Associations between ASA classification, self-estimated physical health, psychological wellbeing and anxiety among Swedish orthopaedic patients.
The evaluation of one's physical health and psychological wellbeing may be subjective. Aspects of functional capacity, including the patients' own estimation of physical health and wellbeing, have been shown to be strong predictors of postoperative outcomes and should be the focus of further research. This study aimed to explore the associations between ASA classification, self-estimated physical health, psychological wellbeing and anxiety among orthopaedic patients. This was a longitudinal study using a quantitative approach. A central county hospital in northern Sweden. A high ASA classification rated by anaesthetists was not associated with physical health and psychological wellbeing self-estimated as less than good. A high ASA classification was significantly associated with self-estimated anxiety prior to surgery. Three days and one month post-surgery, the situation was reversed, and the ASA I/II group, to a significantly higher extent, rated that they felt anxiety. Preoperative screening systems for orthopaedic patients should not only focus on the medical and objective physical issues but also include the patients' own estimation of their physical health and psychological wellbeing. It is essential that orthopaedic patients receive relevant information that provides a realistic outlook, as well as an honest and optimistic future view.


IgG4-related cerebral pseudotumor with perineural spreading along branches of the trigeminal nerves causing compressive optic neuropathy: A case report.
Immunoglobulin G4-related disease (IgG4-RD) is characterized by tumor-like lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD has been described in a variety of organ systems; however, it rarely involves the central nervous system. A 17-year-old woman visited our clinic with a complaint of blurred vision for the past 5 months. She also reported a painless right submandibular mass that had been present for 1 year. Her best-corrected visual acuity (BCVA) was 2.0 LogMAR, with an almost total visual field defect in the right eye. Magnetic resonance imaging (MRI) revealed lobulated parasellar tumors with perineural spreading along branches of the trigeminal nerves causing right optic nerve compression. A craniotomy with tumor removal and submandibular gland biopsy was performed. Histopathological analysis of the tumor revealed stromal fibrosis with atypical lymphoid infiltrations. Histopathological and immunohistochemical analysis of the submandibular gland confirmed the diagnosis of IgG4-RD. The patient was administered 500mg/d of pulse methylprednisolone for 3 days, 500mg of intravenous rituximab every 2 weeks (for a total of 2 doses), and 500mg of intravenous pulse cyclophosphamide every month (for a total of 3 doses). Two months after the initiation of immunosuppressive therapy, the patient's BCVA returned to 0.1 LogMAR with visual field defect recovery. The follow-up MRI showed the almost complete disappearance of the previously contrast-enhanced lesions. Herein, we report a rare case of IgG4-RD presenting as a parasellar tumor and present a review of the related literature. Based on the case report, we propose that aggressive therapy with glucocorticoid, rituximab, and cyclophosphamide may potentially be useful for treating such cases.


Short association fibres of the insula-temporoparietal junction in early psychosis: a diffusion tensor imaging study.
Evidence shows that there are reductions in gray matter volume (GMV) and changes in long association white matter fibres within the left insula-temporoparietal junction (TPJ) during the early stages of psychotic disorders but less is known about short association fibres (sAFs). In this study we sought to characterise the changes in sAFs and associated volumetric changes of the left insula-TPJ during the early stages of psychosis. Magnetic resonance imaging was obtained from a sample of young people with psychosis (n = 42) and healthy controls (n = 45), and cortical parcellations of the left insula-TPJ were used as seeding masks to reconstruct 13 sAFs. Compared to healthy counterparts, the psychosis group showed significant reductions in fractional anisotropy (FA) in the sAFs connecting the superior (STG) and middle temporal gyri (MTG) and as well as reduced GMV within the inferior temporal gyrus and increased white matter volume (WMV) within Heschl's gyrus (HG). Furthermore, adolescent-onset psychosis subjects (onset 18 year or earlier) showed FA reductions in the STG-HG sAF when compared to adult-onset subjects, but this was not associated with changes in GMV nor WMV of the STG or HG. These findings suggest that during the early stages of psychosis, changes in sAFs and associated cortical GMV and WMV appear to occur independently, however age of onset of a psychotic syndrome/disorder influences the pattern of neuroanatomical abnormalities.


Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.
Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.


Xenotopic expression of alternative electron transport enzymes in animal mitochondria and their impact in health and disease.
The mitochondrial respiratory chain in vertebrates and arthropods is different from that of most other eukaryotes because they lack alternative enzymes that provide electron transfer pathways additional to the oxidative phosphorylation (OXPHOS) system. However, the use of diverse experimental models, such as human cells in culture, Drosophila melanogaster and the mouse, has demonstrated that the transgenic expression of these alternative enzymes can impact positively many phenotypes associated with human mitochondrial and other cellular dysfunction, including those typically presented in complex IV deficiencies, Parkinson's, and Alzheimer's. In addition, these enzymes have recently provided extremely valuable data on how, when, and where reactive oxygen species, considered by many as "by-products" of OXPHOS, can contribute to animal longevity. It has also been shown that the expression of the alternative enzymes is thermogenic in cultured cells, causes reproductive defects in flies, and enhances the deleterious phenotype of some mitochondrial disease models. Therefore, all the reported beneficial effects must be considered with caution, as these enzymes have been proposed to be deployed in putative gene therapies to treat human diseases. Here, we present a brief review of the scientific data accumulated over the past decade that show the benefits and the risks of introducing alternative branches of the electron transport into mammalian and insect mitochondria, and we provide a perspective on the future of this research field.


Use of enamel matrix protein derivative before dental reimplantation: a histometric analysis.
The use of enamel matrix protein in the treatment of periodontal defects has shown a favorable action on the proliferation of periodontal ligament cells, as well as on collagen formation and mineralization. The goal was to evaluate, histologically and histometrically, periodontal tissue regeneration after dental reimplantation using enamel matrix protein derivative (Emdogain, Biora AB, Malmö, Sweden). Male rats (Albinus, Wistar), weighing between 180 and 200 g, were divided in 3 groups. Animals in group I (control) had the upper right incisors extracted, the root canal was sealed with calcium hydroxide, and teeth were reimplanted in their alveoli. Group II underwent the same procedure, but the remaining periodontal ligament was removed from the root surfaces by root planing before reimplantation. In group III,following removal of the periodontal ligament, Emdogain was applied to the root surfaces. Animals were sacrificed 7, 20, and 60 days after reimplantation, and the alveoli were fixed, processed, and stained with hematoxylin and eosin. Formation of periodontal ligament, resorption areas, and ankylosis were analyzed. The results showed that group I (control) was better than groups II and III, with statistically significant differences on days 7 and 20 after reimplantation for formation of periodontal ligament. It may be concluded that with the methodology used, Emdogain was unable to stimulate tissue repair in reimplanted teeth.


Vision loss in giant cell arteritis.
Almost two-thirds of patients with giant cell arteritis (GCA) develop ocular symptoms and up to 30% suffer permanent visual loss. We review the three most common mechanisms for visual loss in GCA, describing the relevant ophthalmic arterial anatomy and emphasising how ophthalmoscopy holds the key to a rapid diagnosis. The short posterior ciliary arteries supply the optic nerve head, while the central retinal artery and its branches supply the inner retina. GCA has a predilection to affect branches of posterior ciliary arteries. The most common mechanism of visual loss in GCA is anterior arteritic optic neuropathy due to vasculitic involvement of short posterior ciliary arteries. The second most common cause of visual loss in GCA is central retinal artery occlusion. When a patient aged over 50 years has both anterior ischaemic optic neuropathy and a central retinal artery occlusion, the diagnosis is GCA until proven otherwise, and they should start treatment without delay. The least common culprit is posterior ischaemic optic neuropathy, resulting from vasculitic involvement of the ophthalmic artery and its pial branches. Here, the ophthalmoscopy is normal acutely, but MR imaging of the orbits usually shows restricted diffusion in the optic nerve.


Effects of limonoid cedrelone on MDA-MB-231 breast tumor cells in vitro.
Cancer is the second leading cause of death, preceded only by cardiovascular diseases, and there is epidemiological evidence that demonstrate this tendency is emerging worldwide. Brazil has an extensive vegetal biodiversity with more than 55,000 species listed. Such biodiversity collaborates with the finding of compounds which could be the basis for the design of new anti-tumor drugs, with fewer side effects than the conventional chemotherapy used currently. Cedrelone is a limonoid isolated from Trichilia catigua (Meliaceae) which is a native Brazilian plant. This study demonstrates that cedrelone inhibits proliferation, adhesion, migration and invasion of breast tumor cells from the line MDA-MB-231. The effects of cell migration and invasion on MDA-MB-231 cell may be explained, at least in part, by the ability of cedrelone to inhibit MMP activity. We also demonstrate that cedrelone is able to induce apoptosis in MDA-MB-231 cells. There are only a few works investigating the effect of limonoids in cellular processes closely related to tumor progression such as adhesion, migration and invasion. To the best of our knowledge, this is the first work describing the effects of a limonoid on tumor and non-tumor cell adhesion process.


[Alcoholic liver disease and liver transplantation].
Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.


