Orbitotonography, the dynamic assessment of orbital tension: 1. Results in subjects without known orbital disease.
This paper describes a new orbitotonometer and method of dynamically assessing the orbital tissue resistance ("orbital tension"). In 20 healthy volunteers without known orbital disease the inexpensive instrument proved to be safe and accurate, providing useful, reproducible clinical information. The full diagnostic work-up of patients with orbital disease should include the accurate measurement of orbital tension, as this may provide the ophthalmologist with earlier objective evidence of the disease process as well as a method of following its course.


Modification of growth in small heat shock (hsp27) gene transfected breast carcinoma.
The role of hsp27 in the regulation of cell growth has been investigated in the breast cancer cell line MDA-MB-23 1. Cells were co-transfected with an expression vector carrying the human hsp27 gene (pSG-2711) and a plasmid conferring neomycin resistance (pWlneo). Transfected cells were selected for neomycin resistance. Stable transfectants were used as a pooled population for further experiments, since single-cell colonies were not able to grow into mass culture under continuous selection pressure. Over-expression of hsp27 was analysed by immunohistochemistry and immunoblotting. Cells only transfected for neomycin were used as control cells. The growth rate of the transfected cell line was determined whether overexpression of hsp27 directly influences the growth properties of the cells. Growth analysis of transfected cell lines in vitro revealed a lower proliferation rate of the hsp27 overexpressing cells compared to controls. These data suggest that hsp27 is involved in downregulation of cell proliferation in this human breast cancer cell line.


A review of ecological factors associated with the epidemiology of wildlife trypanosomiasis in the luangwa and zambezi valley ecosystems of zambia.
Trypanosomiasis has been endemic in wildlife in Zambia for more than a century. The disease has been associated with neurological disorders in humans. Current conservation strategies by the Zambian government of turning all game reserves into state-protected National Parks (NPs) and game management areas (GMAs) have led to the expansion of the wildlife and tsetse population in the Luangwa and Zambezi valley ecosystem. This ecological niche lies in the common tsetse fly belt that harbors the highest tsetse population density in Southern Africa. Ecological factors such as climate, vegetation and rainfall found in this niche allow for a favorable interplay between wild reservoir hosts and vector tsetse flies. These ecological factors that influence the survival of a wide range of wildlife species provide adequate habitat for tsetse flies thereby supporting the coexistence of disease reservoir hosts and vector tsetse flies leading to prolonged persistence of trypanosomiasis in the area. On the other hand, increase in anthropogenic activities poses a significant threat of reducing the tsetse and wildlife habitat in the area. Herein, we demonstrate that while conservation of wildlife and biodiversity is an important preservation strategy of natural resources, it could serve as a long-term reservoir of wildlife trypanosomiasis.


Profunda femoris artery pseudoaneurysm following revision for femoral shaft fracture nonunion.
Femoral artery pseudoaneurysms (FAPs) have been described following internal fixation of intertrocantheric, subtrocantheric and intracapsular femoral neck fractures as well as core decompression of the femoral head. The diagnosis of FAP is usually delayed because of non-specific clinical features like pain, haematoma, swelling, occasional fever and unexplained anaemia. Because of the insidious onset and of the possible delayed presentation of pseudoaneurysms, orthopaedic and trauma surgeons should be aware of this complication. We report a case of Profunda Femoris arterial branch pseudoaneurysm, diagnosed in a 40-year-old male 4 wk after revision with Kuntscher intramedullary nail of a femoral shaft nonunion. The diagnosis was achieved by computed tomography angiography and the lesion was effectively managed by endovascular repair. The specific literature and suggestions for treatment are discussed in the paper.


Katanin controls mitotic and meiotic spindle length.
Accurate control of spindle length is a conserved feature of eukaryotic cell division. Lengthening of mitotic spindles contributes to chromosome segregation and cytokinesis during mitosis in animals and fungi. In contrast, spindle shortening may contribute to conservation of egg cytoplasm during female meiosis. Katanin is a microtubule-severing enzyme that is concentrated at mitotic and meiotic spindle poles in animals. We show that inhibition of katanin slows the rate of spindle shortening in nocodazole-treated mammalian fibroblasts and in untreated Caenorhabditis elegans meiotic embryos. Wild-type C. elegans meiotic spindle shortening proceeds through an early katanin-independent phase marked by increasing microtubule density and a second, katanin-dependent phase that occurs after microtubule density stops increasing. In addition, double-mutant analysis indicated that gamma-tubulin-dependent nucleation and microtubule severing may provide redundant mechanisms for increasing microtubule number during the early stages of meiotic spindle assembly.


Atlas instrumentation guided by the medial edge of the posterior arch: An anatomic and radiologic study.
This was an interventional human cadaver study and radiological study. Atlas instrumentation is frequently involved in fusion procedures involving the craniocervical junction area. Identification of the entry point at the center of atlas lateral mass (ALM) is challenging because of its rounded posterior surface and the surrounding venous plexus. This report examines using the medial edge of atlas posterior arch (MEC1) as a fixed and reliable anatomic reference to guide the entry point of ALM screws. Fifty, normal, cervical spine computed tomography studies were reviewed. ALM screw trajectories were planned at one point along MEC1 and another point 2 mm lateral to MEC1. Free-hand ALM instrumentation was performed in ten fresh human cadavers using the 2 mm entry point, with a sagittal trajectory parallel to atlas inferior arch (IAC1); three-dimensional imaging was then performed to confirm instrumentation accuracy. The average ALM diameter was 12.35 mm. Inserting a screw using the entry point 2 mm lateral to MEC1 was closer to ALM midpoint than using the entry point along MEC1 (P < 0.0001). Twenty ALM screws were successfully inserted in the ten cadavers. No encroachments into the spinal canal or foramen transversarium occurred. However, two screws were superiorly directed and violated the occipitocervical joint; they were not parallel to IAC1. MEC1 provides a fixed and reliable landmark for ALM instrumentation. An entry point 2 mm point lateral to MEC1 is close to ALM midpoint. IAC1 also provides a guide for the sagittal trajectory. Attention to anatomic landmarks may help reduce complications associated with atlas instrumentation but should be verified in future clinical studies.


Adenosine-induced cardiac standstill for endovascular treatment of pediatric vein of Galen malformations.
Vein of Galen malformations are congenital high-flow vascular malformations that often present with heart failure, hydrocephalus, developmental delay, and intracranial hemorrhage. Because open surgical treatment is associated with high morbidity and mortality, endovascular embolization is increasingly becoming the preferred method of intervention. However, embolization of these lesions can be difficult because of their high-flow nature. The use of adenosine-induced cardiac standstill for treatment of vein of Galen malformations has not been previously described in neonates. The authors describe 3 treatments in 2 patients that demonstrate that the use of adenosine is well tolerated and allows safe transarterial embolization of high-flow vein of Galen malformations in the pediatric population.


[Consequences of intrauterine hypoxia in the newborn].
In the above paper authors introduced current opinions regarding diagnosis, prevention and management in asphyxiated newborn infants with multiorgan disfunction and injury.


Ultrasonography of the lower extremity veins: anatomy and basic approach.
Ultrasonography is an imaging modality widely used to evaluate venous diseases of the lower extremities. It is important to understand the normal venous anatomy of the lower extremities, which has deep, superficial, and perforating venous components, in order to determine the pathophysiology of venous disease. This review provides a basic description of the anatomy of the lower extremity veins and useful techniques for approaching each vein via ultrasonography.


[Subnational analysis of probability of premature mortality caused by four main non-communicable diseases in China during 1990-2015 and " Health China 2030" reduction target].
Objective: To investigate the current status, temporal trend and achieving Health China 2030 reduction target of probability of premature mortality caused by four main non-communicable diseases (NCDs) including cardiovascular and cerebrovascular diseases, tumour, diabetes, and chronic respiratory disease in China both at national and provincial level during 1990 to 2015. Methods: Using the results of Global Burden of Disease study 2015 (GBD 2015), according to the method of calculating premature mortality probability recommended by WHO, the current status and temporal trend by different gender from 1990 to 2015 were calculated, analyzed, and compared. Referring to " Health China 2030" target of reduction 30% of probability of premature mortality caused by major NCDs, we evaluated the difficulty of achieving the reduction target among provinces (not including Taiwan). Results: From 1990 to 2015, the probabilities of premature mortality in cardiovascular and cerebrovascular diseases, tumour, and chronic respiratory disease were all declined consistently for both men and women in China, the total of four main NCDs decreased from 30.69% to 18.54% with higher decreasing in women (from 25.97% to 12.40%) than that in men (from 34.94% to 24.19%). In 2015, the top five provinces in terms of probability of premature mortality caused by four main NCDs were Qinghai (28.81%), Tibet (25.88%), Guizhou (24.67%), Guangxi (23.56%), and Xinjiang (23.21%) in turn, while the top five provinces with the lowest probability were Shanghai (8.40%), Beijing (9.39%), Hong Kong (10.10%), Macao (10.31%), and Zhejiang (11.70%). If achieving the " Health China 2030" target, the probabilities of premature mortality in Qinghai and Tibet with the highest probability should decline to about 20.17%, and 18.12%, respectively in 2030, while 5.88%, and 6.57% in Shanghai and Beijing, respectively. From 1990 to 2015, the probability of premature mortality of four main NCDs declined by 2.00% a year on average, the top five provinces with the fastest decline were Beijing (3.48%), Shanghai (3.24%), Zhejiang (2.81%), Fujian (2.75%), and Guangdong (2.67%), and 11 provinces including these five provinces could achieve the " Health China 2030" target by the usual rate of decline, while other 22 provinces could not achieve the target, they need greater rate of decline in order to achieve the target. Conclusion: From 1990 to 2015, the probabilities of premature mortality of four main NCDs were declined consistently in China both at national and provincial level, compared with women, the men had higher probabilities and declined slower, there were significant different in probabilities of premature mortality and their change speed among provinces. Based on the results from 1990 to 2015, there were about two thirds of the provinces, which the task of achieving the Health China 2030 target will be daunting.


