Angular position, range of motion and velocity of arm elevation: a study of consistency of performance.
To define the normal range, velocity and consistency of the movement of active arm elevation with humerus in neutral or in external rotation using a simplified kinematic model. Nine normal volunteers and the non-involved side of twenty five patients with unilateral shoulder lesion participated. A 3D optoelectronic tracking system was used to register the movement of raising the arm from the normal upright position to maximal elevation in a repetitive way. Peak humeral position, range of movement, velocity of motion and consistency of cycles were analyzed. Descriptive statistics, correlation between variables and with sex, age and side are presented, including differences between performances of movement done in neutral or external rotation. Data of the six variables were: maximal abduction 142 degrees [137.4-147.0], range of motion 118.1 degrees [112-124], maximal velocity 238 degrees/s [209-265]; mean velocity 113 degrees/s [96-130]; coefficient of variation of maximal angular abduction was 2.2% [1.7-2.7]; coefficient of variation of maximal velocity 8.6% [7.3-9.9]. No significant differences were observed either on side, sex or between the shoulder of normal volunteers or that of the patients with opposite shoulder lesions. Participants older than 45 years old showed only a significant slightly lower average velocity. The study confirms the weak association between dependent (biomechanical) and independent variables. As it is described here, analysis of arm elevation has not been previously studied and shows that has a good consistency in angular position, velocity and repeatability of motion in normal conditions which permits a picture of the overall performance of the shoulder.


Genomic Insights Into the Population History and Biological Adaptation of Southwestern Chinese Hmong-Mien People.
Hmong-Mien (HM) -speaking populations, widely distributed in South China, the north of Thailand, Laos, and Vietnam, have experienced different settlement environments, dietary habits, and pathogenic exposure. However, their specific biological adaptation remained largely uncharacterized, which is important in the population evolutionary genetics and Trans-Omics for regional Precision Medicine. Besides, the origin and genetic diversity of HM people and their phylogenetic relationship with surrounding modern and ancient populations are also unknown. Here, we reported genome-wide SNPs in 52 representative Miao people and combined them with 144 HM people from 13 geographically representative populations to characterize the full genetic admixture and adaptive landscape of HM speakers. We found that obvious genetic substructures existed in geographically different HM populations; one localized in the HM clines, and others possessed affinity with Han Chinese. We also identified one new ancestral lineage specifically existed in HM people, which spatially distributed from Sichuan and Guizhou in the north to Thailand in the south. The sharing patterns of the newly identified homogenous ancestry component combined the estimated admixture times via the decay of linkage disequilibrium and haplotype sharing in GLOBETROTTER suggested that the modern HM-speaking populations originated from Southwest China and migrated southward in the historic period, which is consistent with the reconstructed phenomena of linguistic and archeological documents. Additionally, we identified specific adaptive signatures associated with several important human nervous system biological functions. Our pilot work emphasized the importance of anthropologically informed sampling and deeply genetic structure reconstruction via whole-genome sequencing in the next step in the deep Chinese Population Genomic Diversity Project (CPGDP), especially in the regions with rich ethnolinguistic diversity.


1H MRS spectroscopy evidence of cerebellar high lactate in mitochondrial respiratory chain deficiency.
Cerebellar ataxia is known to occasionally occur in the course of mitochondrial disorders. We report on MR spectroscopy (1H MRS) evidence of elevated brain lactate in the cerebellar area of 11 patients with cerebellar ataxia ascribed to mitochondrial respiratory chain deficiency (RCD). 1H MRS spectroscopy evidence of lactate peak was found in the cerebellum of 9/11 cases, while no lactate was detected in the putamen in 8/11. We suggest using 1H MRS in cerebellar atrophy in the diagnosis of mitochondrial RCD.


Low back pain in the adolescent athlete.
Clinicians must have knowledge of the growth and development of the adolescent spine and the subsequent injury patterns and other spinal conditions common in the adolescent athlete. The management and treatment of spinal injuries in adolescent athletes require a coordinated effort between the clinician, patients, parents/guardians, coaches, therapists, and athletic trainers. Treatment should not only help alleviate the current symptoms but also address flexibility and muscle imbalances to prevent future injuries by recognizing and addressing risk factors. Return to sport should be a gradual process once the pain has resolved and the athlete has regained full strength.


Facing temptation: The neural correlates of gambling availability during sports picture exposure.
Nowadays, sports betting has become increasingly available and easy to engage in. Here we examined the neural responses to stimuli that represent sporting events available for betting as compared to sporting events without a gambling opportunity. We used a cue exposure task in which football (soccer) fans (N = 42) viewed cues depicting scheduled football games that would occur shortly after the scanning session. In the "betting" condition, participants were instructed to choose, at the end of each block, the game (and the team) they wanted to bet on. In the "watching" condition, participants chose the game they would prefer to watch. After the scanning session, participants completed posttask rating questionnaires assessing, for each cue, their level of confidence about the team they believed would win and how much they would enjoy watching the game. We found that stimuli representing sport events available for betting elicited higher fronto-striatal activation, as well as higher insular cortex activity and functional connectivity, than sport events without a gambling opportunity. Moreover, games rated with more confidence towards the winning team resulted in greater brain activations within regions involved in affective decision-making (ventromedial prefrontal cortex), cognitive inhibitory control (medial and superior frontal gyri) and reward processing (ventral and dorsal striatum). Altogether, these novel findings offer a sensible simulation of how the high availability of sports betting in today's environment impacts on the reward and cognitive control systems. Future studies are needed to extend the present findings to a sample of football fans that includes a samilar proportion of female and male participants.


