Rowell Syndrome in Nigeria: Systemic Lupus Erythematosus Presenting as Recurrent Erythema Multiforme in a Young Woman.
Dear Editor, Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by diverse patterns of auto-antibody production with multi-organ affectation. Cutaneous involvement, either alone or in association with other systemic illnesses, is one of its most common manifestations (1). Dermatologic disorders like malar and discoid rashes are quite suggestive of SLE. However, the occurrence of non-specific skin lesions like erythema multiforme (EM) in patients with SLE (Rowell syndrome) can rarely occur (1). In such patients, a diagnosis of SLE may be missed or delayed in the absence of other overt clinical features of lupus. Herein we report a case of recurring EM-like eruptions as the cardinal cutaneous manifestation of previously undiagnosed, active SLE in a young Nigerian woman. A 26-year-old Nigerian woman presented with a three-day history of non-pruritic, generalized, and target-like, erythematous annular patches and plaques which mostly affected the trunk. A few lesions had presented with crusting and erosions at the time of examination (Figure 1). Associated symptoms included oral painful ulcers, low grade fever, and malaise. The patient had no other systemic symptoms and her prior drug history was not remarkable. Her erythrocyte sedimentation rate (ESR) was 66 mm/hour using the Westergren method. Screening for HIV and hepatitis B and C was negative. Herpes simplex, cytomegalovirus, and Epstein Barr viruses could not be screened for. Other baseline investigations (complete blood count, electrolytes, urea and creatinine as well as urinalysis) were within normal limits. The patient was managed as a case of EM of an unidentified inciting agent and her symptoms resolved with supportive care and antibiotics. However, she developed a recurrence about 5 weeks later, with more extensive and coalescent skin lesions (Figure 2). Additionally, there was a new onset of alopecia and pain in the small joints of the hands as well as both knees and ankles. At this time, the patient's ESR had gone up to 112 mm/h and she had developed significant proteinuria, with a protein creatinine ratio of 1.3 g/g (reference <0.5 g/g). Her antinuclear antibody (ANA) titer was high (1:320) with a speckled pattern. Anti-Smith antibody was also positive. A renal biopsy was declined. A tentative diagnosis of Rowell syndrome was made. The patient was started on high-dose steroids and hydroxychloroquine 200 mg twice daily. Subsequent care included the use of mycophenolate mofetil 1 g twice daily for 6 months. This was then changed to azathioprine at 50 mg twice daily. Follow-up after 6 months showed sustained clearance of skin lesions, resolution of fever and joint pains, as well as improvement in the renal profile, with a urine protein-creatinine ratio of 0.77 g/g. The presence of systemic lupus erythematosus, EM-like lesions, and a speckled pattern of antinuclear antibody in our patient fulfils the revised diagnostic criteria for RS put forward by Zeitouni et al. at the turn of the twenty-first century (2). Considering the rarity of EM-like lesions in SLE and the possibility of constitutional symptoms in EM, a diagnosis of RS may be readily overlooked in patients like the one described, whose major cutaneous manifestation of severe active SLE was EM-like lesions. In contrast to classic EM, where skin lesions are concentrated in the extremities, a predominant truncal distribution of EM-like lesions as found in our patient may favor a clinical consideration of RS (3). However, some authors have challenged the existence of Rowell syndrome as a distinct clinical laboratory entity. Arguments put forward in this regard include the fact that none of the immunological markers that have been described in RS are specific to any disorder. Additionally, the annular polycyclic dermatosis seen in sub-acute cutaneous lupus erythematosus (SCLE) can be difficult to clinically and histologically differentiate from EM (4,5). Patients with SLE also have a higher likelihood of developing adverse drug reactions (6). The inherent complexity of SLE may make for delayed and oftentimes difficult diagnosis, especially in a country where immunologic tests are expensive and rheumatologists are scarce. When patients do occasionally present with recurrences of skin lesions in the spectrum of EM, Steven-Johnson syndrome, and toxic epidermal necrolysis in the absence of a definite inciting agent, undiagnosed lupus may indeed be present in some of these individuals and should be considered in the differential diagnosis. In conclusion, while it is very rare, SLE may present first with recurrent episodes of EM-like rash. Despite the various possibilities which underlie their association, prompt identification and treatment of SLE in patients presenting with EM is important to prevent death or irreversible organ damage.


Timing and method of increased carbohydrate intake to cope with heavy training, competition and recovery.
Based upon the fact that fatigue during intense prolonged exercise is commonly due to depletion of muscle and liver glycogen which limits both training and competitive performance, this paper has proposed extraordinary dietary practices which generally advocate high carbohydrate intake at all times before, during and after exercise. The simple goal is to have as much carbohydrate in the body as possible during the latter stages of prolonged intense exercise when the ability for intense exercise usually becomes limiting to performance. This theory is put into practice by recommending that carbohydrate intake after exhaustive exercise should average 50 g per 2 h of mostly moderate and high glycaemic carbohydrate foods. The aim should be to ingest a total of about 600 g in 24 h. Carbohydrate intake should not be avoided during the 4 h period before exercise and in fact it is best to eat at least 200 g during this time. When possible, carbohydrate should be ingested during exercise, generally in the form of solutions containing glucose/sucrose/maltodextrins, at a rate of 30-60 g h-1. Emphasis has been placed upon eating the optimal amount and best type of carbohydrate at the proper times because these practices demand a large amount of food. When diet is not carefully planned according to these guidelines, endurance athletes tend to consume too little carbohydrate because they become satiated with high fat in their diet and they go through periods in the day when recovery of glycogen stores is suboptimal and thus precious time is wasted.


Social familiarity and communication in Down syndrome.
The communication of eight Down syndrome individuals with strangers and with acquaintances was analysed. The spontaneity of their speech and the communicative demands they made on their audiences were found to be low. Some of them broke rules of conversation by not answering questions. Surprisingly, their speech was not more spontaneous with acquaintances. It was further observed that Down syndrome individuals' conversations were in the main restricted to comments on current actions. However, different postures are adopted and different body mobility exhibited depending on partner familiarity. It is concluded that Down syndrome persons prefer to express intimacy/social distance in non-verbal modalities.


Modulation of affect after chronic exposure to the anabolic steroid 17alpha-methyltestosterone in adult mice.
A battery of behavioral tasks in C57BL/6J mice was used to assess changes in affective components of behavior after systemic exposure to the anabolic-androgenic steroid (AAS) 17alpha-methyltestosterone (7.5 mg/kg). Gonadal weight in both sexes was reduced after 16 days of AAS exposure. Changes in discrete components of social behaviors were observed. No changes were recorded in the elevated plus-maze, the light-dark transition, and defensive behavior tests on exposure to 17alpha-methyltestosterone. When compared with controls, AAS-exposed females received a greater number of shocks, and AAS-exposed males displayed a shorter recovery time to consume water after a negative reinforcer in the modified Vogel conflict test. Results show that systemic exposure to a single AAS modified social behaviors, whereas minimal effects on anxiety-related behaviors were observed according to sex.


Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase.
Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric tubular injury; however, whether dysregulation of the renin-angiotensin system (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous Ren2 rats, characterized by renal damage through excessive RAS activation. We also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats received a nonhypotensive dose of candesartan (0.05 mg x kg(-1) x day(-1) sc) or the p38 inhibitor SB-239063 (15 mg x kg(-1) x day(-1) sc) for 4 wk; untreated Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein expression were determined by quantitative PCR and immunohistochemistry, respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1 was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting enzyme inhibition (ramipril, 1 mg x kg(-1) x day(-1) in drinking water for 4 wk). Untreated Ren2 rats showed a >20-fold increase in renal Kim-1 mRNA (expressed as Kim-1-to-GAPDH ratio): 75.5 +/- 43.6 vs. 3.1 +/- 1.0 in SD rats (P < 0.01). Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 +/- 1.5 (P < 0.01) and 9.8 +/- 4.2 (P < 0.05), respectively. Kim-1 protein expression in damaged tubules paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin, alpha-smooth muscle actin, and collagen III expression and with tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38 also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 +/- 70 vs. 27 +/- 2 pg/ml, P < 0.01) rats and abolished in Ren2 rats treated with ramipril (33 +/- 5 pg/ml, P < 0.01). Kim-1 is associated with development of RAS-mediated renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase inhibition reduced Kim-1 in the homozygous Ren2 model.


Urinary incontinence during pregnancy and 1 year after delivery in primiparous women compared with a control group of nulliparous women.
To investigate the impact of the first pregnancy and delivery on the prevalence and types of urinary incontinence during pregnancy and 1 year after delivery. The study was a prospective cohort study with a control group. Primiparous women, who delivered in our department from June 2003 to July 2005, participated. The women filled out a questionnaire 2-3 days after the delivery and a new questionnaire after 1 year. The questionnaires comprised basic characteristics and symptoms of urinary incontinence. An attempted age-matched control group of nulliparous women was included, and filled out similar questionnaires. Prevalences and types of urinary incontinence, and a combined severity- and bother-score (ICIQ-SF score) among the incontinent women, were calculated and compared. The two groups differed significantly in age and most basic characteristics. During pregnancy, the prevalence of any type of urinary incontinence in the primiparous group was 32.1%, compared to 13.8% in the control group. Adjusted OR = 3.3 (95%CI = 2.4-4.4). One year after delivery, the prevalence in the primiparous group was 29.3%, compared to 16.6% in the control group. Adjusted OR = 2.5 (95%CI = 1.8-3.5). ICIQ-SF mean scores among the incontinent women varied insignificantly between 5.8 and 6.2. The prevalence of urinary incontinence during pregnancy was 3.3 times higher compared with a control group of nulliparous women. After 1 year, the difference was reduced, but still 2.5 times higher in the primiparous group. The symptoms and impact on quality of life seemed to be mild to moderate in both groups.