[Plea for quality cytological specimens in the screening of cervical cancer].
In the context of a typical false negative cervical cancer test, the authors discuss the value of such screening tests and the various causes of a lack of success. A poor sample is the main cause of false negatives, and therefore involves everyone taking part in the procedures for this screening test.


A retrospective study of 29 cases of otitis media/interna in dairy calves.
Epidemiological data, clinical findings, laboratory data, medical imaging, and outcomes were reviewed in 29 dairy calves with otitis media/interna. Age at admission ranged from 1 to 24 wk. The majority of calves were referred during winter. Clinical signs included drooping ear, ptosis, head tilt, abnormal nystagmus, strabismus, dysphagia, regurgitation, stiff neck, opisthotonos, facial hyperesthesia, and purulent aural discharge. Intranasal endoscopic examination of 5 animals revealed nasopharyngeal collapse in 4. Cerebrospinal fluid (CSF) was abnormal in all of 7 cases. Mycoplasma bovis was cultured from all but 1 case with external ear or tympanic bullae samples (n = 12), and Mycoplasma arginini was cultured from the remaining ear sample. Radiographs of the tympanic bullae were performed in 24 calves, tomodensitometry (CT) in 3 calves and ultrasound in 4 calves. According to medical imaging techniques or necropsy, 69% of the cases were classified as chronic. Mean duration of treatment was 23.3 d. The rate of clinical recovery was 75%. Epidemiological data, clinical findings, laboratory data, medical imaging, and outcomes were reviewed in 29 dairy calves with otitis media/interna. Age at admission ranged from 1 to 24 wk. The majority of calves were referred during winter. Clinical signs included drooping ear, ptosis, head tilt, abnormal nystagmus, strabismus, dysphagia, regurgitation, stiff neck, opisthotonos, facial hyperesthesia, and purulent aural discharge. Intranasal endoscopic examination of 5 animals revealed nasopharyngeal collapse in 4. Cerebrospinal fluid (CSF) was abnormal in all of 7 cases. Mycoplasma bovis was cultured from all but 1 case with external ear or tympanic bullae samples (n = 12), and Mycoplasma arginini was cultured from the remaining ear sample. Radiographs of the tympanic bullae were performed in 24 calves, tomodensitometry (CT) in 3 calves and ultrasound in 4 calves. According to medical imaging techniques or necropsy, 69% of the cases were classified as chronic. Mean duration of treatment was 23.3 d. The rate of clinical recovery was 75%.


A 3- to 18-Year Follow-Up of Revision Total Hip Arthroplasty With Impacted Bone Allografts and Cemented Lubinus SP II Stem. Clinical, Radiographic, and Survivorship Analysis With Comparison to the Literature.
We present the first medium- to long-term follow-up of revision total hip arthroplasty using impaction bone grafting (IBG) combined with the matte and collared Lubinus SP II stem for cases of severe osteolysis and stem loosening. Sixty-nine femoral revisions were identified for 67 patients consecutively operated with revision femoral arthroplasty using IBG and a cemented Lubinus SP II stem. The mean age was 69 years (standard deviation, 9.9). We retrospectively analyzed 68 cases (1 was lost to follow-up). At the time of the revision surgery, all had substantial femoral bone loss. Fifteen of the revisions were performed due to deep infection. The patients were analyzed by clinical score and radiography. At follow-up, 4 femoral components (6%) had been rerevised or assessed as failure. Of these 4, 3 were assessed as mechanical failure, and 1 for dislocation; none was for infection. Three cups (4%) had been revised for dislocation; 1 of these also had a stem exchange. Three cases (4%) had been reoperated for a periprosthetic fracture in distal femur without stem exchange. Radiologic results were excellent and the clinical Merle d'Aubignè-Postel score had improved from a mean of 12.2 preoperatively to 17.5 at follow-up. IBG combined with the Lubinus SP II stem is safe and results in a low rate of periprosthetic fractures and dislocations. The medium- to long-term clinical result was excellent, with regeneration of living bone in the femur.


Direct alcohol fuel cells: toward the power densities of hydrogen-fed proton exchange membrane fuel cells.
A 2 μm thick layer of TiO2 nanotube arrays was prepared on the surface of the Ti fibers of a nonwoven web electrode. After it was doped with Pd nanoparticles (1.5 mgPd cm(-2) ), this anode was employed in a direct alcohol fuel cell. Peak power densities of 210, 170, and 160 mW cm(-2) at 80 °C were produced if the cell was fed with 10 wt % aqueous solutions of ethanol, ethylene glycol, and glycerol, respectively, in 2 M aqueous KOH. The Pd loading of the anode was increased to 6 mg cm(-2) by combining four single electrodes to produce a maximum peak power density with ethanol at 80 °C of 335 mW cm(-2) . Such high power densities result from a combination of the open 3 D structure of the anode electrode and the high electrochemically active surface area of the Pd catalyst, which promote very fast kinetics for alcohol electro-oxidation. The peak power and current densities obtained with ethanol at 80 °C approach the output of H2 -fed proton exchange membrane fuel cells.


A cost-consequence analysis of eLearning videos designed to supplement the consent process in lower limb arthroplasty.
Since the Montgomery ruling in 2015 surgeons have been tasked with identifying material risk when taking informed consent. Despite this, there has been limited uptake of technological aids to supplement the consent process although such aids are shown to improve patient knowledge and satisfaction. ConsentPLUS is a free-to-access website with bite-sized educational videos designed to clearly explain lower limb arthroplasty procedures to patients and aid their consent. The authors performed a prospective cost-consequence analysis, outlining any costs associated with the intervention and any quantitative or qualitative impacts the intervention may have on patients. A total of 3,143 consecutive patients were identified who were undergoing total knee or hip replacement in 25 elective NHS orthopaedic units. The total cost of development and projected 10-year running fees for ConsentPLUS total £75,000. Health Foundation support means the service is free-to-access for centres throughout the UK. Mean exposure time per patient was 10min 29s, equivalent to £185,437 of additional contact time according to the National Tariff. Mean clinic time was reduced by 17min owing to the earlier identification of material risk. Patient knowledge on pre- and post-video quizzes increased from 7.01 to 9.08 following eLearning (paired t-test = 0.998). The process had an overall satisfaction rate of 97%. Educational eLearning videos are an accessible and digestible way to supplement the consent process. This enables earlier identification of material risk in clinics owing to improved patient knowledge, leading to increased patient satisfaction with arthroplasty consenting.


Clinical and prognostic relevancy of left ventricular trabeculation assessed by cardiac magnetic resonance in patients with dilated cardiomyopathy.
We sought to search for factors associated with the magnitude of trabeculation by cardiac magnetic resonance, and evaluate the impact of trabeculations on outcomes in patients with dilated cardiomyopathy (DCM). We evaluated clinical profiles and outcomes of 276 subjects with DCM (age: 33.2 ± 13.3 years, 160 males). Trabeculation was quantified as trabeculated/total myocardial mass ratio (TM/M). Subjects were stratified into three subgroups (A, B, and C) according to the tertiles of rising TM/M values (33% ranges). A group of 30 healthy subjects served as controls. Patients were prospectively followed-up in search of major adverse cardiovascular events for 2.4 years on average (range 0.2-3.9 years). Dilated cardiomyopathy patients had more trabeculation than controls (27.1 ± 16.9% vs. 17.3 ± 8.1, p < 0.01). Group C subjects had lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) (1445 [984-3843] vs. 873 [440-2633] vs. 529 [206-1221] pg/mL, p < 0.01), higher ejection fraction (23.9 ± 10.4 vs. 25.0 ± 9.2 vs. 32.4 ± 2.7%, p = 0.03), and lower left ventricular mass index (LVMI) (91.3 ± 21.5 vs. 74.3 ± 31.1 vs. 55.7 ± 23.2 g/m2, p < 0.01). They also had fewer areas of late gadolinium enhancement (69 [46.3%] vs. 31 [38.2%] vs. 15 [32.6%], p = 0.01). Male sex (b = 0.21, SE = 0.13; p = 0.01), LVMI (b = -0.32, SE = 0.08, p < 0.01) and NT-proBNP (b = -0.05, SE = 0.02, p = 0.02) were independently related to TM/M. The magnitude of trabeculation was not a predictor of major adverse cardiovascular events. Prognosis was impacted by left ventricular end-diastolic volume index only (HR 2.538, 95% CI -1.734-3.218, p < 0.01). Trabeculation patterns relate to cardiac function and neurohormonal activation but not to survival.


Sam68 is a Ras-GAP-associated protein in mitosis.
Sam68 is the major tyrosine-phosphorylated and Src-associated protein in mitotic cells. Sam68 stimulates G1/S transition and this effect is dependent on the integrity of its KH domain (hnRNPK Homology) which confers nucleic acid binding properties. During mitosis, Sam68 undergoes tyrosine phosphorylation, which negatively regulates its nucleic acid binding properties and mediates the interaction of Sam68 with critical SH2-containing signaling proteins such as Grb2, PLC gamma 1 and Ras-GAP. However, the interaction of Ras-GAP with Sam68 has been brought into question, based on the lack of co-immunoprecipitation between Sam68 and Ras-GAP in interphase cells. Here we show that the choice of anti-Ras-GAP antibodies is critical for the detection of Ras-GAP/Sam68 complex formation, and that this interaction is specific for G2/M transition in both NIH3T3 and Src-transformed cells. Such data reinforce the importance of the interaction of Ras-GAP with RNA binding proteins during cell proliferation through its SH2 and SH3 domains.