Modelling of fermentative bioethanol production from indigenous Ulva prolifera biomass by Saccharomyces cerevisiae NFCCI1248 using an integrated ANN-GA approach.
Third generation biomass (marine macroalgae) has been projected as a promising alternative energy resource for bioethanol production due to its high carbon and no lignin composition. However, the major challenge in the technologies of production lies in the fermentative bioconversion process. Therefore, in the present study the predictive ability of an integrated artificial neural network with genetic algorithm (ANN-GA) in the modelling of bioethanol production was investigated for an indigenous marine macroalgal biomass (Ulva prolifera) by a novel yeast strain, Saccharomyces cerevisiae NFCCI1248 using six fermentative parameters, viz., substrate concentration, fermentation time, inoculum size, temperature, agitation speed and pH. The experimental model was developed using one-variable-at-a-time (OVAT) method to analyze the effects of the fermentative parameters on bioethanol production and the obtained regression equation was used as a fitness function for the ANN-GA modelling. The ANN-GA model predicted a maximum bioethanol production at 30 g/L substrate, 48 h fermentation time, 10% (v/v) inoculum, 30 °C temperature, 50 rpm agitation speed and pH 6. The maximum experimental bioethanol yield obtained after applying ANN-GA was 0.242 ± 0.002 g/g RS, which was in close proximity with the predicted value (0.239 g/g RS). Hence, the developed ANN-GA model can be applied as an efficient approach for predicting the fermentative bioethanol production from macroalgal biomass.


Capitellum fractures: Treatment with headless screws and outcomes.
This study aims to present the results of 21 patients with capitellum fractures treated with open reduction and headless screws by a single experienced surgeon. Twenty-one patients (13 males, 8 females; mean age 39 years; range, 18 to 63 years) who were admitted to our clinic between June 2011 and January 2018 with the diagnosis of capitellum fracture and followed-up for a mean period of 45 months (range, 12 to 90 months) were included in this retrospective study. The fractures were fixed with headless cannulated screws by a single surgeon. The mean range of motion was 102° (range, 65° to 140°) during flexion-extension and 165° (range, 130° to 180°) during supination-pronation. The mean preoperative visual analog scale (VAS) score was 8.5 (range, 6 to 10), whereas the mean postoperative VAS score was 2.2 (range, 0 to 6). According to the Mayo Elbow Performance score, nine patients were evaluated as excellent, six patients as good, four patients as fair, and two as poor. The mean Quick-Disabilities of the Arm, Shoulder and Hand score was 25.1 (range, 4 to 57). Avascular necrosis developed in three patients (14%) and heterotopic ossification was detected in one patient (4%). Capitellum fractures are difficult to diagnose and treat, and good results can only be achieved by an accurate diagnosis, careful surgical technique, and stable fixation. Larger and more comprehensive studies are required to establish a generalization and more accurate inferences on this limitedly studied subject.


Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years of age in eastern Turkey.
In this study, seroprevalence of mumps, varicella and rubella was investigated in 803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16 years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children were studied by enzyme-linked immunosorbent assay (ELISA) method. Information regarding socioeconomic characteristics, number of siblings and disease history was gathered for each participant. No significant difference in seropositivity was detected between girls and boys. Seroprevalence of mumps increased with age, with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in those aged 13-16 years. Seroprevalence of varicella increased with age, with a seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those aged 13-16 years. Seroprevalence of rubella also increased with age, with a seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those aged 13-16 years. There was a statistically significant increase in the rate of seropositivity with advancing age through the group of 13-16 years old (p < 0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and their possible complications, children should be vaccinated against these three diseases before the age of two, since seroprevalence increases with age.


Interferon-γ release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a literature review.
The role of interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51-93 percent for QFT-G/QFT-G-IT and 40-100 percent for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35 percent). Most of the studies on young (less than 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4 percent. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children less than 5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.


Heart failure, renal function, and angiotensin converting enzyme inhibitors.
In nonazotemic patients we suggest that ACE inhibitors initially depress GFR, perhaps due to a fall in renal blood flow in those patients in whom a substantial fall in blood pressure occurs with the first dose. Autoregulation of renal blood flow apparently remains intact, but autoregulation of the GFR is impaired during ACE inhibition. Our experience is that sodium and water retention usually ensue and plasma volume expands, leading to a temporary restoration of renal blood flow and GFR towards baseline. Serum sodium is usually reduced at this time, weight in increased, and blood pressure may be partly restored. After about 1-2 weeks, natriuresis begins, although sodium balance and weight probably are not restored to normal for 4-8 weeks. As the plasma volume contracts again, blood pressure falls further and the GFR declines. Renal blood flow, however, is maintained by preferential reduction in renovascular resistance.


An update on primary hyperoxaluria.
The autosomal recessive inherited primary hyperoxalurias types I, II and III are caused by defects in glyoxylate metabolism that lead to the endogenous overproduction of oxalate. Type III primary hyperoxaluria was first described in 2010 and further types are likely to exist. In all forms, urinary excretion of oxalate is strongly elevated (>1 mmol/1.73 m(2) body surface area per day; normal <0.5 mmol/1.73 m(2) body surface area per day), which results in recurrent urolithiasis and/or progressive nephrocalcinosis. All entities can induce kidney damage, which is followed by reduced oxalate elimination and consequent systemic deposition of calcium oxalate crystals. Systemic oxalosis should be prevented, but diagnosis is all too often missed or delayed until end-stage renal disease (ESRD) occurs; this outcome occurs in >30% of patients with primary hyperoxaluria type I. The fact that such a large proportion of patients have such poor outcomes is particularly unfortunate as ESRD can be delayed or even prevented by early intervention. Treatment options for primary hyperoxaluria include alkaline citrate, orthophosphate, or magnesium. In addition, pyridoxine treatment can be used to normalize or reduce oxalate excretion in about 30% of patients with primary hyperoxaluria type I. Time on dialysis should be short to avoid overt systemic oxalosis. Transplantation methods depend on the type of primary hyperoxaluria and on the particular patient, but combined liver and kidney transplantation is the method of choice in patients with primary hyperoxaluria type I and isolated kidney transplantation is the preferred method in those with primary hyperoxaluria type II. To the best of our knowledge, progression to ESRD has not yet been reported in any patient with primary hyperoxaluria type III.


Enhanced expression of insulin-like growth factor II is not a necessary event in Wilms' tumour progression.
Wilms' tumour (WT) is a paediatric kidney tumour arising from the embryonal metanephrogenic blastema. Recent reports suggest that the expression of messenger RNA (mRNA) for insulin-like growth factor II (IGFII) is elevated in WT. Total cytoplasmic RNA was extracted from 11 sporadic WTs and analysed for IGFII mRNA using dot-blot hybridization. The level of IGFII mRNA expression varied greatly and not all tumours displayed enhanced IGFII expression. Two successive WT xenografts were established in nude mice. The original WT and first passage xenograft showed a blastematous histology, while the second passage xenograft showed epithelioid differentiation and tubule formation. Analysis of the expression patterns of these xenografts showed elevated IGFII expression in the primary undifferentiated tumour and the second differentiated xenograft, while the first undifferentiated xenograft failed to exhibit enhanced IGFII expression. These data show that elevated IGFII mRNA is not an essential component of the progression of WT and that WT tumourigenicity is independent of the level of IGFII expression. Therefore, IGFII overexpression in WT is most likely a tumour epiphenomenon.


The effect of cross-channel synchrony on the perception of temporal regularity.
Temporal models of pitch are based on the assumption that the auditory system measures the time intervals between neural events, and that pitch corresponds to the most common time interval. The current experiments were designed to test whether time intervals are analyzed independently in each peripheral channel, or whether the time-interval analysis in one channel is affected by synchronous activity in other channels. Regular and irregular click trains were filtered into narrow frequency bands to produce target and flanker stimuli. The threshold for discriminating a regular target from an irregular distracter click train was measured in the presence of an irregular masker click train in the target band, as a function of the frequency separation between the target band and a flanker band. The flanker click train was either regular or irregular. The threshold for detecting the regular target was 5-7 dB lower when the flanker was regular. The data indicate that the detection of temporal regularity (and thus, pitch) involves cross-channel processes that can operate over widely separated channels. Model simulations suggest that these cross-channel processes occur after the time-interval extraction stage and that they depend on the similarity, or consistency, of the time-interval patterns in the relevant channels.


Morphology-based prediction of osteogenic differentiation potential of human mesenchymal stem cells.
Human bone marrow mesenchymal stem cells (hBMSCs) are widely used cell source for clinical bone regeneration. Achieving the greatest therapeutic effect is dependent on the osteogenic differentiation potential of the stem cells to be implanted. However, there are still no practical methods to characterize such potential non-invasively or previously. Monitoring cellular morphology is a practical and non-invasive approach for evaluating osteogenic potential. Unfortunately, such image-based approaches had been historically qualitative and requiring experienced interpretation. By combining the non-invasive attributes of microscopy with the latest technology allowing higher throughput and quantitative imaging metrics, we studied the applicability of morphometric features to quantitatively predict cellular osteogenic potential. We applied computational machine learning, combining cell morphology features with their corresponding biochemical osteogenic assay results, to develop prediction model of osteogenic differentiation. Using a dataset of 9,990 images automatically acquired by BioStation CT during osteogenic differentiation culture of hBMSCs, 666 morphometric features were extracted as parameters. Two commonly used osteogenic markers, alkaline phosphatase (ALP) activity and calcium deposition were measured experimentally, and used as the true biological differentiation status to validate the prediction accuracy. Using time-course morphological features throughout differentiation culture, the prediction results highly correlated with the experimentally defined differentiation marker values (R>0.89 for both marker predictions). The clinical applicability of our morphology-based prediction was further examined with two scenarios: one using only historical cell images and the other using both historical images together with the patient's own cell images to predict a new patient's cellular potential. The prediction accuracy was found to be greatly enhanced by incorporation of patients' own cell features in the modeling, indicating the practical strategy for clinical usage. Consequently, our results provide strong evidence for the feasibility of using a quantitative time series of phase-contrast cellular morphology for non-invasive cell quality prediction in regenerative medicine.