Thyroid function in pregnant women: iodine deficiency after iodine enrichment program.
Significant changes in thyroid function occur during pregnancy which can complicate the interpretation of thyroid function tests. Therefore, normative gestational related reference ranges for thyroid hormones tests are required. The aim of this study was to determine the reference ranges for free triiodothyronine (FT3), free thyroxin (FT4) and thyroid stimulating hormone (TSH) in Iranian pregnant women. This study was a cross-sectional observational study conducted in the Obstetrics and Gynecology department, Akbarabadi University Hospital. A single blood sample from 584 pregnant women was analyzed for thyroid function. Serum levels of TSH, FT4, FT3, total T4 (TT4), T3 resin uptake (T3RU) and anti-thyroid peroxidase antibody (TPO Ab) were measured. Urinary iodine was determined in some cases. Reference intervals based on 2.5th and 97.5th percentiles were calculated. The composition of reference population comprising 584 women included 162 in first trimester and 422 in the third trimester. The 2.5th and 97.5th percentiles values were used to determine the reference ranges for FT3, FT4, TT4, T3RU and TSH. These values were T3 1.4 and 2.9 pmol/L, FT4 7.1 and 18 pmol/L, TT4 7.2 and 13.5 µg/dL and TSH 0.5 and 3.9 µg/L, respectively. The level of urinary iodine in 80.5% of the subjects was less than normal. Serum levels of thyroid hormones are different in Iranian population that could be due to racial differences or differences in iodine intake.


Extrapancreatic solid pseudopapillary neoplasm: report of a case of primary ovarian origin and review of the literature.
Solid pseudopapillary neoplasm, an uncommon, intriguing, low-grade malignant tumor of the pancreas, can exceptionally occur in extrapancreatic sites. We report 1 such case occurring as an ovarian primary in a 25-year-old woman, who presented with abdominal fullness. She remained well 12 years after resection of the 1.7-kg right ovarian tumor. Histologically, the tumor showed a solid, dehiscent, and pseudopapillary growth, traversed by fibrous septa and arborizing blood vessels. The polygonal tumor cells had round nuclei, fine chromatin, and lightly eosinophilic granular cytoplasm. In certain areas, eosinophilic hyaline globules were present. On immunostaining, the tumor cells were positive for β-catenin (nuclear translocation), CD10, CD56, and synaptophysin (focal), and were negative for cytokeratin, E-cadherin, and chromogranin. The morphologic and immunohistochemical features were compatible with those of solid pseudopapillary neoplasm. Review of the literature uncovered 10 cases of extrapancreatic solid pseudopapillary neoplasm with adequate data for analysis. They were seen to occur predominantly in young female patients, who presented with a large tumor mass, similar to their pancreatic counterparts. The most common sites of occurrence were the mesocolon (with ectopic pancreatic tissue) and ovary. Awareness of the existence of this tumor in various extrapancreatic sites is essential to avoid misdiagnosis.


Distribution of newly synthesized lipoprotein over the outer membrane and the peptidoglycan sacculus of an Escherichia coli lac-lpp strain.
The insertion of newly synthesized lipoprotein molecules into the cell wall of Escherichia coli was studied topographically by immunoelectron microscopy. Lipoprotein was briefly induced with isopropyl-beta-D-thiogalactopyranoside in cells carrying lac-lpp on a low-copy-number plasmid in an E. coli lpp host. Specific antibodies bound to the newly inserted lipoprotein molecules, which were exposed at the cell surface after treatment of the cells with Tris-EDTA, were detected with a protein A-gold probe. The average distribution of the gold particles over the cell surface of noninduced cells was determined for cells induced for 5 and 10 min. Analysis of 250 to 350 cells showed that the distribution of newly synthesized lipoprotein over the cell surface was homogeneous in both cases. The binding of lipoprotein to the peptidoglycan layer was studied by the same technique, and visual inspection again revealed a homogeneous distribution of bound lipoprotein over the entire sacculus surface. It is therefore concluded that free lipoprotein is inserted equally over the entire cell wall of E. coli, while binding to peptidoglycan also occurs over the entire cell surface. The rate of lipoprotein synthesis increased with cell length in nondividing cells, whereas it was constant in cells which had initiated constriction. Analysis of cells having different amounts of lipoprotein in their cell wall revealed that the cell shape depended on the total lipoprotein content of the cell. Cells having no or only a small amount of lipoprotein grew as spheres, whereas cells with increasing numbers of lipoprotein molecules gradually changed their shape to short rods.


Inhibitory Activity of Shrimp Waste Extracts on Fungal and Oomycete Plant Pathogens.
(1) Background: This study was aimed at determining the in vitro inhibitory effect of new natural substances obtained by minimal processing from shrimp wastes on fungi and oomycetes in the genera Alternaria, Colletotrichum, Fusarium, Penicillium, Plenodomus and Phytophthora; the effectiveness of the substance with the highest in vitro activity in preventing citrus and apple fruit rot incited by P. digitatum and P. expansum, respectively, was also evaluated. (2) Methods: The four tested substances, water-extract, EtOAc-extract, MetOH-extract and nitric-extract, were analyzed by HPLC-ESI-MS-TOF; in vitro preliminary tests were carried out to determine the minimal inhibitory/fungicidal concentrations (MIC and MFC, respectively) of the raw dry powder, EtOAc-extract, MetOH-extract and nitric-extract for each pathogen. (3) Results: in the agar-diffusion-assay, nitric-extract showed an inhibitory effect on all pathogens, at all concentrations tested (100, 75, 50 and 25%); the maximum activity was on Plenodomus tracheiphilus, C. gloeosporioides and Ph. nicotianae; the diameters of inhibition halos were directly proportional to the extract concentration; values of MIC and MFC of this extract for all pathogens ranged from 2 to 3.5%; the highest concentrations (50 to 100%) tested in vivo were effective in preventing citrus and apple fruit molds. (4) Conclusions: This study contributes to the search for natural and ecofriendly substances for the control of pre- and post-harvest plant pathogens.


There's Danger in the Drops: Systemic Effects of Ophthalmic Drops Used to Treat Glaucoma.
Glaucoma is a common eye disorder and an irreversible cause of blindness worldwide. There are several treatment options for this condition, with the traditional first-line treatment being ophthalmologic drops. Although administered topically, it is associated with inadvertent systemic absorption leading to a potential for both local and systemic side effects. We discuss the case of a 71-year-old male who presented with a complaint of recurring episodes of distressing sensations including lightheadedness, dyspnea, chest pressure, and faintness. His past medical history included congestive heart failure, hypertension, hyperlipidemia, Barrett's esophagus, and glaucoma. Upon a thorough review of the patient's medications, it was discovered that he had recently been started on timolol ophthalmic drops. The patient then noted that his symptoms had begun after he started using the eye drops. After we recommended that the patient hold the use of the eye drops, these episodes stopped. When prescribing topical ophthalmologic drops, providers must educate patients on common systemic side effects of such drugs.


Psychosocial predictors of needle sharing among intravenous drug users.
This study examined the relationship between health beliefs and needle sharing in a sample of 226 heroin detoxification clients. Zero-order correlations revealed that needle sharing was positively associated with perceived susceptibility and AIDS anxiety, and negatively associated with self-efficacy and communication skill in negotiating safe needle practices. Logistic regression analysis showed that demographic and situational factors also play a role in needle sharing. White race and injection of drugs in shooting galleries or other public places increase the odds of sharing a "dirty" needle, while that probability decreases sharply as a function of drug users' self-efficacy. This last finding suggests that preventive clinical interventions such as counseling or psychoeducational groups maybe needed to help drug users develop confidence in resisting needle sharing.


Mica-associated pulmonary interstitial fibrosis.
We present the clinical and biopsy findings of a 63-yr-old white male with interstitial pulmonary fibrosis and a long history of extensive exposure to mica while working in the rubber industry. The patient presented 30 yr after the initial exposure with complaints of progressive shortness of breath and a chronic nonproductive cough. Pulmonary function testing revealed restrictive lung function with a mild reduction in the total lung capacity (80% of predicted) and a moderate-to-severe reduction in the diffusing capacity of carbon monoxide (50% of predicted). The chest radiogram and high-resolution chest CT scan showed diffuse fibrosis and focal honeycombing involving the upper and lower lung zones bilaterally. Bronchoalveolar lavage revealed 20% neutrophils in the lavage fluid with abundant rectangular flaking crystals. Open-lung biopsy exhibited extensive fibrosis and architectural remodeling with abundant sheets and fragments of engulfed polarizable crystalline material. Energy-dispersive spectroscopy and electron diffraction studies confirmed the material to have the features of mica. Asbestos and other silicates were not identified. The documentation of prolonged exposure to mica, the clinical and radiographic features of severe interstitial fibrosis, and the histopathologic delineation of the interstitial lesion, including spectroscopic and crystallographic verification of crystalline mica, support the causal relationship between mica and interstitial fibrosis.


Cytochrome c-dependent and -independent induction of apoptosis in multiple myeloma cells.
Cytochrome c is a mitochondrial protein that induces apoptosis when accumulated in the cytosol in response to diverse stress inducers. This protein has also been shown to cause apoptosis when added to cell free extracts. In this report, we studied the role of cytochrome c (cyto-c) in dexamethasone (Dex), anti-Fas monoclonal antibody (mAb), and ionizing radiation-induced apoptosis in multiple myeloma cells. The results demonstrate that ionizing radiation-induced apoptosis is associated with an increase in cytosolic cyto-c levels, whereas apoptosis induced by Dex or anti-Fas mAb has no detectable effect on cyto-c release. By contrast, caspase-3 was activated in response to all of these agents. Thus, our findings suggest that Dex or anti-Fas mAb-induced apoptosis is not accompanied by cyto-c release and that there are at least two different pathways leading to activation of caspases and induction of apoptosis in multiple myeloma cells that can be distinguished by accumulation of cytosolic cyto-c.