At first glance, informal payments experience on track: why accept or refuse? Patients' perceive in cardiac surgery department of public hospitals, northeast of Iran 2013.
Patient's Informal payments is among the main source of health care financing in some countries. This paper aimed at determining the patient informal payments and relative factors in Cardiac Surgery Departments (CSD) in hospitals affiliated to Mashhad University of Medical Sciences (MUMS) in 2013. In this cross-sectional study, 316 discharged patients were selected using multi-stage sampling. Data gathering tool was a questionnaire which was filled by structured telephone interviews. We used quantitative content analysis for open-ended questions besides descriptive statistics and nonparametric tests by SPSS 16 at 0.05 Sig level. Sixteen (5.93%) patients made voluntary informal payments. The purpose of payment was: "gratitude" (43.75%), satisfaction with health services provided" (31.25%) and (18.75%) for better quality of services. About 75% of the payments were occurred during receiving health care services. The main causes were "no request for informal payments" (98.14%), "not affording to pay for informal payments" (73.33%) and "paying the hospital expenses by taking out a loan" (55.91%). Responders said they would pay informally in demand situation (51.85%) just for patient's health priority, 40.71% would also "search for other alternative solutions" and 27.33% "accepted the demand as a kind of gratitude culture". Twenty four patients (8.9%) had experienced mandatory informal payments during the last 6 months. The minimum amount of payment was 62.5$ and the maximum was 3125$. There was a significant relationship between the way of referring to medical centers and informal patient's payment (P ≤0.05). Despite the widespread prevalent belief about informal payments in public hospitals -particularly to the well-known physicians - such judgment cannot be generalized. The main reasons for the low informal payments in the current study were the personality characteristics of the physicians and hospital staff, their moral conscience and commitment to professional ethics, cultural factors and social-economic status of the patients. Health care system should notify people about their rights specially the payments calculation mechanism and methods. Better communication with the public and especially the media can help to correct attitude toward these payments.


Recovery of suppressed male reproduction in mice exposed to progesterone during embryonic development by testosterone.
The present study aimed to examine whether transplacental exposure to progesterone caused male reproductive abnormalities and whether the changes can be reversed after testosterone administration. Progesterone was injected to mice on day 1, 3, and 7 of pregnancy. The male pups (F1 generation) were allowed to grow for 50 days and assessed for reproductive performance. Gestational exposure to progesterone (7 mg/kg body weight) resulted in significant body weight gain with a decrease in reproductive tissue indices in mice. Total sperm count, viable sperm, and motile sperm decreased in experimental mice. Hypo-osmotic swelling test revealed that experimental mice sperm membrane integrity was severely altered. The activity levels of testicular steroidogenic marker enzymes (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B) and hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B)) decreased significantly in mice exposed to progesterone during embryonic development when compared with the controls. The levels of serum testosterone decreased with an increase in serum FSH and LH in mice exposed to progesterone during embryonic development. Prenatal exposure to progesterone caused significant reduction in the number of spermatozoa and increase in the lumen of seminiferous tubule. The experimental mice that cohabited with normal females showed fertility reduction. Administration of testosterone (4.16 mg/kg body weight) on postnatal day 20, 30, and 40 to progesterone-exposed prenates resulted in recovery of progesterone-induced suppressed male reproduction. It is suggested that the impairment of male reproduction in mice exposed to progesterone during embryonic development could be mediated through the inhibition of testosterone production. These results also indicate that in utero exposure to progesterone affects male reproduction and that supplementation of testosterone restores the suppressed male reproduction.


Biomarkers of Planarian Dugesia japonica in Response to Herbicide Glyphosate Exposure.
As the worldwide top-selling herbicide, glyphosate is ubiquitously distributed in the natural environment, and its influence on the ecological safety and human health has being increasingly concerned. In this study, mRNA expressions of GPX and three heat shock protein genes in freshwater planarian Dugesia japonica in response to glyphosate were determined, and two oxidative stress parameters were measured. The results suggested that GPX activity can be used as a more sensitive biomarker in contrast with GPX gene expression, and mRNA expressions of Hsp70, Hsp90 genes are more sensitive than Hsp40 for planarians in response to glyphosate stress. Besides, the deduced T-AOC as well as varied GPX activity and mRNA expression levels of Hsps also indicated that glyphosate exposure would inhibit antioxidation and induce oxidative stress in D. japonica, while specific antioxidant systems and stress proteins tried to protect cells by their own regulation. The results of this study will be helpful to elucidate the stress response mechanisms of freshwater planarians to herbicide glyphosate.


Hymenoptera venom allergy.
For most people, hymenoptera stings produce only a transient and bothersome local inflammatory reaction characterised by pain, redness and swelling. Alternatively, for those who are allergic to components of the venom, a re-sting may cause life-threatening, even fatal, reactions. In such patients correct diagnosis is an absolute prerequisite for effective management, i.e. specific venom immunotherapy (VIT) and generally consists of appropriate skin testing and quantification of venom-specific IgE-antibodies (sIgE). In spite the high efficiency of properly administered VIT, the molecular and cellular mechanisms of the desensitisation process are incompletely understood and remain subject of intense research. Besides the general principles and management of hymenoptera venom allergy, this review will focus on the current knowledge on the underlying tolerogenic mechanisms of VIT.


Laparoscopic repair of female genitourinary fistulae: 10-year single-center experience.
Laparoscopic repair of different female genitourinary fistulae has been recently reported, including both conventional and laparoendoscopic single-site surgery (LESS). We present our 10-year single-center experience of the laparoscopic repair of different types of female genitourinary fistulae. A retrospective analysis of our records over the last 10 years was performed. Type of fistula, etiology, laparoscopic approach, operative data, postoperative outcome, and follow-up were recorded. Overall, 46 patients with laparoscopic repair of genitourinary fistulae were reported: 25 had vesicovaginal fistulae (VVF), 14 had vesicouterine fistulae (VUF), and 7 had ureterovaginal fistulae (UVF). Thirty-three patients had conventional laparoscopic repair, whereas 7 VVF and 6 VUF had LESS repair. In all patients with VVF and VUF, extravesical repair was carried out by excising the fistulous tract and closing both the bladder and the vagina or the uterus with interposing tissue in-between. In patients with UVF, extravesical ureteric re-implantation was performed. Mean operative time was 176 ± 25 min. Mean blood loss was 105 ± 25 cc. No intraoperative or postoperative complications occurred. None was converted to open surgery. Mean postoperative hospital stay was 3.2 ± 1.2 days. After a mean follow-up of 6.3 ± 3.1 years, all patients had undergone successful repair, except for one patient with complex VVF. Laparoscopic repair of VVF, VUF, and UVF is a feasible procedure with a high success rate and low morbidity. LESS repair of VVF and VUF has a comparable success rate to conventional laparoscopy, but with a shorter hospital stay and fewer analgesic requirements.


Efficacy of intratympanic methylprednisolone acetate in treatment of drill-induced sensorineural hearing loss in guinea pigs.
Intratympanic steroids offer direct access to the inner ear with high concentration and without systemic effects. In this study, the efficacy of intratympanic methylprednisolone acetate (IT-MPA) was evaluated in a guinea-pig model of drill-induced inner ear trauma. Twenty-five guinea pigs were divided into a control group to document the baseline distortion product otoacoustic emissions (DPOAEs) and the normal scanning electron microscopic (SEM) morphology of the inner ear. The animals in the study group were subdivided into a steroid-only group (S), a trauma-only group (T), a trauma-plus-time group (TT), and a trauma-plus-steroid (TS) group. IT-MPA was found to have no damaging effect on the inner ear. Twelve days after trauma, there was spontaneous although incomplete recovery of the DPOAEs amplitudes and SEM morphology with scar tissue replacing lost outer hair cells. Statistically higher DPOAEs amplitudes (p < 0.05) were recorded in the TS group that had nearly normal SEM morphology compared to the TT group. The authors conclude that IT-MPA significantly improves drill-induced sensorineural hearing loss and inner ear morphological changes in guinea pigs.


Spatiotemporally Explicit Mapping of Built Environment Stocks Reveals Two Centuries of Urban Development in a Fairytale City, Odense, Denmark.
The urban built environment stocks such as buildings and infrastructure provide essential services to urban residents, and their spatiotemporal dynamics are key to the circular and low-carbon transition of cities. However, spatiotemporally explicit characterization of urban built environment stocks remains hitherto limited, and previous studies on fine-grained mapping of built environment stocks often focus on an urban area without consideration of temporal dynamics. Here, we combined the emerging geospatial data and historical maps to quantify the spatially and temporally refined stocks of buildings and infrastructure and developed a novel indexing method to track the construction, demolition, and renovation for each building across various historical snapshots, with a case study of Odense, Denmark, from 1810 to 2018. We show that built environment stock in Odense increased from 80 t/cap in 1810 to 279 t/cap in 2018. Their dynamics appear overall in line with urban development of Odense over the past two centuries and well reflect the combined effects of industrialization, infrastructure development, socioeconomic characteristics, and policy interventions. Such spatiotemporally explicit stock mapping offers a physical and resource perspective for measuring urbanization and provides the public and government insight into urban spatial planning and related resource, waste, and climate strategies.


The Immediate Effect of Neuromuscular Joint Facilitation (NJF) Treatment on Hip Muscle Strength.
[Purpose] This study investigated the change in hip muscle strength of younger persons after neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 45 healthy young people, who were divided into two groups: a NJF group and a proprioceptive neuromuscular facilitation (PNF) group. The NJF group consisted of 21 subjects (11 males, 10 females), and the PNF group consisted of 24 subjects (11 males, 13 females). [Methods] Participants in the NJF group received NJF treatment. We measured the maximal flexor strength and the maximal extensor strength during isokinetic movement of the hip joint before and after intervention in both groups. The angular velocities used were 60°/sec and 180°/sec. [Results] The NJF group showed significant increases in the maximal flexor strength and the maximal extensor strength after the intervention at each angular velocity. In the PNF group, the maximal flexor strength of 60°/sec and the maximal extensor strength of 180°/sec were significant increases. [Conclusion] These results suggest that there is an immediate effect of NJF intervention on hip muscle strength.


The medical librarian as chief information officer.
The position of chief information officer (CIO) is gaining popularity, especially in the health care field. The results of an informal electronic and telephone survey indicate that few medical librarians have made a career move to CIO even though this might seem like a logical step. This paper examines the qualities required of an effective information management executive, the role CIOs play within organizations, and the career advancement strategies for librarians interested in becoming CIOs. Questionnaire responses are reported from three medical librarians who have made the transition to CIO-type positions, and a case study illustrates the responsibilities of CIOs in health care organizations.


Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture.
Estrogen deficiency is associated with cerebral aneurysm rupture, but the precise mechanism is unknown. To test the hypothesis that IL-6 is required for the increase in aneurysm rupture rate observed in estrogen-deficient mice. We analyzed IL-6 expression in human cerebral aneurysms. We induced cerebral aneurysms in estrogen-deficient female C57BL/6 mice that had undergone 4-vinylcyclohexene diepoxide (VCD) treatment or bilateral ovariectomy (OVE). Mice were blindly randomized to selective IL-6 inhibition (IL-6 receptor [IL-6R] neutralizing antibody, n = 25) or control (isotype-matched IgG, n = 28). Murine cerebral arteries at the circle of Willis were assessed for aneurysm rupture and macrophage infiltration. IL-6 is expressed in human cerebral aneurysms, but not in control arteries. Serum IL-6 is elevated in ovariectomized female mice compared to sham control (14.3 ± 1.7 pg/mL vs 7.4 ± 1.5 pg/mL, P = .008). Selective IL-6R inhibition suppressed cerebral aneurysm rupture in estrogen-deficient mice compared with control (VCD: 31.6% vs 70.0%, P = .026; OVE: 28.6% vs 65.2%, P = .019). IL-6R inhibition had no effect on formation or rupture rate in wild-type mice. IL-6R neutralizing antibody significantly reduced macrophage infiltration at the circle of Willis (1.9 ± 0.2 vs 5.7 ± 0.6 cells/2500 μm2; n = 8 vs n = 15; P < .001). IL-6 is increased in the serum of estrogen-deficient mice and appears to play a role in promoting murine estrogen deficiency-associated cerebral aneurysm rupture via enhanced macrophage infiltration at the circle of Willis. Inhibition of IL-6 signaling via IL-6 receptor neutralizing antibody inhibits aneurysm rupture in estrogen-deficient mice. IL-6 receptor inhibition had no effect on aneurysm formation or rupture in wild-type animals.


Evolution of right ventricular size over time after tetralogy of Fallot repair: a longitudinal cardiac magnetic resonance study.
It is commonly believed that pulmonary regurgitation (PR) after surgical repair of tetralogy of Fallot (TOF) leads to progressive right ventricular (RV) enlargement. However, progressive RV dilatation has never clearly been documented in this patient population. Therefore, we studied the size of the RV over time in patients after surgical TOF repair. Fifty-one consecutive patients after surgical TOF repair underwent at least two cardiovascular magnetic resonance (CMR) exams using a single CMR scanner. Patients with RV outflow tract obstruction, interventions other than the initial repair and CMR exams with use of sedation were excluded. Three subgroups with different repair techniques were studied: transannular patch repair [n = 22, age 17 ± 10 years], subvalvular patch repair [n = 15, age 22 ± 8 years], or non-patch repair/infundibulectomy (n = 14, age 28 ± 11 years). Right ventricular end-diastolic volume index (RVEDVI) and PR fraction did not change during the 37 ± 21 months follow-up between first and last CMR in the whole group (RVEDVI: 118 ± 23 mL/m2 vs. 119 ± 23 mL/m2, P = 0.720; PR fraction: 33% (23-40%) vs. 32% (24-39%), P = 0.268). RVEDVI remained stable in all subgroups (transannular patch: 120 ± 21 mL/m2 vs. 122 ± 22 mL/m2, subvalvular patch: 112 ± 23 mL/m2 vs. 111 ± 23 mL/m2, non-patch: 123 ± 28 mL/m2 vs. 123 ± 23 mL/m2, P = 0.827). RVEDVI at last CMR did not differ between groups (P = 0.301). This study shows no progression of RV dilatation in patients after surgical repair of TOF with moderately dilated RVs and significant PR during a 3-year follow-up. RV dilatation in our patient group seems to be independent from surgical repair techniques.


Penetrating atheroma in cervical carotid artery stenosis.
A 61-year-old male presented with left hand motor weakness associated with cerebral infarction in the right frontal lobe. Right common carotid angiography demonstrated a 66% stenosis and carotid duplex scan demonstrated intermediate echogenic plaque, indicating typical carotid plaque. Carotid endarterectomy was performed 22 weeks after the ischemic onset. During exposure of the carotid artery, a soft and yellowish mass (5 x 5 mm) was observed in the lateral wall of the carotid bulbus, which was not covered with adventitia but with thin connective tissue. The mass was removed en-bloc with a small part of the surrounding arterial wall combined with ordinary endarterectomy. The artery was closed with a collagen-impregnated polyester patch graft (Hemashield patch) to maintain adequate arterial lumen. Histological examination of the removed plaque confirmed that atheroma had protruded from the intima through the media as well as the adventitia and formed an extra-arterial mass. Such a case requires great care to dissect the carotid artery to prevent premature disintegration of the atheroma.


Cerebrospinal Fluid Aβ42/Aβ40 as a Means to Limiting Tube- and Storage-Dependent Pre-Analytical Variability in Clinical Setting.
Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for AD diagnosis. Unfortunately, their wider use in routine and interpretation require more standardization, particularly for the pre-analytical steps. In particular, amyloid-β (Aβ)42 peptide measurement is strongly influenced by the type of collection tube and by repeated freeze/thaw cycles. The objectives of this study were to compare, in clinical setting, the impact of collection tubes and the repetition of freeze/thaw cycles on Aβ42 and Aβ40 concentrations and consequently determine if the Aβ42/Aβ40 ratio could resolve the diagnosis difficulties related to these pre-analytical parameters. CSF from 35 patients was collected in different polypropylene (PP) and stored at - 80°C after sampling. For CSF collected in the reference tube, three successive freeze-thaw cycles were done. Aβ42 and Aβ40 concentrations were determined in each condition in order to calculate the Aβ42/Aβ40 ratio. Our results showed that CSF Aβ42 and Aβ40 values were significantly different according to the type of collection tube and the number of freeze/thaw cycles. Although the calculation of the Aβ42/Aβ40 ratio eliminated the effect of PP tube-dependent variation, this was not the case for freeze-thaw cycle-associated variation. The use of Aβ42/Aβ40 ratio rather than Aβ42 alone could contribute toward pre-analytical standardization, thus allowing the general use of CSF AD biomarkers in routine practice.


Effects of nociceptin and analogues of nociceptin upon spontaneous dorsal root activity recorded from an in vitro preparation of rat spinal cord.
The 17 amino acid peptide nociceptin has been implicated in pain modulation in the central nervous system. The effects of bath applied nociceptin, and some analogues of nociceptin, upon spontaneous lumbar dorsal root activity have been investigated in an isolated preparation of rat spinal cord. Nociceptin was found to reversibly depress spontaneous dorsal root activity at concentrations of 1.0 microM and 10.0 microM (IC50 2.0 microM), whereas acetyl-nociceptin at concentrations up to 10 microM had no detectable effect. Omission of the last four amino acids (nociceptin 1-13), increased the potency of the effect upon dorsal root activity by approximately 100-fold (IC50 30 nM), but activity was lost when only the first seven amino acids of the nociceptin molecule (nociceptin 1-7) were tested.


[Results following the surgical treatment of acromioclavicular joint dislocations. A comparison of direct trans- and extra-articular fixation].
During the years 1985-1988, a total of 41 patients were treated for acromioclavicular dislocations. 25 (61%) were followed postoperatively for an average of 21 months. Two different methods of direct fixation of the AC-joint were compared: in 13 patients the transarticular fixation with two Kirschner wires and a 7.5 mm biodegradable Polydioxanon band (group I); in 12 patients an extraarticular fixation with PDS-band alone (group II). In both groups the ruptured ligament were sutured. In the first group physiotherapy was instituted immediately with limitation in abduction range to ninety degrees. After six weeks the Kirschner wires were removed under local anaesthesia and physiotherapy progressed to full range of motion. The shoulders of the second group patients were immobilized for 4 weeks. All of the patients were evaluated at follow-up on a subjective (pain, stiffness), objective (strength, range of motion, stability of the AC-joint) and roentgenographic (degree of displacement, posttraumatic arthritis, calcifications around the injured ligaments) basis. In both groups we saw good and satisfying results in more than 90%. A significant difference exists only as far as rehabilitation time is concerned. It was shorter in group I. In spite of the complications we observed with the metallic implants, which didn't have any negative influence on the results, we prefer the transarticular fixation method, because an immobilization postoperatively is not necessary and the time of rehabilitation is shortened.


Distal ureter and bladder cuff excision using the "Keyhole Technique" during Robotic Radical Nephroureterectomy.
Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumors (1). Radical nephroureterectomy (RNU) remains the standard treatment for high, and low-grade UTUC (2). Although the open approach has been considered the gold standard, robotic techniques have shown comparable oncological outcomes with potential advantages in terms of peri-operative morbidity (3). We present a novel "Keyhole" technique for management of distal ureter and bladder cuff during robotic RNU. This technique allows the surgeon to directly visualize the ureteric orifices, delineate resection borders, and maintain oncologic principles of en-bloc excision without necessitating secondary cystotomy incision or concomitant endoscopic procedure. Descriptive demographic characteristics, surgical, pathological, and oncological outcomes were analyzed. Complications were reported using the Clavien-Dindo classification system. Between 2015 and 2020, ten patients underwent robotic RNU with bladder cuff excision using the Keyhole technique (single-dock, single-position). Median age was 75 years. Eight patients underwent surgery for right-sided tumors. Median operative time, estimated blood loss, and length of hospital stay were 287 min, 100 mL, and 3 days, respectively. No intraoperative complications occurred, and one grade II complication occurred during the 90-day postoperative period. All patients had high-grade UTUC, being 90% pure urothelial. Bladder recurrences occurred in 30% of patients with an overall median follow-up of 11.2 months. Keyhole technique for the management of distal ureter and bladder cuff during RNU represents a feasible approach with minimal 90-day complications and low bladder recurrence rate at centers of experience.