Interaction of C-9 aldehydes with microtubular protein in vitro and in cultured cells in the presence of taxol.
Some aldehydes have previously been shown to alter the microtubular system in a concentration-dependent manner. This paper examines the effects of taxol on the impairment of in vitro functionality of microtubular protein and of cytoplasmic microtubules by C-9 aliphatic aldehydes. Taxol-induced polymerization was inhibited by aldehydes in a similar way to GTP-induced polymerization, even though to a different degree. The addition of taxol restored the ability of aldehyde-impaired tubulin to polymerize, but only in the presence of nonanal. Colchicine binding activity in the presence of taxol was slightly modified by aldehydes at 20 degrees C, while it increased at 37 degrees C, compared to controls. Immunofluorescence showed a low disruption of microtubules in fibroblasts incubated with aldehydes and pretreated with taxol, probably as a consequence of its stabilizing activity. Anyway, aldehydes studied behaved differently, indicating a structure-activity relationship.


Early home-supported discharge of stroke patients: a health technology assessment.
A comprehensive and systematic assessment (HTA) of early home-supported discharge by a multidisciplinary team that plans, coordinates, and delivers care at home (EHSD) was undertaken and the results were compared with that of conventional rehabilitation at stroke units. A systematic literature search for randomized trials (RCTs) on "early supported discharge" was closed in April 2005. RCTs on EHSD without information on (i) death or institution at follow-up, (ii) change in Barthél Index, (iii) length of hospital stay, (iv) intensity of home rehabilitation, or (v) baseline data are excluded. Seven RCTs on EHSD with 1,108 patients followed 3-12 months after discharge are selected for statistical meta-analysis of outcomes. The costs are calculated as a function of the average number of home training sessions. Economic evaluation is organized as a test of dominance (both better outcomes and lower costs). The odds ratio (OR) for "Death or institution" is reduced significantly by EHSD: OR = .75 (confidence interval [CI], .46-.95), and number needed to treat (NNT) = 14. Referrals to institution have OR = .45 (CI, .31-.96) and NNT = 20. The reduction of the rate of death is not significant. Length of stay is significantly reduced by 10 days (CI, 2.6-18 days). All outcomes have a nonsignificant positive covariance. The median number of home sessions is eleven, and the average cost per EHSD is 1,340 USD. The "action mechanism" and financial barriers to EHSD are discussed. EHSD is evidenced as a dominant health intervention. However, financial barriers between municipalities and health authorities have to be overcome. For qualitative reasons, a learning path of implementation is recommended where one stroke unit in a region initiates EHSD for dissemination of new experience to the other stroke units.


Tuberculosis complications after BCG treatment for urinary bladder cancer.
Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis that has been effectively used in the treatment of non-muscle invasive bladder carcinoma. The complications of this treatment are uncommon, and the causes of dissemination are still discussed. We report a case of disseminated tuberculosis in a 66-year-old smoking man without a history of pulmonary diseases, who underwent immunotherapy with BCG after the initial surgical treatment of bladder cancer. After the last BCG instillation, he developed a fever. The diagnosis of sepsis was not confirmed, and miliary pulmonary tuberculosis was suspected. The diagnosis was confirmed by clinical manifestation, computed tomography of the lungs, and histological examination.


Regulation of sympathetic nerve activity by L-carnosine in mammalian white adipose tissue.
Previously, we showed that l-carnosine, a bioactive dipeptide, influences the sympathetic nerve activity innervating kidney and brown adipose tissue. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of L-carnosine on the sympathetic nerve activity innervating white adipose tissue (SNA-WAT) and lipolysis. We found that intraperitoneal (ip) administration of L-carnosine at doses of 100 ng/rat and 10 microg/rat elevated and suppressed SNA-WAT, respectively. The effect of lower dose of L-carnosine (100 ng/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of higher dose of L-carnosine (10 microg/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, ip administration of 100 ng and 10 microg of L-carnosine increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The changes of plasma FFAs resulting from the exposure to 100 ng and 10 microg of L-carnosine were diminished by the beta-adrenergic receptor blocker propranolol hydrochloride and the muscarinic receptor blocker atropine sulfate, respectively; and eliminated by the corresponding histamine receptor antagonists, which eliminated the changes in SNA-WAT. Our results suggest that low doses of L-carnosine may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. High doses of L-carnosine, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3) receptor, and the muscarinic receptor may be related to this response.


Are protein folds atypical?
Protein structures are a very special class among all possible structures. It has been suggested that a "designability principle" plays a crucial role in nature's selection of protein sequences and structures. Here, we provide a theoretical base for such a selection principle, using a simple model of protein folding based on hydrophobic interactions. A structure is reduced to a string of 0s and 1s, which represent the surface and core sites, respectively, as the backbone is traced. Each structure is therefore associated with one point in a high dimensional space. Sequences are represented by strings of their hydrophobicities and thus can be mapped into the same space. A sequence that lies closer to a particular structure in this space than to any other structures will have that structure as its ground state. Atypical structures, namely those far away from other structures in the high dimensional space, have more sequences that fold into them and are thermodynamically more stable. We argue that the most common folds of proteins are the most atypical in the space of possible structures.


[Effects of different pH conditions on ffh gene expression in Streptococcus mutans].
This research aimed to detect the expression levels of ffh gene in Streptococcus mutans (S. mutans) UA159 under different pH conditions, analyze the effect of pH on the expression of ffh gene in S. mutans, and identify the factors regulating the ffh gene expression. Samples of S. mutans were collected at different growth stages (4 h, 18 h) and pH values (pH 4.0-7.0). Fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the relative mRNA expression and trend of the target gene ffh in S. mutans at different growth stages and pH values. qRT-PCR results showed that the ffh gene expression decreased along with pH at 4 h, but the expression increased with decreasing pH at 18 h. Under the same pH conditions, the ffh gene expression was significantly different between 4 h and 18 h (P < 0.05). Growth stage and pH value influenced the ffh gene expression in S. mutans.


Effect of a Drinking Water Conditioner on Stability and Efficacy of Fluralaner in Laying Hens Infested with Poultry Red Mites.
Concurrent use of a colorant during drinking water treatment could contribute to the correct application of fluralaner to poultry. The present studies therefore examined whether the blue-colored drinking water conditioner Vac-Safe has an influence on the stability of fluralaner in water and/or on its efficacy for the control of poultry red mites (PRM). Laboratory trials showed that fluralaner dissolved at various concentrations in water conditioned with Vac-Safe retained full stability for at least 27 hr at temperatures up to 40 C. Further, a field trial demonstrated that the efficacy of fluralaner in eliminating PRM from two infested houses of laying hens was equal when administered through drinking water with or without Vac-Safe. Consistently in both flocks, after treatment PRM could not be detected and sharp increases in laying percentage and produced egg mass were observed. It was concluded that Vac-Safe does not reduce the stability and treatment efficacy of fluralaner when administered simultaneously through drinking water.


Abnormal Haemoglobin in a Psqriatic Family.
A Sindhi family with psoriasis and abnormal haemoglobin Hb D in some of the members of the family isreported. The significance of this finding as an added genetic marker of psoriasis is discussed.


Interplay between shear flow and elastic deformations in liquid crystals.
We study shear flow in liquid crystal cells with elastic deformations using a lattice Boltzmann scheme that solves the full, three-dimensional Beris-Edwards equations of hydrodynamics. We consider first twisted and hybrid aligned nematic cells, in which the deformation is imposed by conflicting anchoring at the boundaries. We find that backflow renders the velocity profile non Newtonian, and that the director profile divides into two regions characterized by different director orientations. We next consider a cholesteric liquid crystal, in which a twist deformation is naturally present. We confirm the presence of secondary flow for small shear rates, and are able to follow the dynamical pathway of shear-induced unwinding, for higher shear rates. Finally, we analyze how the coupling between shear and elastic deformation can affect shear banding in an initially isotropic phase. We find that for a nematic liquid crystal, elastic distortions may cause an asymmetry in the dynamics of band formation, whereas for a cholesteric, shear can induce twist in an initially isotropic sample.


External assistance to the health sector in developing countries: a detailed analysis, 1972-90.
This study, which was conducted for the World Bank's World development report 1993: investing in health, provides an objective analysis of the external assistance to the health sector by quantifying in detail the sources and recipients of such assistance in 1990, by analysing time trends for external assistance to the health sector over the last two decades, and, to the extent possible, by describing the allocation of resources to specific activities in the health sector. The main findings of the study are that total external assistance to the health sector in 1990 was US$ 4800 million, or only 2.9% of total health expenditures in developing countries. After stagnation in real terms during the first half of the 1980s, health sector assistance has been increasing since 1986. Despite their small volume, external assistance at the margins may play a critical role in capital investment, research and strategic planning. The study confirms prior findings that health status variables per se are not related to the amount of aid received. Comparing investments to the burden of disease shows tremendous differences in the funding for different health problems. A number of conditions are comparatively under-financed, particularly noncommunicable diseases and injuries.