Imaging of en bloc renal transplants: normal and abnormal postoperative findings.
Cadaveric kidneys from donors less than 5 years old, previously considered inferior graft material, are now being successfully transplanted en bloc into children and adults. On the basis of our experience with 132 patients, we describe the general principles of the procedure and review the spectrum of normal and abnormal imaging findings in patients who have undergone this promising transplantation procedure. Paired cadaveric kidneys obtained from donors less than 5 years old (mean age, 24 months) were transplanted en bloc to 132 patients (mean age, 37 years) at our institution between 1981 and 1991. All available medical, surgical, pathologic, and imaging records were retrospectively reviewed to define the surgical technique, 1-year survival rate of the graft, appearance of the transplant on postoperative imaging studies, and the prevalence of and imaging findings caused by vascular, urinary, infectious, and neoplastic complications after transplantation. Complications were confirmed by a definitive imaging study, surgical exploration, or study of a pathologic specimen. Paired donor kidneys were transplanted en bloc extraperitoneally into the recipient's right or left iliac fossa, with intact portions of the donor aorta and inferior vena cava anastomosed to the recipient's external iliac artery and vein. One-year graft survival was 70% during the first 8 years of the study and 78% during the last 2 years. Postoperative imaging, particularly sonography and scintigraphy, clearly depicted the normal individual kidneys, urinary collecting systems, and en bloc vasculature. Postoperative complications were vascular (arterial stenoses and thromboses, venous thromboses, and pseudoaneurysms) in 18%, urinary (obstruction and anastomotic leak) in 11%, infectious (caliceal fungal balls) in 1%, and neoplastic (posttransplant lymphoma) in 1%. The complications involved one kidney in 60% of the patients and both kidneys in 40%. The imaging findings caused by these complications were similar to those caused by complications occurring after transplantation of single cadaveric kidneys; however, their detection was more difficult because of the complexity of the en bloc graft. Because of the shortage of available donor organs, en bloc renal transplantation will most likely become increasingly popular. Familiarity with the imaging appearance of the normal transplant and of posttransplantation complications will allow radiologists to perform effective postoperative imaging evaluations.


Isolation and Partial Characterization of the Major Amide-Linked Conjugate of Indole-3-Acetic Acid from Phaseolus vulgaris L.
A major indole-3-acetic acid conjugate from Phaseolus vulgaris seed has been isolated and partially characterized. It is a 3 kilodalton peptide with apparently 2 indole-3-acetyl moieties in amide linkage per peptide. The indole-3-acetic acid component was identified by gas chromatography-mass spectrometry and the peptide characterized by polyacrylamide gel electrophoresis, by amino acid analysis using dabsyl derivatives and by its Fourier transform-infrared spectrum. This is the first higher molecular weight amide-linked indole-3-acetic acid conjugate to be characterized from higher plants.


New estimates for CRNA vacancies.
A national survey to estimate vacancy rates of Certified Registered Nurse Anesthetists (CRNAs) in hospitals and ambulatory surgical centers was conducted in 2007. Poisson regression methods were used to improve the precision of the estimates. A significant increase in the estimated vacancy rate was reported for hospitals relative to an earlier study from 2002, although it is important to note that there were some methodological differences between the 2 surveys explaining part of the increase. Results from this study found the vacancy rate was higher in rural hospitals than in nonrural hospitals, and it was lower in ambulatory surgical centers. A number of simulations were run to predict the effects of relevant changes in the market for surgeries and number of CRNAs, which were compared to the predictions from the previous survey. The remarkable factor since the last survey was the unusually large rate of new CRNAs entering the market, yet the vacancy rates remain relatively high.


Expression and regulation of alphaB-crystallin in the kidney in vivo and in vitro.
alphaB-crystallin, a major component of the mammalian eye lens, is a small heat shock protein and molecular chaperone that is also abundant in the mammalian kidney. The present study aimed to characterize more closely the intrarenal expression and regulation of alphaB-crystallin in vivo and in vitro. In normal rat kidney, the expression of alphaB-crystallin mRNA and protein were both close to the detection limit in cortex, but increased steeply from the outer to the inner medulla where alphaB-crystallin constitutes approximately 2% of total tissue protein. Immunohistochemistry disclosed papillary collecting duct cells and thin limbs as the major sites for intrapapillary alphaB-crystallin immunoreactivity. In rats subjected to sucrose diuresis for 3 days, alphaB-crystallin mRNA expression was reduced by 27 and 46% in outer and inner medulla, respectively. In agreement with the results obtained in vivo, in Madine-Darby canine kidney cells, alphaB-crystallin mRNA and protein were induced significantly by elevating the medium osmolality to 500 mosm/kg H(2)O by the addition of NaCl and raffinose, and also by urea. The NaCl-induced increase in alphaB-crystallin expression was concentration-dependently blunted by SP600125, a specific JNK inhibitor. Overexpression of alphaB-crystallin in 293 cells resulted in increased tolerance to acute osmotic stress. These results indicate that alphaB-crystallin may be regulated by papillary interstitial tonicity in a JNK-dependent process. Moreover, the high abundance of alphaB-crystallin in the renal medulla may be important for cell survival in an environment characterized by extreme interstitial solute concentrations as present during antidiuresis.


The role of aging on the control of contractile force by Na(+)-Ca2+ exchange in rat papillary muscle.
Sarcolemmal Na(+)-Ca2+ exchange system is believed to be fundamental to the control of cardiac contractility. However, the relation between Na(+)-Ca2+ exchange and the control of contractile force has not been studied in senescent myocardium. The role of Na(+)-Ca2+ exchange in the regulation of the cardiac muscle's contractile force was studied in adult and senescent papillary muscles by simultaneously measuring intracellular sodium activity (aNai), action potential, and contractile force while varying extracellular concentration of sodium and/or calcium. Reduction of [Na+]o decreased aNai from 8.0 +/- 1.8 to 4.1 +/- 0.8 in adult (-3.9 mM) and from 8.7 +/- 1.9 to 4.7 +/- 0.9 in senescent (-4.0 mM) papillary muscles, while developed tension (DT) increased by 80.2% in adult and by 135.6% in senescent papillary muscles (p < .01 vs adult). During low [Ca2+]o and high [Na+]o, aNai and DT modifications were similar both in adult and senescent papillary muscles. During high [Ca2+]o, aNai decreased to a similar extent in both adult and senescent papillary muscles, while DT increased by 37.8% in adult and by 67.8% in senescent (p < .05 vs adult). Simultaneous reduction of [Na+]o and [Ca2+]o decreased aNai from 8.1 +/- 1.2 to 6.8 +/- 1.1 mM in adult (-1.3 mM), and from 8.4 +/- 1.0 to 7.2 +/- 1.0 mM in senescent (-1.2 mM) papillary muscles while DT decreased by 22.1% in adult and by only 12.0% in senescent (p < .01 vs adult) papillary muscles. Simultaneous increase of [Na+]o and [Ca2+]o similarly increased aNai in both adult senescent papillary muscles, but decreased DT by 28.5% in adult and by 11.7% in senescent (p < .01 vs adult). After [Na+]o modifications, the equilibration time for the ratio of external and internal sodium ion activities was slowed in senescent papillary muscles (i.e., in low [Na+]o solution the equilibration time was 4.6 +/- 0.9 min in adult and 6.3 +/- 1.2 min in senescent papillary muscles, p < .001). Similar changes of aNai during transmembrane Na+ and Ca2+ gradients modifications associated to changes in contractile force seem to demonstrate that Na(+)-Ca2+ exchange is probably not modified by the aging process. However, the slow equilibration time for the ratio of Na+ activities might reflect an age-related reduction of the Na(+)-K+ pump activity.


Characterization of craniomaxillofacial battle injuries sustained by United States service members in the current conflicts of Iraq and Afghanistan.
To characterize and describe the craniomaxillofacial (CMF) battlefield injuries sustained by US Service Members in Operation Iraqi Freedom and Operation Enduring Freedom. The Joint Theater Trauma Registry was queried from October 19, 2001, to December 11, 2007, for CMF battlefield injuries. The CMF injuries were identified using the "International Classification of Diseases, Ninth Revision, Clinical Modification" codes and the data compiled for battlefield injury service members. Nonbattlefield injuries, killed in action, and return to duty cases were excluded. CMF battlefield injuries were found in 2,014 of the 7,770 battlefield-injured US service members. In the 2,014 injured service members were 4,783 CMF injuries (2.4 injuries per soldier). The incidence of CMF battlefield injuries by branch of service was Army, 72%; Marines, 24%; Navy, 2%; and Air Force, 1%. The incidence of penetrating soft-tissue injuries and fractures was 58% and 27%, respectively. Of the fractures, 76% were open. The location of the facial fractures was the mandible in 36%, maxilla/zygoma in 19%, nasal in 14%, and orbit in 11%. The remaining 20% were not otherwise specified. The primary mechanism of injury involved explosive devices (84%). Of the injured US service members, 26% had injuries to the CMF region in the Operation Iraqi Freedom/Operation Enduring Freedom conflicts during a 6-year period. Multiple penetrating soft-tissue injuries and fractures caused by explosive devices were frequently seen. Increased survivability because of body armor, advanced battlefield medicine, and the increased use of explosive devices is probably related to the elevated incidence of CMF battlefield injuries. The current use of "International Classification of Diseases, Ninth Revision, Clinical Modification" codes with the Joint Theater Trauma Registry failed to characterize the severity of facial wounds.


Metallaboranes of the Early Transition Metals: Direct Synthesis and Characterization of [{(eta5-C5Me5)Ta}2BnHm] (n=4, m=10; n=5, m=11), [{(eta5-C5Me5)Ta}2B5H10(C6H4CH3)], and [{(eta5-C5Me5)TaCl}2B5H11].
Reaction of [Cp*TaCl4] (Cp*=eta5-C5Me5) with a sixfold excess of LiBH(4)thf followed by BH3thf in toluene at 100 degrees C led to the isolation of hydrogen-rich metallaboranes [(Cp*Ta)2B4H10] (1), [(Cp*Ta)2B5H11] (2), [(Cp*Ta)2B5H10(C6H4CH3)] (3), and [(Cp*TaCl)2B5H11] (4) in modest yield. Compounds 1-3 are air- and moisture-sensitive but 4 is reasonably stable in air. Their structures are predicted by the electron-counting rules to be a bicapped tetrahedron (1), bicapped trigonal bipyramids (2, 3), and a nido structure based on a closo dodecahedron 4. Yellow tantalaborane 1 has a nido geometry with C2v symmetry and is isostructural with [(Cp*M)2B4H8] (M=Cr and Re); whereas 2 and 3 are C3v-symmetric and isostructural with [(Cp*M)2B5H9] (M=Cr, Mo, W) and [(Cp*ReH)2B5Cl5]. The most remarkable feature of 4 is the presence of a hydride ligand bridging the ditantalum center to form a symmetrical tantalaborane cluster with a long Ta--Ta bond (3.22 A). Cluster 4 is a rare example of electronically unsaturated metallaborane containing four TaHB bonds. All these new metallaboranes have been characterized by mass spectrometry, 1H, 11B, and 13C NMR spectroscopy, and elemental analysis, and the structural types were unequivocally established by crystallographic analysis of 1-4.