Animal research guidelines.
In the next-to-last paragraph of the letter from Adrian R. Morrison and Peter J. Hand (31 Aug. 1984, p. 878), the first sentence was incorrectly punctuated. It should have read, "On the basis of knowledge we have gained as expert witnesses for the defense in two court trials, an appeal before a Public Health Service board, and the HHS meeting, we can make one thing immediately clear."


Rapid formation of Small Unilamellar Vesicles (SUV) through low-frequency sonication: An innovative approach.
Liposomes are membrane models and excellent Drug Delivery Systems. However, their preparation is expensive, labor intensive, time consuming, and sometimes toxic. Recently, we published an innovative methodology for the production of homogeneous Small Unilamellar Vesicles (SUV) through a simple, fast, relatively low cost, and reproducible process that resulted in very stable vesicles. The methodology involves a small amount of F127 triblock Pluronic® copolymer (0.02% m/V) to a phospholipid (DPPC, DOPC, and DSPC), followed by the solid dispersion methodology. After that, during the thin-film hydration process (of lipids and F127), SUVs are quickly formed after 30 s of sonication using bath equipment at a low frequency of 42 kHz. The resultant colloidal solution was homogeneous with liposomes lower than ˜100 nm of hydrodynamic diameter. The SUV formation is highly temperature dependent. However, it functions independently from the lipid´s phase (gel or liquid-crystal phases). A preparation with Pluronic P123 did not lead to homogeneous SUV. We found that the conditions for SUV formation feature a mixture of F127 and lipids at above a critical temperature. This temperature is not the copolymer´s CMT (micelle is not required). Interestingly, the long PEO groups of F127 play an essential role in this SUV formation, which is proposed to be governed by the "Budding Off" model. The findings show a complex combination of factors: a sum of the sonoporation, the oscillation effects of the compressed/dilated regions, the frequency of oscillation, and the temperature-dependence on long PEO groups. Also, the outer lipid monolayer interaction might by responsible for generating "daughter" vesicles from "mother" vesicles in the mechanism.


Self-adhesive resin cements: a new perspective in luting technology.
Many materials are available for the fabrication of indirect restorations such as, metal alloys, resin-based composites and ceramics. Resin cements have long been valued as luting agents for indirect restorations because of their high retentive strength, resistance to wear, and low solubility. However, one of the common discouraging factors regarding their chairside use is the need of multiple-steps (etching, drying, priming and luting) for bonding. Thus the current impetus is towards the use of self-adhesive cements that require no etching, priming or bonding agents to bond to the tooth surface. Their increased popularity can be judged by the commercial availability of more than a dozen self-adhesive resin products/brands, in a short span of time. This article reviews the composition, physical and biological properties, adhesion characteristics and clinical performance of self-adhesive (resin) cements. Self-adhesive resin cements are dual-cured and adhere to tooth structure without the requirement of a separate etching step and application of an adhesive/bonding agent.


The practice and perception of precautionary allergen labelling by the Australasian food manufacturing industry.
The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL® ) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason. To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process. A web-based questionnaire was distributed to Australasian food and grocery manufacturers. One hundred and thirty-seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19-28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30-38), (n=204/600) of products that had undergone another (non-VITAL® ) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55-91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31-72) reported that it was too time-consuming and 36% (CI 95% 18-57) identified a concern with it not being endorsed by the government. Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.


Synthesis, Characterization, and Biological Study of Carboxyl- and Amino-Rich g-C₃N₄ Nanosheets by Different Processing Routes.
Graphitic-phase carbon nitride (g-C₃N₄) is a graphene analogue, which has attracted much attention for its unique physicochemical properties. The bulk g-C₃N₄ is often fragmented and ionized to nanosheets, obtaining improved performance or confer novel properties. It is reported that g-C₃N₄ nanosheets using different processing methods can be modified with different functional groups, resulting in different electrical characteristics. However, the surface charge of g-C₃N₄ nanosheets is seldom mentioned as a factor influencing their biological applications. In our present study, we prepared two kinds of uniformly dispersed g-C₃N₄ nanosheets of high quality, the carboxyl- and amino-rich g-C₃N₄ nanosheets. Although both the carboxyl- and amino-rich g-C₃N₄ nanosheets displayed good biocompatibility in vitro and in vivo, however, they are at very different levels of surface charge, which are relative to different cellular uptake, penetration mechanism and lysosome escape ability of the nanosheets.


Utilization of recombinant activated factor VII in southern Ontario in 85 patients with and without haemophilia.
Recombinant activated factor VII (rFVIIa) is licensed for the treatment of bleeding in individuals with haemophilia and inhibitors. The use of rFVIIa appears to be increasing, and an increase in unlicensed use is suspected. There are currently few data about the specific indications for its use. The aim of this study was to describe the patterns of utilization of rFVIIa. We performed a retrospective cohort study using rFVIIa infusion data collected prospectively and clinical data collected retrospectively. Patients were identified using a tracking system designed to account for use of all coagulation factor concentrates issued in southern Ontario. Between 1 January 2001 and 31 December 2005, 85 patients received rFVIIa. 1164 infusions were given (8246.4 mg). Haemophilia patients with inhibitors accounted for 82.9% of rFVIIa infused and represented 8.2% of patients. The total amount of rFVIIa used increased each year from 2001 to 2004 and then decreased in 2005. The total number of infusions of rFVIIa administered annually increased. Both on-label and off-label use of rFVIIa increased. The number of patients with haemophilia receiving rFVIIa remained small and constant. The number of patients receiving rFVIIa for off-label indications increased markedly. Most rFVIIa infusions were given for licensed indications; however, these infusions represented <10% of patients treated. Overall, the utilization of rFVIIa is increasing, mostly for approved indications; however, the number of patients being prescribed rFVIIa for off-label indications has increased. The tracking system used in this study is a valuable tool to describe ongoing utilization patterns of rFVIIa.


[A case of advanced colon cancer with multiple liver metastases treated by two-stage laparoscopic surgery].
We report a case of advanced colon cancer with multiple liver metastases treated by two-stage laparoscopic surgery. An 82-year-old woman, whose main complaint was constipation, was diagnosed with stage IV sigmoid colon cancer. With the aim of decompressing the colon, a transanal decompression tube was inserted. She underwent laparoscopic-assisted sigmoidectomy and D3 lymph node dissection, and an ileostomy was created. Systemic chemotherapy was administered immediately after the operation. After 4 courses of chemotherapy, she underwent the second operation, i.e., laparoscopic- assisted partial hepatectomy and radiofrequency ablation of liver metastases. Cases of obstructive colon cancer are more advanced than cases of non-obstructive colon cancer. Systemic treatments are required after the resection of primary tumors. We aim to improve the prognosis of patients with obstructive colon cancer by the use of laparoscopic surgery.


The environmental behaviour of polychlorinated phenols and its relevance to cork forest ecosystems: a review.
Pentachlorophenol (PCP) has been used as a herbicide, biocide and preservative worldwide since the 1930s and as a result, extensive and prolonged contamination exists. The environmental impact increases when its many degradation products are taken into consideration. A number of chloroanisols and their related chlorophenols have been found in cork slabs collected from Portuguese oak tree forests before stopper manufacturing, and contamination by PCP and polychlorinated anisole (PCA) has been detected in Canadian forests. It is suggested that the use of polychlorinated phenols, in particular PCP, is thought to be a cause of the cork taint problem in wine, a major socio-economic impact not only for industry but on sensitive and highly biodiverse ecosystems. It also highlights particular issues relating to the regional regulation of potentially toxic chemicals and global economics world wide. To fully understand the impact of contamination sources, the mechanisms responsible for the fate and transport of PCP and its degradation products and assessment of their environmental behaviour is required. This review looks at the current state of knowledge of soil sorption, fate and bioavailability and identifies the challenges of degradation product identification and the contradictory evidence from field and laboratory observations. The need for a systematic evaluation of PCP contamination in relation to cork forest ecosystems and transfer of PCP between trophic levels is emphasised by discrepancies in bioaccumulation and toxicity. This is essential to enable long term management of not only transboundary contaminants, but also the sustainable management of socially and economically important forest ecosystems.


Transcatheter tricuspid valve repair: early experience in the Netherlands.
Symptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands. All consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks. Twenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success. The current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.


Human umbilical cord blood cells and diabetes mellitus: recent advances.
Stem cell therapy for patients with diabetes is an area of great interest to both scientists and clinicians. Human umbilical cord blood cells (HUCBCs) are being increasingly used as a source of stem cells for cell-based therapy for diabetes because these cells can differentiate into pancreatic islet β-cells. Administration of HUCBCs has been shown to lower blood glucose levels in diabetic animal models. The use of autologous HUCBC transfusion in type 1 diabetic children has not shown any benefit. However, "Stem Cell Educator" therapy has shown promise in long term lowering of blood glucose levels in both type 1 and type 2 diabetic patients. In this review, we will briefly discuss recent advances in HUCBC therapy in the treatment of diabetes and some of its complications.


Distinct Chemokine Dynamics in Early Postoperative Period after Open and Robotic Colorectal Surgery.
Stress response to robot-assisted colorectal surgery is largely unknown. Therefore, we conducted a prospective comparative nonrandomized study evaluating the perioperative dynamics of chemokines: IL-8/CXCL8, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, and eotaxin-1/CCL11 in 61 colorectal cancer patients following open colorectal surgery (OCS) or robot-assisted surgery (RACS) in reference to clinical data. Postoperative IL-8 and MCP-1 increase was reduced in RACS with a magnitude of blood loss, length of surgery, and concomitant up-regulation of IL-6 and TNFα as its independent predictors. RANTES at 8 h dropped in RACS and RANTES, and MIP1α/β at 24 h were more elevated in RACS than OCS. IL-8 and MCP-1 at 72 h remained higher in patients subsequently developing surgical site infections, in whom a 2.6- and 2.5-fold increase was observed. IL-8 up-regulation at 24 h in patients undergoing open procedure was predictive of anastomotic leak (AL; 94% accuracy). Changes in MCP-1 and RANTES were predictive of delayed restoration of bowel function. Chemokines behave differently depending on procedure. A robot-assisted approach may be beneficial in terms of chemokine dynamics by favoring Th1 immunity and attenuated angiogenic potential and postoperative ileus. Monitoring chemokine dynamics may prove useful for predicting adverse clinical events. Attenuated chemokine up-regulation results from less severe blood loss and diminished inflammatory response.