The correlation among the percentage of positive biopsy cores from the dominant side of prostate, adverse pathology, and biochemical failure after radical prostatectomy.
The aim of this study was to evaluate the correlation among various preoperative clinical variables, including certain prostate needle biopsy parameters, biochemical failure, and adverse pathology, after radical retropubic prostatectomy (RRP). We retrospectively evaluated the records of our 156 patients who underwent RRP because of localized prostate cancer. Serum prostate-specific antigen level, clinical stage, and the information obtained from biopsy [Gleason score, number of positive cores, percentage of positive cores (PPCs) from the dominant side of prostate, and overall PPC] were evaluated as predictors of adverse pathology and biochemical failure. Of the patients, 30.2% (n=38) had nonorgan-confined disease, 19.1% (n=24) had positive surgical margins, 11.9% (n=15) had positive seminal vesicle invasion, and 16.7% (n=21) had biochemical failure after RRP. Multivariate analysis demonstrated that a PPC value of 55% or more from the dominant side of prostate is the only independent predictor of nonorgan-confined disease and seminal vesicle invasion. Clinical stage (T2b), biopsy Gleason score, and PPC values of 55% or more from the dominant side of prostate were found to be statistically significant predictors of positive surgical margin and biochemical failure. Our results support that PPC from the dominant side of prostate is a useful parameter for the prediction of adverse pathology and biochemical failure after RRP.


Posttranslational arginylation as a global biological regulator.
Posttranslational modifications constitute a major field of emerging biological significance as mounting evidence demonstrates their key role in multiple physiological processes. Following in the footsteps of protein phosphorylation studies, new modifications are being shown to regulate protein properties and functions in vivo. Among such modifications, an important role belongs to protein arginylation - posttranslational tRNA-mediated addition of arginine, to proteins by arginyltransferase, ATE1. Recent studies show that arginylation is essential for embryogenesis in many organisms and that it regulates such important processes as heart development, angiogenesis, and tissue morphogenesis in mammals. This review summarizes the key data in the protein arginylation field since its original discovery to date.


Validation of the Brazilian version of the Spinal Cord Independence Measure III.
The Spinal Cord Independence Measure (SCIM III) specifically assesses individuals with spinal cord injuries. To translate and validate the Brazilian version of SCIM III. SCIM III was translated, back-translated and adapted to the Portuguese language. Two interviewers assessed 83 subjects with spinal cord injuries in each one of seven collaborating rehabilitation centers. Functional Independence Measure (FIM™) and ASIA motor and sensory indices were also used. After six months, subjects were re-evaluated with the same instruments. Examiners clearly understood the Brazilian version of SCIM III. Inter-rater intraclass correlation coefficient (ICC) was 0.918, and test-retest ICC was 0.991. After six months, the variation of gains in the FIM™ positively correlated with gains in SCIM III. The Brazilian version of the SCIM III is easy to understand, has good psychometric properties, and is valid.


Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses.
Histiocytic disorders are currently identified by their component cells. The non-Langerhans Cell Histiocytoses (non-LCH) are a group of disorders defined by the accumulation of histiocytes that do not meet the phenotypic criteria for the diagnosis of Langerhans cells (LCs). The non-LCH consist of a long list of diverse disorders which have been difficult to categorize. A conceptual way to think of these disorders that make them less confusing and easier to remember is proposed based on immunophenotyping and clinical presentation. Clinically the non-LCH can be divided into 3 groups, those that predominantly affect skin, those that affect skin but have a major systemic component, and those that primarily involve extracutaneous sites, although skin may be involved. Immunohistochernically many of the non-LCH appear to arise from the same precursor cell namely the dermal dendrocyte. Juvenile Xanthogranuloma (JXG) is the model of the dermal dendrocyte-derived non-LCH. Other non-LCH with differing clinical presentation and occurring at different ages but with an identical immunophenotype appear to form a spectrum of the same disorder, deriving from the same precursor cell at different stages of maturation. They should be considered as members of a JXG family. Non-JXG family members include Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). The non-LCH can be classified as JXG family and non-JXG family and subdivided according to fairly clear-cut clinical criteria. Utilization of this type of approach will allow better categorization, easier review of the literature and more accurate therapy decision-making.


Plasma cortisol suppression test used to predict the development of primary open-angle glaucoma.
Forty patients classified as high responders (GG) to dexamethasone testing (intraocular pressure greater than 31 mm Hg) without visual field loss were subjected to plasma cortisol suppression testing. After a five-year follow-up adequate data were available on 35 patients. Eighteen responded to 1.0 mg of dexamethasone-diphenylhydantoin suppression testing in a similar fashion to patients with primary open-angle glaucoma while 17 responded in a similar fashion to subjects classified as low (NN, intraocular pressure less than 20 mm Hg) and intermediate (NG, intraocular pressure 20 to 31 mm Hg) responders to dexamethasone testing. Eight of the 35 patients developed glaucomatous visual field loss during the follow-up period. These eight patients were not more sensitive to suppression of plasma cortisol than the 27 patients maintaining normal visual fields. Thus, plasma cortisol suppression testing failed to predict the development of primary open-angle glaucoma in GG responders.


