Robotic surgery in gynecologic oncology fellowship programs in the USA: a survey of fellows and fellowship directors.
In order to understand how robotic surgery impacts gynecologic oncology fellowship training and surgical practices, a survey of fellows and fellowship directors was conducted. Questionnaires designed to determine the prevalence, application, and acceptance of robotics were sent to fellows and fellowship directors in approved U.S. programs. Of the respondents, 95% have a robot at their institution and 95% utilize it. Most responding fellowship directors (70%) reported that fellow education is enhanced by robotic surgery. Most fellows (65%) who responded feel comfortable using the robot, and 94% plan on performing robotic surgery upon completion of fellowship training. This survey demonstrates that robotic surgery is utilized in the majority of responding gynecologic oncology fellowship programs for a wide array of indications. Fellowship directors and fellows-in-training generally have a favorable view of this evolving technology. Based on these responses, robotic surgery will play an increasingly important role in the future.


Studies of the spin-Hamiltonian parameters and defect structures for the tetragonal and cubic Yb3+ centers in AgCl crystal.
The spin-Hamiltonian parameters, g factors and hyperfine structure constants, for the tetragonal and cubic Yb(3+) centers in AgCl crystal are calculated from the complete diagonalization (of energy matrix) method. The calculations are based on the defect models that the tetragonal Yb(3+) center is formed by the substitutional Yb(3+) associated with two nearest Ag(+) vacancy (V(Ag)) along <001> and <001¯> axes (i.e., C(4) axis) owing to charge compensation and in cubic Yb(3+) center the two compensators V(Ag) are remote. From the calculations, the spin-Hamiltonian parameters of both Yb(3+) centers in AgCl are explained reasonably, the signs of hyperfine structure constants A(i)((171)Yb(3+)) and A(i)((173)Yb(3+)) are suggested, the above defect models of both Yb(3+) centers are confirmed and their defect structures are determined.


Computed tomography in detecting calvarial metastases: a comparison with skull radiography and radionuclide scanning.
A clinical study comparing the relative sensitivities of computed tomography, skull radiography, and radionuclide scanning in the detection of skull metastases indicated that CT was the least sensitive of these three modalities. CT could however detect a majority of lesions if scans were viewed at appropriate window settings. Phantom studies showed that the limitations of CT can be related to limited spatial resolution, the density of the lesions, partial volume averaging, and plane of section.


Does longevity impact the severity of traffic crashes? A comparative study of young-older and old-older drivers.
This article analyzes the effect of driver's age in crash severity with a particular focus on those over the age of 65. The greater frequency and longevity of older drivers around the world suggests the need to introduce a possible segmentation within this group at risk, thus eliminating the generic interval of 65 and over as applied today in road safety data and in the automobile insurance sector. We investigate differences in the severity of traffic crashes among two subgroups of older drivers -young-older (65-75) and old-older (75+), and findings are compared with the age interval of drivers under 65. Here, we draw on data for 2016 provided by Spanish Traffic Authority. Parametric and semi-parametric regression models are applied. We identified the factors related to the crash, vehicle, and driver that have a significant impact on the probability of the crash being slight, serious, or fatal for the different age groups. We found that crash severity and the expected costs of crashes significantly increase when the driver is over the age of 75. Practical Applications: Our results have obvious implications for regulators responsible for road safety policies - most specifically as they consider there should be specific driver licensing requirements and driving training for elderly - and for the automobile insurance industry, which to date has not examined the impact that the longevity of drivers is likely to have on their balance sheets.


[Medication-overuse and chronic headaches in Brazzaville: patients' profile and therapeutic approach].
Medication-overuse headaches (MOHs) are the least studied of all headaches in Africa. We conducted a longitudinal study in order to describe our experience with patients placed in Neurology Outpatient observation in Brazzaville over a period of 4 years, from September 2010 to August 2014. All patients with chronic primary headaches, according to the International Classification of Headache Disorders (ICHD) (2nd edition), were included in the study. All patient with secondary headaches or who hadn't given consent were excluded. The patients were divided into two groups: those who had progressed to medication-overuse and those who didn't meet the criteria for medication-overuse (without-MOH). The variables used were the sociodemographic characteristics of patients, the clinical features of primary headaches and MOH treatment. The study population was constituted by 193 patients out of 212. The average age of patients was 42 ± 14 years, of whom 66.32% were women. MOH rate was 35.75%. The associated factors were: early age (p=0.003), concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (p=0.0001) as well as self-medication (p<0.0001). By contrast, higher education (p<0.0001) and the use of NSAID alone (0.002) were protective factors against the onset of MOH. Ambulatory withdrawal was the most practiced treatment and amitriptyline was the most commonly used medication. Medication-overuse headaches are frequent in patients placed in Neurology Outpatient observation in Africa and deserve identification for a better management.


Fermentative glycolysis with purified Escherichia coli enzymes for in vitro ATP production and evaluating an engineered enzyme.
Each of the twelve enzymes for glycolytic fermentation, eleven from Escherichia coli and one from Saccharomyces cerevisiae, have been over-expressed in E. coli and purified with His-tags. Simple assays have been developed for each enzyme and they have been assembled for fermentation of glucose to ethanol. Phosphorus-31 NMR revealed that this in vitro reaction accumulates fructose 1,6-bisphosphate while recycling the cofactors NAD(+) and ATP. This reaction represents a defined ATP-regeneration system that can be tailored to suit in vitro biochemical reactions such as cell-free protein synthesis. The enzyme from S. cerevisiae, pyruvate decarboxylase 1 (Pdc1; EC 188.8.131.52), was identified as one of the major 'flux controlling' enzymes for the reaction and was replaced with an evolved version of Pdc1 that has over 20-fold greater activity under glycolysis reaction conditions. This substitution was only beneficial when the ratio of glycolytic enzymes was adjusted to suit greater Pdc1 activity.


Association between freezing of gait and bone mineral density in patients with Parkinson's disease.
Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.


Quantitative and qualitative assessment of non-contrast-enhanced pulmonary MR imaging for management of pulmonary nodules in 161 subjects.
This study aimed at prospectively compared efficacy of non-contrast-enhanced (non-CE) MRI and MDCT for management of pulmonary nodules. A total of 161 patients with 200 nodules underwent MDCT and non-CE MRI (T1WI, T2WI, and STIR) in conjunction with pathological and/or more than 2 years of follow-up examinations. To compare qualitative detection rates between both modalities, all nodules were visually assessed. To compare quantitative and qualitative diagnostic capabilities of MRI, calculation of contrast ratio and visual assessment of probability for malignancy in each nodule were performed. Then, detection rate and diagnostic capability were statistically compared. Although the overall detection rate of each MR sequence (82.5%) was significantly lower than that of MDCT (97.0%, p<0.05), that of malignant nodules showed no significant difference (p>0.05). The diagnostic capability of STIR was significantly higher than those of other MR sequences (p<0.05). Non-CE MR imaging was found to be as useful as MDCT for management of pulmonary nodules.


Effect of N-terminal modification on the mode of action between the Xyn11A and Xylotetraose.
The purpose of this study was to gain an insight into the effects of mutation-induced binding pocket tilting of the Xyn11A xylanase from Bacillus firmus K-1 in producing a unique hydrolysis characteristic. In this study, the wildtype Xyn11A and its K40L mutant were compared for their hydrolysis patterns on beechwood xylan and xylooligosaccharides of sizes 2 to 6. According to our thin-layer chromatography experiment, the K40L mutant produced a larger amount of xylotetraose leftover than the wildtype. Kinetic determination of the WT and K40L mutant suggested that the higher X4 leftover on TLC was reflected in the decreasing catalytic efficiency (kcat/Km) between enzyme and X4. The mechanisms underlying this efficiency loss were examined through atomistic molecular dynamics (MD) simulations. The MD trajectory analysis showed that the mutation-induced binding pocket tilting resulted in an additional hydrophobic contact between the reducing end of X4 and Trp128. Meanwhile, the interactions between the non-reducing end and the Arg112 residue near the active site became lost, which could decrease the catalytic efficiency. This work suggested that the protein engineering to fine-tune the hydrolysis pattern for some desired xylooligosaccharide products was possible.


Antibody-dependent cellular cytotoxicity and natural killer activity against HTLV-1 infected cells.
Antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity were examined using MT-2 cells persistently infected by HTLV-1 as target cells, and mononuclear cells as effector cells, from healthy one-week-old newborn babies, infants, children and adults. More than 10% of ADCC was observed in 17 newborn babies out of 22 (77.3%) and in all 67 healthy one-month-old babies to adults, by adding serum from anti-HTLV-1 positive carriers. When anti-HTLV-1 negative serum was added, less than 10% of ADCC was observed. If infants without anti-HTLV-1 antibodies were breast-fed they had the possibility of HTLV-1 vertical transmission. There was no significant decrease in NK activity between 90 healthy newborn babies, infants, children, or adults. These results suggest that ADCC and NK activity protect against the transmission of HTLV-1 from mother to child.


Protective effect of a PAF-acether antagonist, BN 52021, in trichothecene toxicosis.
Trichothecenes are mycotoxins which produce lethal toxicosis in humans and animals, yet no adequate therapeutic regimen has been developed. This study provides evidence that the selective platelet activating factor (PAF) antagonist, BN 52021 (5-15 mg/kg i.v.) can prolong the survival of conscious rats exposed to a highly lethal T-2 toxicosis. These data also suggest that PAF is an important mediator of this unique toxicosis.


Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer.
The increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12-21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death.