Central nervous system functions of PAK protein family: from spine morphogenesis to mental retardation.
Several of the genes currently known to be associated, when mutated, with mental retardation, code for molecules directly involved in Rho guanosine triphosphatase (GTPase) signaling. These include PAK3, a member of the PAK protein kinase family, which are important effectors of small GTPases. In many systems, PAK kinases play crucial roles regulating complex mechanisms such as cell migration, differentiation, or survival. Their precise functions in the central nervous system remain, however, unclear. Although their activity does not seem to be required for normal brain development, several recent studies point to a possible involvement in more subtle mechanisms such as neurite outgrowth, spine morphogenesis or synapse formation, and plasticity. This article reviews this information in the light of the current knowledge available on the molecular characteristics of the different members of this family and discuss the mechanisms through which they might contribute to cognitive functions.


Comparative hemodynamic effects of intravenous dobutamine and dibutyryl cyclic AMP, a new inotropic agent, in severe congestive heart failure.
In nine patients with chronic congestive heart failure, the acute hemodynamic response to intravenous (i.v.) dibutyryl cyclic AMP (DBcyclicAMP) administration was compared with i.v. dobutamine administration. Both agents led to a significant and similar increase in cardiac index. Dobutamine caused a significant increase in mean arterial pressure but did not produce a significant change in pulmonary capillary wedge, mean pulmonary artery, or mean right atrial pressures. In contrast, DBcyclicAMP caused a significant decrease in mean arterial, mean pulmonary capillary wedge, mean pulmonary artery, and mean right atrial pressures, reflecting vasodilator activity. The fall in systemic vascular resistance was larger after DBcyclicAMP than after dobutamine. DBcyclicAMP achieves an optimal improvement in cardiovascular hemodynamics in concert with substantial vasodilating effect. This pharmacologic action constitutes the mainstay of i.v. therapy for severe congestive heart failure (CHF).


Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.
Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.


Single-tube multiplex PCR and capillary electrophoresis for the detection of bcl2-IgH chimeras.
The molecular background of follicular lymphoma is the formation of chimera(s) by the bcl2 gene and one of the immunoglobulin genes, mainly the heavy chain gene. While the diagnosis of follicular lymphoma is based on histological study, the histology cannot be recommended for the follow-up of efficiency of treatment(s). Sensitive detection of the chimera genes in blood or bone marrow samples can serve as informative data without invasive sampling. In this study, a single-tube multiplex reaction was developed for the simultaneous detection of different chimeras of the bcl2 and immunoglobulin heavy chain genes, molecular hallmarks of follicular lymphoma. The method was optimized for the highest yield of reaction and for reproducing the ratio of components in artificial mixtures of two different chimeras. The method is suitable for fast and accurate molecular characterization of follicular lymphomas and for follow-up of residual disease.


Larvicidal toxins from Bacillus thuringiensis subspp. kurstaki, morrisoni (strain tenebrionis), and israelensis have no microbicidal or microbiostatic activity against selected bacteria, fungi, and algae in vitro.
The insecticidal toxins from Bacillus thuringiensis subspp. kurstaki (antilepidopteran), morrisoni strain tenebrionis (anticoleopteran), and israelensis (antidipteran) did not affect the growth of a variety of bacteria (8 gram-negative, 5 gram-positive, and a cyanobacterium), fungi (2 Zygomycetes, 1 Ascomycete, 2 Deuteromycetes, and 2 yeasts), and algae (primarily green and diatoms) in pure and mixed culture, as determined by dilution, disk-diffusion, and sporulation assays with purified free and clay-bound toxins. The insecticidal crystal proteins from B. thuringiensis subspp. kurstaki and israelensis had no antibiotic effect on various gram-positive bacteria.


Anthropometric Profile in Different Event Categories of Acrobatic Gymnastics.
There is a specific anthropometric profile for each sport, which may be differentiated even in relation to the position, role or event category within each sport discipline. However, there are few studies on acrobatic gymnastics, and the goal of this work was to determine the anthropometric profile depending on the event category, as well as factors that predisposed to performance in these categories. The sample consisted of 150 gymnasts from Spain, divided into 8 groups according to the event category and the role played. The kinanthropometric measurements were taken through the procedures established by the International Society for the Advancement of Kineantropometry. The anthropometric characteristics, including body mass index, somatotype, body composition and proportionality using the Phantom stratagem were analyzed, and the results obtained from the different groups were compared. A regression analysis was performed with particular groups of gymnasts. No significant differences (p < 0.05) were observed between groups of female tops or male bases, although differences were found between female group bases and female pair bases. It could be suggested that higher values of body height, sitting height, the minimum abdominal circumference, percentage of fat and low biliocristal breadth predispose female bases to work in pairs rather than in groups. The conclusion is that the anthropometric measurements are not decisive when guiding a gymnast toward choosing one event category or another, except for female bases.


Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis.
Beta-blocker therapy has a mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Comprehensive searches were performed of the EMBASE, MEDLINE and CINAHL databases from 1966 to May 2001, and identified articles and related reviews were scanned. Randomised, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 s (FEV1) or symptoms in patients with COPD were included in the analysis. Interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Outcomes measured were the change in FEV1 from baseline and the number of patients with respiratory symptoms. Eleven studies of single-dose treatment and 8 of continued treatment were included. Cardioselective beta-blockers produced no significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (-2.05% [95% CI, -6.05% to 1.96%]) or for longer duration (-2.55% [CI, -5.94% to 0.84]), and did not significantly affect the FEV1 treatment response to beta2-agonists. Subgroup analyses revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. In conclusion, cardioselective beta-blockers given to patients with COPD do not produce a significant reduction in airway function or increase the incidence of COPD exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD.


Wavefront's role in corneal refractive surgery.
In the 5 years since the first wavefront-based LASIK treatment on normal eyes, the ophthalmology profession has had to confront a new language based on astronomy, optics and mathematics. Over this time wavefront technology has been used for diagnosis and treatment, and its application has made the profession define what is meant by good vision, and determine whether, with psychophysical and psychometric tests, it is possible understand how an individual perceives the world. The clinical application of wavefront technology has forced ophthalmologists and vision scientists with an engineering bias to talk to those with a biological bias, and to appreciate that if you try and change the corneal shape, its biological, anatomical and optical properties exist within a complex external eye environment. This perspective article demonstrates that wave-front analysis is a useful diagnostic tool, and that wavefront-based corneal refractive surgery is an improvement over conventional techniques. Its use by an ophthalmologist is a clinical decision specific to an individual patient.


Decision-making regarding organ donation in Korean adults: A grounded-theory study.
The aim of this study was to identify the hidden patterns of behavior leading toward the decision to donate organs. Thirteen registrants at the Association for Organ Sharing in Korea were recruited. Data were collected using in-depth interview and the interview transcripts were analyzed using Glaserian grounded-theory methodology. The main problem of participants was "body attachment" and the core category (management process) was determined to be "pursuing life." The theme consisted of four phases, which were: "hesitating," "investigating," "releasing," and "re-discovering. " Therefore, to increase organ donations, it is important to find a strategy that will create positive attitudes about organ donation through education and public relations. These results explain and provide a deeper understanding of the main problem that Korean people have about organ donation and their management of decision-making processes. These findings can help care providers to facilitate the decision-making process and respond to public needs while taking into account the sociocultural context within which decisions are made.


A dynamical process of optically trapped singlet ground state 85Rb133Cs molecules produced via short-range photoassociation.
We investigate the dynamical process of optically trapped X1Σ+ (v'' = 0) state 85Rb133Cs molecules distributed in J'' = 1 and J'' = 3 rotational states. The considered molecules, formed from short-range photoassociation of mixed cold atoms, are subsequently confined in a crossed optical dipole trap. Based on a phenomenological rate equation, we provide a detailed study of the dynamics of 85Rb133Cs molecules during the loading and holding processes. The inelastic collisions of 85Rb133Cs molecules in the X1Σ+ (v'' = 0, J'' = 1 and J'' = 3) states with ultracold 85Rb (or 133Cs) atoms are measured to be 1.0 (2) × 10-10 cm3 s-1 (1.2 (3) × 10-10 cm3 s-1). Our work provides a simple and generic procedure for studying the dynamical process of trapped cold molecules in the singlet ground states.


The Staffordshire arthritis, musculoskeletal, and back assessment (SAMBA) study: a prospective observational study of patient outcome following referral to a primary-secondary care musculoskeletal interface service.
Recent healthcare policy has shifted the management of musculoskeletal conditions in the UK away from secondary care towards Clinical Assessment and Treatment Services at the primary-secondary care interface. However, little is known about the outcome of patients with musculoskeletal conditions referred from primary care to Clinical Assessment and Treatment Services or how best to identify those patients at high risk of poor outcome in this setting. We describe the protocol for a twelve-month prospective observational study which aims to describe the outcome of patients referred to musculoskeletal and back pain services at the primary-secondary care interface and to develop simple prognostic measures to guide clinical prioritisation and triage. All patients referred over a twelve-month period from primary care to musculoskeletal and back pain clinics in the primary-secondary care interface Clinical Assessment and Treatment Service in North Staffordshire will be mailed a postal questionnaire prior to their consultation. This will collect information on quality of life, general health, anxiety and depression, pain, healthcare utilisation including medication use, occupational characteristics, and socio-demographics. At the consultation in the interface clinic, the clinical diagnosis, investigations requested, and clinical interventions will be recorded. Follow-up data for the twelve-month period subsequent to recruitment will be collected via mailed follow-up questionnaires at 6 and 12 months, and review of medical records. This twelve-month prospective observational study of patients referred to a musculoskeletal Clinical Assessment and Treatment Service will assess the management and outcome of musculoskeletal care at the primary-secondary care interface as proposed in the Musculoskeletal Services Framework.