A comparison of passive hindlimb cycling and active upper-limb exercise provides new insights into systolic dysfunction after spinal cord injury.
Active upper-limb and passive lower-limb exercise are two interventions used in the spinal cord injury (SCI) population. Although the global cardiac responses have been previously studied, it is unclear how either exercise influences contractile cardiac function. Here, the cardiac contractile and volumetric responses to upper-limb (swim) and passive lower-limb exercise were investigated in rodents with a severe high-thoracic SCI. Animals were divided into control (CON), SCI no exercise (NO-EX), SCI passive hindlimb cycling (PHLC), or SCI swim (SWIM) groups. Severe contusion SCI was administered at the T2 level. PHLC and SWIM interventions began on day 8 postinjury and lasted 25 days. Echocardiography and dobutamine stress echocardiography were performed before and after injury. Cardiac contractile indexes were assessed in vivo at study termination via a left ventricular pressure-volume conductance catheter. Stroke volume was reduced after SCI (91 µl in the NO-EX group vs. 188 µl in the CON group, P < 0.05) and was reversed at study termination in the PHLC (167 µl) but not SWIM (90 µl) group. Rates of contraction were reduced in NO-EX versus CON groups (6,079 vs. 9,225 mmHg, respectively, P < 0.05) and were unchanged by PHLC and SWIM training. Similarly, end-systolic elastance was reduced in the NO-EX versus CON groups (0.67 vs. 1.37 mmHg/µl, respectively, P < 0.05) and was unchanged by PHLC or SWIM training. Dobutamine infusion normalized all pressure indexes in each SCI group (all P < 0.05). In conclusion, PHLC improves flow-derived cardiac indexes, whereas SWIM training displayed no cardiobeneficial effect. Pressure-derived deficits were corrected only with dobutamine, suggesting that reduced β-adrenergic stimulation is principally responsible for the impaired cardiac contractile function after SCI.NEW & NOTEWORTHY This is the first direct comparison between the cardiac changes elicited by active upper-limb or passive lower-limb exercise after spinal cord injury. Here, we demonstrate that lower-limb exercise positively influences flow-derived cardiac indexes, whereas upper-limb exercise does not. Furthermore, neither intervention corrects the cardiac contractile dysfunction associated with spinal cord injury.


Ice-Templated Assembly Strategy to Construct 3D Boron Nitride Nanosheet Networks in Polymer Composites for Thermal Conductivity Improvement.
Owing to the growing heat removal issue of modern electronic devices, polymer composites with high thermal conductivity have drawn much attention in the past few years. However, a traditional method to enhance the thermal conductivity of the polymers by addition of inorganic fillers usually creates composite with not only limited thermal conductivity but also other detrimental effects due to large amount of fillers required. Here, novel polymer composites are reported by first constructing 3D boron nitride nanosheets (3D-BNNS) network using ice-templated approach and then infiltrating them with epoxy matrix. The obtained polymer composites exhibit a high thermal conductivity (2.85 W m(-1) K(-1)), a low thermal expansion coefficient (24-32 ppm K(-1)), and an increased glass transition temperature (T(g)) at relatively low BNNSs loading (9.29 vol%). These results demonstrate that this approach opens a new avenue for design and preparation of polymer composites with high thermal conductivity. The polymer composites are potentially useful in advanced electronic packaging techniques, namely, thermal interface materials, underfill materials, molding compounds, and organic substrates.


Deficient fear recognition in regular cocaine users is not attributable to elevated impulsivity or conduct disorder prior to cocaine use.
We previously reported that regular recreational intranasal cocaine users exhibit impaired recognition of facial expressions of fear compared to occasional cocaine users and cocaine-naïve controls. The aim of the present study was to re-investigate this phenomenon after controlling for impulsivity, conduct disorder (CD) and anti-social personality disorder (ASPD). We employed a cross-sectional design to compare 31 cocaine-naïve participants, 35 occasional cocaine users and 20 regular recreational cocaine users. An emotional facial expression (EFE) task which comprised a male and a female face expressing six basic emotions morphed to differing degrees of emotional intensity was administered together with questionnaires to assess: CD, ASPD and impulsiveness. ASPD was not a significant covariate for EFE performance but impulsiveness and CD were significant covariates. After treating impulsiveness and CD as covariates we again observed a group difference in fear recognition ability attributable to the particularly impaired performance of regular cocaine users. This suggests that, although elevated impulsiveness and CD before the age of 15 years, may predispose a relative inability to recognize facial expressions of fear in adulthood, subsequent regular recreational use of cocaine represents an additional factor that is specifically associated with a selective deficit in fear recognition.


Social work and general practice: a review article.
Closer collaboration with social workers may be a means of enabling the general practitioner to deal with the psychosocial problems expressed in his practice. Emerging interest on the part of general practitioners in exploring the potential contribution of the social worker to patient care is accompanied by some anxiety and ambivalence. Reports of collaborative projects have come mainly from the United Kingdom, and although these offer some guidelines, it is imperative that any policy proposals for the development of closer general practitioner-social worker collaboration in Australia be grounded in an Australian data base.


[Methods for controlling and evaluating residual confounding in the association analysis of observational study with a multicenter database].
The observational research based on big data in healthcare has attracted increasing attention, with the control and evaluation of residual confounding being the critical issue that needs to be solved urgently. This review summarized the methods for statistical adjustment and sensitivity analysis of residual confounding in the association analysis with a multicenter database. Based on individual-level data, the residual confounding can be adjusted in each subcenter using methods such as regression discontinuity design, while the pooled estimate can be obtained as a weighted average. Based on the center-level results, the Bayesian Meta-analysis method can adjust the pooled estimates. The sensitivity analysis of residual confounding can also be carried out using center-level data to calculate the E-value, p^(q), T^(r, q) and G^r,q. The abovementioned methods should be selected reasonably according to the requirements for practical applications, advantages, and disadvantages. For example, the use of subcenter individual data for residual confounding adjustment usually needs strict study design and frequent coordination; the Bayesian Meta-analysis is based on some strong assumptions; the interpretation of the results in the sensitivity analysis, such as E-value requires professional judgment to assess the risk of residual confounding. Therefore, the methods for controlling and evaluating residual confounding in association analysis based on multicenter databases still need further development and improvement.


C-C and C-H bond activation reactions in N-heterocyclic carbene complexes of ruthenium.
Thermolysis of Ru(PPh3)3(CO)H2 with the N-heterocyclic carbene bis(1,3-(2,4,6-trimethylphenyl)imidazol-2-ylidene) (IMes) results in C-C activation of an Ar-CH3 bond in one of the mesityl rings of the carbene ligand. Upon addition of IMes to Ru(PPh3)3(CO)H2 at room temperature in the presence of an alkene, C-H bond activation is observed instead. The thermodynamics of these C-C and C-H cleavage reactions have been probed using density functional theory.


Cardiac output determinations with ear piece densitometry.
The results of cardiac output determinations by a dye dilution technique were compared using (a) a dichromatic earpiece which was calibrated as a flow-through cuvette, but also permitted automatic computing by virtue of a pressure capsule, and (b) an ordinary flow-through densitometer. Eleven subjects, some with cardio-pulmonary disease, were investigated. Cardiac outputs were systematically overestimated when automatically computed. The results obtained by manual calculation with the ear-piece corresponded more nearly with those derived from the flow-through cuvette, but still with a deviation from the identity line and with a residual standard deviation of 0.8 l/min. Double determinations had a residual standard deviation of 0.7 l/min. Despite its ease of handling, an earpiece densitometer seems to be too unreliable to be suitable for routine use.


p114RhoGEF governs cell motility and lumen formation during tubulogenesis through a ROCK-myosin-II pathway.
Tubulogenesis is fundamental to the development of many epithelial organs. Although lumen formation in cysts has received considerable attention, less is known about lumenogenesis in tubes. Here, we utilized tubulogenesis induced by hepatocyte growth factor (HGF) in MDCK cells, which form tubes enclosing a single lumen. We report the mechanism that controls tubular lumenogenesis and limits each tube to a single lumen. Knockdown of p114RhoGEF (also known as ARHGEF18), a guanine nucleotide exchange factor for RhoA, did not perturb the early stages of tubulogenesis induced by HGF. However, this knockdown impaired later stages of tubulogenesis, resulting in multiple lumens in a tube. Inhibition of Rho kinase (ROCK) or myosin IIA, which are downstream of RhoA, led to formation of multiple lumens. We studied lumen formation by live-cell imaging, which revealed that inhibition of this pathway blocked cell movement, suggesting that cell movement is necessary for consolidating multiple lumens into a single lumen. Lumen formation in tubules is mechanistically quite different from lumenogenesis in cysts. Thus, we demonstrate a new pathway that regulates directed cell migration and formation of a single lumen during epithelial tube morphogenesis.


Site-specific chlorhexidine: a periodontal alternative.
Three case reports demonstrate the clinical use of an adjunctive chlorhexidine chip capable of sustaining local antimicrobial activity for 7-10 days. The chip is easy to place, requires no additional chair time for removal, is self-adherent, and can be provided to periodontal maintenance patients on a recurring basis. This is another adjunct that can be part of the clinician's armamentarium when presented with a clinically challenging localized periodontal defect.


Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.
Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient <620×10−6 mm2/s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume <70 mL, mismatch volume ≥15 mL, and a mismatch ratio ≥1.8. Twenty-nine children (median 8 years old, interquartile range, 4.4–14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3–11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5–25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small (<3.5 mL). Overall, 3 children, imaged at 3.75, 11, and 23.5 hours had favorable mismatch profiles. This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics.