Atractylenolide II prevents radiation damage via MAPKp38/Nrf2 signaling pathway.
Ionizing radiation (IR) can act as a negative factor for human homeostasis, by causing and even aggravating a series of pathological conditions. To protect the intactness of normal tissues, effective anti-radiation drugs are urgently needed for alleviating the outcomes of radioactive damage. In this study, we demonstrate that atractylenolide II (ATR II), a sesquiterpenoid monomer extracted from traditional Chinese medicine atractylodes macrocephala, can markedly suppress IR damage by promoting the expression of antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone oxido-reductase 1 (NQO-1), which are mediated by nuclear factor-erythroid 2-like 2 (Nrf2) signaling pathway. Furthermore, here we reveal that ATR II effectively upregulates the expression of mitogen-activated protein kinase p38 (MAPKp38), which also acts as a regulator of Nrf2 signaling cascade. Indeed, treatment with a MAPKp38 inhibitor can significantly downregulate the expression of Nrf2 and its downstream target genes HO-1 and NQO-1 and, consequently, abolish the protective effect of ATR II against IR. Consistently, ATR II also has a protective function against IR-induced damage in animal models. In conclusion, our study provides an unexpected function of ATR II in preventing IR-induced damage by modulating MAPKp38/Nrf2 signaling pathway.


Transcranial direct current stimulation in attention-deficit/hyperactivity disorder: A meta-analysis of clinical efficacy outcomes.
Evidence for the application of transcranial direct current stimulation (tDCS) in the clinical care of attention-deficit/hyperactivity disorder (ADHD) is limited. Therefore, we aimed to summarize study results using meta-analyses of measures of the cardinal symptoms of ADHD. We conducted a systematic literature search (PubMed/pubpsych/PsychInfo/WOS) until 01/05/2020 for randomized controlled trials (RCTs) evaluating tDCS vs. control condition in patients with ADHD. A random effects meta-analysis of symptom-related outcomes was performed separately for data on the immediate effect and follow-up. Subgroup- and metaregression analyses for patient characteristics and tDCS parameters were included. Meta-analyzing 13 studies (n=308, age=23.7±13.3), including 20 study arms, tDCS had an immediate effect on overall symptom severity, inattention, and impulsivity, but not on hyperactivity. Results were significant in children and adolescents (8 studies, n=133, age=12.4±3.0). Follow-up data (3 days-4 weeks after stimulation) suggested an ongoing beneficial effect regarding overall symptom severity and a delayed effect on hyperactivity. TDCS seems to be a promising method to treat clinical symptoms in ADHD with long-lasting effects. Still, more research considering the individual neuropsychological and anatomical dispositions of the subjects is needed to optimize tDCS protocols and efficacy. Safety issues of tDCS treatment in children and adolescents are addressed.


A Path Analysis of Patient and Social-Level Factors on Health Literacy and Retention in Care Among African Americans Living with HIV.
Low health literacy and poor retention in care may contribute to HIV health disparities among African Americans, but causal pathways have not been examined. We utilized an adapted health literacy model to examine the role of health literacy on racial disparities in retention in care. Retention in care for 699 participants was assessed 24-months post survey and operationalized as 100% visit adherence versus less than 100% visit adherence. Most participants were African American (60%) and virally suppressed (93%). Results from a path analysis revealed that non-African American race was related to greater health literacy (p = .023) and to 100% visit adherence (p = .024). Greater health literacy was associated with 100% visit adherence (p = .008), which was in turn related to viral suppression (p < .001). Findings indicate that health literacy partially mediates the relationship between race and retention in care and are among the first to suggest these causal pathways.


A comparison of heterotopic and orthotopic intestinal transplantation in rats.
Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans.


The biosynthetic pathway to a novel derivative of 4,4'-diapolycopene-4,4'-oate in a red strain of Sporosarcina aquimarina.
In a red bacterial strain SF238 belonging to Sporosarcina aquimarina, a C(30) carotenoid biosynthetic pathway was identified. It has been reconstructed by analysis of intermediates that accumulate in two different pigment mutants. It starts with the synthesis of 4,4'-diapophytoene and proceeds with its desaturation to 4,4'-diapolycopene, which is then oxidized to 4,4'-diapolycopene-4,4'-dioate. Using a combination of HPLC-PDA and LC-MS/MS analyses, the final product of this pathway was identified as acetyl-4,4'-diapolycopene-4,4'-dioate. This is a novel carotenoid not reported in any organisms to date. It could be demonstrated that this carotenoid has excellent antioxidative properties to protect from photosensitized peroxidation reactions like other related 4,4'-diapolycopene-4,4'-dioate derivatives.


Doping cobalt into a [Zn₇] cluster-based MOF to tune magnetic behaviour and induce fluorescence signal mutation.
An in situ doping strategy was successfully applied to tune the magnetic behaviour and induce fluorescence signal mutation of a spindle heptanuclear zinc cluster-based MOF, by only modifying its structural composition. The Co(II)-doped Zn(II)-MTV-M'MOF exhibits canted antiferromagnetism and weaker fluorescence properties.