Skin picking as a symptom of body dysmorphic disorder.
Skin picking, traditionally considered a type of "neurotic excoriation," has received little investigation. In particular, its association with body dysmorphic disorder (BDD) has not been studied. A total of 123 subjects with DSM-IV BDD were assessed with a variety of instruments; the descriptive characteristics of the 33 subjects who picked their skin were assessed and compared with those of the 90 subjects who did not pick. Of the 14 men and 19 women who engaged in picking behavior, 97 percent had preoccupations involving the skin. Nearly all had experienced impairment in social (97%) or occupational (82%) functioning, 33 percent had attempted suicide, and 67 percent had received dermatologic treatment, which was generally ineffective. Of 35 trials with a serotonin reuptake inhibitor (SRI), 17 (49%) resulted in significant improvement, in contrast to only 4 of 40 (10%) trials with other psychotropics. Subjects who picked were more likely than those who did not pick to have skin preoccupations, to have actual physical defects, to excessively groom and camouflage, and to have received dermatologic treatment. These preliminary findings suggest that compulsive skin picking is an under-recognized problem that commonly occurs as a symptom of BDD, is associated with significant morbidity, and may respond to psychiatric rather than dermatologic treatment.


Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.
Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology.


Ligand-based virtual screening interface between PyMOL and LiSiCA.
Ligand-based virtual screening of large small-molecule databases is an important step in the early stages of drug development. It is based on the similarity principle and is used to reduce the chemical space of large databases to a manageable size where chosen ligands can be experimentally tested. Ligand-based virtual screening can also be used to identify bioactive molecules with different basic scaffolds compared to already known bioactive molecules, thus having the potential to increase the structural variability of compounds. Here, we present an interface between the popular molecular graphics system PyMOL and the ligand-based virtual screening software LiSiCA available at http://insilab.org/lisica-plugin and demonstrate how this interface can be used in the early stages of drug discovery process.Graphical AbstractLigand-based virtual screening interface between PyMOL and LiSiCA.


[Treatment tactics in giant cell tumor of the bone].
The data on 76 patients treated for benign or malignant giant-cell tumor (GCT) of the bone are presented. Surgery involving bone reconstruction and endoprosthetics was the basic therapeutic procedure. Cases with lytic benign GCT received 36-40 Gy of radiation prior to surgery whereas whose with malignant tumors were subjected to complex treatment including preoperative irradiation, surgery and chemotherapy. Recurrence was observed in two patients with benign and in one--with malignant GCT. There were four fatalities. Five-year survival was 82%.


Health-related quality of life and survival among HIV-infected patients receiving highly active antiretroviral therapy: a study of patients in the AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort.
Previous studies have shown that health-related quality of life (HRQL) predicts survival in patients infected with human immunodeficiency virus (HIV). However, these studies predated the highly active antiretroviral therapy (HAART) era, included only a few patients receiving HAART, or had a limited duration of follow-up. This study investigates whether HRQL predicts survival among HIV-infected patients receiving HAART. HIV-infected patients participating in the focus group of the AIDS Therapy Evaluation in the Netherlands (ATHENA) study and starting or already receiving HAART completed the Medical Outcomes Study HIV Health Survey at study entry (1 May 1998 through 31 December 2000). The physical health summary (PHS) and mental health summary (MHS) scores were calculated. All-cause mortality was established at 31 March 2008. Kaplan-Meier analysis and Cox regression models were performed to predict survival. The median follow-up was 8.4 years. Sixty-six patients (11.8%) died during follow-up. We found a significant relation between quartiles of PHS and survival (P < .001, log-rank test). Of patients with a PHS, 26 (20%) died in quartile 1 (indicating worst HRQL), 17 (13%) died in quartile 2, 10 (8%) died in quartile 3, and 5 (4%) died in quartile 4 (indicating best HRQL) (P< .001). The prediction of PHS on survival was independent of other (clinical) parameters (P< .001). No relation was found between MHS and survival (P= .13). Patient-reported HRQL predicted survival among HIV-infected patients receiving HAART. This information could be highly useful for physicians in determining the prognosis of their patients.


Regulation of protein synthesis in heat-shocked Drosophila cells. Soluble factors control translation in vitro.
We have developed an in vitro translation system from heat-shocked and normal Drosophila cultured cells. The lysates retain regulation of translation typical of the whole cells from which they were prepared, both when programmed by endogenous mRNA and when RNA-dependent. These systems have been used to investigate the mechanism of shutdown of normal protein synthesis and selection of heat shock mRNAs for translation in heat shock in Drosophila. Supplementation of intact RNA-dependent lysates with separated ribosome or supernatant fractions from normal or heat-shocked translation systems showed the normal supernatant fraction could "rescue" normal protein synthesis in a heat shock lysate. Normal ribosomes had no rescuing activity and neither heat shock fraction affected translation in normal lysates. Reconstitution of the system from separated ribosomes and supernatant in normal and mixed combinations showed heat shock and normal ribosomes were both competent to support normal protein synthesis with normal supernatant. Heat shock supernatant did not support normal protein synthesis with ribosomes from either source. We conclude that the factors regulating translation in heat-shocked Drosophila cells are soluble factors in the lysate and that the soluble factors present in the normal lysate are dominant.


Cyclin-dependent kinase 1-dependent activation of APC/C ubiquitin ligase.
Error-free genome duplication and segregation are ensured through the timely activation of ubiquitylation enzymes. The anaphase-promoting complex or cyclosome (APC/C), a multisubunit E3 ubiquitin ligase, is regulated by phosphorylation. However, the mechanism remains elusive. Using systematic reconstitution and analysis of vertebrate APC/Cs under physiological conditions, we show how cyclin-dependent kinase 1 (CDK1) activates the APC/C through coordinated phosphorylation between Apc3 and Apc1. Phosphorylation of the loop domains by CDK1 in complex with p9/Cks2 (a CDK regulatory subunit) controlled loading of coactivator Cdc20 onto APC/C. A phosphomimetic mutation introduced into Apc1 allowed Cdc20 to increase APC/C activity in interphase. These results define a previously unrecognized subunit-subunit communication over a distance and the functional consequences of CDK phosphorylation. Cdc20 is a potential therapeutic target, and our findings may facilitate the development of specific inhibitors.


[Suture materials in urology].
Since ancient times, sutures have been a fundamental part of the surgeon's practice. Beside the vegetable and animal origin materials, in the last decades different refined synthetic materials have been introduced in the clinical practice. More recently, different devices, such as staplers and tissue sealers have been developed. Thus, more than ever, urologists are faced with a multitude of suture materials, and research of safe, effective materials and devices seems to be continuously growing. The introduction and widespread diffusion of laparoscopic and robotic surgery has further boosted this research. Given there is no single material that is ideal for all situations, the surgeon must choose the best material for each particular case. The aim of this non-systematic review is to summarize the more innovative suture materials and devices and to describe the different surgical methods to utilize them both in general and in urologic surgery.


Can payment incentives improve quality and efficiency of care?
Faced with increasing health care costs, America's major corporations are beginning to explore a variety of mechanisms to assure that health care providers are delivering high quality care. The General Motors Corporation (GM), with approximately two million employees, retirees and family members, and annual health care expenditures of approximately $3 billion, has developed a quality review system and a hospital payment mechanism that includes incentives to enhance the quality of care provided to GM beneficiaries. The following article describes this project.


Adhesion to dentin.
The bond strengths of dentinal bonding systems to dentin and the microleakage at the dentinal bonding system to dentin interface are often determined in laboratory studies prior to the clinical evaluation of these systems. The shear bond strengths of some of the third generation dentinal bonding systems to dentin and the microleakage at the dentinal bonding system to dentin interface are discussed. In addition, the shear bond strengths of fluoride-containing liners/bases and the fluoride release from these systems are evaluated.


Significance of Samples Taken for Bacterial Counts from Reduced Areas of Bovine Carcasses.
The purpose of this study was to investigate if small sampling areas (10 and 100 cm2) from bovine carcasses allowed obtaining bacterial counts that were characteristic of the hygiene level in abattoirs during the slaughtering process and, as a consequence, to know the hygiene level of the carcasses. Two abattoirs were classified according to the infrastructure and the operations as Good (G) and Fair (F). At these abattoirs, samples were taken from two sites (brisket and round), from two sampling areas (10 and 100 cm2 for each site), corresponding to nine carcasses per visit. Each abattoir was visited five times. The count of total viable microorganisms at 20°C was taken as an indicator of the microorganisms present. The differences between abattoirs, considering the sites, were not statistically significant. On the other hand, the differences between areas sampled (10 and 100 cm2) were significant and showed that the count will depend on the size of the area sampled. The conclusion is that small sampling areas are not adequate to evaluate the hygiene of bovine carcasses.