Spermatogenesis does not require the local production of follistatin.
It has been proposed that follistatin can modulate the actions of activins and/or other members of the transforming growth factor-beta superfamily of proteins on testicular function, since mice overexpressing follistatin showed spermatogenic disruption. However, since mice with targeted disruption of the follistatin gene die soon after birth, it is not feasible to determine the effect of the absence of follistatin on testicular function using this model. To further understand the role of follistatin on the development and maintenance of spermatogenesis, fetal testes, collected by Caesarean section at day 18 of gestation from follistatin null mice, were transplanted to the external ear of castrated recombination activating gene 1 immunocompromised male mice. The testicular grafts were then analysed 7-8 weeks after transplantation and showed that full spermatogenesis developed in both the testes of wild-type and follistatin null mice. This study indicates that, if follistatin is required to modulate spermatogenic development, it is not supplied by local testicular production but by circulating follistatin from the host mouse.


Including people with intellectual and other cognitive disabilities in research and evaluation teams: A scoping review of the empirical knowledge base.
We conducted a rapid scoping review of empirical studies to identify how persons with intellectual and other cognitive disabilities have been engaged as active members of research and evaluation teams. We conducted a literature search using a systematic method that accessed peer reviewed studies in relevant library databases and all major evaluation journals. The search resulted in 6,624 potential articles, of which 32 met the inclusion criteria for this study. The findings address three categories of interest: 1) methodological underpinnings and practical justifications for using inclusive approaches, 2) different inclusion processes, and 3) reflections by researchers with and without intellectual and other cognitive disabilities. Findings provide conceptual and practical insights for researchers and evaluators when designing inclusive methods involving persons with intellectual and other cognitive disabilities. Gaps in inclusive research and evaluation are discussed and suggestions for future research are proposed.


Cardiac nuclear medicine.
In this paper, the principal applications of nuclear medicine to studies of the heart are described. First, gated cardiac blood pool imaging is discussed, then thallium-201 myocardial imaging, myocardial infarct scintigraphy with 99mTc pyrophosphate, and evaluation of intracardiac shunts. In gated cardiac blood pool imaging, the patient's red blood cells are labeled with 99mTc. Images of the cardiac blood pool are then obtained in multiple projections and displayed in an endless-loop cine display. Quantitative indices of cardiac function are readily obtained, and a variety of functional images can be generated. Blood pool imaging may also be performed with use of a first-pass technique that yields similar information. Applications of blood pool imaging are discussed. The theory and techniques of planar and tomographic thallium-201 myocardial imaging are described, together with their application in the diagnosis of coronary artery disease. The prognostic value of thallium imaging is also examined. Myocardial infarct imaging with 99mTc pyrophosphate is described, and clinical indications are reviewed. Left-to-right cardiac shunts can be evaluated by following the first transit of a bolus of radiopharmaceutical through the lungs. Right-to-left shunts may be evaluated by injection of 99mTc macroaggregated albumin.


Axillary reverse mapping in N0 patients requiring sentinel lymph node biopsy - A systematic review of the literature and necessity of a randomised study.
Axillary reverse mapping (ARM) is a technique to map and preserve arm lymphatics which may be damaged during surgery, resulting in lymphoedema. This work systematically reviews the incidence of lymphoedema following sentinel lymph node biopsy (SLNB) + ARM, compared to SLNB alone, for clinically node negative disease, as well as recurrence rate, other morbidity and the feasibility and difficulties of ARM. The following databases were searched: PubMed, Embase, Cochrane Library. Abstracts submitted to recognised societies dedicated to research in oncology were included. Studies were eligible if performed within the last 10 years; ARM was used in any form; ARM performed during SLNB ± axillary lymph node dissection (ALND). Studies were analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. No studies were found meeting the initial inclusion criteria. Therefore, studies reporting use of SLNB + ARM (i.e. no comparison to SLNB) were reviewed. A second search was performed to identify studies reporting outcome following SLNB alone. Twelve studies reported data on patients undergoing SLNB + ARM and 23 studies on patients undergoing SLNB. Incidence of lymphoedema following SLNB + ARM was quoted between 0-4% and 0-63.4% following SLNB. Few studies commented on recurrence rate. Studies included were of mainly low level of evidence. Evidence is beginning to emerge for the use of ARM in order to reduce lymphoedema following axillary surgery. However, data regarding oncological safety of ARM is not clear and randomised controlled trials, with adequate follow-up, need to be performed to determine this.


Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying.
Self-microemulsifying drug delivery systems (SMEDDS) are useful to improve the bioavailability of poorly water-soluble drugs by increasing their apparent solubility through solubilization. However, very few studies, to date, have systematically examined the level of drug apparent solubility in o/w microemulsion formed by self-microemulsifying. In this study, a mixture experimental design was used to simulate the influence of the compositions on simvastatin apparent solubility quantitatively through an empirical model. The reduced cubic polynomial equation successfully modeled the evolution of simvastatin apparent solubility. The results were presented using an analysis of response surface showing a scale of possible simvastatin apparent solubility between 0.0024 ~ 29.0 mg/mL. Moreover, this technique showed that simvastatin apparent solubility was mainly influenced by microemulsion concentration and, suggested that the drug would precipitate in the gastrointestinal tract due to dilution by gastrointestinal fluids. Furthermore, the model would help us design the formulation to maximize the drug apparent solubility and avoid precipitation of the drug.


Announcement: National Kidney Month - March 2017.
Each year, March is designated National Kidney Month to raise awareness about the prevention and early detection of kidney disease. In the United States, kidney disease is the ninth leading cause of death (1). Approximately one in seven (15%) U.S. adults aged ≥20 years are estimated to have chronic kidney disease, most of whom are unaware of their condition (2). If left untreated, chronic kidney disease can lead to kidney failure, requiring dialysis or transplantation for survival (3).


Clinic efficacy and safety of ultrasound-guided Mammotome-assisted surgery for patients with breast benign tumors.
The aim of this study was to assess the efficacy of ultrasound-guided Mammotome-assisted resection vs. conventional open surgery for benign breast tumors. From July 2019 to December 2020, 134 suitable patients with benign breast cancers treated at our institution (Breast Surgery Department) were recruited and randomly allocated (1:1) to receive either Mammotome-assisted tumor excision (observation group) or open surgery (control group). The primary endpoint was clinical effectiveness, with surgical outcomes, complications, and satisfaction as secondary endpoints. Mammotome-assisted surgery resulted in shorter operative time, scar length, and postoperative healing time and less intraoperative bleeding volume vs. open surgery (p<0.001). Mammotome-assisted surgery was associated with a significantly higher clinical efficacy vs. open surgery (p<0.05). Patients receiving Mammotome-assisted surgery had a lower incidence of complications vs. those given open surgery (p<0.05). A significantly higher satisfaction was observed in patients given Mammotome-assisted surgery vs. open surgery (p<0.05). In comparison to standard open surgery, ultrasound-guided Mammotome-assisted surgery provides a viable alternative for breast benign tumor removal with superior efficacy, shorter operating time, less trauma, higher safety, fewer complications, and higher patient satisfaction.


Racial differences in mortality among men hospitalized in military hospitals.
A comparative study was conducted on patients in military hospitals in response to recent studies at veterans hospitals showing the possibility that access to an equal-access health care system may reduce or reverse racial differences in mortality outcomes. Using a cohort study of 14,122 military retirees admitted to military hospitals with any of six common medical diagnoses between October 2000 and September 2004, we evaluated differences in patient and hospital characteristics and evaluated race-specific hospital mortality. Despite long-term equal access to comprehensive medical care, there were significant racial differences in patient- and hospital-level risk factors among male military retirees hospitalized with common medical diagnoses. In unadjusted analyses, risk of hospital mortality was significantly lower in African Americans and other non-Caucasians when compared to Caucasians, but differences disappeared after adjustment for all risk factors.


Early experience with retrievable inferior vena cava filters in high-risk trauma patients.
This study describes the use of retrievable IVC filters in a select group of trauma patients at high risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). Retrievable IVC filters were placed in selected trauma patients who met high-risk criteria for deep vein thrombosis and PE according to institutional clinical management guidelines. All filters were placed percutaneously in the interventional radiology suite. Indications for filter placement were based on injury complex, weight-bearing status, and contraindications to enoxaparin or pneumatic compression devices. IVC filters were either removed or maintained. Retrievable IVC filters were placed in 35 patients after blunt trauma. Twenty-six patients (74%) sustained at least one orthopaedic injury; 17 patients (49%) were diagnosed with a pelvis fracture. Activity was limited to bed rest or spinal precautions in 18 patients (51%). Enoxaparin was contraindicated in 32 patients (91%) and injuries precluded the use of pneumatic compression devices in 11 (31%). IVC filters were removed in 18 patients (51%), with no reported complications. Patients with orthopaedic injuries and pelvis fractures were less likely to have their filters maintained (p = 0.040). Retrievable IVC filters offer a versatile option for prophylaxis in trauma patients at high risk for PE. Filter retrieval potentially spares the longterm complications of permanent filters in younger trauma patients. Retrievable filters warrant consideration in patients who meet high-risk criteria for deep vein thrombosis or PE who cannot receive effective mechanical prophylaxis and in whom contraindications to anticoagulation are expected to be temporary.


Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.
After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.