Impact of Different Preparations of Tooth Graft vs Xenogeneic Bone Graft on Bone Healing: An Experimental Study.
This study aims to compare the effect of demineralized xenogeneic tooth graft in its two forms, particulate and block, with bovine xenograft in the healing of a rabbit tibial bone defect model. Two monocortical bony defects were made in the right tibias of 36 rabbits, and were divided into four groups. Group I defects were left empty, while group II, III, and IV were filled with bovine xenograft, demineralized particulate tooth graft, and demineralized perforated block tooth graft, respectively for evaluation of the bone healing process. Three rabbits from each group were euthanized at 2, 4, and 6 weeks after surgery. The bone specimens were processed and stained with hematoxylin and eosin (H&E) and osteopontin (OPN) immunohistochemical staining. The results were subjected to image analysis and quantitative evaluation. Demineralized particulate tooth graft showed the best bone healing capacity compared to all other groups at all time points tested, as it showed a large amount of the formed bone, rapid closure of the defect with a significant increase in OPN expression, and the least amount of the residual grafted particles. In comparison to bovine xenograft and demineralized dentin block graft, the demineralized particulate tooth grafting material is a promising bone grafting substitute as it proved to be osteoconductive, biocompatible, and bioresorbable. Demineralized tooth grafting material can aid in the regeneration of large bone defects, leading to improvement in the filling of the bone defects which can help in oral and maxillofacial reconstruction.


Renal failure after intravesical mitomycin C.
Severe side effects, local or systemic, are uncommon with intravesically administered mitomycin C. Bladder fibrosis and contracture, with resultant renal failure, are unusual but possible.


Feasibility of low doses of I-131 for thyroid ablation in postsurgical patients with thyroid carcinoma.
The feasibility of using low doses of I-131 (30 mCi) for ablation of thyroid remnants following surgery for papillary and follicular thyroid carcinoma was examined in 21 patients. Six weeks following near-total thyroidectomy and three days following intramuscular thyroid-stimulating hormone (10 IU), patients were given 30 mCi of I-131 and scans were performed 24 to 72 hours later. Remaining thyroid tissue was identifiable in the thyroid bed in 19 patients, and two patients also had evidence of cervical metastases. Patients with metastases received an additional 100 mCi of I-131. Follow-up I-131 scans were performed at nine to 15-month intervals in ten patients who initially received 30 mCi of I-131, and only one patient showed complete ablation of the residual thyroid tissue, whereas the remaining nine patients had persistent uptake of I-131 in the same regions in which the uptake was seen in the initial postoperative scans. One of the nine patients had evidence of a cervical metastasis as well. It is therefore apparent that total or near-total thyroidectomy rarely removes all thyroid tissue and that an "out-patient" dose of I-131 is not adequate for ablation of postoperative thyroid remnants.


Establishing a magnetic resonance safety program.
Establishing a magnetic resonance (MR) safety program is crucial to ensuring the safe MR imaging of pediatric patients. The organizational structure includes a core safety council and broader safety committee comprising all key stakeholders. These groups work in synchrony to establish a strong culture of safety; create and maintain policies and procedures; implement device regulations for entry into the MR setting; construct MR safety zones; address intraoperative MR concerns; guarantee safe scanning parameters, including complying with specific absorption rate limitations; adhere to national regulatory body guidelines; and ensure appropriate communication among all parties in the MR environment. Perspectives on the duties of the safety council members provide important insight into the organization of program oversite. Ultimately, the collective dedication and vigilance of all MR staff are crucial to the success of a safety program.


Genetic Spectrum in F13A1 Detected by Next-Generation Sequencing Among North Indian Patients with FXIII Deficiency.
The study aimed to explore the molecular defects underlying FXIII deficiency. Sixteen unrelated cases were enrolled based on the indication of the urea clot solubility test and Factor XIII-A antigen levels. Cases were further subjected to targeted next-generation sequencing (custom gene panel: F7, F8, VWF, F9, F13A1, F13B). The pathogenic/likely pathogenic variants were validated by Sanger sequencing in the patients and family members. Mean age of referral to our center was 27.2 years (8 week-67 years). Consanguinity was found in only one of the 16 cases and 9 cases presented in infancy. The most common symptoms were skin bleeds (69%) and umbilical cord bleed (50%). The clot solubility test was positive in 12, inconclusive in 1, and normal in 3. Mean FXIII-A levels were 15.7 IU/dL (range 0.6 to 49.5 IU/dL). Pathogenic/likely pathogenic variants in F13A1 were found in 11 (69%). Nine cases (82%) were homozygous, and two were compound heterozygous. Total eleven variants were found of which four were missense (c.1226G>A; c.998C>T; c.631G>C; c.2134A>C); three deletion (c.521delG; c.742delA; c.1405_1408delCAAA); two nonsense (c.1112G>A; c.1127G>A) and two splice site (c.1909-1G>C; c.2045G>A). No probably pathogenic variant was found in the F13B. Inherited FXIII deficiency with bleeding is associated with genetic defects in predominantly the F13A1 gene. A variety of variants were seen in this cohort. A nonsense variant c.1127G>A found in three of our cases seems to be recurrent. This data will contribute to designing functional studies and antenatal testing in affected families. The online version contains supplementary material available at 10.1007/s12288-022-01579-1.


Hormones and Neuropeptide Receptor Heteromers in the Ventral Tegmental Area. Targets for the Treatment of Loss of Control of Food Intake and Substance Use Disorders.
Hormones and neuropeptides represent biological correlates of internal homeostatic signals detected and integrated in the hypothalamus, which establishes a robust functional connection with the ventral tegmental area (VTA). The hypothalamus-VTA connection determines the ability of these signals to influence central dopaminergic neurotransmission and, therefore, their ability to increase responsiveness to their reward-associated stimuli and to establish appropriate associative learning. The hypothalamus also provides the main source of the multiple neuropeptides that are released in the VTA. With volume transmission of neuropeptides and hormones, extrasynaptic receptors within the VTA provide a fine-tune mechanism, which depends on the ability of molecularly different G protein-coupled receptors (GPCRs) to form heteromers. GPCR heteromer is defined as a macromolecular complex composed of at least two different receptor units (protomers) with biochemical properties that are demonstrably different from those of its individual components. GPCR heteromers can provide unique allosteric properties to specific ligands, which provides new avenues for drug development. We have identified specific GPCR heteromers in the VTA that integrate orexin and CRF neurotransmission and opioid and galanin neurotransmission, which play a very significant role in the modulation of dopaminergic neuronal activity and which can constitute targets for the treatment of loss of control of food intake and substance use disorders.