Streptococcus gallolyticus infection: A neglected marker for colorectal cancer?
Colorectal cancer (CRC) is the second most common cancer in Malaysia and mostly detected at advanced stages due to lack of awareness of CRC symptoms and signs. CRC pathogenesis is multifactorial, and there is ambiguous evidence on association of Streptococcus gallolyticus infection with CRC that needs further attention. Thus, a case-control study was conducted to determine whether S. gallolyticus infection is a predictor for CRC occurrence among patients attending Sultan Ahmad Shah Medical Centre@IIUM (SASMEC@IIUM). A total of 33 stool samples from patients diagnosed with CRC and 80 from patients without CRC attending surgical clinic of SASMEC@IIUM were collected and analyzed with iFOBT test and PCR assay to detect S. gallolyticus. In this study, the proportion of S. gallolyticus infection was higher among patients with CRC (48.5%) compared with the control group (20%). Univariate analysis shows that occult blood in stool, S. gallolyticus infection and family history were significantly associated with the development of CRC (P < 0.05). Using the multivariate logistic regression model, positive stool PCR for S. gallolyticus had the lowest relative standard error and almost five times the odds of developing CRC after adjusting other factors (adjusted odds ratio = 4.7, 95% confidence interval = 1.7-12.6, relative standard error = 59.6%). This finding suggests that S. gallolyticus infection was the strongest predictor of CRC's development in our study and potentially serves as a predictive marker for early detection of disease progression.


Fibromuscular dysplasia of the brachial artery in patients with spontaneous coronary artery dissection: a case series and literature review.
Spontaneous coronary artery dissection (SCAD) is diagnosed in a very small percentage of patients with suspected acute coronary syndromes who undergo emergency coronary angiography. Although fibromuscular dysplasia (FMD) is known to coexist in patients with SCAD, the vascular sites of FMD and their frequency have not yet been clarified. We retrospectively reviewed the medical records of 16 patients who were diagnosed with and treated for SCAD at our hospital between 1 January 2011 and 31 January 2023. We have summarized their baseline and clinical characteristics and medical variables, including coronary and upper extremity angiography and in-hospital outcomes. One of our patients had concurrent cardiac tamponade requiring pericardial drainage, and another went into hemorrhage shock the following day from dissection of the gastric retroperitoneal artery. Characteristic angiographic features of partial or diffuse nonatherosclerotic stenosis were observed mainly in the distal parts of the coronary arteries or their branches. Notably, in six patients with SCAD who underwent upper extremity angiography, FMD of the brachial artery was revealed. For the first time, to our knowledge, we found a high prevalence of multifocal FMD of the brachial artery in patients with SCAD.


Serial peak expiratory flow rates in mothers during caesarean section under extradural anaesthesia.
Peak expiratory flow rate (PEFR) was measured in 19 mothers during elective Caesarean section under unsupplemented extradural anaesthesia. In 18 mothers, serial measurements of peak expiratory flow rate indicated adequate expiratory reserve and residual abdominal muscle power consistent with an effective cough. In one mother, with severe respiratory disease, PEFR decreased to a value indicative of inadequate cough. Data for one other mother who came for emergency Caesarean section after 4 h of an extradural infusion also indicated an inability to cough.


[Bladder cancer radiotherapy margins].
Radical cystectomy is the gold standard treatment of invasive bladder carcinoma, but conservative treatment is a serious option for selected patients. It comprises a transurethral resection, as complete as possible, before a radiation therapy of the whole bladder and pelvis, with a concomitant chemotherapy. Bladder wall movements during the treatment course lead to the use of wide margins to cover the clinical target volume. Planning target volume margins must be anisotropic to correspond to the mobility of each bladder zone: 10mm in the inferior portion, 15 mm in lateral directions, and 20 to 25 mm in anterior and superior directions. The development of image-guided radiotherapy and adaptative radiotherapy should lead to a reduction of these margins. Besides, partial bladder radiotherapy is showing encouraging results, by reducing the clinical target volume in well-selected patients.


Antinociceptive effects of synthetic chalcones obtained from xanthoxyline.
A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote region of the body. Here, we show that chalcones can inhibit the pain provoked by the administration of an intraperitoneal acetic acid (AA). This study investigates the effects of 17 synthetic chalcones in the writhing test, a visceral pain model in mice. The majority of these compounds proved more active than some analgesic drugs, such as aspirin and acetaminophen, two reference drugs used here for comparison. Four chalcones, 9, 10, 16, and 17, were selected for more detailed studies, since they exhibited significant antinociceptive activities and chemical structures of interest. They caused dose-related inhibitions, proving about 15-, 10-, 9-, and 8-fold more active than the standard drugs. When administrated orally, only chalcone 9 proved to be effective. These chalcones might be further used as a model to obtain new and more potent analgesic drugs.


'Do as I say, not as I do': Medical Education and Foucault's Normalizing Technologies of Self.
Medical training as a process of professional socialization has been well explored within the fields of medical education, medical sociology and medical anthropology. Our contribution is to outline a bio-power, more specifically an anatomo-politics, of medical education. The current research aimed to explore perspectives on what is commonly termed the 'hidden curriculum'. We conducted interviews with pre-clinical medical students, clinical teachers and medical educators within a New Zealand medical school. In this paper, we outline ways that respondents described the juxtaposition of the undeclared or hidden aspects of medical education with the formal declared curriculum. Our respondents were aware of incongruencies across these components that resulted in mixed messages to students. Curricula initiatives aim to encourage new forms of subjectivity so that students are often expected to be the kinds of doctors that their teachers are not. However, the success of such initiatives is dependent on the degree of alignment between informal and formal components of the curriculum.


Circannual rhythm of laboratory test parameters among chronic haemodialysis patients.
Seasonal variations in laboratory test results have been pointed out in dialysis patients. Although the mechanism for this phenomenon is not clear, this could result in changes in dialysis and medication prescriptions. We investigated the effect of the circannual rhythm on laboratory test parameters in chronic haemodialysis patients. Data of 38 laboratory test parameters were collected every month and analyzed for 150 stable haemodialysis patients, with non-linear sine wave regression and paired t test between data of peak and trough months. Serum urea nitrogen, unsaturated iron binding capacity, lactate dehydrogenase, alkaline phosphatase, amylase, and neutrophil count showed significant circannual rhythms with high amplitudes. Additionally, serum creatinine, uric acid, chloride, calcium, phosphate, magnesium, total cholesterol, total protein, leucocyte count, mean corpuscular haemoglobin level, mean corpuscular haemoglobin concentration, and platelet count showed significant circannual rhythms with little amplitudes. The circannual rhythm of laboratory test parameters could be attributed to seasonal variations in food intake. Awareness of these variations should be taken into account in the interpretation of laboratory results.


Influence of dexniguldipine-HC1 on rhodamine-123 accumulation in a multidrug-resistant leukaemia cell line: comparison with other chemosensitisers.
In the clinical therapy of cancer, resistance to many cytostatic drugs is a major cause of treatment failure. Among other mechanisms, the expression and pumping activity of P-glycoprotein (PGP) in the membrane of resistant cancer cells is responsible for the reduced uptake of cytostatics. The blockade or inhibition of PGP activity by chemosensitisers seems to be a tenable way to restore sensitivity to antineoplastic drugs and therapeutic efficacy. In the present work the influence of the new chemosensitiser dexniguldipine on rhodamine-123 accumulation in multidrug-resistant leukaemia cells was investigated. Dexniguldipine increases cellular rhodamine-123 accumulation dose-dependently.pEC50 values (-log concentration of drug showing a half maximal effect) in accumulation studies are dependent on pH of the test system and are in the range of 6.5 (pH 7.2) to 7.2 (pH 8.0) for dexniguldipine. In comparison with other chemosensitisers such as SDZ PSC 833, cyclosporin A, verapamil, dipyridamole, quinidine and amiodarone, dexniguldipine is the most potent drug in this test system. In addition to equilibrium measurements of rhodamine-123 accumulation, efflux of rhodamine-123 was analysed in the absence and presence of chemosensitisers. A clear dose-dependency was seen and, moreover, a dramatic decrease in efflux rates was achieved in the presence of chemosensitisers. The described system can be used to investigate PGP-mediated drug transport on a pharmacological and biochemical basis.


Insulin uptake by the human alcoholic cirrhotic liver.
Insulin uptake by the human cirrhotic liver was studied in six patients with Laennec's cirrhosis, and the result was compared with that found in ten control patients with varying diseases affecting the biliary system. All patients had portal catheters for diagnostic purposes. The fractional hepatic uptake of insulin was calculated from the clearance rates for insulin obtained after a constant rate infusion into a peripheral vein and the portal vein in each patient. The fractional hepatic extraction of insulin was 13% +/- 5 in cirrhotic patients and differed significantly from the fractional hepatic extraction found in controls (51% +/- 5;P less than 0.001).


Electrochemical and homogeneous electron transfers to the Alzheimer amyloid-beta copper complex follow a preorganization mechanism.
Deciphering the electron transfer reactivity characteristics of amyloid β-peptide copper complexes is an important task in connection with the role they are assumed to play in Alzheimer's disease. A systematic analysis of this question with the example of the amyloid β-peptide copper complex by means of its electrochemical current-potential responses and of its homogenous reactions with electrogenerated fast electron exchanging osmium complexes revealed a quite peculiar mechanism: The reaction proceeds through a small fraction of the complex molecules in which the peptide complex is "preorganized" so as the distances and angles in the coordination sphere to vary minimally upon electron transfer, thus involving a remarkably small reorganization energy (0.3 eV). This preorganization mechanism and its consequences on the reactivity should be taken into account for reactions involving dioxygen and hydrogen peroxide that are considered to be important in Alzheimer's disease through the production of harmful reactive oxygen species.