Implant to Fat: A Breast Augmentation Technique Validated by BREAST-Q.
Implant-based breast augmentation is the number one cosmetic procedure performed in the United States. However, it is associated with relatively high revision rates, reaching up to 24% at 4 years. This case series presents our experience in implant explantation with simultaneous breast augmentation using fat. This case series was conducted by the authors in Cairo, Egypt, during the period from January 2018 to June 2019. Following a detailed data collection, careful physical examination was done. Implant-to fat conversion was done for all cases. None of the cases needed >1 session of fat injection following the implant removal. Size of the implants removed ranged from 200 -350 cm3 (average of 310). Volume of fat injected ranged from 300 to 550 ml (average of 430). Patients' satisfaction was evaluated using the BREAST-Q questionnaire. Twenty patients were included, with a mean age of presentation of 33.1 years (range, 26 -42 years; SD, 5.3). Mean body mass index was 26.9 kg/m2 (range, 24 -30; SD, 1.9). Implant complications were as follows: capsular contracture (10cases), implant migration (3 cases), breast asymmetry (3 cases), poor aesthetic outcome (3 cases), and palpable implant (1 case). Overall patient's satisfaction was evaluated by the BREAST-Q 1-year following surgery. The overall satisfaction score was 3.8, where a score of 4 indicates very satisfied and a score of 1 indicates very dissatisfied. Implant-to-fat conversion is a good option for complicated breast implant cases, with good long-term results and excellent patient's satisfaction as verified by the BREAST-Q.


BiPh3--a convenient synthon for heavy alkaline-earth metal amides.
Environmentally friendly, commercially available BiPh3 reacts with heavy alkaline-earth metals (Ae) and bulky trimethylsilylamines to give the corresponding amides [Ae{N(SiMe3)(R)}2(thf)n] (R=SiMe3, 2,4,6-Me3C6H2, 2,6-iPr2C6H3) in good yields, providing proof of concept for a general synthetic method.


Structural, Culinary, Nutritional and Anti-Nutritional Properties of High Protein, Gluten Free, 100% Legume Pasta.
Wheat pasta has a compact structure built by a gluten network entrapping starch granules resulting in a low glycemic index, but is nevertheless unsuitable for gluten-intolerant people. High protein gluten-free legume flours, rich in fibers, resistant starch and minerals are thus a good alternative for gluten-free pasta production. In this study, gluten-free pasta was produced exclusively from faba, lentil or black-gram flours. The relationship between their structure, their cooking and Rheological properties and their in-vitro starch digestion was analyzed and compared to cereal gluten-free commercial pasta. Trypsin inhibitory activity, phytic acid and α-galactosides were determined in flours and in cooked pasta. All legume pasta were rich in protein, resistant starch and fibers. They had a thick but weak protein network, which is built during the pasta cooking step. This particular structure altered pasta springiness and increased cooking losses. Black-gram pasta, which is especially rich in soluble fibers, differed from faba and lentil pasta, with high springiness (0.85 vs. 0.75) and less loss during cooking. In comparison to a commercial cereal gluten-free pasta, all the legume pasta lost less material during cooking but was less cohesive and springy. Interestingly, due to their particular composition and structure, lentil and faba pasta released their starch more slowly than the commercial gluten-free pasta during the in-vitro digestion process. Anti-nutritional factors in legumes, such as trypsin inhibitory activity and α-galactosides were reduced by up to 82% and 73%, respectively, by pasta processing and cooking. However, these processing steps had a minor effect on phytic acid. This study demonstrates the advantages of using legumes for the production of gluten-free pasta with a low glycemic index and high nutritional quality.


Abnormal topological characteristics of brain white matter network relate to cognitive and emotional deficits of non-small cell lung cancer (NSCLC) patients prior to chemotherapy.
Cancer and chemotherapy are correlated with brain functional and structural changes in cancer patients, which may lead to cognitive dysfunction. However, little is known about the structural abnormalities of brain in patients with non-small cell lung cancer (NSCLC). The aim of this study was to explore the topological properties within the brain white matter network of NSCLC patients prior to chemotherapy. To explore the neurobiological biomarkers of NSCLC, brain magnetic resonance imaging (MRI) data were acquired in 24 non-nervous system metastatic NSCLC patients and 25 matched healthy controls. The topological properties of the brain structural networks of NSCLC were measured by the parameters of local and global efficiency. Treatment-naïve NSCLC patients showed cognitive and emotional deficits. In addition, NSCLC patients also exhibited decreased global efficacy in the left inferior frontal gyrus (triangular part), left inferior frontal gyrus (orbital part), right rolandic operculum, right gyrus rectus, right lenticular nucleus (putamen), left superior temporal gyrus and right inferior temporal gyrus. Decreased local efficacy were found in the left middle frontal gyrus (orbital part) and left superior temporal gyrus in NSCLC patients. Moreover, the aberrant brain regions were associated with the impaired cognitiion and emotion of NSCLC patients. Overall our results suggested that altered local and global efficiency of brain white matter network were associated with cancer-induced cognitive and emotional deficits of NSCLC patients. These findings demonstrated that disrupted topological characteristics of the brain network might underlie the impaired cognition and emotion in NSCLC.


Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway.
Rearrangements involving the fibroblast growth factor receptor 1 (FGFR1) gene result in 8p11 myeloproliferative syndrome (EMS), which is a rare and aggressive hematological malignancy that is often initially diagnosed as myelodysplastic syndrome (MDS). Clinical outcomes are typically poor due to relative resistance to tyrosine kinase inhibitors (TKIs) and rapid transformation to acute leukemia. Deciphering the transcriptomic signature of FGFR1 fusions may open new treatment strategies for FGFR1 rearrangement patients. DNA sequencing (DNA-seq) was performed for 20 MDS patients and whole exome sequencing (WES) was performed for one HOOK3-FGFR1 fusion positive patient. RNA sequencing (RNA-seq) was performed for 20 MDS patients and 8 healthy donors. Fusion genes were detected using the STAR-Fusion tool. Fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), and Sanger sequencing were used to confirm the HOOK3-FGFR1 fusion gene. The phosphorylation antibody array was performed to validate the activation of nuclear factor-kappaB (NF-kappaB) signaling. We identified frequently recurrent mutations of ASXL1 and U2AF1 in the MDS cohort, which is consistent with previous reports. We also identified a novel in-frame HOOK3-FGFR1 fusion gene in one MDS case with abnormal monoclonal B-cell lymphocytosis and ring chromosome 8. FISH analysis detected the FGFR1 break-apart signal in myeloid blasts only. qRT-PCR and Sanger sequencing confirmed the HOOK3-FGFR1 fusion transcript with breakpoints located at the 11th exon of HOOK3 and 10th exon of FGFR1, and Western blot detected the chimeric HOOK3-FGFR1 fusion protein that is presumed to retain the entire tyrosine kinase domain of FGFR1. The transcriptional feature of HOOK3-FGFR1 fusion was characterized by the significant enrichment of the NF-kappaB pathway by comparing the expression profiling of FGFR1 fusion positive MDS with 8 healthy donors and FGFR1 fusion negative MDS patients. Further validation by phosphorylation antibody array also showed NF-kappaB activation, as evidenced by increased phosphorylation of p65 (Ser 536) and of IKBalpha (Ser 32). The HOOK3-FGFR1 fusion gene may contribute to the pathogenesis of MDS and activate the NF-kappaB pathway. These findings highlight a potential novel approach for combination therapy for FGFR1 rearrangement patients.


Induction and release of manganese superoxide dismutase from mitochondria of human umbilical vein endothelial cells by tumor necrosis factor-alpha and interleukin-1 alpha.
The effects of tumor necrosis factor-alpha (TNF alpha) on cultured human umbilical vein endothelial cells (EC) and 2 cancer cell lines, A549 and ME180, were compared. The effects of interleukin-1 alpha (IL-1 alpha) on EC were also examined. While A549 cells were fairly resistant to the cytolytic effects of TNF alpha and IL-1 alpha, ME180 cells were sensitive. EC were also less sensitive to TNF alpha than ME180 cells, as judged by viability of individual cells and by the release of lactate dehydrogenase (LDH) into the medium. Both manganese superoxide dismutase (Mn-SOD) and its mRNA were markedly induced by these cytokines in EC and in A549 cells but not in ME180 cells. The levels of Mn-SOD in the conditioned medium of EC were markedly increased after stimulation with cytokines, whereas those in ME180 and A549 cells were relatively low. The amount of Mn-SOD released appears to be comparable to that from cells lysed due to the cytocidal effect of cytokines, as assessed by measuring intra- and extra-cellular LDH activity. These data suggest that, in vivo, the TNF alpha and IL-1 alpha produced by cancer cells and other cells may induce Mn-SOD in vascular endothelial cells as well as other host tissues, resulting in release of a relatively large amount of this protein into the serum.


Galactosyltransferases involved in galactolipid biosynthesis are located in the outer membrane of pea chloroplast envelopes.
The galactosylation steps in the biosynthesis of galactolipids involve two different enzymes; a UDP-Gal:diacylglycerol galactosyltransferase and a galactolipid:galactolipid galactosyltransferase. Previous localization studies have shown that in spinach these enzymes are located in the chloroplast envelope. Our results with peas (Pisum sativum var Laxton's Progress No. 9) confirm these results and extend the localization by providing evidence that the galactosyltransferases are in the outer membrane of the envelope. The specific activity of UDP-Gal:diacylglycerol galactosyltransferase in outer membrane preparations was 6 to 10 times greater than that exhibited by inner membrane preparations. In addition, using quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was possible to show that the UDP-Gal:diacylglycerol galactosyltransferase activity associated with inner membrane preparations could be accounted for by outer membrane contamination. It is concluded from these results that this enzyme is located predominantly, if not exclusively, in the outer membrane of the envelope. An analysis of the galactolipid products synthesized by the highly purified outer membrane showed that the galactolipid:galactolipid galactosyltransferase is also present, suggesting that this enzyme is also an outer membrane enzyme. The implication of these results is that the final assembly of galactolipids is carried out on the outer membrane of the chloroplast envelope.


GABA-mediated baroreceptor inhibition of reticulospinal neurons.
A total of 45 cells with spinal projections, pulse-synchronous discharges, and extreme sensitivity to changes in arterial pressure were recorded in the retrofacial portion of nucleus paragigantocellularis lateralis (PGCL) in halothane-anesthetized rats. Every unit tested was inhibited by iontophoretic applications of gamma-aminobutyric acid (GABA), glycine, and taurine and excited by glutamate or the GABA receptor antagonist bicuculline methiodide. The inhibitory effect of GABA was antagonized by bicuculline methiodide but not by strychnine; the effect of glycine was eliminated by strychnine but unaffected by bicuculline. Iontophoretically applied bicuculline completely antagonized the time-locked reduction in unit activity resulting from increases in arterial pressure while strychnine was ineffective. 1-Glutamate, applied in a dose that produced a larger increase in the unit discharge rate than bicuculline, did not significantly alter the magnitude of the inhibition associated with increases in arterial pressure. It is concluded that GABA or a related substance mediates the inhibition of PGCL reticulospinal neurons resulting from the activation of arterial baroreceptors.