Experimental cryosurgical lesion of the optic nerve.
The right optic nerves of three cynomolgus monkeys were frozen under direct visualization after a modified Kröhnlein operation. Left optic nerves were subjected to an identical procedure without freezing. Postoperatively, visual evoked responses (VERs) could not be obtained by stimulating right eyes, while electroretinograms from both eyes and VERs obtained by stimulating left eyes were normal. Extensive lesions which were found in the right optic nerves of all animals were histologically similar to those obtained by freezing in the brain.


Plasma prilocaine and mepivacaine concentrations after combined lumbosacral plexus block.
In a pharmacokinetic study of combined sciatic/3-in-1 block for lower limb surgery, the two moderate-acting local anaesthetics prilocaine and mepivacaine were compared. The mean maximum venous plasma concentrations of mepivacaine were more than twice as high as when prilocaine was used as anaesthetic (5.1 micrograms/ml vs. 2.37 micrograms/ml). When used in combination with the former, ornipressin did not reduce plasma concentrations of mepivacaine to values which were below the threshold for toxic symptoms (5-6 mg/ml). The peak plasma concentrations exceeded the threshold of 5 micrograms/ml in four of the nine patients of the mepivacaine group (maximum value 7.21 mg/ml) and in two of the nine patients of the mepivacaine+ornipressin group (maximum value 8.61 micrograms/ml).


Intravenous iron in heart failure and chronic kidney disease.
Intravenous iron therapy is increasingly being used worldwide to treat anemia in chronic kidney disease and more recently iron deficiency in heart failure. Promising results were obtained in randomized clinical trials in the latter, showing symptomatic and functional capacity improvement with intravenous iron therapy. Meanwhile, confirmation of clinical benefit in hard-endpoints such as mortality and hospitalization is expected in large clinical trials that are already taking place. In chronic kidney disease, concern about iron overload is being substituted by claims of direct cardiovascular benefit of iron supplementation, as suggested by preliminary studies in heart failure. We discuss the pitfalls of present studies and gaps in knowledge, stressing the known differences between iron metabolism in heart and renal failure. Systemic and cellular iron handling and the role of hepcidin are reviewed, as well as the role of iron in atherosclerosis, especially in view of its relevance to patients undergoing dialysis. We summarize the evidence available concerning iron overload, availability and toxicity in CKD, that should be taken into account before embracing aggressive intravenous iron supplementation.


Sodium ion translocation and ATP synthesis in methanogens.
Methanogens are the only significant biological producers of methane. A limited number of C(1) substrates, such as methanol, methylamines, methyl sulfate, formate, H(2)+CO(2) or CO, and acetate, serve as carbon and energy source. During degradation of these compounds, a primary proton as well as a primary sodium ion gradient is established, which is a unique feature of methanogens. This raises the question about the coupling ion for ATP synthesis by the unique A(1)A(o) ATP synthase. Here, we describe how to analyze and determine the Na(+) dependence of two model methanogens, the hydrogenotrophic Methanothermobacter thermautotrophicus and the methylotrophic Methanosarcina barkeri. Furthermore, the determination of important bioenergetic parameters like the ΔpH, ΔΨ, or the intracellular volume in M. barkeri is described. For the analyses of the A(1)A(O) ATP synthase, methods for measurement of ATP synthesis as well as ATP hydrolysis in Methanosarcina mazei Gö1 are described.


Obesity index and the risk of diabetes among Chinese women with prior gestational diabetes.
There is some confusion regarding which anthropometric measurement of adiposity should be used to indicate diabetes, especially for Asians. The present study was to evaluate different indicators of adiposity (BMI, waist circumference and body fat) with Type 2 diabetes risk among women with prior gestational diabetes mellitus. We performed a cross-sectional survey in 1263 women with gestational diabetes at 1-5 years after delivery. Logistic regression models were used to estimate the association of BMI, waist circumference and body fat with Type 2 diabetes risk. BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes among women with prior gestational diabetes (all P(trend) < 0.001). After adjustment for waist circumference and body fat, the positive association of BMI with Type 2 diabetes risk became non-significant and reversed. There was a significantly positive association of waist circumference with Type 2 diabetes risk after adjustment for BMI, and a significantly positive association of body fat with Type 2 diabetes risk after adjustment for both BMI and waist circumference. When the joint effects were examined, the significantly positive associations of waist circumference or body fat with Type 2 diabetes risk were consistent among women with different levels of BMI, and the positive association of BMI and Type 2 diabetes risk was significant among women with gestational diabetes with a waist circumference of ≥ 50% or body fat ≥ 50%. BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes, and waist circumference and body fat were better indicators than BMI for Type 2 diabetes risk among Chinese women with prior gestational diabetes.