Does catastrophic midline failure of upper thoracic lamina screws violate the spinal canal? A cadaveric biomechanical analysis using two lamina screw techniques.
Lamina screws have been reported to be a biomechanically sound alternative to pedicle screws in the proximal thoracic spine. However, concerns have been raised that midline failure may result in a spinal canal breach. To evaluate the catastrophic failure of proximal thoracic lamina screws using two techniques for lamina screw purchase. Biomechanical study with human cadaveric vertebrae. Not applicable. Not applicable. Nineteen fresh-frozen T1-T2 vertebrae were Dual energy X-ray absorptiometry scanned for bone mineral density. Caliper measurements of lamina thickness and lateral mass width for bicortical purchase were obtained. Ten specimens had right-to-left 26-mm lamina screws inserted entirely within the length of the lamina (unicortical). Nine specimens had right-to-left 42-mm lamina screws inserted as to extend the length of the lamina and breach the cortex behind the first and second ribs (bicortical). All screws were placed by experienced spine surgeons under fluoroscopic visualization using 4.5-mm cervicothoracic screws. Insertional torque was recorded while placing all implants and reported in "in-lbs." Tensile loading to failure was performed with the force oriented in the parasagittal plane along the vertebral midline. Pullout loading was applied at a rate of 0.25 mm/s using an MTS 858 MiniBionix II System (MTS Systems, Inc., Minneapolis, MN, USA) with the maximum pullout strength (POS) recorded in Newtons. Video fluoroscopy was performed during midline pullout to evaluate screw failure and ascertain spinal canal breach. After testing, all specimens were visually inspected for spinal canal breach. Neither the unicortical nor the bicortical lamina screws violated the spinal canal during catastrophic midline failure. The ventral lamina cortex remained intact for both the lamina screw techniques. All of the unicortical lamina screws resulted in dorsal avulsion of the spinous process and lamina. All nine bicortical lamina screws separated the dorsal lamina from the ventral but were able to maintain lateral mass purchase. The peak insertional torque for both lamina screw techniques was not significantly different (p = .20). However, bicortical lamina screw POS (584.8 ± 150.2 N) was significantly greater than unicortical lamina screw POS (455.6 ± 100.2 N) (p = .04). Bone mineral density showed a moderate correlation with unicortical (r = 0.67) and bicortical (r = 0.47) lamina screw POS. Our results suggest that catastrophic midline failure of lamina screws does not violate the spinal canal. Of the two techniques tested, bicortical lamina screws have a biomechanical advantage. Lamina screws present a viable option for instrumenting the proximal thoracic spine.


A novel multiplex real-time polymerase chain reaction for the molecular diagnosis of metacestode infections in human patients.
The diagnosis of larval cestodiases in humans primarily depends on using imaging techniques in combination with serological tests. However, in case of atypical imaging results, negative serology results due to immunosuppression, or infection with rare taeniid species, traditional diagnostic tools may not provide a definitive species-level diagnosis. We aimed to validate a rapid, reliable, and cost-effective single-step real-time PCR method that can identify and differentiate larval cestodiases from biopsy material. We validated a real-time PCR technique able to distinguish Echinococcus multilocularis, E. granulosus sensu lato (s.l.), and Taenia spp. from biopsy or cytology material in a single-step analysis. Further Sanger sequencing of E. granulosus s.l. and Taenia spp. amplicons enables differentiation of various Echinococcus and Taenia species. The assay was validated on (a) a reference sample collection of 69 clinical and veterinary cases confirmed by imaging, serology, and morphological analysis, (b) 38 routine human patient samples confirmed for aforementioned pathogens by a conventional end-point PCR, and (c) 127 samples from patients with suspected echinococcosis that were submitted to our laboratory for diagnostic analysis. Compared to a conventional reference end-point PCR approach, the quadruplex real-time PCR exhibited a lower limit of detection in a serial dilution with 5-log dilutions for all three targets (2 log for E. multilocularis, 1 log for E. granulosus s.s., and 1 log for T. saginata). We were able to detect DNA from E. multilocularis, E. granulosus s.l. (E. granulosus s.s., E. canadensis, E. ortleppi, and E. felidis), a wide range of Taenia spp., as well as from non-echinococcal metacestodes such as Hydatigera taeniaformis, Hymenolepis spp., Versteria sp., and Spirometra erinaceieuropaei. We suggest that the presented real-time PCR method is a suitable tool to be routinely used in a clinical microbiology laboratory to rapidly detect and identify larval cestodiases in human tissue.


Reoperation rate after fusion and non-fusion surgery for degenerative lumbar spine disease.
The number of reoperations increases with the growing number of operations performed. The clinical material included a group of 2194 patients treated surgically due to degenerative disease of the lumbar spine; we selected a total of 332 patients who were reoperated, and the indications for reoperation were analysed. The percentage of patients operated due to adjacent segment disease in the group of patients with stabilization was on average 8.9%. Indications for stabilizing or preservation of the mobility of the operated segment should provide for the nature of the lesions, and anatomical and surgical conditions.


Does comorbidity increase the risk of mortality among children under 3 years of age?
Diarrhoea and pneumonia remain leading causes of morbidity and mortality in children under 5 years of age. Little data is available to quantify the burden of comorbidity and the relationship between comorbid diarrhoea and pneumonia infections and mortality. We sought to quantify the relationship between comorbidity and risk of mortality among young children in two community-based studies conducted among South Asian children. Secondary data analysis of two cohort studies. We identified two cohort studies of children under 3 years of age with prospective morbidity at least once every 2 weeks and ongoing mortality surveillance. We calculated the mortality risk for diarrhoea and acute lower respiratory infection (ALRI) episodes and further quantified the risk of mortality when both diseases occur at the same time using a semiparametric additive model. Among Nepali children, the estimated additional risk of mortality for comorbid diarrhoea and ALRI was 0.0014 (-0.0033, 0.0060). Among South Indian children, the estimated additional risk of mortality for comorbid diarrhoea and ALRI was 0.0032 (-0.0098, 0.0162). This risk is in addition to the single infection risk of mortality observed among these children. We observed an additional risk of mortality in children who experienced simultaneous diarrhoea and ALRI episodes though the CI was wide indicating low statistical support. Additional studies with adequate power to detect the increased risk of comorbidity on mortality are needed to improve confidence around the effect size estimate.


Development of the Swedish anticholinergic burden scale (Swe-ABS).
Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.


Histological evidence for lichen planus in clinically normal perilesional tissue.
The objective of this study was to examine the histological features of apparently normal oral mucous membrane adjacent to lesions of oral lichen planus. Twenty-six patients attending an oral medicine unit with clinical lesions typical of oral lichen planus had biopsies of lesional and perilesional sites. Biopsies were examined for histopathological features of oral lichen planus. Twenty-two (85%) of lesional biopsies and 12 (46%) of the perilesional biopsies were reported as either typical or showing some features of lichen planus. Twelve of these 22 cases (55%) had both lesional and perilesional biopsies reported as either typical or showing some features of lichen planus. These 12 cases represented 46% of all cases. In four cases (15%) neither the lesional nor the adjacent perilesional biopsy was reported as lichen planus. The inflammatory process in oral lichen planus may extend beyond the confines of the clinical lesion into adjacent mucous membrane of normal appearance.


Energy requirements for diphtheria toxin translocation are coupled to the maintenance of a plasma membrane potential and a proton gradient.
Translocation of diphtheria toxin (DT) or ricin to the cytosol is the rate-limiting step responsible for (pseudo) first-order decline in protein synthesis observed in intoxicated cell populations. The requirements for energy utilization in the translocation of both toxins are examined by perturbing the intoxication during this period of protein synthesis decline. Translocation of either toxin is blocked at 4 degrees C and requires energy. Ricin translocation is tightly coupled to ATP hydrolysis with no involvement of membrane potential. Cell depolarization slows the rate of DT translocation but does not block completely. Elimination of transmembrane pH gradients alone does not affect DT translocation; however, in combination with depolarization, translocation is blocked virtually completely. Energy requirements for DT intoxication are mediated by establishing a plasma membrane potential and a pH gradient across some cellular membrane. It is proposed that a postendocytotic vesicle containing processed DT fuses with the plasma membrane. Either component of the proton motive force across the plasma membrane then drives DT translocation. Ricin apparently utilizes a different energy coupling mechanism at a different intracellular site, thus demonstrating toxin specificity in the translocation mechanism.


Training requirements for DXA technologists in the United States.
The purposes of this study were to determine, by state, the requirements for dual-energy X-ray absorptiometry(DXA) operators' training, knowledge of these state requirements, and factors that predicted state and International Society of Clinical Densitometry (ISCD) certification of DXA technologists. Seventeen states required registered technologist (RT) certification or authorized/licensed limited certification for DXA operators, 16 had no certification requirements, 12 required RT certification, and 5 had state-specific requirements. There were 9745 surveys mailed toDXA users including 50% Hologic Inc., 50% GE Lunar, and 100% Norland; 3148 surveys are included in this analysis. Among responders who indicated that their state did not have any certification requirements (n=1673), 1095(65.5%) were incorrect; there were requirements. Possession of state and ISCD certification was significantly correlated with the number of patients scanned per week (p<or=0.05), the number of technologists employed within a center (p<0.01), and the subspecialty of the practitioner (p<or=0.02). Our study uncovered a lack of uniformity amongstates with respect to central DXA operator training requirements. Additionally, in those states with requirements, DXA operators were often unaware of these requirements. Uniform national training requirements for central DXA operators to ensure adequate DXA scan quality are urgently needed.


Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia.
Zambia is among the 30 high tuberculosis burden countries in the world. Despite increasing reports of multidrug-resistant tuberculosis (MDR-TB) in routine surveillance, information on the transmission of MDR Mycobacterium tuberculosis strains is largely unknown. This study elucidated the genetic diversity and transmission of MDR M. tuberculosis strains in Lusaka, Zambia. Eighty-five MDR M. tuberculosis samples collected from 2013 to 2017 at the University Teaching Hospital were used. Drug-resistance associated gene sequencing, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), and multiplex PCR for RD-Rio sub-lineage identification were applied. The identified clades were LAM (48%), CAS (29%), T (14%), X (6%) and Harlem (2%). Strains belonging to SITs 21/CAS1-Kili and 20/LAM1 formed the largest clonal complexes. Combined spoligotyping and 24 loci-MIRU-VNTR revealed 47 genotypic patterns with a clustering rate of 63%. Ninety-five percent of LAM strains belonged to the RD-Rio sub-lineage. The high clustering rate suggested that a large proportion of MDR-TB was due to recent transmission rather than the independent acquisition of MDR. This spread was attributed to clonal expansion of SIT21/CAS1-Kili and SIT20/LAM1 strains. Therefore, TB control programs recommending genotyping coupled with conventional epidemiological methods can guide measures for stopping the spread of MDR-TB.


The efficacy of double-balloon enteroscopy for intrahepatic bile duct stones after Roux-en-Y hepaticojejunostomy for choledochal cysts.
Intrahepatic bile duct (IHBD) stones are one of the most complicated morbidities that occur after Roux-en-Y hepaticojejunostomy (RYH); however, the optimal therapeutic approach is controversial. Double-balloon enteroscopy (DBE) has been widely and frequently performed even in pediatric patients. We herein report the successful management of IHBD stones by biliary lithotripsy using DBE after RYH for a choledochal cyst (CC). DBE has made it possible to perform endoscopic therapeutic intervention, including balloon dilatation of an anastomotic stricture and removal of IHBD stones, without any major complications. DBE is a less invasive and safe treatment method for IHBD stones in pediatric patients, which is capable of reaching the bilioenteric anastomosis after RYH for CC.


A G1528C Hadha knock-in mouse model recapitulates aspects of human clinical phenotypes for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a fatty acid oxidation disorder (FAOD) caused by a pathogenic variant, c.1528 G > C, in HADHA encoding the alpha subunit of trifunctional protein (TFPα). Individuals with LCHADD develop chorioretinopathy and peripheral neuropathy not observed in other FAODs in addition to the more ubiquitous symptoms of hypoketotic hypoglycemia, rhabdomyolysis and cardiomyopathy. We report a CRISPR/Cas9 generated knock-in murine model of G1528C in Hadha that recapitulates aspects of the human LCHADD phenotype. Homozygous pups are less numerous than expected from Mendelian probability, but survivors exhibit similar viability with wildtype (WT) littermates. Tissues of LCHADD homozygotes express TFPα protein, but LCHADD mice oxidize less fat and accumulate plasma 3-hydroxyacylcarnitines compared to WT mice. LCHADD mice exhibit lower ketones with fasting, exhaust earlier during treadmill exercise and develop a dilated cardiomyopathy compared to WT mice. In addition, LCHADD mice exhibit decreased visual performance, decreased cone function, and disruption of retinal pigment epithelium. Neurological function is affected, with impaired motor function during wire hang test and reduced open field activity. The G1528C knock-in mouse exhibits a phenotype similar to that observed in human patients; this model will be useful to explore pathophysiology and treatments for LCHADD in the future.


A pulmonary mass with invasion into the heart.
We describe the case of a 58 year old woman who presented with bronchial atypical carcinoid found at surgery to invade the left atrium along the pulmonary veins. A right pneumonectomy and removal of a portion of the left atrium was performed. The patient made an excellent post operative recovery. Three years later she presented in acute respiratory failure secondary to local recurrence. This is first case described in which recurrence after resection of bronchial carcinoid metastatic to the heart is described.


Two siblings with Niemann-Pick disease (NPD) type B: clinical findings and novel mutations of the acid sphingomyelinase gene.
Acid sphingomyelinase deficiency leads to the accumulation of sphingomyelin in cells, causing Niemann-Pick disease (NPD) types A/B. RF (13.66 y) and HF (3 y) are brother and sister. RF growth was markedly delayed at the age of 12.66 y (123 cm; -3.25 SD), while at the age 3 y his sister is 86 cm (-2.75 SD). The brother had a huge liver (13 cm) and spleen (12 cm). His sister also had an enlarged liver, but presented no other symptoms. The fibroblast cultivation had a reduced sphingomyelinase activity in the fibroblasts (0.68 mkat/kg protein), β-galaktosidase (937 mkat/kg) and glucosilceramidase (125.4 mkat/kg) were elevated. Mutational analysis demonstrated the siblings are compound heterozygotes (V112M and H554Y). The mother is carrier of V112M and the father carries H554Y. This is the first report of NPD type B in Macedonia. The novel mutation results in a moderately severe phenotype of NPD type B.


Some factors connected with alveolar bone resorption.
In this study correlations are described between alveolar bone resorption, patient's age, duration of edentulousness, the number of dentures which have been worn, and dentures being worn day and night. The sample of patients for this study consisted of 92 edentulous persons treated with complete dentures at a dental school clinic. The test subjects were asked to fill in a questionnaire to obtain data regarding the research factors. A method for the classification of alveolar bone resorption was developed and the test subjects were divided into classes for alveolar bone resorption according to this method. All data were processed by means of a computer program. The longer the test subjects had been edentulous and the more dentures they had worn, the more intensive was the alveolar bone resorption, particularly in the lower jaw. No significant correlation was found between alveolar bone resorption and dentures being worn day and night.


[The effect of prolonged hypokinesia on hemodynamics and myocardial contraction in patients with ischemic heart disease after amputation of the extremities].
Echocardiographic investigation revealed changes in central hemodynamics and myocardial contractility, associated with lasting hypokinesia, in coronary patients after the amputation of a limb that differed significantly from those recorded in patients with intact limbs. Amputation of a limb, lasting hypokinesia, physical overstrain, negative emotions, disorders of myocardial electric and contractile functions, central and peripheral hemodynamic disorders all contribute to the risk of coronary disease, myocardial infarction and death in post-amputation patients.


Advanced glycation end products delay corneal epithelial wound healing through reactive oxygen species generation.
Delayed healing of corneal epithelial wounds is a serious complication in diabetes. Advanced glycation end products (AGEs) are intimately associated with the diabetic complications and are deleterious to the wound healing process. However, the effect of AGEs on corneal epithelial wound healing has not yet been evaluated. In the present study, we investigated the effect of AGE-modified bovine serum albumin (BSA) on corneal epithelial wound healing and its underlying mechanisms. Our data showed that AGE-BSA significantly increased the generation of intracellular ROS in telomerase-immortalized human corneal epithelial cells. However, the generation of intracellular ROS was completely inhibited by antioxidant N-acetylcysteine (NAC), anti-receptor of AGEs (RAGE) antibodies, or the inhibitor of NADPH oxidase. Moreover, AGE-BSA increased NADPH oxidase activity and protein expression of NADPH oxidase subunits, p22phox and Nox4, but anti-RAGE antibodies eliminated these effects. Furthermore, prevention of intracellular ROS generation using NAC or anti-RAGE antibodies rescued AGE-BSA-delayed epithelial wound healing in porcine corneal organ culture. In conclusion, our results demonstrated that AGE-BSA impaired corneal epithelial wound healing ex vivo. AGE-BSA increased intracellular ROS generation through NADPH oxidase activation, which accounted for the delayed corneal epithelial wound healing. These results may provide better insights for understanding the mechanism of delayed healing of corneal epithelial wounds in diabetes.


Treatment of postoperative non-union with internal fixation loosening of Garden IV femoral neck fracture with teriparatide in a young adult: A case report.
Postoperative non-union of femoral neck fracture often needs secondary operation. We report a case of a postoperative non-union of femoral neck fracture treated with teriparatide. A young male patient with Garden IV femoral neck fracture who showed no obvious signs of healing 3 months after percutaneous hollow nail fixation in which the fracture line was enlarged and the hollow nail was withdrawn. Bone non-union healed after 6 months of continuous subcutaneous injection of teriparatide at a dosage of 20 mg/day after the patient refused a secondary surgery. As far as we know, there have been no relevant reports on this type of fracture yet. Teriparatide is expected to be beneficial in treating young patients with a displaced femoral neck fracture who have difficulty in healing from non-union and who are keen on avoiding secondary surgery.


The biological basis for defining bi-parental or tri-parental origin of offspring from cytoplasmic and spindle transfer.
The bi-parental genetic state is not a given after assisted reproduction. This is based on a biological definition of parentage that concerns generational inheritance of genetic material. Often three or more individuals may participate in artificial reproduction. Only cytoplasmic and spindle transfer can result in the genetic tri-parental state. All other forms involving three or more assisting persons with no heritable genetic contribution must be considered differently. Can a cytoplasmic donor be a biological parent based on a potential contribution of mitochondrial DNA to the offspring? - only if the mitochondrial DNA sequence can be traced back to the donor, a phenomenon which may not be very common. When considering spindle transfer for avoiding transmission of mitochondrial disease, all offspring is likely to be tri-parental.