A revitalized battle against diabetes mellitus for the new millennium.
Despite great advances in control and treatment, diabetes mellitus (DM) remains a formidable opponent for the health care team. A major cause of morbidity and mortality throughout the world, DM continues to increase in prevalence. Nurses are in a strategic position to employ new research findings and aggressive strategies to fight this killer disease.


Beyond citation analysis: a model for assessment of research impact.
Is there a means of assessing research impact beyond citation analysis? The case study took place at the Washington University School of Medicine Becker Medical Library. This case study analyzed the research study process to identify indicators beyond citation count that demonstrate research impact. The authors discovered a number of indicators that can be documented for assessment of research impact, as well as resources to locate evidence of impact. As a result of the project, the authors developed a model for assessment of research impact, the Becker Medical Library Model for Assessment of Research. Assessment of research impact using traditional citation analysis alone is not a sufficient tool for assessing the impact of research findings, and it is not predictive of subsequent clinical applications resulting in meaningful health outcomes. The Becker Model can be used by both researchers and librarians to document research impact to supplement citation analysis.


Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.
A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.


Leading Change: Implementation of a New Care Coordination Model.
Today's healthcare environment is characterized by a multitude of changes: acquisitions and mergers, streamlining of operations, restructuring and leadership shifts, new regulatory requirements with the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, implementation and meaningful use, and advances in technology driven by the employment of electronic health records. The impact of these changes is complex and fraught with challenges in an industry that historically and culturally is cautious and slow to change. .


Pathways to chromothripsis.
Chromothripsis is a recently recognized mode of genetic instability that generates chromosomes with strikingly large numbers of segmental re-arrangements. While the characterization of these derivative chromosomes has provided new insights into the processes by which cancer genomes can evolve, the underlying signaling events and molecular mechanisms remain unknown. In medulloblastomas, chromothripsis has been observed to occur in the context of mutational inactivation of p53 and activation of the canonical Hedgehog (Hh) pathway. Recent studies have illuminated mechanistic links between these 2 signaling pathways, including a novel PTCH1 homolog that is regulated by p53. Here, we integrate this new pathway into a hypothetical model for the catastrophic DNA breakage that appears to trigger profound chromosomal rearrangements.


[Complementary neuromotor examination of infants at risk for sequelae.Why? How?].
In many cases the traditional neurological examination of high risk newborns for neurological problems secondary to perinatal difficulties does not identify easily the absence or the presence of cerebral palsy before walking. To help the neuromoteur follow up in these children, the authors suggest a complementary neuromotor examination that is successful only in normal infants. This examination is done in front of a mirror in the presence of the parents in order to increase the attention of the child, whose participation is necessary for a successful examination. Two motor responses are evaluated: the lateral support on, alternately, right and left superior limbs, and the lateral abduction reaction of the hip of each limb. When normal these two motor responses allow an early affirmation of integrity of motor paths if the examination is performed under carefully controlled conditions.


Comparison of the Effects of Quality Improvement Strategies on Prevention of Mother-to-Child HIV Transmission in a Public and a Private Hospital in Lesotho.
We compared quality improvement (QI) interventions for prevention of mother-to-child transmission in a private hospital and a government hospital (GH). From November 2013 to October 2016, data were extracted retrospectively for HIV-positive mothers and HIV-exposed infants. The overall number of mother-baby pairs (MBPs) was significantly (P < .001) higher at the GH (mean = 294, standard deviation [SD] = 180) than the private hospital (mean = 72, SD = 27). There was a significantly higher number of MBPs receiving care (P < .001) and routine services (P < .001) at the GH. The proportion of MBPs retained in care (P < .001) and receiving the routine service package (P < .001) was significantly higher at the private hospital. Overtime, indicators at the private hospital peaked significantly in year 2 and reduced moderately in the final year. The trend for the GH showed gradual but nonsignificant improvement in 2 indicators. QI showed positive results in the private hospital. If systematically applied in GHs, QI can support improved services for larger patient volumes.


Social stigma and negative consequences: factors that influence college students' decisions to seek testing for sexually transmitted infections.
College students often delay or avoid seeking testing for sexually transmitted infections (STIs), even if the services are readily available. We used in-depth, semistructured interviews to survey 41 college students aged 18 to 23 years about factors that influence decisions about STI testing. We grouped statements into 9 themes that represent influences on the decision. The most frequently mentioned factors were negative consequences of testing and perceived vulnerability to infection; other issues that influenced decision making included perceived benefits, perceived severity of diseases, public knowledge and opinion, social norms, provider characteristics, test-site characteristics, and personal considerations. Social stigmas and negative consequences appear to represent significant barriers to college students' being tested, which could increase the risk of spreading infections to others. Clinicians and health educators should raise students' awareness of the need for screening and should work to reduce the barriers to screening, including social stigmas and negative consequences.


Effect of protein kinase C activation on the release of [3H]acetylcholine in the presence of vesamicol.
The present work tested whether pharmacological activation of protein kinase C (PKC) influences the release of [3H]acetylcholine ([3H]ACh) synthesized in the presence of vesamicol, an inhibitor of the vesicular acetylcholine transporter (VAChT). Newly synthesized [3H]ACh was released from hippocampal slices by field stimulation (15 Hz) in the absence of vesamicol, but as expected [3H]ACh synthesized during exposure to vesamicol was not released significantly by stimulation. Treatment of slices with the PKC activator phorbol myristate acetate (PMA) decreased the inhibitory effect of vesamicol on [3H]ACh release. The effect of PMA was dose-dependent, was sensitive to calphostin C, a PKC-selective inhibitor, and could not be mimicked by alpha-PMA, an inactive phorbol ester. PMA did not alter the release of [3H]ACh in the absence of vesamicol, suggesting that the site of PKC action could be related to the VAChT. In agreement with this observation, immunoprecipitation of VAChT from 32P-labeled synaptosomes showed that phosphorylation occurs and that incorporation of 32P in the VAChT protein increases in the presence of PMA. We suggest that PKC alters the output of [3H]ACh formed in the presence of vesamicol and also provide circumstantial evidence for a role of phosphorylation of VAChT in this process.


Schizophrenia as a disorder of neurodevelopment.
A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.


Performance evaluation of the Champagne source reconstruction algorithm on simulated and real M/EEG data.
In this paper, we present an extensive performance evaluation of a novel source localization algorithm, Champagne. It is derived in an empirical Bayesian framework that yields sparse solutions to the inverse problem. It is robust to correlated sources and learns the statistics of non-stimulus-evoked activity to suppress the effect of noise and interfering brain activity. We tested Champagne on both simulated and real M/EEG data. The source locations used for the simulated data were chosen to test the performance on challenging source configurations. In simulations, we found that Champagne outperforms the benchmark algorithms in terms of both the accuracy of the source localizations and the correct estimation of source time courses. We also demonstrate that Champagne is more robust to correlated brain activity present in real MEG data and is able to resolve many distinct and functionally relevant brain areas with real MEG and EEG data.


Visual exploration of three-dimensional gene expression using physical views and linked abstract views.
During animal development, complex patterns of gene expression provide positional information within the embryo. To better understand the underlying gene regulatory networks, the Berkeley Drosophila Transcription Network Project (BDTNP) has developed methods that support quantitative computational analysis of three-dimensional (3D) gene expression in early Drosophila embryos at cellular resolution. We introduce PointCloudXplore (PCX), an interactive visualization tool that supports visual exploration of relationships between different genes' expression using a combination of established visualization techniques. Two aspects of gene expression are of particular interest: 1) gene expression patterns defined by the spatial locations of cells expressing a gene and 2) relationships between the expression levels of multiple genes. PCX provides users with two corresponding classes of data views: 1) Physical Views based on the spatial relationships of cells in the embryo and 2) Abstract Views that discard spatial information and plot expression levels of multiple genes with respect to each other. Cell Selectors highlight data associated with subsets of embryo cells within a View. Using linking, these selected cells can be viewed in multiple representations. We describe PCX as a 3D gene expression visualization tool and provide examples of how it has been used by BDTNP biologists to generate new hypotheses.


The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in chronic kidney disease patients on haemodialysis.
It is becoming increasingly more common to administer intravenous (i.v.) darbepoetin alfa to haemodialysis (HD) patients at less frequent dosing intervals in routine clinical practice. This study investigated extending the dosing interval for i.v. darbepoetin alfa treatment from once a week (QW) to once every 2 weeks (Q2W) at the same dose in order to maintain target haemoglobin (Hb) concentrations (11-13 g/dl). Stable HD patients in routine clinical practice receiving i.v. darbepoetin alfa QW for a period of 6 months (n = 105) (treatment period 1) were switched to i.v. Q2W darbepoetin alfa for a further 6 months (treatment period 2) (n = 90). The dose of i.v. darbepoetin alfa was titrated to maintain Hb concentrations between 11 and 13 g/dl throughout the full 12-month study period. The mean change in Hb for treatment period 2 was 0.04 +/- 1.1 g/dl (+/-SD), which was not clinically relevant (11.7 +/- 0.8 g/dl vs 11.7 +/- 1.0 g/dl; P = 0.8). The mean weekly doses of darbepoetin alfa were similar throughout the treatment periods (34.0 +/- 17.1 microg/week vs 32.1 +/- 17.3 microg/week; P = 0.3, respectively for QW and Q2W dosing). Intravenous darbepoetin alfa was well tolerated. The treatment of renal anaemia in HD patients with i.v. Q2W darbepoetin alfa effectively and safely maintains Hb concentrations at a less frequent dosing regimen than observed with QW administration. Dose requirements for i.v. darbepoetin alfa administered QW or Q2W were not different. The results of this study demonstrate that i.v. darbepoetin alfa administered Q2W is an effective regimen for HD patients requiring anaemia treatment in routine clinical practice.