Treatment of skin defects with growth factors and biodegradable collagen carrier: histological evaluation in animal model.
The aim of the present study is to evaluate the effects on skin regeneration of a new collagen matrix (CM-10826) when used in different combination with or without growth factors, using skin regeneration without membrane as control. An area of 10x15 cm on rabbit back was shaved and three circular wounds on test side were covered with a differently soaked membrane. The first wound was soaked with Epidermal Growth Factor (EGF, 26mg/130mL) (Test EGF), the second with Platelet-Derived Growth Factor (PDGF, 6mg/120mL) (Test PDGF) and the third with EGF (13mg/65mL) and PDGF (3mg/60mL) (Test EGF+PDGF). On the control side, there was a dry membrane. After 7 days, the experiment was concluded. Healing process was evaluated at day 2 and 6 postoperatively. Analysis was made clinically and with light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Analyses with LM of Test EGF showed evidence of neoangiogenesis and good epithelium growth. Test PDGF resulted in moderate angiogenesis, less evident epithelial growth and more evident mesenchymal growth than Test EGF. Test EGF+PDGF showed rich angiogenesis, massive growth of epithelium and mesenchymal tissue. Control side showed weak angiogenesis, regenerating wound margin with normal epithelium and less dense mesenchymal layer. Analysis at TEM and SEM confirmed what was noticed at LM. In vivo studies on rabbits have shown that membrane CM10826 is well tolerated, it gives neither inflammation nor foreign body reactions and does not disturb healing process. CM10826 is safe, modulates angiogenesis and induces migration and proliferation of keratinocytes.


Late redo-port access surgery after port access surgery.
This study presents the first report on short- and long-term outcomes in redo-port access surgery after previous port access surgery (redo-PAS-PAS) for new or recurrent mitral valve (MV) and tricuspid valve (TV) disease. Our current surgical team performed redo-PAS-PAS in 26 consecutive patients who had previous port access surgery (mean age 65.8 ± 13.3 years, 46.2% female, 42.3% older than 70 years, mean logistical EuroSCORE 22.5 ± 21.6%) between 1 February 1997 and 30 June 2014. Surgical indications included among others MV prosthesis dysfunction (n = 8, 30.8%), endocarditis (n = 10, 38.5%) and TV dysfunction (n = 3, 11.5%). The mean time interval between primary PAS and redo-PAS-PAS was 70.32 ± 57.4 months. Redo-PAS-PAS procedures included MV replacement (n = 19, 73.1%), MV repair (n = 5, 19.2%), and TV repair (n = 2, 7.7%). Sternotomy conversion was required in 5 patients (19.2%), of which 4 (15.4%) were early conversions due to lung adhesion and 1 (3.8%) due to a late intraoperative complication. The mean cardiopulmonary bypass and cross-clamp times were 163.3 ± 57.9 and 101.2 ± 43.8 min, respectively. Postoperative mechanical ventilation longer than 72 h was required in 4 patients (15.4%). In-hospital morbidities included hospital-acquired pneumonia (n = 3, 11.5%), postoperative air leaks (n = 2, 7.7%) and revision for bleeding (n = 1, 3.8%). The mean length of hospital stay was 16.1 days. Long-term clinical and echocardiographic follow-up were 48.3 ± 39.2 and 44.6 ± 32.9 months, respectively. The Kaplan-Meier analyses for survival and freedom from mitral and tricuspid valve reintervention (n = 26) at 5 years were 83.9 and 95.8%, respectively, with 91.3% of surviving patients classified as being NYHA II or less. Echocardiographic follow-up showed no residual mitral regurgitation more than grade I in all redo mitral valve repairs and no paravalvular leak post-valve replacement. Redo-PAS-PAS is our routine approach and we apply this strategy in the majority of patients who had previous port access surgery. The predicted procedure-related mortality, morbidities, patient satisfaction and long-term outcomes are favourable.


[Evaluation of a DEET-based repellent on 3 vectors of malaria in central Africa].
As part of the framework of studies on personal protection against disease-transmitting mosquitoes, a field evaluation was carried out in a forest area of Cameroon on human subjects to assess the efficacy of a common repellent: DEET (a 50% active ingredient formulation). One ml of DEET applied to the legs of resting persons gave an 85% reduction in Anopheles bites during the 5 hours following application. The repellent effect decreased gradually with time. The effect was more than 90% maximum after 3 hours, 50% by about the seventh hour and declined to 0% from the fifteenth hour onwards. No difference was found between the three Anopheles species: Anopheles gambiae ss, An. nili and An. funestus. The longevity and infectivity of Anopheles populations caught on humans with repellent and on untreated controls were similar. Thus the reduction of biting rate can be considered equivalent to the reduction in malaria transmission. The effect of sweating on the loss of the applied repellent was studied. Moderate sweating, corresponding to normal activity, did not reduce the efficacy of the repellent. More profuse sweating did not significantly reduce repellent efficacy. We conclude that the tested formulation of DEET has the same efficacy as commercial formulations already on the market. Protection did not last the whole night, which is the time required for protection against malarial infection. However, good protection levels lasted more than 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical Effect of Intrauterine 3-Dimensional Ultrasound on the Function of the Intrauterine Cavity of Puerpera With Intrauterine Adhesions and Safety of Pregnancy.
This study aimed to analyze the diagnostic value of intrauterine 3-dimensional ultrasound and the functional characteristics of the intrauterine cavity for puerpera with intrauterine adhesions, and to explore the safety of pregnancy after treatment. A total of 102 puerperas with intrauterine adhesions were randomly selected, and intrauterine 3-dimensional ultrasound and 2-dimensional ultrasound were performed, respectively. Patients were followed up for 3 years to observe the pregnancy outcome and safety. The overall accuracy of diagnosing intrauterine adhesions through intrauterine 3-dimensional ultrasound was significantly higher than that through 2-dimensional ultrasound, and the accuracy of detecting mild intrauterine adhesions was significantly higher than that through 2-dimensional ultrasound, with statistically significant difference ( P < 0.05). There was no significant difference in the accuracy between intrauterine 3-dimensional and 2-dimensional ultrasound in detecting moderate and severe intrauterine adhesions ( P > 0.05). The difference in missed diagnosis and misdiagnosis rates between the 2 methods was statistically significant ( P < 0.05). All patients received hysteroscopic surgery, and 78 cases (76.47%) were naturally fertilized during postoperative follow-up, including 24 cases of mature delivery, 45 cases of cesarean delivery, and 9 cases of spontaneous abortion. The intrauterine 3-dimensional ultrasound examination of the intrauterine cavity will provide intuitive and comprehensive diagnostic information for a parturient with intrauterine adhesion. Its detection accuracy is higher, and the clinical application is noninvasive and safe, which has certain guiding significance for treatment.


Should deciduous teeth be preserved in adult patients? How about stem cells? Is it reasonable to preserve them?
When seeking orthodontic treatment, many adolescents and adult patients present with deciduous teeth. Naturally, deciduous teeth will inevitably undergo exfoliation at the expected time or at a later time. Apoptosis is the biological trigger of root resorption. In adult patients, deciduous teeth should not be preserved, as they promote: infraocclusion, traumatic occlusion, occlusal trauma, diastemata and size as well as morphology discrepancy malocclusion. Orthodontic movement speeds root resorption up, and so do restoring or recontouring deciduous teeth in order to establish esthetics and function. Deciduous teeth cells are dying as a result of apoptosis, and their regeneration potential, which allows them to act as stem cells, is limited. On the contrary, adult teeth cells have a greater proliferative potential. All kinds of stem cell therapies are laboratory investigative non authorized trials.


Parturition-related changes in insulin-like growth factors-I and -II in the perinatal lamb.
Specific radioligand assays for the two somatomedins, insulin-like growth factor (IGF)-I and IGF-II, have been used to study the ontogeny of somatomedin secretion in the perinatal lamb. Plasma samples were obtained from sheep fetuses from 54 days of gestation to term (147 days) and from neonatal lambs. All samples were first extracted in acid-ethanol to remove the somatomedin-binding proteins. Concentrations of IGF-I measured by radioimmunoassay were lower (P less than 0.01) in the fetus than in the adult sheep (0.96 +/- 0.17 (S.D.) units/ml, n = 11). Fetal IGF-I values rose (P less than 0.01) from 0.29 +/- 0.15 units/ml (n = 6) at 50-80 days to 0.79 +/- 0.18 units/ml (n = 13) at 140-150 days. While values were similar 0-2 days after birth, they rose (P less than 0.01) to 2.4 +/- 1.3 units/ml (n = 15) 3-7 days after birth. By 60 days they had fallen to adult values. In contrast, IGF-II levels measured by rat placental membrane radioreceptor assay were higher (P less than 0.001) in the fetus (2.71 +/- 1.06 units/ml, n = 18) than in the adult (1.0 +/- 0.17 units/ml) and showed no gestational trend between 50 and 140 days of gestation. Longitudinal studies showed a fall (P less than 0.01) in IGF-II values starting several days before birth. By 12 h after birth, IGF-II concentrations were similar to the adult and showed no subsequent postnatal change. These results demonstrate that IGF-I and IGF-II are not secreted in parallel in the perinatal lamb. There are major changes in the regulation of both IGF-I and IGF-II in relationship to birth. It is suggested that the high fetal IGF-II concentrations appear to be maintained by a stimulus withdrawn before birth. The postnatal rise in IGF-I may be related to the increase in hepatic somatogenic receptors at this age.