Monoclonal glucose-oxidase-anti-glucose-oxidase (GAG) immunosandwich assay for the detection of monoclonal antibodies on routine hematological smears.
A murine monoclonal antibody specific for aspergillus niger glucose oxidase has been prepared and used in an unlabeled antibody bridge technique for the detection of monoclonal antibodies. This procedure--the monoclonal glucose oxidase anti-glucose oxidase (GAG) immunosandwich assay--provides excellent immunocytochemical labeling of routine hematological films in combination with optimal preservation of cellular details. In contrast to conventional immunofluorescence procedures, routine hematological films can be used, and these can be stored before and after the immunolabeling. Compared with other immunoenzyme techniques such as those using alkaline phosphatase or peroxidase, the GAG assay is as sensitive and has the advantage that no problems with endogenous enzyme activity are encountered. The availability of alcohol-resistant disclosing reagents allows for routine hematological counterstaining which provides a very clear visualization of both the immunoreaction and the individual morphology of the blood cells.


Synthesis of oxindolyl pyrazolines and 3-amino oxindole building blocks via a nitrile imine [3 + 2] cycloaddition strategy.
The [3 + 2] dipolar cycloaddition reaction of nitrile imines with 3-alkylidene oxindoles is described. The pyrazoline spiroadducts were obtained in high yields and with excellent regio- and diastereoselectivities. These spirocyclic intermediates have been elaborated to synthetically versatile 3-amino oxindole building blocks such as β-amino nitrile, 1,3-diamine, and pyrrolo[2,3-b]indoline derivatives.


Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts.
The noninvasive detection of transplanted cells in damaged organs and the longitudinal follow-up of cell fate and graft size are important for the evaluation of cell therapy. We have shown previously that the overexpression of the natural iron storage protein, ferritin, permits the detection of engrafted cells in mouse heart by MRI, but further imaging optimization is required. Here, we report a systematic evaluation of ferritin-based stem cell imaging in infarcted mouse hearts in vivo using three cardiac-gated pulse sequences in a 3-T scanner: black-blood proton-density-weighted turbo spin echo (PD TSE BB), bright-blood T(2) -weighted gradient echo (GRE) and black-blood T(2) -weighted GRE with improved motion-sensitized-driven equilibrium (iMSDE) preparation. Transgenic C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black-blood T(2) -weighted iMSDE (p < 0.05) and a 30% reduction in bright-blood T(2) -weighted GRE (p < 0.0001). Graft size measurements by T(2) iMSDE and T(2) GRE were highly correlated with histological assessments (r = 0.79 and r = 0.89, respectively). Unlabeled wild-type C2C12 cells transplanted to mouse heart did not change the MRI signal intensity, although endogenous hemosiderin was seen in some infarcts. These data support the use of ferritin to track the survival, growth and migration of stem cells transplanted into the injured heart.


Comparison of sonohysterography and hysteroscopy: lessons learned and avoiding pitfalls.
We compared ultrasound images of the uterine cavity obtained by sonohysterography (SHG) with those of hysteroscopy in an attempt to avoid inaccurate interpretations. Women referred for abnormal bleeding or infertility underwent SHG before treatment. Those with an abnormal study underwent hysteroscopy for confirmation and treatment. Abnormal SHG studies are frequent, with false positive images including blood clots, mucus plugs, and shearing of normal endometrium relatively common. Uterine pathology generally seen on SHG, including anomalies, polyps, and myomas, is consistent with that seen at hysteroscopy. Performing intraoperative SHG concomitantly with hysteroscopy adds value due to SHG's three-dimensional images to confirm depth of pathology and false negative hysteroscopy findings.


Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes.
The low density lipoprotein receptor-related protein (LRP) is a cell surface receptor that binds and internalizes several macromolecules including apolipoprotein E-enriched remnant lipoproteins and protease/antiprotease complexes such as activated alpha 2-macroglobulin. Its function has been studied primarily in cultured fibroblasts and in liver. In the current studies, we provide evidence that LRP is present on the surface of primary adipocytes isolated from rat epididymal fat pads. The activity of the receptor increases 2-3-fold within minutes after the adipocytes are exposed to physiological concentrations of insulin as indicated by an increase in the uptake of 125I-labeled activated alpha 2-macroglobulin. There is a corresponding increase in the uptake of [3H]cholesteryl esters from radiolabeled apoE-enriched beta-very low density lipoprotein. The latter uptake was inhibited by an antibody against LRP and by a fusion protein containing the 39-kDa protein, also called receptor-associated protein, a known inhibitor of LRP function. In vivo, rats that had been fed ad libitum accumulated approximately 24-fold more chylomicron cholesteryl esters in their epididymal fat pads than did fasted control animals. We suggest that insulin stimulation of LRP, in a synergistic action with lipoprotein lipase, increases the endocytic uptake of cholesteryl esters and triglycerides from remnant lipoproteins in postprandial adipocytes.


Free-Weight and Machine-Based Training Are Equally Effective on Strength and Hypertrophy: Challenging a Traditional Myth.
This study aimed to compare the effects of free-weight and machine-based resistance training on strength, hypertrophy, and joint discomfort. Thirty-eight resistance-trained men participated in an 8-wk resistance program allocated into free-weight ( n = 19) or machine-based ( n = 19) groups. Training variables were identical for both modalities, so they only differed in the use of barbells or machines to execute the full squat, bench press, prone bench pull, and shoulder press exercises. The velocity-based method was implemented to accurately adjust the intensity throughout the program. Strength changes were evaluated using eight velocity-monitored loading tests (four exercises × two modalities) and included the relative one-repetition maximum (1RM Rel ), as well as the mean propulsive velocity against low (MPV Low ) and high (MPV High ) loads. Ultrasound-derived cross-sectional area of quadriceps (proximal and distal regions), pectoralis major, and rectus abdominis was measured to examine hypertrophy. Complementarily, Western Ontario and McMaster Universities and Disabilities of the Arm, Shoulder and Hand questionnaires were administrated to assess changes in lower- and upper-limb joint discomfort. Outcomes were compared using ANCOVA and percentage of change (∆) statistics. Each group significantly ( P < 0.001) increased 1RM Rel , MPV Low , and MPV High for both modalities tested, but especially in the one they trained. When considering together the eight exercises tested, strength changes for both modalities were similar (∆ differences ≤1.8%, P ≥ 0.216). Likewise, the cross-sectional area of all the muscles evaluated was significantly increased by both modalities, with no significant differences between them (∆ difference ≤2.0%, P ≥ 0.208). No between-group differences ( P ≥ 0.144) were found for changes in stiffness, pain, and functional disability levels, which were reduced by both modalities. Free-weight and machine-based modalities are similarly effective to promote strength and hypertrophy without increasing joint discomfort.


Involuntary attention and brightness contrast.
Carrasco, Ling, and Read (2004) reported that involuntary attention increased perceived contrast. We replicated Carrasco et al. and then tested an alternative hypothesis: With stimuli near threshold, a peripheral cue biased observers to believe a stimulus had been presented in the cued location. Consistent with this hypothesis, the effect disappeared when we used higher-contrast stimuli. We further tested the guessing-bias hypothesis in three ways: (1) In a detection experiment, the cue affected bias, but did not increase d'; (2) when the cue followed the stimulus, we obtained the same results as when the cue preceded the stimulus; (3) in one experiment, some trials contained no stimulus, yet observers responded that the cued blank stimulus had higher contrast than the uncued blank stimulus. The results suggest that the effects of a noninformative peripheral cue are best described in terms of nonperceptual biases.


Early Treatment in HIV Patients: A Cost-Utility Analysis from the Italian Perspective.
Highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections and mortality. Several recent studies show early antiretroviral therapy reduces the risk of AIDS and HIV-related disease. The aim of this study was to perform an economic analysis to estimate the cost-utility of early antiretroviral therapy in Italy for managing HIV-infected patients. The incremental cost-utility analysis was carried out to quantify the benefits of the early-treatment approach in HIV subjects. A Markov simulation model including direct costs and health outcomes was developed from a third-party (Italian National Healthcare Service) payer's perspective for four CD4 strata. 5000 Monte Carlo simulations were performed on two distinct scenarios: Standard of care (SoC) in which 30% of patients started HAART with a CD4 count ≥500 cells/mm(3) versus the early-treatment scenario (ETS), where the number of patients starting HAART with a CD4 count ≥500 cells/mm(3) increased to 70%. A systematic literature review was carried out to identify epidemiological and economic data, which were subsequently used to inform the model. In addition, a one-way probabilistic sensitivity analysis was performed in order to measure the relationship between the effectiveness of the treatments and the number of patients to undergo early treatment. The model shows, in terms of the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) gained, that early treatment appeared to be the most cost-effective option compared to SoC (ICER = €13,625) over a time horizon of 10 years. The cost effectiveness of ETS is more sustainable as it extends the time horizon analysis (ICER = €7526 per QALY to 20 years and €8382 per QALY to 30 years). The one-way sensitivity analysis on the main variables confirmed the robustness of the model for the early-treatment approach. Our model represents a tool for policy makers and health-care professionals to provide information on the cost effectiveness of the early-treatment approach in HIV-infected patients in Italy. Starting HAART earlier keeps HIV-infected patients in better health and reduces the incidence of AIDS- and non-AIDS-related events, generating a gain in terms of both patients' health and correct resource allocation.


Comparison of the influence of cationic polysaccharides on the stability properties of montmorillonite suspensions in the presence of sodium dodecyl sulphate.
The mixtures of cationic cellulose (CC) or cationic guar gum (CGG) with the anionic sodium dodecyl sulfate surfactant (SDS) were used as stabilizers for the aqueous suspensions of montmorillonite (Mt). The stabilization processes and the stabilization mechanism were investigated using the UV-VIS. The obtained results show that both polysaccharides can be used as stabilizers of the water suspensions of montmorillonite due to the effective adsorption of CC and CGG with or without SDS on the Mt. surface. To obtain complete information on the studied systems, the additional measurements of the surface tension, zeta potential, FT-IR, XRD and SEM were made. The results prove that the intermolecular complexes formed between the polysaccharides and SDS can adsorb on the Mt. surface, change the structure of the electrical double layer and the stability properties of the studied suspensions.


