (p=<0.001) and HDL-C (p=<0.001) and significantly high level of FBG (p=<0.001), HbAlc (p=<0.001), TC (p=<0.05), TG (p=<0.05) and LDL-C (p=<0.05). Serum adiponectin level showed a significant negative correlation with FBG (r = -0.332; p= 0.04), HbAlc (r = -0.818; p=<0.01) and TG (r = -0.640; p=<0.01) in type-2 diabetic men with coronary heart disease. Adiponectin showed a significant positive association with HDL-C in controls (r = 0.948; p=<0.01) and patients of type-2 diabetes with CHD (r = 0.650; p=<0.01). Serum adiponectin concentration is markedly decreased in patients of type-2 diabetes with coronary heart disease. Hypoadiponectinemia is related with deranged lipid profile, i.e., high TG and low HDL-C levels in type-2 diabetic men with CHD. Moreover, adiponectin is associated positively with HDL-C and negatively with HbAlc and TG levels in the studied population.


The Frozen Elephant Trunk Technique: European Association for Cardio-Thoracic Surgery Position and Bologna Experience.
Complex lesions of the thoracic aorta are traditionally treated in 2 surgical steps with the elephant trunk technique. A relatively new approach is the frozen elephant trunk (FET) technique, which potentially allows combined lesions of the thoracic aorta to be treated in a 1-stage procedure combining endovascular treatment with conventional surgery using a hybrid prosthesis. These are very complex and time-consuming operations, and good results can be obtained only if appropriate strategies for myocardial, cerebral, and visceral protection are adopted. However, the FET technique is associated with a non-negligible incidence of spinal cord injury, due to the extensive coverage of the descending aorta with the excessive sacrifice of intercostal arteries. The indications for the FET technique include chronic thoracic aortic dissection, acute or chronic type B dissection when endovascular treatment is contraindicated, chronic aneurysm of the thoracic aorta, and chronic aneurysm of the distal arch. The FET technique is also indicated in acute type A aortic dissection, especially when the tear is localized in the aortic arch; in cases of distal malperfusion; and in young patients. In light of the great interest in the FET technique, the Vascular Domain of the European Association for cardio-thoracic Surgery published a position paper reporting the current knowledge and the state of the art of the FET technique. Herein, we describe the surgical techniques involved in the FET technique and we report our experience with the FET technique for the treatment of complex aortic disease of the thoracic aorta.


DNA gyrase inhibitory and antimicrobial activities of some diphenic acid monohydroxamides.
The synthesis and inhibitory activity against DNA gyrase of a series of diphenic acid monohydroxamides 4a-f are described. A protocol of two biological assays showed conclusively that inhibition occurs specifically at the DNA-DNA gyrase complex and is not attributable to nonspecific inhibition. In the enzyme assays, 4c was potent as the prototypical quinolone, nalidixic acid (1), with an IC50 value of 58.3 micrograms/mL compared to 52 micrograms/mL for 1. MIC activity against bacterial strains showed a systematic drop for all compounds relative to 1. For compounds 4c-e, the addition of PMBN produced dramatic increases in MIC activity indicating that activity is likely to be related to membrane transport. Molecular modeling of 4a indicates that the diphenic acid monohydroxamides can bind to the DNA-DNA gyrase complex in a similar fashion as that hypothesized for the quinolone series according to the hypothesis suggested by Shen et al. but may not self-associate by pi-pi stacking. In contrast to the quinolone series, as the diphenic acid monohydroxamides are shown by molecular mechanics minimizations to be nonplanar, they may present novel approaches for chemotherapeutic intervention with a potential for decreased side effects.


Co-Assembly of Graphene Oxide and Albumin/Photosensitizer Nanohybrids towards Enhanced Photodynamic Therapy.
The inactivation of photosensitizers before they reach the targeted tissues can be an important factor, which limits the efficacy of photodynamic therapy (PDT). Here, we developed co-assembled nanohybrids of graphene oxide (GO) and albumin/photosensitizer that have a potential for protecting the photosensitizers from the environment and releasing them in targeted sites, allowing for an enhanced PDT. The nanohybrids were prepared by loading the pre-assembled nanoparticles of chlorin e6 (Ce6) and bovine serum albumin (BSA) on GO via non-covalent interactions. The protection to Ce6 is evident from the inhibited fluorescence and singlet oxygen generation activities of Ce6⁻BSA⁻GO nanohybrids. Importantly, compared to free Ce6 and Ce6 directly loaded by GO (Ce6⁻GO), Ce6⁻BSA⁻GO nanohybrids showed enhanced cellular uptake and in vitro release of Ce6, leading to an improved PDT efficiency. These results indicate that the smart photosensitizer delivery system constructed by co-assembly of GO and albumin is promising to improve the stability, biocompatibility, and efficiency of PDT.


Overexpression of FADD and Bcl-XS proteins as novel prognostic biomarkers for surgically resected non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is one of the most widespread cancer with increasing morbidity and mortality. FAS-associated protein with death domain (FADD) is considered as an essential instrument in cell death, whereas Bcl-XS promotes apoptosis through inhibiting the activity of Bcl-2 and Bcl-XL. We detected the expression of FADD and Bcl-XS in resected NSCLC tissues by immunohistochemistry, and investigated their association with clinicopathological characteristics and prognostic significance of NSCLC patients. Bcl-XS expression was significantly increased in well and moderate differentiated lung SCC (P= 0.004). Lung ADC patients with overexpression of FADD and lung SCC patients with low expression of Bcl-XS had importantly lower overall survival rates by Kaplan-Meier analysis (P= 0.033, P= 0.02, respectively). Multivariate analysis confirmed that elevated expression of FADD was an independent poor prognostic factor for patients with surgically resected lung ADC (P= 0.027) and increased expression of Bcl-XS was an independent good prognostic factor for patients with surgically resected lung SCC (P= 0.016)CONCLUSION: Elevated expression of FADD was identified as independent poor prognostic factor for patients with surgically resected lung ADC, however, increased expression of Bcl-XS was an independent good prognostic biomarker for patients with surgically resected lung SCC.