The role of perceived control and overconfidence in pathological gambling.
Two studies sought to determine whether perceived control has different effects on confidence assessment and betting decisions among pathological and problem gamblers than among non-problem gamblers. In Study 1, 200 college students who were frequent gamblers (80 female and 120 male, median age 20) completed the South Oaks Gambling Screen (SOGS) and then engaged in a task in which they answered questions, assessed confidence in each answer, and considered bets on their answers that were fair if they were well-calibrated, but unfavorable if they were overconfident. Probable pathological and problem gamblers earned significantly fewer points than non-problem gamblers. This was due to greater overconfidence among pathological and problem gamblers, which led to systematically less favorable bets. In Study 2, using 384 participants (105 female and 279 male, median age 20), control was independently manipulated and bets were constructed to make point value independent of overconfidence. Problem and pathological gamblers showed both greater overconfidence and greater bet acceptance. They were less affected by control in their betting decisions than non-problem gamblers, but more affected in the slope of their betting function. It is concluded that pathological and problem gamblers process information about confidence and control differently from non-problem gamblers.


Development of an enzymatic fiber-optic biosensor for detection of halogenated hydrocarbons.
An enzyme-based biosensor was developed by co-immobilization of purified enzyme haloalkane dehalogenase (EC 184.108.40.206) and a fluorescence pH indicator on the tip of an optical fiber. Haloalkane dehalogenase catalyzes hydrolytic dehalogenation of halogenated aliphatic hydrocarbons, which is accompanied by a pH change influencing the fluorescence of the indicator. The pH sensitivity of several fluorescent dyes was evaluated. The selected indicator 5(6)-carboxyfluorescein was conjugated with bovine serum albumin and its reaction was tested under different immobilization conditions. The biosensor was prepared by cross-linking of the conjugate in tandem with haloalkane dehalogenase using glutaraldehyde vapor. The biosensor, stored for 24 h in 50 mM phosphate buffer (pH 7.5) prior to measurement, was used after 15 min of equilibration, the halogenated compound was added, and the response was monitored for 30 min. Calibration of the biosensor with 1,2-dibromoethane and 3-chloro-2-(chloromethyl)-1-propene showed an excellent linear dependence, with detection limits of 0.133 and 0.014 mM, respectively. This biosensor provides a new tool for continuous in situ monitoring of halogenated environmental pollutants.


The influence of oracin on reduction and toxicity of doxorubicin in hepatocytes and mammary epithelial cells MCF-10A.
The ways, how to increase effectiveness of doxorubicin (DOX) in cancer cells and decrease its toxicity in normal cells, have been intensively studied. In breast cancer cells MCF-7, isoquinoline derivative oracin (ORC) inhibited DOX reduction and increased DOX antiproliferative effect. The aim of this study was to test the influence of ORC on the reduction of DOX and its toxicity in hepatocytes and non-tumourous breast cells. The kinetics of DOX reduction was measured in cytosols from rat liver, human liver and human mammary epithelial cells MCF-10A. Activity and expression of carbonyl reductase 1 (CBR1) were assayed using menadione as a substrate and western blot analysis. End-point tests of viability served for study of cytotoxicity of DOX, ORC and DOX+ORC combinations in rat hepatocytes and MCF-10A cells. The inhibitory effect of ORC on DOX reductases was almost none in MCF-10A cells and mild in liver. CBR1 expression and activity was lower in non-tumourous MCF-10A cells than in cancer MCF-7 cells. Cytotoxicity tests showed that DOX+ORC combinations had significantly lower toxicity than DOX alone in MCF-10A cells as well as in hepatocytes. ORC significantly decreases DOX toxicity in MCF-10A and in hepatocytes. Therefore, concomitant use of ORC and DOX may protect normal cells against DOX toxicity.


Effect of maternal overnutrition on predisposition to insulin resistance in the foal: Maternal parameters and foal pancreas histoarchitecture.
Results from previous studies indicate that maternal overnutrition during late gestation predisposes foals to metabolic disease, however, specific mechanisms resulting in disease remain unknown. Quarter Horse mares (n = 16), were randomly assigned to dietary treatments, beginning on gestational day 235, and consisted of a control group (CON- diet meeting nutrient requirement; n = 8) or an overfed diet (HIGH; n = 8) where mares received an additional 40 % above CON. On gestational days 285 and 315, an intravenous glucose tolerance test (FSIGTT) was conducted. Following parturition, foals were separated from the mare, prohibited from nursing, and an FSIGTT was conducted at 2 h postpartum. Foals were immediately euthanized and tissues preserved for analyses. There was no effect of treatment on foal BW (P = 0.50), pancreas weight (P = 0.60), or FSIGTT area under the curve for glucose (P = 0.80) and insulin (P = 0.70). Colocalization of α-amylase to isolate pancreatic islets of Langerhans indicated increased islet number and size in foals from HIGH mares (P < 0.01). Immunofluoresent analysis of insulin, glucagon, and somatostatin indicate no difference in intensity of staining (P> 0.10). Foals exposed to overnutrition during peak fetal growth had altered pancreatic islet development that may lead to adult-onset metabolic disease.


Hysterectomy in a phenotypic male with congenital adrenal hyperplasia (CAH).
A young adult patient with 46XX congenital adrenal hyperplasia (CAH) presented with recurrent painful haematuria. CAH was diagnosed at birth following ambiguous genitalia. Hormonal treatment was started, female gender was assigned and feminising genitoplasty was planned, however the patient was lost to follow-up. Gender dysphoria started to occur during childhood which prompted the family to raise the patient as a boy. He eventually identified himself as a male. Examination revealed a male phenotype with severely virilised genitalia. Imaging studies confirmed the presence of uterus with low confluent urogenital sinus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, and the troublesome symptoms were cured.


Tuberculosis among elderly Chinese in residential homes: tuberculin reactivity and estimated prevalence.
Objectives of this study were to determine the prevalence of positive tuberculin reactivity and associated factors among elderly nursing home residents in a population with a relatively high tuberculosis notification rate, to estimate the prevalence of active tuberculosis, and to assess tuberculin reactivity as a screening tool. A stratified, disproportional, randomized cluster sample of residents was selected and the Mantoux test (using 0.1 ml of 5 tuberculin units of purified protein derivative of tuberculin) carried out. All subjects with a positive test had a chest X-ray followed by sputum smear and culture if the X-ray was abnormal. Sputum examination was also carried out in a random sample of controls, matched for age and gender, drawn from subjects with a negative Mantoux test. Information regarding medical history, tobacco smoking habits, symptoms related to tuberculosis, and communal eating habits were gathered. Also anthropometric data were collected. Sixteen nursing homes in the catchment area of a major district hospital in Hong Kong comprising 587 residents (136 men, 451 women, mean age 80 +/- 8 years) participated in this study. The weighted prevalence of tuberculin reactivity was 43.8%. It was higher in men, among those who took their meals in a common area, in the younger age group, and in those with no previous history of hospitalization. No association was found between prevalence and duration of residence, smoking, skinfold thickness, past medical history, or any relevant symptoms. Following radiological and sputum examination, the estimated prevalence of active tuberculosis ranged from 1.2 to 2.6%. The sensitivity of the tuberculin test was 86, the specificity 30%. The prevalence of active tuberculosis in nursing homes in Hong Kong is high, but it is unclear whether cross-infection or poor health of the residents is the major contributing factor. Tuberculin skin testing does not appear to be a useful screening method in this population.


An annotated description of shallow water holothurians (Echinodermata: Holothuroidea) from Cayos Cochinos, Honduras.
Taxonomic and biological aspects are presented on five species of shallow water holothurians from the Cayos Cochinos Biological Reserve-CCBR located on the northern Honduran shelf, western Caribbean at 16 degrees N, 86 degrees W. This article provides a taxonomic key of the recorded holothurians and morphometric/morphologic descriptions of their corresponding spicules. These five species belong to a single order (Aspidochirotida) and two families: Stichopodidae (Isostichopus badionotus) and Holothuriidae (Holothuria mexicana, H. thomasi, H. arenicola and Actinopyga agassizi). In addition, the commensal pearlfish, Carapus bermudensis is recorded from H. mexicana and A. agassizi.


Relationship of skeletal pattern and nasal form.
This article investigates the relationship of skeletal facial pattern and soft-tissue nasal form. The case sample comprises 123 white female subjects, aged 11.0 to 20.6 years, with no histories of pathology, trauma, surgical intervention, or orthodontic treatment. Measurements were made from cephalometric radiographs, posteroanterior radiographs, and the physioprint photographs. Skeletal classifications were based on the relationship of the maxilla to the mandible; the three classifications were straight profile, retrusive chin profile, and prognathic profile. Pearson product--moment correlation coefficients were used to test intercorrelations of all quantitative variables (including age) with each other. Correlations were highly significant for age, the three profile measurements, and two of the frontal measurements. Hence, noses and skeletal structures showed, as expected, increases with age. Also, profile measurements were highly significantly correlated; larger noses were larger in all profile dimensions. A stepwise discriminant analysis was used to study nonquantitative categories of nasal shape (straight, convex, and concave). This analysis indicated that more than 86% of patients in the sample of 123 demonstrated a correlation of nasal shapes with specific skeletal groupings. Patients with straight profiles tended to have straight noses; convex profiles accompanied convex nasal shapes; and concave profiles were found with concave nasal shapes. The clinical significance of this research is to emphasize the importance of total facial harmony (especially nasal shape) during orthodontic diagnosis and treatment planning.


An update on crimean congo hemorrhagic Fever.
Crimean Congo hemorrhagic fever (CCHF) is one of the deadly hemorrhagic fevers that are endemic in Africa, Asia, Eastern Europe, and the Middle East. It is a tick-borne zoonotic viral disease caused by CCHF virus of genus Nairovirus (family Bunyaviridae). CCHF not only forms an important public health threat but has a significant effect on the healthcare personnel, especially in resource-poor countries. India was always a potentially endemic area until an outbreak hit parts of Gujarat, taking four lives including the treating medical team. The current review is an attempt to summarize the updated knowledge on the disease particularly in modern era, with special emphasis on nosocomial infections. The knowledge about the disease may help answer certain questions regarding entry of virus in India and future threat to community.