Pleural fluids associated with metastatic lung tumors are rich in progelatinase B/proMMP-9.
Gelatinase B/MMP-9 is a member of matrix metalloproteinases with a major role in extracellular matrix degradation, cell proliferation and migration. Its proenzyme form has also been reported in pleural fluids as an inducible species, but its relation to pleural pathology has not yet been fully clarified. The primary goal of this study was to evaluate proMMP-9 as a potential marker for differentiating pleural effusions of both malignant and non-malignant origin. Pleural fluid samples were studied from 194 patients, including tumor etiology in 133 cases, inflammatory disorders in 33, transudates in 12, and unspecified disorders in 16 patients. The concentrations of proMMP-9 were estimated by means of immunoassays and/or by scanning zymography. Samples were also examined for C-reactive protein (CRP). The analysis of proMMP-9 showed significant differences among the etiological groups with the highest concentrations in para-inflammatory exudates, intermediate in para-neoplastic exudates, and the lowest in transudates. However, the analysis of the para-neoplastic group revealed a distinct heterogeneity with a minor portion of fluids reaching values typical for para-inflammatory effusions. A subsequent sorting based on tumor histology showed increased levels particularly in exudates associated with metastatic tumors. Interestingly, proMMP-9 values in general correlated with CRP, a systemic marker of inflammation. Thus, MMP-9 proenzyme appears to complement traditional markers distinguishing pleural fluids of different origin. Yet, the differentiation between paraneoplastic and para-inflammatory exudates must be regarded with caution due to the presence of a high-expressive paraneoplastic sub-population, including effusions associated with metastatic tumors.


Synthesis, structure, and magnetic properties of a [Mn22] wheel-like single-molecule magnet.
The synthesis and magnetic properties of the compound [Mn(22)O(6)(OMe)(14)(O(2)CMe)(16)(tmp)(8)(HIm)(2)] 1 are reported. Complex 1 was prepared by treatment of [Mn(3)O(MeCO(2))(6)(HIm)(3)](MeCO(2)) (HIm = imidazole) with 1,1,1-tris(hydroxymethyl)propane (H(3)tmp) in MeOH. Complex 1.2MeOH crystallizes in the orthorhombic space group Pbca. The molecule consists of a metallic core of 2 Mn(IV), 18 Mn(III), and 2 Mn(II) ions linked by a combination of 6 micro(3)-bridging O(2)(-) ions, 14 micro(3)- and micro(2)-bridging MeO(-) ions, 16 micro-MeCO(2)(-) ligands, and 8 tmp(3)(-) ligands, which use their alkoxide arms to bridge in a variety of ways. The metal-oxygen core is best described as a wheel made from [Mn(3)O(4)] partial cubes and [Mn(3)O] triangles. Variable-temperature direct current (dc) magnetic susceptibility data were collected for complex 1 in the 1.8-300 K temperature range in a 1 T applied field. The chi(M)T value steadily decreases from 56 cm(3) K mol(-)(1) at 300 K to 48.3 cm(3) K mol(-)(1) at 30 K and then increases slightly to reach a maximum value of 48.6 cm(3) K mol(-)(1) at 15 K before dropping rapidly to 40.3 cm(3) K mol(-)(1) at 5 K. The ground-state spin of complex 1 was established by magnetization measurements in the 0.1-2.0 T and 1.80-4.00 K ranges. Fitting of the data by a matrix-diagonalization method to a model that assumes only the ground state is populated and incorporating only axial zero-field splitting (DS(z)()(2)), gave a best fit of S = 10, g = 1.96 and D = -0.10 cm(-)(1). The ac magnetization measurements performed on complex 1 in the 1.8-8 K range in a 3.5 G ac field oscillating at 50-1000 Hz showed frequency-dependent ac susceptibility signals below 3 K. Single-crystal hysteresis loop and relaxation measurements indicate loops whose coercivities are strongly temperature and time dependent, increasing with decreasing temperature and increasing field sweep rate, as expected for the superparamagnetic-like behavior of a single-molecule magnet, with a blocking temperature (T(B)) of approximately 1.3 K.


Modulatory role of protein kinase C on the signal transduction pathway utilized by platelet-activating factor in eosinophil activation.
To determine the role of protein kinase C (PKC) in the signal transduction in eosinophil pathways, we have assessed the effects of the phorbol ester phorbol 12-acetate 13-myristate (PMA) on guinea pig peritoneal eosinophils challenged with platelet-activating factor (PAF). Pretreatment with PMA completely inhibited the PAF-induced release of eosinophil peroxidase (EPO) and superoxide anions and the rise in intracellular Ca2+ concentration ([Ca2+]i), with IC50s of 2 to 10 nM. This inhibition was reversed when the cells were preincubated with the PKC inhibitor staurosporine for 5 min before the addition of PMA. Staurosporine also inhibited PAF-induced EPO release but not the rise in [Ca2+]i. The inactive ester 4 alpha-phorbol 12,13-didecanoate had no inhibitory effect on eosinophil activation. Finally, PMA inhibited the binding of the PAF antagonist [3H]WEB 2086 to intact eosinophils. Taken together, these data suggest that PKC may have a physiologic role in regulating PAF-induced eosinophil responses through expression of PAF receptors on the cell surface.


[Carcinoma of Bellini's collecting ducts].
Description of one case of carcinoma of Bellini's ducts, a very uncommon renal neoplasia. The existing literature is reviewed, commenting on its clinical manifestations, etiology, diagnostic methodology and therapeutical manoeuvres.


Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy.
The tumor interstitial pH and its modification play a significant role in cancer treatment. Current in vivo pH measurement techniques are invasive and/or provide poor spatial resolution. Therefore, there are no data on perivascular interstitial pH gradients in normal or tumor tissue. We have optically measured interstitial pH gradients with high resolution in normal and tumor (VX2 carcinoma) tissue in vivo by combining a fluorescence ratio imaging microscopy technique and the rabbit ear chamber preparation. The strengths of our approach include the ability to follow pH in the same location for several weeks and to relate these measurements to local blood flow and vascular architecture. Our results show: (a) tumor interstitial pH (6.75 units; N = 6 animals, n = 324 measurements) is significantly (P < 0.001) less than normal interstitial pH (7.23; N = 5, n = 274). This increased acidity in the tumor interstitium is in agreement with the previously reported data on this tumor; (b) with respect to pH spatial gradients in normal tissue, the interstitial pH decreased by approximately 0.32 pH units over a distance of 50 microns away from the blood vessel, while in tumor tissue, interstitial pH decreased by approximately 0.13 units over the same distance. Although the pH gradient near the vessel wall was steeper in normal tissue compared to tumor, the proton concentration gradient in normal tissue was less than that in the tumor. The approximate increase in proton concentration from 0-50 microns from the vessel was 4.5 x 10(-8)M in normal versus 5.7 x 10(-8)M in tumor tissue; (c) a simple one-dimensional diffusion-reaction model suggested that tumor tissue was producing protons at a rat 65-100% greater than normal tissue; (d) feasibility studies of temporal dynamics resulting from hyperglycemia (6 g/kg) or hypercapnia (10% CO2) led to significant (P < 0.05) interstitial pH reductions. During hyperglycemia, pH dropped by more than 0.2 pH units in about 90 min in tumor tissue but remained constant in normal tissue. Hypercapnia dramatically reduced pH by approximately 0.3 pH units in tumor tissue. Our limited studies on hyperglycemia and hypercapnia are in agreement with the previously published studies and demonstrate the capability of fluorescence ratio imaging microscopy to measure spatial as well as temporal changes in interstitial pH. Fluorescence ratio imaging microscopy should permit noninvasive evaluation of new pH-modifying agents and offer unique mechanistic information about tumor pathophysiology in tissue preparations where the surface of the tissue can be observed.


Reactive Oxygen Species-Mediated Autophagy Defines the Fate of Cancer Stem Cells.
Significance: A fraction of tumorigenic cells, also known as tumor initiating or cancer stem cells (CSCs), is thought to drive tumor growth, metastasis, and chemoresistance. However, little is known regarding mechanisms that convey relevant pathways contributing to their self-renewal, proliferation, and differentiation abilities. Recent Advances: Recent works on CSCs provide evidence on the role of redox disruption and regulation of autophagic flux. This has been linked to increased DNA repair capacity and chemoresistance. Critical Issues: The current review summarizes the most recent studies assessing the role of redox homeostasis, autophagy, and chemoresistance in CSCs, including some novel findings on microRNAs and their role in horizontal transfer within cancer cell populations. Future Directions: Rational anticancer therapy and prevention should rely on the fact that cancer is a redox disease with the CSCs being the apex modulated by redox-mediated autophagy. Antioxid. Redox Signal. 28, 1066-1079.