Neoplastic associations of rheumatic diseases and rheumatic manifestations of cancer.
Associations between rheumatic diseases and malignant neoplasms are still inferential and based largely on epidemiologic data. Rheumatoid arthritis predisposes weakly to the occurrence of lymphoreticular neoplasms. This is more clearly true of Sjögren's disease, whether or not it is associated with RA. A subset of DM/PM which becomes manifest in close temporal proximity to a neoplasm may be a paraneoplastic reaction, but DM/PM, in general, does not predispose to neoplasia. Scleroderma in its early phase is associated with the development of breast cancer in women, and after a decade or longer, if pulmonary fibrosis has developed, with lung cancer. Of the drugs that have been used to treat these diseases, cyclophosphamide is most strongly implicated as a carcinogenic agent, particularly inducing lymphoreticular neoplasms and carcinoma of the bladder. Musculoskeletal symptoms that may be clues to the existence of cancer may either be caused by invasion of the neoplasm or be mediated by unidentified neurohumoral mechanisms. Except for multiple myeloma, primary neoplasms of skeletal tissues tend to occur under the age of 50 years. Metastatic disease occurs congruently with the age incidence of the primary neoplasm. Metastases may mimic mono- or oligoarticular arthritis if they happen to be periarticular or synovial. These metastases result most often from carcinoma of the lung or, in women, carcinoma of the breast. Hypertrophic pulmonary osteoarthropathy usually is due to carcinomas of the lung other than the small cell variety, and infrequently from other intrathoracic primary or secondary neoplasms. RA may be mimicked. Both skeletal metastases and HPOA are detected with greater sensitivity, but not specificity, by isotopic scanning techniques than by radiography. Of the other paraneoplastic musculoskeletal syndromes, neuromyopathy is the most frequent. It must be distinguished from cachexia, polymyositis, polymyalgia rheumatica, and the myasthenic syndrome. Both neuromyopathy and Eaton-Lambert (myasthenic) syndrome are predominantly associated with small cell carcinoma of the lung and both are best diagnosed by electromyography. Carcinomatous polyarthritis and the palmar fasciitis-arthritis syndrome occur with various neoplasms, although the latter appears to be particularly associated with ovarian carcinomas. The paraneoplastic arthritides test negatively for the rheumatoid factor, but no reliable positive immunochemical clues have as yet been identified.


Efficient inhibition of hepatitis B virus replication by hammerhead ribozymes delivered by hepatitis delta virus.
Although it has been suggested that hepatitis delta virus (HDV) can be used as a vector to deliver biologically active RNAs into hepatocytes, modified HDV as a specific transporting and replicating vector in anti-viral research has not been investigated. In this study, we focused on the development of HDV as a replicative vector to deliver hammerhead ribozyme into hepatocytes and the study of the roles of delivered hammerhead ribozyme on the replication of hepatitis B virus (HBV). To investigate the effects of ribozyme delivered by HDV on HBV replication, we designed two hammerhead ribozymes that specifically target the hepatitis B virus genome. These two ribozymes were then inserted into the genome of hepatitis delta virus. Results showed that transfection of cells with tandem modified HDV cDNA resulted in the production of monomer form of sense and anti-sense genomic RNA indicating the recombinant HDV-ribozyme could replicate effectively. Our data also indicated that ribozymes delivered by the modified HDV had higher level of inhibition activity against HBV replication than that of ribozyme alone. This system provides a new approach for the study of mechanisms of HBV replication as well as for the potential treatment of HBV infection.


Monitoring of electricity generation from exhaust waste heat and wireless data recording from a mobile phone in real driving conditions of a vehicle.
In this study, a system is designed to generate electrical energy from the exhaust waste heat of vehicles using a thermoelectric generator. Electronic hardware that can communicate wirelessly, firmware, and mobile software specific to the system have been developed to control and monitor this system. The system comprises hexagonal aluminum components, thermoelectric generators, a cooler, sensors, software, and electronic hardware. The easily removable hexagonal modular aluminum component is designed to transmit heat from the exhaust pipe to thermoelectric generators. It used a thermoelectric generator (TEG-SP1848) on each edge of this hexagonal component and a heatsink to cool the generator. The voltage and current values of the electrical energy produced in the observations made under real driving conditions are recorded on the SD card on the system. In addition, system-specific mobile software has been developed by the work team. With this software, the system can be controlled, as well as visualizing the instantaneous parameters of the system. According to the results obtained from the test drives, electrical energy was obtained at a maximum voltage of 9.8 V and a current of 0.32 A. This electrical energy from the exhaust waste heat can be stored in the vehicle's existing battery. In this way, since the alternator used for the vehicle's electricity generation will be activated less, fuel savings will be achieved in the engine, and harmful exhaust emissions will be reduced. In addition, the electrical energy obtained by this method can be stored in an external battery independent of the vehicle battery and used for various purposes. In contrast, the vehicle is stationary or has a portable battery.


Selection and characterization of high affinity VEGFR1 antibodies from a novel human binary code scFv phage library.
VEGFR1 is a receptor tyrosine kinase that has been implicated in cancer pathogenesis. It is upregulated in angiogenic endothelial cells and expressed on human tumor cells as well. VEGFR1 positive hematopoietic progenitor cells home to sites of distant metastases prior to the arrival of the tumor cells thus establishing a pre-metastatic niche. To discover high affinity human antibodies selective for VEGFR1 molecular imaging or for molecularly targeted therapy, a novel phage display scFv library was assembled and characterized. The library was constructed from the humanized 4D5 framework that was mostly comprised tyrosine and serine residues in four complimentary determining regions (CDRs). The library produced diverse and functional antibodies against a panel of proteins, some of which are of biomedical interest including, CD44, VEGFA, and VEGFR1. After panning, these antibodies had affinity strong enough for molecular imaging or targeted drug delivery without the need for affinity maturation. One of the anti-VEGFR1 scFvs recognized its cognate receptor and was selective for the VEGFR1.


Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization.
In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects' ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.


Both low circulating insulin-like growth factor-1 and high-density lipoprotein cholesterol are associated with hair loss in middle-aged women.
Multiple biomarkers have been associated with hair loss in women, but studies have shown inconsistent results. We investigated the associations between markers of cardiovascular disease risk (e.g. serum lipid levels and hypertension) and ageing [e.g. 25-hydroxyvitamin D and insulin-like growth factor (IGF)] with hair loss in a population of middle-aged women. In a random subgroup of 323 middle-aged women (mean age 61·5 years) from the Leiden Longevity Study, hair loss was graded by three assessors using the Sinclair scale; women with a mean score > 1·5 were classified as cases with hair loss. Every 1 SD increase in high-density lipoprotein (HDL) cholesterol was associated with a 0·65-times lower risk [95% confidence interval (CI) 0·46-0·91] of hair loss. For IGF-1 the risk was 0·68 times lower (95% CI 0·48-0·97) per 1 SD increase, independently of the other studied variables. Women with both IGF-1 and HDL cholesterol levels below the medians of the study population had a 3·47-times higher risk (95% CI 1·30-9·25) of having hair loss. Low HDL cholesterol and IGF-1 were associated with a higher risk of hair loss in women. However, further studies are required to infer causal relationships.


Regulation of the human papillomavirus oncoproteins by differential phosphorylation.
Human papillomaviruses (HPVs) are intimately associated with the development of cervical cancer. The virus encodes two oncoproteins, E6 and E7, that are primarily responsible for inducing malignant transformation. The last few years have seen significant progress in elucidating the mechanisms by which these two viral proteins bring about cell transformation. Both proteins interact with a large number of cellular targets, many of which are involved in regulating diverse functions such as cell cycle regulation, transcription, differentiation and apoptosis. However both E6 and E7 are normally present at low levels within the virally infected cell, and how all these interactions are achieved and regulated has, until recently, been unclear. We have found that both E6 and E7 are subject to differential phosphorylation, the net results of which regulate their abilities to interact with some of their respective target proteins. In the case of E6, phosphorylation by Protein Kinase A (PKA) negatively regulates its ability to interact with the Discs Large (Dlg) tumour suppressor. In the case of E7, phosphorylation by Casein Kinase II (CKII) significantly increases its ability to interact with the TATA Box Binding Protein (TBP). Further, CKII regulation of E7 appears to vary during the cell cycle, therefore this provides a means of specifically targeting E7 to a given substrate at a given point within the cell cycle. This differential regulation of E6 and E7 by phosphorylation thus provides specificity to a diverse set of protein-protein interactions.


Human umbilical cord Wharton's jelly stem cells: immune property genes assay and effect of transplantation on the immune cells of heart failure patients.
Stem cells derived from umbilical cord Wharton's jelly (WJSCs) are not immunogenic and have immunosuppressive effects. To evaluate the related mechanisms and the effect of transplantation on body immune cells, we examined immune property genes expression in WJSCs and levels of T-lymphocytes subgroups and immunoglobulins (Ig) in heart failure (HF) patients with and without WJSCs transplantation. WJSCs express immune tolerance genes HLA-E, HLA-G and HLA-F and immunomodulation genes VEGF, TGFβ1, HGF, HMOX1, IL1β, IL-6, LIF, LGALS-1/3/8, COX1/2 and PTGE, while they do not express immune response-related genes HLA-DR, HLA-DQ, HLA-DP, CD80, CD86, CD40 and CD40L. No obvious changes of T-lymphocytes subgroups and plasma IgG/IgM were observed in HF patients with WJSCs transplantation. Our results suggest that the immune properties of WJSCs are due to the expression of immune avoidance and immunomodulation genes in the absence of immune response-related genes. WJSCs are secure in immunological aspects when used as seed cells for cardiac repair.