Public Knowledge About COVID-19 Booster Vaccines in Pakistan: A Study Conducted in a Tertiary Care Hospital in Karachi.
The coronavirus disease 2019 (COVID-19) pandemic has deteriorated the healthcare system and economy worldwide. Globally, by making the primary vaccination against the coronavirus necessary, the surge in cases waned, but as the effects of this vaccination decreased after some time, to prevent another pandemic, vaccination was still necessary. As a result, receiving a COVID-19 booster shot can boost immunity against the coronavirus. This study aimed to assess knowledge of COVID-19 booster vaccines in Pakistan among the general public and understand the factors affecting the vaccination process in the state. In this cross-sectional study, non-probability convenience sampling was done. Its physical data collection was conducted in September 2022 in a tertiary care hospital in Karachi, Pakistan. Data were collected from 384 individuals who visited the hospital with consent before filling out the questionnaire. The mean age of respondents was 35.81 (standard deviation (SD) = ±13.006), and 98.7% of individuals were primarily vaccinated for COVID-19, but out of these, only 60.1% received the booster jab. The most commonly reported side effects of primary doses of COVID-19 and its booster were pain at the injection site, fatigue, and fever, but these effects did not appear to have as much of an impact on the vaccination process as education did. The results are evident that out of primarily vaccinated individuals against COVID-19, 40.16% are reluctant to receive its booster. Therefore, it is essential to create awareness among the masses about vaccination and its importance.


A virus with a mutation in the ICP4-binding site in the L/ST promoter of herpes simplex virus type 1, but not a virus with a mutation in open reading frame P, exhibits cell-type-specific expression of gamma(1)34.5 transcripts and latency-associated transcripts.
The herpes simplex virus type 1 L/S junction-spanning transcripts (L/STs) are a family of multisized transcripts expressed at high levels in cells infected with mutant viruses that (i) do not express ICP4, (ii) specify forms of ICP4 unable to bind to the consensus ICP4 binding site, or (iii) contain mutations in the ICP4 binding site located at the transcriptional start site of the L/STs. By extension, the failure to detect the L/STs in wild-type virus-infected cells is due to the repressive effect of ICP4 bound to its cognate binding site upstream of the L/ST transcription initiation site. ORF-P, the first and largest open reading frame (ORF) encoded by the L/STs, overlaps >90% of the ORF encoding ORF-34.5, a putative neurovirulence factor, which is transcribed from the opposite DNA strand. Viruses with mutations in the overlapping region of ORF-P and ICP34.5 exhibit premature shutoff of infected-cell protein synthesis and are highly attenuated following intracranial inoculation of juvenile mice. To determine whether the premature protein shutoff and neuroattenuated phenotypes of ORF-P ORF-34.5 double mutants are a consequence of alterations in ORF-P, ORF-34.5, or both, viruses containing mutations only in ORF-P or only in the ICP4 binding site in the L/ST promoter were isolated and characterized. Mutant virus L/ST-n38 contains a single-base-pair transition mutation in ORF-P codon 38, resulting in translational termination of the ORF-P protein (OPP). This mutation does not alter the amino acid sequence of ICP34.5. Expression of a truncated form of OPP by mutant virus L/ST-n38 did not result in premature shutoff of infected-cell protein synthesis and produced no other observable phenotype relative to wild-type virus in in vitro tests. Moreover, the 50% lethal dose (LD50) of L/ST-n38 was comparable to that of wild-type virus following intracranial inoculation of 3-week-old mice, as were the latency and reactivation phenotypes of the virus. These properties of L/ST-n38 indicate that the attenuated phenotype of ORF-P ORF-34.5 double mutants is a consequence of mutations that affect the function of ICP34.5 and not the function of OPP. Mutant virus LST-4BS contains four single-base-pair substitutions in the ICP4 binding site in the L/ST promoter that abrogate the binding of ICP4 to this site, leading to high-level expression of the L/STs and OPP. LST-4BS induced premature shutoff of viral and cellular protein synthesis and was slightly growth restricted in cells of neural lineage (SK-N-SH human neuroblastoma cells) but was wild type for these two parameters in cells of nonneural lineage (immortalized primate Vero cells). Of particular interest was the observation that L/ST-4BS exhibited cell-type-specific expression of both the gamma(1)34.5 transcripts and the latency-associated transcripts (LATs). Thus, expression of these transcripts was barely detectable in cells of neural lineage (NB41A3 mouse neuroblastoma cells) but was wild type in Vero cells. In vivo, L/ST-4BS was reactivated from mouse trigeminal ganglia with reduced efficiency and delayed kinetics relative to wild-type virus. L/ST-4BS was completely attenuated for neurovirulence (LD50 > 10(6) PFU) relative to wild-type virus (LD50 < 900 PFU), although the four single-base-pair substitutions lie outside the coding region for the neurovirulence factor, ICP34.5. Collectively, the complex in vitro and in vivo phenotypes of L/ST-4BS can be attributed to (i) disruptions of the ICP4 binding site in the L/ST promoter and subsequent overexpression of the L/STs and OPP; (ii) alterations in ORF-O, which is also mutated in L/ST-4BS; or (iii) alterations in other cryptic genes or cis-acting elements.


Treatment of pulmonary aspergilloma in Srinagarind Hospital.
Controversy still exists concerning the optimum management of aspergilloma. To evaluate clinical data of patients, the indications for surgery, postoperative complications and results of all treatments of pulmonary aspergillosis compare with data from review literature, to find out the optimum management. The authors retrospectively reviewed medical records of 45 patients at Srinagarind Hospital who had pulmonary aspergilloma between 1993 and 2008. General data, associated diseases, symptoms, organs involvement, treatments, surgical indications, procedures and complications, and outcome were collected for analysis. Associated diseases were found in 33 patients (73.3%). Tuberculosis was the most common underlying causes. Hemoptysis, the most frequent symptom, occurred in 29 patients (64.4%0). If 40 patients, they only had lung lesion although 5 patients had multiple organ-involvement. Surgery was performed in 24 patients (53.3%). Hemoptysis was the most common indication and lobectomy was the most frequent procedure. Postoperative complications occurred in 5 cases (20.80%) and mortality rate after surgery = 4.2%. Embolization was done on 4 patients; none of them re-bled. Clinical outcome improved in 36 cases (80%), did not improved in 6 patients (13.3%), and resulted in 3 patients' death (6. 7%). The most common indication for surgery was hemoptysis. Recurrence of hemoptysis was found in all patients who received selective bronchial artery embolization. Surgical resection is the treatment of choice with acceptable postoperative complications and mortality rate.


[Enzyme kinetics of schizandrin metabolism and sex differences in rat liver microsomes].
To study the enzyme kinetics of schizandrin metabolism in different gender in rat liver microsomes, liver microsomes were prepared from male or female rats. Schizandrin was incubated with rat liver microsomes. Schizandrin and its metabolites were isolated and identified by HPLC-UV method. Vmax, Km and Cl(int) of schizandrin in male and female rat liver microsomes were (21.88 +/- 2.30) and (0.61 +/- 0.07) micromol x L(-1) x min(-1) x mg(-1) (protein), (389.00 +/- 46.26) and (72.64 +/- 13.61) micromol x L(-1), (0.0563 +/- 0.0007) and (0.0084 +/- 0.0008) min x mg(-1) (protein), respectively. The major metabolites of schizandrin in female and male rat liver microsomes were 7,8-dihydroxy-schizandrin (M1) and 7, 8-dihydroxy-2-demethyl schizandrin (M2b), respectively. Ketoconazole, quinidine, and orphenadrine had different level effects on schizandrin metabolism in both male and female rat liver microsomes, and cimetidine still had some inhibitory effect in male liver microsomes. CYP3A and CYP2C11 may be the main P450 enzymes in schizandrin metabolism and their difference in rat liver microsomes may be the main reason for the sex difference of metabolic enzyme kinetics and metabolites of schizandrin in rats.


Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs.
The objective of this study was to evaluate intra-articular dextrose prolotherapy for osteoarthritis of the elbow or stifle in dogs in a randomized, double-blind, placebo-controlled, prospective pilot study. Seventeen dogs were evaluated with 10 meeting inclusion criteria for this study. Evaluations included orthopedic exam, visual lameness scoring, Canine Brief Pain Inventory (CBPI), goniometry, kinetic gait analysis, and radiography. Initial lameness score, age, body weight, duration of lameness, and CBPI scores did not differ between groups. Change in CBPI pain severity score in the prolotherapy group from wk 6-12 was significantly less improved than in the placebo group, with no other significant differences in pain severity or pain interference scores between groups. Range of motion and radiographic scores did not differ between groups at any time. Mean kinetic forces improved in prolotherapy dogs but were not significantly different between treatment groups at any time. Although easily performed and well-tolerated, there were no statistically significant benefits of dextrose prolotherapy for treatment of osteoarthritis of the elbow and stifle in dogs. Post hoc power analysis of these sample means and standard deviations found that 29-106 animals per group would be necessary to demonstrate significant differences in kinetic forces, providing useful guidance for future studies.


Follistatin like-1 (Fstl1) is required for the normal formation of lung airway and vascular smooth muscle at birth.
Fstl1, a secreted protein of the BMP antagonist class, has been implicated in the regulation of lung development and alveolar maturation. Here we generated a Fstl1-lacZ reporter mouse line as well as a Fstl1 knockout allele. We localized Fstl1 transcript in lung smooth muscle cells and identified Fstl1 as essential regulator of lung smooth muscle formation. Deletion of Fstl1 in mice led to postnatal death as a result of respiratory failure due to multiple defects in lung development. Analysis of the mutant phenotype showed impaired airway smooth muscle (SM) manifested as smaller SM line in trachea and discontinued SM surrounding bronchi, which were associated with decreased transcriptional factors myocardin/serum response factor (SRF) and impaired differentiation of SM cells. Fstl1 knockout mice also displayed abnormal vasculature SM manifested as hyperplasia SM in pulmonary artery. This study indicates a pivotal role for Fstl1 in early stage of lung airway smooth muscle development.