Loss of Par1b/MARK2 primes microglia during brain development and enhances their sensitivity to injury.
Microglia, the resident immune cells of the brain, exhibit various morphologies that correlate with their functions under physiological and pathological conditions. In conditions such as aging and stress, microglia priming occurs, which leads to altered morphology and lower threshold for activation upon further insult. However, the molecular mechanisms that lead to microglia priming are unclear. To understand the role of Par1b/MARK2 in microglia, we first expressed shRNA targeting luciferase or Par1b/MARK2 in primary microglial cells and imaged the cells using fluorescent microscopy to analyze for morphological changes. A phagocytosis assay was then used to assess functional changes. We then moved in vivo and used a Par1b/MARK2 knockout mouse model to assess for changes in microglia density, morphology, and phagocytosis using immunohistochemistry, confocal imaging, and 3D image reconstruction. Next, we used two-photon in vivo imaging in live Par1b/MARK2 deficient mice to examine microglia dynamics. In addition, a controlled-cortical impact injury was performed on wild-type and Par1b/MARK2-deficient mice and microglial response was determined by confocal imaging. Finally, to help rule out non-cell autonomous effects, we analyzed apoptosis by confocal imaging, cytokine levels by multiplex ELISA, and blood-brain barrier permeability using Evans Blue assay. Here, we show that loss of the cell polarity protein Par1b/MARK2 facilitates the activation of primary microglia in culture. We next found that microglia in Par1b/MARK2 deficient mice show increased density and a hypertrophic morphology. These morphological changes are accompanied with alterations in microglia functional responses including increased phagocytosis of neuronal particles early in development and decreased surveillance of the brain parenchyma, all reminiscent of a primed phenotype. Consistent with this, we found that microglia in Par1b/MARK2 deficient mice have a significantly lower threshold for activation upon injury. Together, our studies show that loss of Par1b/MARK2 switches microglia from a surveillant to a primed state during development, resulting in an increased neuroinflammatory response to insults.


The natural history of dystonia.
We have analyzed 226 patients with a diagnosis of dystonia musculorum deformans seen in our clinica between 1955 and 1974. These were evenly divided between male and female, but of the 226 patients, 225 were white and only one was black. Forty-two percent were Jewish, as contrasted with 3% Jewish population in the United States. It is interesting to note that a family history was obtained in 28% of both the Jewish and the non-Jewish groups. Thirty of the patients reported a significant viral infection within 3 months preceding the onset of symptoms. Only six patientss had a history of one or more remissions during the course of their illness. The mean duration of symptoms before examination in this series was 8.6 years with a duration of 1 to 42 years. Fifty-six of the patients had been diagnosed as having conversion hysteria at some time during the course of their illness. The majority of the patients had the onset of symptoms between the ages of 5 and 10, although the age span was from 2 to 45 years of age. Seventy-six of the patients had an IQ statistically significant above average (3). Each symptom, rate of progress of the disease, and various other factors in the history were corrolated with age, sex, ethnic group, mode of onset, and 20 other variables. The most pertinent subgroupings affecting the natural history were the age on onset and the ethnic group and family history. Trunkal involvement was most common in the non-Jewish group with a positive family history. This particular sub-group of patients showed predominately midline symptomatology. In the groups below the age of 13, the onset was almost invariably in one of the four limbs. However, in the group 14 years of age and older, 30% had their initial dystonic symptoms in the neck and a total of 40% of the patients whose onset was at age 14 or later, had marked nuchal symptoms. This clear-cut predominance of limb involvement in the youngest groups is also indicated by the observation that 38% in the youngest group had become confined to a wheelchair because of gait abnormalities, whereas none of those whose age of onset was 14 or older were disabled to this degree by gait abnormality. The most rapidly progressive and incapacitating symptomatology was seen in those patients with onset of symptoms below the age of 8 so that in general the younger the age at onset, the more rapid the progress of the symptoms.


Optimal Choice of Adjuvant Treatment for Renal Cell Carcinoma Following Nephrectomy.
Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide. In about 55% of cases, it is diagnosed at a localised and/or locally advanced stage and therefore amenable to a curative approach. Although nephrectomy still represents the cornerstone of non-metastatic RCC (nmRCC) treatment, a relapse is observed in about 25-30% of patients undergoing curative surgery. Prognosis is drastically influenced by lymph nodal involvement. After the first disappointing results with a cytokine-based strategy, tyrosine kinase inhibitors (TKIs) were tested as adjuvant agents. Despite their efficacy in the metastatic setting, results in terms of disease-free survival (DFS) are not unequivocal and the overall survival (OS) benefit has not been demonstrated. Moreover, their toxicity profile induced a remarkable percentage of patients to discontinue the treatment. On the contrary, the KEYNOTE-564 trial showed the benefit of adjuvant pembrolizumab compared with placebo in terms of DFS with promising results in term of OS. Patients included were at intermediate or high risk of relapse, or patients with no evidence of disease after metastasectomy (M1 NED). The updated analysis presented at the American Society of Clinical Oncology Genito-Urinary (ASCO GU) 2022 confirmed the benefit of pembrolizumab versus placebo over time, although OS data are still immature. A longer follow-up and the several ongoing trials with immune checkpoint inhibitors (ICIs) will provide further data about adjuvant immuno-oncology (IO). Furthermore, the patients' selection based on clinical or biological features will be crucial in order to identify who benefits most from treatments.


[MiR-26b inhibits proliferation, invasion, and migration of glioma by targeting cyclooxygenase-2].
To explore the expressions of miR-26b and cyclooxygenase (COX)-2 in different grades of gliomas and the effect of miR-26b on glioma cell proliferation, invasion and migration. Methods: Western blot and Real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of miR-26b and COX-2 in different grades of gliomas. Human glioma cells were transfected with miR-26b mimics. qRT-PCR was employed to detect the mRNA expressions of miR-26b and COX-2 after miR-26b mimics transfection, while dual-luciferase reporter assay was used to investigate the regulatory effect of miR-26b on COX-2. Cell counting kit-8 (CCK8), trans-well invasion assay and scratch assay were used to detect the proliferation, invasion and migration of human U87 glioma cells after miR-26b mimic transfection, respectively. The antitumor effect of miR-26b was verified by evaluating the volume and weight of tumor in nude mice. Results: With the increase in tumor grades, the expression of miR-26b was significantly decreased (P<0.05), while COX-2 expression was increased (P<0.001). Dual luciferase assay confirmed that miR-26b could directly regulate the protein expression of COX-2. MiR-26b mimics could significantly reduce the expression of COX-2 (P<0.05) and suppress the proliferation, invasion and migration of glioma cell (P<0.05). The volume and weight of tumor in MiR-26b mimics transfection group were smaller than those in the control group. Conclusion: Overexpression of miR-26b may inhibit proliferation, invasion, and migration of glioma by suppressing the expression of COX-2. Therefore, the miR-26b/COX-2 pathway might be a therapeutic target in glioma.


Effects of an Occupation-Based Intervention on Hand and Upper Extremity Function, Daily Activities, and Quality of Life in People With Burn Injuries: A Randomized Controlled Trial.
Occupational performance and function are affected in people with burn injuries to the hand and upper extremity; this can lead to the development of some disabilities and endanger quality of life. To investigate the effects of occupation-based intervention on hand and upper extremity function, daily activities, and quality of life in people with burn injuries. Randomized controlled trial. Specialized burn hospital in Iran. Patients (N = 20) with burn injuries to the hand and upper extremity. The control group received only traditional rehabilitation, and the intervention group received traditional rehabilitation and took part in the Cognitive Orientation to daily Occupational Performance (CO-OP) protocol (18 sessions, 45 min/day, for both groups). Assessments included the CO-OP; Michigan Hand Outcomes Questionnaire; Shortened Disabilities of the Arm, Shoulder and Hand Questionnaire; Modified Barthel Index; World Health Organization Quality-of-Life Scale-Brief; a visual analogue scale; measurements with a goniometer and dynamometer; and the figure-of-eight method. These evaluations were conducted with both groups before the rehabilitation program commenced and at Wk 2, 6, and 14 (follow-up). The results showed that there were notable changes in all the study variables except edema in both groups. However, these changes (p [V] ≤ .05) were not statistically significant between the two groups. According to the results, the occupation-based interventions are as effective as traditional therapeutic interventions for the improvement of hand and upper extremity function, ability to perform daily activities, and quality of life in people with burn injuries. What This Article Adds: The CO-OP protocol, as an occupation-based intervention, can improve hand performance, ability to perform daily activities, and quality of life in people with burn injuries, and thus it can be useful in rehabilitation clinics.


Ultrastructural localization of complex carbohydrates in odontoblasts, predentin, and dentin.
Glycosaminoglycans (GAGs) and glycoproteins (GPs) are essential components for dentinogenesis. We have examined rat odontoblasts, predentin, and dentin decalcified with EDTA and stained with: 1) Spicer's hig-iron diamine-thiocarbohydrazide-silver proteinate (HID-TCH-SP) method for sulfated glycoconjugates, and 2) Thiéry's periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method for vicinal glycol-containing glycoconjugates. HIS-TCH-SP stained distended portions of Golgi saccules and secretory granules. The predentin contained three times the number of HID-TCH-SP stain precipitates when compared to the mineralization front of the dentin matrix. PA-TCH-SP weakly stained membranes of Golgi saccules and cisternae of rough endoplasmic reticulum (RER), whereas stronger staining was observed in secretory granules, lysosomes, and multivesicular bodies (MVBs). Collagen fibrils in predentin demonstrated moderate PA-TCH-SP staining. In contrast, strong PA-TCH-SP staining was observed on and between collagen fibrils in the mineralization front of the dentin matrix. TCH-SP controls of unosmicated specimens lacked significant staining, however, osmicated control specimens did contain some TCH-SP stain deposits in the mineralization front. These results indicate that sulfated and vicinal glycol-containing glycoconjugates are packaged in the same type of secretory granule and released into the extracellular matrix; subsequently vicinal glycol-containing glycoconjugates concentrate in the calcification front, whereas sulfated glycoconjugates accumulate in the predentin and are either removed or masked to staining in the dentin.