[The mechanism of the therapeutic action of the EHF therapy of spinal osteochondrosis].
Microwave therapy (millimetric waves) was used for treatment of spinal osteochondrosis. The effect was manifest as early as the first sessions. The pain alleviated, muscular tension decreased, movements recovered, convulsions and numbness of the legs ceased. Possible biophysical mechanisms of EHF waves are discussed.


Novel catecholate-type siderophore analogs based on a myo-inositol scaffold.
A novel 1,3,5-triamino-myo-inositol derivative is presented as a readily available scaffold for the design of tripodal siderophore mimetics. Based on this scaffold, various hexadentate catecholate-type siderophore analogs were synthesized by attaching the catechols to the inositol scaffold via spacer units of different structure and length. The potential to tune the polarity of the inositol containing siderophore analogs has also been demonstrated by varying the protection group strategy. The siderophore activity of the prepared siderophore analogs was examined by cross-feeding tests with various Gram-negative bacteria and mycobacteria.


Central autonomic innervation of the lower urinary tract--a neuroanatomy study.
Knowledge about the central innervation of the lower urinary tract is limited. The spinal cord and the pontine micturition center have been investigated most thoroughly, whereas high centers have received little attention. Pseudorabies virus (PRV), a self-amplifying and transneuronal tracer was injected into the bladder trigone of 21 Sprague-Dawley rats. The animals were killed after 72, 96, and 120 h. The whole CNS was sectioned and immunostained for PRV. CNS centers directly connected to the bladder include the intermedio lateral cell column, the central autonomic nucleus, and the nucleus intercalatus at the spinal cord levels T12-L2 and L6-S2. The raphe pallidus et magnus, the A5 nor-adrenergic area, the pontine micturition center, the locus coeruleus, the periaquaductal gray, the nucleus para- et periventricularis of the hypothalamus, the red nucleus, the medial preoptic area, and the cortex are supraspinal centers connected to the bladder. Lower urinary tract function is a complex multilevel and multineuronal interaction. It involves facilitation and inhibition at many levels of the CNS.


Solid lipid nanoparticles self-assembled from spray dried microparticles.
We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (IMC) and hydrophilic (5-FU) drugs. They show extended release profiles over more than 24 h, and in permeation studies the drug cargo is seen to accumulate inside cancer cells. This overcomes major issues with achieving local intestinal delivery of these active ingredients, in that IMC permeates well and thus will enter the systemic circulation and potentially lead to side effects, while 5-FU remains in the lumen of the small intestine and will be secreted without having any therapeutic benefit. The SLN formulations are as effective as the pure drugs in terms of their ability to induce cell death. Our approach represents a new and simple route to the fabrication of SLNs: by assembling these from spray-dried microparticles on demand, we can circumvent the low storage stability which plagues SLN formulations.


Measurement of carotid intima-media thickness to assess progression and regression of atherosclerosis.
Imaging modalities have been developed to assess atherosclerosis in vivo in the arterial wall because large clinical end-point studies are time-consuming and costly. Historically, in-hospital angiography and Doppler ultrasonography have been used to assess atherosclerosis development. Investigations of the arterial lumen are, however, increasingly being replaced by modalities that can measure changes in the arterial wall itself-intravascular ultrasonography, MRI and multislice CT. The fact that intravascular ultrasonography is invasive, CT involves substantial radiation exposure and requires contrast agents, and that MRI is time-consuming and technically challenging all limit the widespread use of these techniques. Moreover, all modalities have high associated costs. B-mode ultrasonographic imaging of the carotid arterial walls occupies a unique position in atherosclerosis research. This method enables sensitive, reproducible and noninvasive assessment of intima-media thickness (IMT) as a continuous variable. Epidemiological and clinical trial evidence as well as digitization and standardization have made carotid IMT a validated and accepted marker for generalized atherosclerosis burden and vascular disease risk. Here we describe the application of carotid IMT measurements as a tool in risk evaluation of individuals and in studies of atherosclerosis progression and regression.


Sauna-related burns: a review of 154 cases treated in Kuopio University Hospital Burn Center 1994-2000.
Bathing in sauna has been customary for Finnish people for centuries. However, there are no actual reviews on sauna-related burns in the literature. This 7-year retrospective analyses of 598 burn patients treated in Kuopio University Hospital Burn Unit revealed that every fourth burn in our unit was sauna-related, giving a total of 154 cases. Most of these burns were minor but 54% required operative treatment. A total of 71% of patients were male and 40% of all patients were under the influence of alcohol. The incidence of sauna-related burns in Finland according to our material is 7/100,000, giving a total of 357 patients annually. Hence, there is one sauna-related burn per day requiring hospitalization in Finland.


Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice.
A genetic predisposition to hepatic steatosis may be associated with dietary patterns. We hypothesized that a common variant in human methylenetetrahydrofolate reductase (MTHFR 677C→T) was previously associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between the human MTHFR polymorphism and NAFLD using fructose-fed male C57BL/6 Mthfr+/+ and Mthfr+/- mice, a model for the human gene variant. Mice were fed an 8% fructose solution for 12 weeks. Mthfr+/- mice had significantly increased abdominal fat mass and hepatic triglyceride (TG) but displayed a similar liver mass when compared with Mthfr+/+ mice. Liver morphology showed that mild MTHFR deficiency induced liver lipid droplet deposition and inflammatory cell infiltration, suggesting accelerated lipid accumulation in the liver. Moreover, mild MTHFR deficiency increased hepatic xanthine oxidase activity and uric acid accumulation. Using untargeted lipidomics, we identified 116 differentially expressed lipids species in the liver of Mthfr+/- mice when compared with Mthfr+/+ animals. The most significant lipid increase was observed in 47 TGs, followed by 33 phosphatidylcholines in Mthfr+/- mice liver. When compared with Mthfr+/+ liver, 9 TGs were dramatically decreased in Mthfr+/- liver. These changes were associated with upregulated gene expressions related to triglyceride synthesis and storage. Thus, Mthfr+/- mice developed NAFLD disease. These findings suggested the Mthfr variant may be at an increased risk of liver steatosis on a fructose solution diet.


The peroxisome-proliferator activated receptor-γ agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus.
PPAR-γ agonists can suppress autoimmune responses and renal inflammation in murine lupus but the mechanisms implicated in this process remain unclear. We tested the effect of the PPAR-γ agonist pioglitazone in human lupus and control PBMCs with regard to gene regulation and various functional assays. By Affymetrix microarray analysis, several T cell-related pathways were significantly highlighted in pathway analysis in lupus PBMCs. Transcriptional network analysis showed IFN-γ as an important regulatory node, with pioglitazone treatment inducing transcriptional repression of various genes implicated in T cell responses. Confirmation of these suppressive effects was observed specifically in purified CD4+ T cells. Pioglitazone downregulated lupus CD4+ T cell effector proliferation and activation, while it significantly increased proliferation and function of lupus T regulatory cells. We conclude that PPAR-γ agonists selectively modulate CD4+ T cell function in SLE supporting the concept that pioglitazone and related,-agents should be explored as potential therapies in this disease.


Effects of Temperature on the Compressive Strength Parallel to the Grain of Bamboo Scrimbe.
The objective of this study was to investigate the compressive strength parallel to the grain of bamboo scrimber during and after exposure to various temperatures, in a range from 20 to 225 °C. These data were used to provide a basis for the evaluation of the fire performance of bamboo structures. A total of 152 specimens, assembled as group "during-fire" and "post-fire", were tested during and after exposure to high temperatures. The experimental results indicated that there were significant differences in compressive properties between the "during-fire" and "post-fire" groups. At one temperature level, the compressive strength and modulus of elasticity of the "post-fire" group were significantly higher than those properties of the "during fire" group, but the ductility coefficient was reversed. FTIR analysis results showed that 175 °C was a key turning point, at which thermal decomposition occurred in the cellulose of the bamboo and phenolic resin.


Behavioural, physiological and molecular responses of the Antarctic fairy shrimp Branchinecta gaini (Daday, 1910) to polystyrene nanoplastics.
Plastic pollution represents an emerging environmental issue in terrestrial Antarctica, especially in the Antarctic Peninsula and Maritime Antarctica, which have been recently recognized as hot spots for plastic litter. In these regions, freshwater (FW) environments such as lakes host isolated ecosystems and species that can be severely affected by increasing environmental and anthropogenic stressors, which include plastics that are still overlooked. In this study, we investigated for the first time the impact of nanoplastics on adults of the fairy shrimp Branchinecta gaini (Order Anostraca) populating Antarctic FW ecosystems, using surface charged polystyrene nanoparticles (PS NPs) as a proxy. Short-term acute toxicity (48 h) was investigated by exposing adults to carboxyl (-COOH, 60 nm) and amino-modified (-NH2, 50 nm) PS NPs at 1 and 5 μg mL-1. Biodisposition of PS NPs and lethal and sub-lethal effects (i.e., swimming, moulting, histology, gene expression) were assessed. Behaviour of PS NPs in Antarctic FW media was monitored through 48 h of exposure showing that both PS NPs kept their nanoscale size in the Antarctic FW media. Survival of fairy shrimp adults over short-term exposure was not affected, on the other hand an increase in moulting rate and alterations in the gut epithelium were observed upon exposure to both PS NPs. Significant alterations at the behavioural (ventilation rate) and molecular (up-regulation of Hsp70mit, Hsp83, Sod, P450) levels were related to PS NP surface charge and associated with PS-NH2 exposure only. Nanoplastics could represent a threat for Antarctic FW biodiversity and the Antarctic fairy shrimp could be a valuable model for assessing their impact on such remote and pristine aquatic ecosystems.