Synthesis and reactivity with beta-lactamases of a monobactam bearing a retro-amide side chain.
The monobactam sodium 3-benzylcarbamoyl-2-oxo-1-azetidinesulfonate, bearing a retro (vs classical beta-lactam)-amide side chain, has been synthesized and the kinetics of its reaction with typical beta-lactamases studied. The new compound is generally a poorer substrate than the analogous compound with a normal side chain but its formation of a transiently stable complex with a class C beta-lactamase sustains the retro-amide side-chain concept.


Sympathetic and metabolic mechanisms of the cerebrovasomotor function of the caudal ventrolateral medulla in rats.
We attempted to elucidate the cerebrovasomotor function of the caudal ventrolateral medulla. Sixty-one rats were anaesthetized, paralysed and artificially ventilated. The microsphere method was employed for the measurement of blood flow. Microinjection of an antagonist of excitatory amino acids, kynurenate (2 nmol), into functionally identified depressor sites within the caudal ventrolateral medulla produced arterial hypertension of about 140 mmHg. We found that the cerebral blood flow was substantially increased, but was maintained at the same level (17 rats) as that observed under phenylephrine-induced hypertension (26 rats). Bilateral severing of the cervical sympathetic trunks resulted in a further increase in blood flow in all brain regions studied (18 rats). The response was most significant in the cerebral parasagittal cortex (164 +/- 31% of baseline without, and 211 +/- 43% with sympathectomy; mean +/- S.D.; P < 0.001). The contributions of the cerebral metabolic mechanism to this flow increase under denervation was minimal, as evidenced by the observation of disproportionately smaller changes in cerebral metabolic rate for oxygen during any type of hypertension. We conclude that the cerebrovasomotor functions of the caudal ventrolateral medulla may operate to keep an equilibrium between simultaneously working tonic inhibitions against sympathetic vasoconstriction as well as against vasodilatation. This dual effect is mediated by excitatory amino acid receptors located within this particular brain area. The vasodilator mechanism may be of neurogenic origin. When the function of the brain area is suppressed, the subsequently disinhibited vasodilator mechanism dominates the cerebrovascular autoregulatory function.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical features of the localized girdle sensation of mid-trunk (false localizing sign) appeared in cervical compressive myelopathy patients.
Cervical compressive myelopathy patients sometimes show localized girdle sensation in the mid trunk (so-called false localizing sign). This symptom often confuses physicians, but the clinical features and mechanism of this symptom are still unclear. We investigated the clinical features and possible mechanism. In each of five cases of cervical compressive myelopathy disease with and without mid-truncal girdle sensation, the clinical features, degree and shape of cord compression were analysed. The girdle sensation was expressed as a vague or burning sensation, and was localized with a width of 3 or 4 dermatomes from the T3 to T11 level. There was no correlation between the appearance of the girdle sensation and etiology and level of cervical cord compression. Pyramidal tract signs and disturbance of superficial sensation were observed in all cases. Furthermore, on axial MRI, the midline ventral surface of the cervical cord was remarkably compressed in cases with girdle sensation, as if the compressive lesion entered the anterior medial fissure of the cervical cord. From these findings, this false localizing sign may be caused by severe compression of midline ventral structure of the cervical cord. Ischemia of the thoracic watershed zone of the anterior spinal artery from the compression of the anterior spinal artery at the cervical level might also be considered to be a possible cause.


Outcome of Mandibular Dentigerous Cysts 1 to 10 Years After Decompression Using a Custom-Made Appliance.
The aim of this study was to examine the long-term results of mandibular dentigerous cysts treated with decompression using a custom-made appliance. This retrospective study included 34 patients with dentigerous cysts who were treated as outpatients at the Faculty of Dentistry, Marmara University. Medical history, complaints, intraoral and extraoral clinical findings, treatment time, and complications of these patients were collected. The average age of the patients was 7.94 years. Three tooth buds (canine, first permanent premolar [P1], and second permanent premolar) in 2 cases, two tooth buds in 7 cases (P1 and second permanent premolar in 6 cases and P1 and canine in 1 case), and one tooth bud in 25 cases were related to the cyst. The mean decompression time was 5.97 months (range, 3 to 9 months). No major complications occurred during or after decompression. No evidence of infection, breakdown and/or dehiscence of the soft tissue, or inferior alveolar nerve paresthesia was observed. The complications and complaints were minor and straightforward to resolve. Decompression is a very effective and successful method for the treatment of mandibular dentigerous cysts.