Hope and deception.
Convinced of hope's therapeutic benefits, physicians routinely support patients' false hopes, often with family collusion and vague, euphemistic diagnoses and prognoses, if not overt lies. Bioethicists charge them with paternalistic violations of Patient Autonomy. There are, I think, too many morally significant exceptions to accept the physician's rationales, or the bioethicist's criticisms, stated sweepingly. Physicians need to take account of the harms caused by loss of hopes, especially false hopes due to deception, as well as of the harms of successfully maintained deceptive hopes. As for autonomy, hopes -- even if based on deception -- can protect and enhance autonomy, understood broadly as the capacity to lead a chosen or embraced life. Deception aside, patients' hopes often rest on beliefs about possible rather than probable outcomes -- beliefs themselves supported by optimism, 'denial', or self-deception. Such 'possibility-hopes' may conflict with physicians' often more fact-sensitive 'probability hopes.' To resolve such conflicts physicians may try to 'down-shift' patients' or parents' hopes to lesser, more realistic hopes. Alternatively, physicians may alter or enlarge their own professional hopes to include the 'vital hopes' that define the lives of patients or parents, as well as 'survival hopes' needed to face and bear the loss of loved ones, especially children. A principle of Hope-giving might help guide such sympathetic hope-accommodations. More generally, it would give Hope a distinct place among Beneficence, Autonomy, and the other moral factors already highlighted by canonical principles of Medical Ethics. To formulate such a principle, however, we will need a collective Project Hope to pursue deeper philosophical and psychological studies.


Association of human papillomavirus with denture wearing.
To determine the prevalence of human papillomavirus in the oral cavity of denture wearers. Swabs were collected from 72 denture wearers and 72 controls (non-denture wearers) to obtain DNA. Amplification of the β-globin gene was performed by polymerase chain reaction to check the integrity of extracted DNA. The presence of human papillomavirus in the DNA sample was detected by nested polymerase chain reaction. The prevalence of human papillomavirus was found to be significantly higher in the oral cavity of denture wearers (38/72, 52.8%) than in the controls (17/72, 23.6%; odds ratio = 3.612, confidence interval = 1.771/7.385, P = <0.001). When adjusted for variables, including age, sex, ethnicity, and smoking habit, human papillomavirus was still found to be significantly associated with denture wearing, with an adjusted odds of 3.2 (P = 0.008). No association of human papillomavirus positivity was found with denture variables, including denture type, denture material type, duration of denture wearing, and denture hygiene (P > 0.05). Low-risk human papillomavirus types were found to be more frequent in both groups. The prevalence of human papillomavirus in the oral cavity of denture wearers was found to be significantly higher compared to controls; however, it was mainly low-risk types.


In Silico Models to Discriminate Compounds Inducing and Noninducing Toxic Myopathy.
Toxic myopathy is a muscular disease in which the muscle fibers do not function and which results in muscular weakness. Some drugs, such as lipid-lowering drugs and antihistamines, can cause toxic myopathy. In this work, a dataset containing 232 chemical compounds inducing toxic myopathy (IM-compounds) and 117 drugs not inducing toxic myopathy (notIM-compounds) was collected. The dataset was split into a training set (containing 270 compounds) and a test set (containing 79 compounds). A Kohonen's self-organizing map (SOM) and a support vector machine (SVM) were applied to develop classification models to differentiate IM-compounds and notIM-compounds. Polarizibity related descriptors, electronegativity related descriptors, atom charges related descriptors, H-bonding related descriptor, atom identity and molecular shape descriptors were used to build models. Using the SOM method, classification accuracies of 88.4 % for the training set and 88.2 % for the test set were achieved; using the SVM method, classification accuracies of 95.6 % for the training set and 86.1 % for the test set were achieved. In addition, extended connectivity fingerprints (ECFP_4) were calculated and analyzed to find important substructures of molecules relating to toxic myopathy.


Diffraction tomography with Fourier ptychography.
This paper presents a technique to image the complex index of refraction of a sample across three dimensions. The only required hardware is a standard microscope and an array of LEDs. The method, termed Fourier ptychographic tomography (FPT), first captures a sequence of intensity-only images of a sample under angularly varying illumination. Then, using principles from ptychography and diffraction tomography, it computationally solves for the sample structure in three dimensions. The experimental microscope demonstrates a lateral spatial resolution of 0.39 μm and an axial resolution of 3.7 μm at the Nyquist-Shannon sampling limit (0.54 and 5.0 μm at the Sparrow limit, respectively) across a total imaging depth of 110 μm. Unlike competing methods, this technique quantitatively measures the volumetric refractive index of primarily transparent and contiguous sample features without the need for interferometry or any moving parts. Wide field-of-view reconstructions of thick biological specimens suggest potential applications in pathology and developmental biology.


Ecosystem state change in the Arabian Sea fuelled by the recent loss of snow over the Himalayan-Tibetan Plateau region.
The recent trend of global warming has exerted a disproportionately strong influence on the Eurasian land surface, causing a steady decline in snow cover extent over the Himalayan-Tibetan Plateau region. Here we show that this loss of snow is undermining winter convective mixing and causing stratification of the upper layer of the Arabian Sea at a much faster rate than predicted by global climate models. Over the past four decades, the Arabian Sea has also experienced a profound loss of inorganic nitrate. In all probability, this is due to increased denitrification caused by the expansion of the permanent oxygen minimum zone and consequent changes in nutrient stoichiometries. These exceptional changes appear to be creating a niche particularly favorable to the mixotroph, Noctiluca scintillans which has recently replaced diatoms as the dominant winter, bloom forming organism. Although Noctiluca blooms are non-toxic, they can cause fish mortality by exacerbating oxygen deficiency and ammonification of seawater. As a consequence, their continued range expansion represents a significant and growing threat for regional fisheries and the welfare of coastal populations dependent on the Arabian Sea for sustenance.


Current and Emerging Treatment Strategies for Graves' Orbitopathy.
Graves' orbitopathy is a debilitating disorder which occurs in patients with autoimmune thyroid disease, mainly Graves' disease, and adds layers of complexity to management of both conditions. We conducted a comprehensive review of literature for publications relating to established and new management options for Graves' orbitopathy and have summarized key articles in this review. Initial evaluation of patients with Graves' disease should also include clinical evaluation for orbitopathy. If eye disease is present, patients are best managed by a multi-specialty team including an endocrinologist and ophthalmologist. All patients with Graves' orbitopathy benefit from risk factor modification and normalization of thyroid function tests. Patients with active, mild disease generally benefit from local therapies and selenium, while patients with moderate-to-severe disease usually require the addition of intravenous glucocorticoid therapy. If there is an inadequate response to glucocorticoid therapy, several second-line therapies have been investigated for use, including orbital radiotherapy (with additional glucocorticoids), rituximab, cyclosporine, mycophenolate mofetil, and methotrexate. Use of new biologic agents, mainly teprotumumab and tocilizumab, have demonstrated impressive reductions in disease activity and severity. If these results are confirmed, the treatment paradigm is likely to change in the future. Finally, there are several novel immunotherapies being investigated for Graves' disease, which may have treatment implications for Graves' orbitopathy as well. Overall, there are many encouraging advances in the therapy of Graves' orbitopathy that are making the future more promising for patients suffering from this disease.


Experimental induction and termination of acute psychological stress in human volunteers: effects on immunological, neuroendocrine, cardiovascular, and psychological parameters.
The present research investigated the effects of controlled experimental manipulations of stress on biological and psychological reactions. Fifty young adult male volunteers were exposed to a 12-min period of stress induced by the threat of an unavoidable, painful electric shock. A 12-min period without this threat preceded or followed the stress period. Blood was drawn during the 4th and the 12th minute of each period. Anticipatory threat led to significant elevations in the proportions and cytotoxic activity of natural killer (NK) lymphocytes, plasma epinephrine levels, pulse rate, and reported level of tension, and to a reduction in the CD4/CD8 ratios. The no-threat period induced a return to baseline values for epinephrine, pulse rate, and tension, and lower than baseline levels for cytotoxic activity of NK lymphocytes, within a similarly short time span. The findings underline the rapidity with which physiological changes may transpire in the course of a brief and acute period of psychological stress, and the rapidity of their reversal upon relief from the stressor.


Optimization of Coffee Oil Extraction from Defective Beans Using a Supercritical Carbon Dioxide Technique: Its Effect on Volatile Aroma Components.
Defective green coffee beans are typically discarded due to their negative impacts on coffee qualities compared to normal beans. However, there are some types of defective beans that can cause volatile aroma compounds after roasting similar to those produced by normal beans. This study aimed to optimize conditions for coffee oil extraction by supercritical carbon dioxide using the response surface methodology (RSM). Furthermore, the investigation assessed the aroma-active compounds and sensory quality in extracted coffee oil. Thus, operational temperatures (33.2-66.8 °C), pressure (10-30 MPa) and ethanol (g) to roasted coffee (g) ratio (0.25:1-1.5:1) were optimized for coffee oil extraction. As a result, different oil yields with different key volatile aroma compounds concentrations were obtained and it was found that the optimum conditions for extraction were a temperature of 50 °C, pressure of 30 MPa, and ethanol (g) to roasted coffee (g) ratio of 1:1 to obtain 6.50% (w/w) coffee oil yield. Key volatile aroma compounds, including furfuryl alcohol, 5-methyl furfural, 2,5-dimethylpyrazine, 4-vinylguaiacol, furfuryl acetate, 3-ethyl-2,5-dimethylpyrazine, thiazole, 1-furfurylpyrrole, pyridine, 2,3-butanediol, and 3-methyl-1,2-cyclopentanedione which contributed to the most preferable burnt, sweet, bready, chocolate-like, and roasted flavors, were quantified. Overall, the results suggested that coffee oil extracted from defective beans could be potentially used as a flavoring agent.