[Differential diagnosis of diseases of the Achilles tendon. A clinico-sonographic concept].
Ultrasound of the Achilles tendon is a suitable means of differentiating various diseases of the tendon and the surrounding tissue. Different forms of degenerative disease (tendinitis, peritendinitis or bursitis, fibroosteitis, and Haglund's disease) can be discriminated from rheumatic and metabolic diseases. Congenital and developmental abnormalities can also be detected. Tendon degeneration mainly occurs in the ventral part of the medial third of the tendon ("critical zone"). Immature tissue in this area leads to temporary [correction of temorary] instability of the tendon with a high risk of rupture ("vulnerable phase"). With sonography, lesions of the Achilles tendon are visible early in the course of the disease.


[How much is the decrease in blood pressure shown by repeated measurements during the same examination?].
The recommendations for blood pressure determination by sphygmomanometer encourage repeated measurements. In 430 subjects aged 56-87 years, three recordings were obtained at one minute intervals. On average, the blood pressure decreased 10/3 mm Hg from the first to the third recording (p < 0.001). The decrease was more pronounced in hypertensives (12/4 mmHg) than in normotensives (7/2 mm Hg) (p < 0.01), but was little influenced by sex, age, or body mass. A change of 10/3 mm Hg is relevant with respect to the risk of cardiovascular disease, diagnosis of hypertension, and antihypertensive therapy. Also, repeated measurements may reduce the number of falsely positive hypertensives, and is recommended as the standard procedure in conventional blood pressure determination.


[Methylene blue staining in fiberoptic bronchoscopy in the diagnosis of bronchial tumors].
47 patients were stained by using methylene blue in fiberoptic bronchoscopy. Of these, 35 had central lung cancer, and 12 bronchitis. 40 patients with central lung cancer were detected by general fibreoptic endoscopy. The results demonstrated that normal bronchial mucosa was not stained, 97.14% central malignant bronchial tumors stained, and 8.33% bronchitis stained. X2test showed the marked difference. Positive diagnosis was 97.06% in biopsy specimens stained, it was higher than 77.05% in the general investigated (P < 0.05). Using methylene blue in fiberoptic bronchoscopy would help diagnose central lung cancer, determine tumors limits, permit accurate biopsy. The stain was not related to the pathological classification, differentiation of cancer cells, and classification of clinical pathology (P > 0.05).


The safe administration of long-acting depot antipsychotics.
Injectable long-acting antipsychotics are a well-established and common treatment for schizophrenia and other mental health problems. While these medicines have traditionally been injected into the dorsogluteal muscle, the primacy of this site has been challenged over recent years, both through the emergence of the deltoid muscle as a less intrusive alternative, and through a groundswell of opinion raising concerns over the safety of injecting into the gluteal muscle. As these concerns have included calls for the dorsogluteal site to no longer be considered suitable for the administration of injections, there is a need to clarify the basis of such claims and the appropriateness of continued use of this area. Review of relevant literature allowed exploration of the evidence used in supporting these claims and identified that UK licencing agreements for these medicines fails to support such wholesale change and that there are considerable inconsistencies in the evidence presented. Recommendations are made for further study in this area and for measured change to practice if required, particularly around use of the deltoid site and for review of the licencing agreements for these medicines.


Identification of a novel lipin homologue from the parasitic protozoan Trypanosoma brucei.
Arginine methylation is a post-translational modification that expands the functional diversity of proteins. Kinetoplastid parasites contain a relatively large group of protein arginine methyltransferases (PRMTs) compared to other single celled eukaryotes. Several T. brucei proteins have been shown to serve as TbPRMT substrates in vitro, and a great number of proteins likely to undergo methylation are predicted by the T. brucei genome. This indicates that a large number of proteins whose functions are modulated by arginine methylation await discovery in trypanosomes. Here, we employed a yeast two-hybrid screen using as bait the major T. brucei type I PRMT, TbPRMT1, to identify potential substrates of this enzyme. We identified a protein containing N-LIP and C-LIP domains that we term TbLpn. These domains are usually present in a family of proteins known as lipins, and involved in phospholipid biosynthesis and gene regulation. Far western and co-immunoprecipitation assays confirmed the TbPRMT1-TbLpn interaction. We also demonstrated that TbLpn is localized mainly to the cytosol, and is methylated in vivo. In addition, we showed that, similar to mammalian and yeast proteins with N-LIP and C-LIP domains, recombinant TbLpn exhibits phosphatidic acid phosphatase activity, and that two conserved aspartic acid residues present in the C-LIP domain are critical for its enzymatic activity. This study reports the characterization of a novel trypanosome protein and provides insight into its enzymatic activity and function in phospholipid biosynthesis. It also indicates that TbLpn functions may be modulated by arginine methylation.


Expression of palmitoyl protein thioesterase in neurons.
Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder in childhood that is caused by mutations in the gene encoding lysosomal palmitoyl protein thioesterase (PPT). INCL is characterized by massive and selective loss of cortical neurons. Here we have analyzed the intracellular processing and localization of adenovirus-mediated PPT in mouse primary neurons and NGF-induced PC-12 cells. The neuronal processing of PPT was found to be similar to that observed in peripheral cells, and a significant amount of the PPT enzyme was secreted in the primary neurons. Immunofluorescence analysis of the neuronal cells infected with wild-type PPT showed a granular staining pattern in the cell soma and neuronal shafts. Interestingly, PPT was also found in the synaptic ends of the neuronal cells and the staining pattern of the enzyme colocalized to a significant extent with the synaptic markers SV2 and synaptophysin. These in vitro data correspond with the distribution of endogeneous PPT in mouse brain and suggest that PPT may not solely be a lysosomal hydrolase. The specific targeting of PPT into the neuritic shafts and nerve terminals indicates that PPT may be associated with the maintenance of synaptic function. Furthermore, since a substantial amount of PPT is secreted by neurons, it is tempting to speculate that the enzyme could also have an extracellular substrate.


Patient care outside of office visits: a primary care physician time study.
Patient care provided by primary care physicians outside of office visits is important for care coordination and may serve as a substitute for office visits. To describe primary care physicians' ambulatory patient care activities outside of office visits ("AOVs") and their perceptions of the extent to which AOVs substitute for visits and may be performed by support staff. Cross-sectional direct observational study. Thirty-three general internists in 20 practices in two health care systems (one public, one private) in the New York metropolitan area. Duration of AOVs by type of activity and whether they pertain to a patient visit on the study day (visit specific) or not (non-visit specific). Physician perceptions of the: (1) extent that non-visit-specific AOVs substitute for visits that would have otherwise occurred, (2) extent that visits that occurred could have been substituted for by AOVs, and (3) potential role of support staff in AOVs. Physicians spent 20% of their workday performing AOVs, 62% of which was for non-visit specific AOVs. They perceived that a median of 37% of non-visit-specific AOV time substituted for visits, representing a potential five visits saved per day. They also perceived that 15% of total AOV time (excluding charting) could be performed by support staff. Forty-two percent of physicians indicated that one or more visits during the study day could be substituted for by AOVs. Though time spent on AOVs is generally not reimbursed, primary care general internists spent significant time performing AOVs, much of which they perceived to substitute for visits that would otherwise have occurred. Policies supporting physician and staff time spent on AOVs may reduce health care costs, save time for patients and physicians, and improve care coordination.


Is Increased Intracranial Pressure a Factor in Persistent Headache After Coronavirus Disease 2019?
This study aimed to determine pain characteristics in patients with persistent headache after COVID-19 and to investigate the role of increased intracranial pressure (ICP) in the pathogenesis of this headache. This is a case-control study comparing the parameters and measurements indicating increased ICP based on magnetic resonance imaging between COVID-19-diagnosed patients with persistent headache and a control group. Optic nerve sheath diameter (ONSD) and eyeball transverse diameter (ETD) were performed on the left eye of each participant. Seventeen of the patients (53.12%) met the diagnostic criteria for new daily persistent headache. Seven patients (21.87%) had migraine, and eight (25%) had tension headache characteristics. No significant difference was observed between the patient and control groups in terms of the ONSD and ETD values. It is possible that the etiopathogenesis is multifactorial. We consider that future studies that will evaluate ICP measurements in large patient groups can present a different perspective for this subject.


Surface-Confined Winding Assembly of Mesoporous Nanorods.
Bending and folding are important stereoscopic geometry parameters of one-dimensional (1D) nanomaterials, yet the precise control of them has remained a great challenge. Herein, a surface-confined winding assembly strategy is demonstrated to regulate the stereoscopic architecture of uniform 1D mesoporous SiO2 (mSiO2) nanorods. Based on this brand-new strategy, the 1D mSiO2 nanorods can wind on the surface of 3D premade nanoparticles (sphere, cube, hexagon disk, spindle, rod, etc.) and inherit their surface topological structures. Therefore, the mSiO2 nanorods with a diameter of ∼50 nm and a variable length can be bent into arc shapes with variable radii and radians, as well as folded into 60, 90, 120, and 180° angular convex corners with controllable folding times. Additionally, in contrast to conventional core@shell structures, this winding structure induces partial exposure and accessibility of the premade nanoparticles. The functional nanoparticles can exhibit large accessible surface and efficient energy exchanges with the surroundings. As a proof of concept, winding-structured CuS&mSiO2 nanocomposites are fabricated, which are made up of a 100 nm CuS nanosphere and the 1D mSiO2 nanorods with a diameter of ∼50 nm winding the nanosphere in the perimeter. The winding structured nanocomposites are demonstrated to have fourfold photoacoustic imaging intensity compared with the conventional core@shell nanostructure with an inaccessible core because of the greatly enhanced photothermal conversion efficiency (increased by ∼30%). Overall, our work paves the way to the design and synthesis of 1D nanomaterials with controllable bending and folding, as well as the formation of high-performance complex nanocomposites.