Estimation of the degradability of dietary protein in the sheep rumen by in vivo and in vitro procedures.
Estimates of degradability of nitrogen in the sheep rumen for a basal hay diet and for soya-bean meal (SBM), groundnut meal (GNM) and fish meal (FM), when given together with the hay, were determined from measurements of duodenal N flow, ammonia kinetics and rumen N disappearance from polyester bags and rumen outflow rate. The ability of various in vitro procedures to predict in vivo N degradability was also examined. Four sheep were given a basal hay diet (800 g dry matter (DM) and 19 g N/d) either alone or supplemented with isonitrogenous amounts (15 g N/d) of SBM, GNM or FM. Duodenal non-ammonia-N flow (g/d) was increased more by FM (8.0) than by GNM (5.9) and SBM (5.8), whilst microbial N flow (g/d) was increased more by SBM (3.9) than by GNM (2.3) and FM (1.6). N degradability values calculated from these results were 0.88, 0.76 and 0.57 for the SBM, GNM and FM respectively. The corresponding value for hay was calculated to be 0.76. The irreversible loss of ammonia in the forestomachs (g N/d) was increased more by SBM (11.9) than by GNM (7.2) and FM (5.8), whilst ammonia outflow from the rumen (g N/d) was increased to a similar extent by all supplements (1.1, 0.9 and 0.8 respectively), as was the amount of microbial N (g/d) synthesized from sources other than rumen ammonia (1.8, 2.0 and 1.9 respectively). N degradability values calculated from these results were 0.84, 0.54 and 0.45 for the SBM, GNM and FM respectively. The fractional rate of N disappearance (/h) when the feedstuffs were incubated in polyester bags in the rumen of sheep receiving the basal hay diet (800 g DM/d) was the highest for SBM (0.145) and lowest for FM (0.037), with the hay (0.082) and GNM (0.071) intermediate, whilst the fractional outflow rates from the rumen (/h) of the three supplements were similar (0.034, 0.038 and 0.030 for SBM, GNM and FM respectively). N degradability values calculated from these results were 0.82, 0.67 and 0.60 for the SBM, GNM and FM respectively; the value for the hay was 0.73. Of a number of in vitro procedures tested, only N solubility in sodium hydroxide and ammonia or total non-protein-N (NPN) production during incubation with rumen fluid in the absence of hydrazine sulphate ranked the supplements, although not the hay, in the same order as in the vivo degradability procedures.(ABSTRACT TRUNCATED AT 400 WORDS)


Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial.
Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders. This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress. This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h. Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups. Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007). The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress. IRCT2016102430459N1 on Iranian Registry of Clinical Trials.


A Review of Randomized Controlled Trials in Cleft and Craniofacial Surgery.
This study presents a systematic review of randomized controlled trials (RCTs) in cleft and craniofacial surgery. All studies reporting on RCTs in cleft and craniofacial surgery were identified on PubMed using the search terms "cleft," "velopharyngeal insufficiency," "velopharyngeal dysfunction," "nasoalveolar molding," "gingivoperiosteoplasty," "Pierre Robin sequence," "craniofacial," "craniosynostosis," "craniofacial microsomia," "hemifacial microsomia," "hypertelorism," "Le Fort," "monobloc," "distraction osteogenesis," "Treacher Collins," and "Goldenhar." Studies were excluded if they were not randomized, did not focus primarily on topics related to cleft or craniofacial surgery, included repeat publications of data, or were unavailable in English. Studies were evaluated on demographic and bibliometric data, study size, specific area of focus, and findings reported. Four hundred forty-seven unique studies were identified. One hundred eighty-three papers met inclusion criteria (115 cleft lip and palate, 65 craniofacial, and 3 spanning both disciplines). Sixty-six (36%) were dedicated to topics related to surgical techniques. There were no studies comparing current cleft lip or soft palate repair techniques and no studies on cleft rhinoplasty. The most frequently reported surgical topic was cleft palate. There were several studies on orthognathic techniques which compared distraction osteogenesis to traditional advancement. Most craniofacial operations, such as cranial vault remodeling and frontofacial advancement/distraction, were not represented. Several standard operations in cleft and craniofacial surgery are not supported by Level I evidence from randomized controlled trials. Our community should consider methods by which more RCTs can be performed, or redefine the acceptable standards of evidence to guide our clinical decisions.


The efficacy of local anaesthetic for pain after iliac bone harvesting: a randomised controlled trial.
Autogenous bone grafting is commonly used in reconstructive surgery but postoperative pain from the donor site can be severe, delaying early mobilisation and preventing discharge from hospital. An RCT of levobupivacaine infusion (16.25mg/h for 24h) of iliac crest wounds versus placebo. Postoperative pain was recorded immediately on returning to the ward, then at 1, 2, 3, 4, 5, 6h, morning and evening on subsequent days until discharge, and at the 7-day clinic appointment. Mobility was recorded twice daily and at 7days. Of 46 evaluable patients, 25 were randomised to levobupivacaine and 21 to placebo. Mean pain scores for (i) average pain from initial assessment to 6h; (ii) 1day in the morning; (iii) 1day in the evening; (iv) at 2days; and (v) follow-up were all statistically significant in favour of lower pain scores in the levobupivicaine group (p-values all <0.01). Comparison between the study groups for mobility found 6 patients unable to get out of bed in the placebo group and none in the local anaesthetic group at the initial assessment (Fisher's exact test p-value=0.005), and 2 patients at 24h. Patients in the local anaesthetic group were always more mobile and this was statistically significant even at 7days for gait disturbance, limp, deviation of gait and unequalness of stride. There were no complications relating to the infusion system. Local anaesthetic significantly reduced postoperative pain and improved mobility. We recommend that surgeons use a local anaesthetic infusion to improve the postoperative experience for their patients undergoing iliac crest grafting.


Bioactive Lipids in Shoulder Tendon Tears.
This commentary highlights the article by Dakin et al that demonstrates critical roles of bioactive lipids in the resolution of inflammation in shoulder tendon tears.


Iturin lipopeptides: interactions of mycosubtilin with lipids in planar membranes and mixed monolayers.
The interactions between the antifungal lipopeptide mycosubtilin and lipids are studied. Mycosubtilin increases the ion permeability of planar lipid membranes by forming ion conducting pores. The lifetime of these pores is greatly increased when the membrane contains cholesterol. In mixed monolayers the interaction between mycosubtilin and DMPC leads to the formation of a mycosubtilin/DMPC 1:2 complex non miscible in the excess DMPC monolayer but miscible in the mycosubtilin monolayer. Mycosubtilin and cholesterol interact strongly in monolayers in all proportions and form a mycosubtilin-cholesterol (1:2) complex. These results are analyzed with reference to the overall view of the activity of iturins and the importance of the lipopeptide conformation is outlined.