Iris-fixated phakic intraocular lens implantation after retinal detachment surgery: long-term clinical results.
To assess the efficacy and safety of iris-fixated phakic intraocular lens (pIOL) implantation to correct myopia in eyes with previous retinal detachment (RD) surgery. Department of Ophthalmology, Soonchunhyang University College of Medicine, Seoul, South Korea. Retrospective case series. Patients having pIOL implantation in both eyes were enrolled. Eyes that had scleral buckling or encircling (RD group) and healthy fellow eyes (non-RD group) were evaluated over a 6-year follow-up. The corrected distance visual acuity (CDVA), endothelial cell density (ECD), intraoperative complications, and long-term complications were safety outcomes. Uncorrected distance visual acuity (UDVA), predictability, and stability of refraction were efficacy outcomes. The study comprised 34 eyes (17 patients). The mean postoperative CDVA and ECD were not significantly different between groups, and no patient lost CDVA. The rate of transient intraocular pressure spike was significantly higher in the RD group (P=.043). After 3 years and 6 years, the mean postoperative UDVA was 0.06 logMAR ± 0.09 (SD) and 0.08 ± 0.10 logMAR, respectively, in the RD group and 0.04 ± 0.08 logMAR and 0.04 ± 0.09 logMAR, respectively, in the non-RD group (P=.518 and P=.478, respectively). The rate of eyes within ±0.50 diopter of the desired refraction and the postoperative refraction was not significantly different between groups. No eye had vitreoretinal changes requiring secondary surgical intervention. Iris-fixated pIOL implantation corrected the myopic refractive error in patients who had scleral buckling or encircling surgery for RD with a high degree of efficacy, safety, and long-term stability. No author has a financial or proprietary interest in any material or method mentioned.


Surface degradation and biofilm formation on hybrid and nanohybrid composites after immersion in different liquids.
This study evaluated the association of surface degradation and formation of Streptococcus mutans (S. mutans) biofilm in resin-based composites (RBCs) after storage in different acidic liquids. To evaluate microhardness and surface micromorphology, hybrid and nanohybrid RBC discs were stored in artificial gastric acid, cola drink, orange juice, artificial saliva, and distilled water for three intervals of 15 min per day for 7, 15, and 30 days. After 30 days of storage, surface roughness was analyzed, and the RBC discs were placed in a biofilm reactor inoculated with S. mutans to evaluate surface biofilm formation. As compared with nanohybrid RBCs, roughness and surface microhardness values were significantly lower (P < 0.05) for hybrid RBCs stored in artificial gastric acid, followed by specimens stored in cola drink and orange juice. Artificial gastric acid caused greater surface degradation, which increased the biomass of S. mutans on the surface of both RBC types. Surface degradation of hybrid and nanohybrid RBCs correlated with the pH of the liquid, while S. mutans biofilm formation was associated with increased surface roughness in hybrid RBCs.


How Do Medical Schools Identify and Remediate Professionalism Lapses in Medical Students? A Study of U.S. and Canadian Medical Schools.
Teaching and assessing professionalism is an essential element of medical education, mandated by accrediting bodies. Responding to a call for comprehensive research on remediation of student professionalism lapses, the authors explored current medical school policies and practices. In 2012-2013, key administrators at U.S. and Canadian medical schools accredited by the Liaison Committee on Medical Education were interviewed via telephone or e-mail. The structured interview questionnaire contained open-ended and closed questions about practices for monitoring student professionalism, strategies for remediating lapses, and strengths and limitations of current systems. The authors employed a mixed-methods approach, using descriptive statistics and qualitative analysis based on grounded theory. Ninety-three (60.8%) of 153 eligible schools participated. Most (74/93; 79.6%) had specific policies and processes regarding professionalism lapses. Student affairs deans and course/clerkship directors were typically responsible for remediation oversight. Approaches for identifying lapses included incident-based reporting and routine student evaluations. The most common remediation strategies reported by schools that had remediated lapses were mandated mental health evaluation (74/90; 82.2%), remediation assignments (66/90; 73.3%), and professionalism mentoring (66/90; 73.3%). System strengths included catching minor offenses early, emphasizing professionalism schoolwide, focusing on helping rather than punishing students, and assuring transparency and good communication. System weaknesses included reluctance to report (by students and faculty), lack of faculty training, unclear policies, and ineffective remediation. In addition, considerable variability in feedforward processes existed between schools. The identified strengths can be used in developing best practices until studies of the strategies' effectiveness are conducted.


Phenotypic and Genotypic Characterization of Streptococcus mutans Strains Isolated from Endodontic Infections.
Streptococcus mutans plays an important role in caries etiology and eventually in systemic infections. However, it is often found in infected root canals, but the pathophysiological characteristics of strains residing in this site are largely unknown. Here, we characterized strains of S. mutans isolated from root canals of primary (PI) and secondary/persistent (SI) endodontic infections in relation to serotype and genotype; presence of genes coding for collagen binding proteins (CBPs); collagen binding activity and biofilm formation capacity; ability to withstand environmental stresses; systemic virulence in Galleria mellonella; and invasion of human coronary artery endothelial cells and human dental pupal fibroblasts. Samples from 10 patients with PI and 10 patients with SI were collected, and a total of 14 S. mutans isolates, belonging to 3 genotypes, were obtained. Of these, 13 were serotype c, and 1 was serotype k. When compared with the reference strains, the clinical isolates were hypersensitive to hydrogen peroxide. Remarkably, all 14 strains harbored and expressed the CBP-encoding gene cbm, showing increased binding to collagen, enhanced systemic virulence in G. mellonella, and ability to invade human coronary artery endothelial cells and human dental pupal fibroblasts when compared with CBP-negative strains. Whole genome sequence analysis of PI and SI isolates revealed that these strains are phylogenetically related but genetically distinct from each other. Our findings highlight the importance of CBPs in facilitating colonization and persistence of S. mutans in collagenous substrates such as root canals and their potential role in the pathogenesis of endodontic infections.


Effects of training versus non-training in identification of infant cry-signals: a longitudinal study.
The effects of training on the ability to identify 4 infants' cry-signals (birth, hunger, pain, and pleasure) were studied in 60 college students (aged 18 to 30 yr.). Subjects with training scored significantly higher than those without in identifying all but the pleasure cry-signal. In a follow-up retest 10 wk. later, scores for the birth and hunger cry-signals improved significantly (p less than .05) for subjects without training, while scores for subjects with training remained about the same. The suggestion that repeated exposure to cry-signals may serve as training was discussed.


Association Between Brain Volumes and Patterns of Physical Activity in Community-Dwelling Older Adults.
Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown. Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age = 77 [SD = 7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: (a) total daily PA minutes and (b) activity fragmentation (mean number of PA bouts / total PA minutes × 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (eg, fragmentation covariate included in the PA minutes model). Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6 [SE = 1.0] and 3.8 [0.9] min/day, respectively; p < .009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (-0.16% [0.05], p = .003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant. Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging.


Stopped-flow studies of spectral changes in bilirubin-human serum albumin following an alkaline pH jump and following binding of bilirubin.
A stopped-flow technique was used to study the spectral changes occurring in bilirubin-albumin following a pH jump as well as following binding of bilirubin at 25 degrees C. The changes were studied in two wavelength ranges, 280-310 nm (tyrosine residues) and 400-510 nm (bound bilirubin). The changes were analyzed according to a scheme of consecutive unimolecular reactions. Spectral monitoring of a pH jump from 11.3 to 11.8 reveals that the bilirubin-albumin complex changes its structure in several steps. The UV absorption spectra show that 3.8 tyrosine residues ionize in the first step, 2.5 in the second, none in the third, and 0.8 in the fourth and following steps. The visible absorption spectrum of bound bilirubin changes in the second, third, and fourth steps. The bilirubin spectra of the different bilirubin-albumin complexes occurring in the transition show a common isosbestic point at 445 nm, indicating a change of the dihedral angle between the two bilirubin chromophores in a three-step reaction. It is suggested that 1 tyrosine residue is located close to the bilirubin site and is externalized in the second step. Bilirubin binding to albumin was monitored at two pH values, 11.3 and 11.8. At pH 11.3 the complex changes its structure in a three-step relaxation sequence. A change of the dihedral angle between the bilirubin chromophores can explain the spectral changes observed in the second and third relaxations. Protonation of 0.7 tyrosine residues occurs in the third relaxation, suggesting internalization of a tyrosine residue as a late consequence of bilirubin binding. At pH 11.8 a two-step relaxation sequence follows bilirubin binding. No tyrosine protonation occurs. Bilirubin is probably bound more superficially at pH 11.8 than at pH 11.3.


Anatomical risks of transobturator suburethral tape in the treatment of female stress urinary incontinence.
The objective of this study was to define the anatomical structures crossed by transobturator tape. Ten fresh, female anatomical subjects aged 74 to 89 years. Transobturator tape was inserted by outside-in way. The position of the tape was verified by perineal and abdominal dissection. Transobturator tape has a transverse course. It crosses the adductor muscles close to their pubic insertion and passes over the inferior border of the obturator foramen by crossing the obturator membrane, before reaching the middle plane of the perineum after having crossed the obturator internus muscle. The tape passes above the internal pudendal pedicle and then under the levator ani muscle, under the tendinous arch of the pelvic fascia and continues in the middle third of the urethrovaginal septum. It avoids femoral and obturator vessels in the thigh and pudendal vessels in the perineum. The anatomical course of transobturator tape shows that the anatomical structures crossed by the tape are muscle and fascia and, when the technique is performed correctly, no major neurovascular structures are in contact with the tape.