Measuring and validating a nurse's caring performance.
This article describes the importance of clear, specific methods of evaluating nursing care. Nursing standards and job descriptions are explained within the context of performance evaluations for nurses.


Metabolic syndrome, aging, physical inactivity, and incidence of type 2 diabetes in general African population.
The first objective of this study was to determine the baseline prevalence of metabolic syndrome and its individual components using the NCEP-R/ATPIII criteria, IDF criteria for Europe, and IDF criteria for Africa: waist circumference of at least 94 cm for men and women. The second objective was to investigate the incidence and the determinants of type 2 diabetes in a prospective cohort of 807 non-diabetic Central Africans aged >or= 40 years from December 2004 to September 2008. During 3,156 person-years of median follow up, there were 93 type 2 diabetes cases (11.5%), corresponding to an incidence of 29 (95% CI 15-43) per 1,000 person-years. The independent predictors of incident type 2 diabetes were age >or= 45 years, physical inactivity, non-diabetic hyperglycaemia and metabolic syndrome regardless of criteria used. In conclusion, urgent prevention strategies are needed to curb the type 2 diabetes epidemic in Africa.


Esophageal Second Primary Tumors in Patients With Head and Neck Squamous Cell Carcinoma: Incidence, Risk Factors, and Overall Survival.
The aim of this registry-based cohort study was to evaluate the potential role of endoscopic esophageal surveillance for esophageal second primary tumors (ESPTs) in Western patients with head and neck squamous cell carcinoma (HNSCC). Outcomes were cumulative incidence and risk factors for ESPTs and its effect on overall survival. A total of 47 ESPTs were observed in 1,708 patients with HNSCC, with 10-year cumulative incidence (95% confidence interval) of 2.9% (2.1-3.7). Alcohol and HNSCC location were significant predictors for ESPTs. ESPTs significantly increased the risk of dying (adjusted hazard ratio 3.36, 95% confidence interval 2.16-5.22). Endoscopic esophageal surveillance of Western patients with HNSCC with high risk of ESPTs seems justified.


Cutting-edge platforms in cardiac tissue engineering.
As cardiac disease takes a higher toll with each passing year, the need for new therapies to deal with the scarcity in heart donors becomes ever more pressing. Cardiac tissue engineering holds the promise of creating functional replacement tissues to repair heart tissue damage. In an attempt to bridge the gap between the lab and clinical realization, the field has made major strides. In this review, we will discuss state of the art technologies such as layer-by-layer assembly, bioprinting and bionic tissue engineering, all developed to overcome some of the major hurdles faced in the field.


A Review Electroconvulsive Therapy in Cochlear Implant Patients.
The use of electroconvulsive therapy (ECT) in cochlear implant (CI) users is debatable. Currently, no consensus statement exists about the safety for the patients and the implants. Here, we present a summary of the existing literature on ECT in CI users, consisting of 4 case reports and a cadaveric study. No harm to the patients or the CIs was reported. Based on our review, we have found no evidence to indicate that ECT in CI users is contraindicated.


A study of the interaction of catecholamines and antidiuretic hormone on water permeability and the cyclic AMP system in isolated papillae of the rat.
The diffusional water permeability of collecting ducts in vitro and the cyclic A.M.P. content of isolated papillae were measured after exposure to different concentrations of antidiuretic hormone, isoproterenol and noradrenalin. Antidiuretic hormone 25 mu units/ml. caused a 25% increase in diffusional water permeability. This response was not affected by isoproterenol (10(-6) M) or noradrenalin (2 x 10(-6) M). Antidiuretic hormone 100 mu unit ml-1 caused a 50% increase in diffusional water permeability which likewise was not altered by isoproterenol or noradrenalin. Isoproterenol (10(-6) M) and noradrenalin (2 x 10(-6) M) had no significant effect on basal levels of diffusional water permeability. Isoproterenol had no significant effect on the tissue concentration of cyclic A.M.P. concentration induced by antidiuretic hormone. Noradrenalin (2 x 10(-6) and 10(-4)) had no significant effect on basal cyclic A.M.P. concentration. However, noradrenalin inhibited the stimulation of cyclic A.M.P. induced by antidiuretic hormone. This effect was inhibited by phentolamine. This study suggests that catecholamines do not alter water handling by a direct action on the water permeability of the kidney but probably exert their action through an effect of A.D.H. release.


On periodic responses of a mathematical neuron model.
The periodic responses of a mathematical neuron model, when periodically varying input stimuli are applied to the model, are investigated. An explicit representation of periodic responses is obtained. It is shown that a periodic response as a 0-1 string is a "uniform string". That is, the 1's of the 0-1 string are distributed uniformly in the string.


Identification of disease treatment mechanisms through the multiscale interactome.
Most diseases disrupt multiple proteins, and drugs treat such diseases by restoring the functions of the disrupted proteins. How drugs restore these functions, however, is often unknown as a drug's therapeutic effects are not limited to the proteins that the drug directly targets. Here, we develop the multiscale interactome, a powerful approach to explain disease treatment. We integrate disease-perturbed proteins, drug targets, and biological functions into a multiscale interactome network. We then develop a random walk-based method that captures how drug effects propagate through a hierarchy of biological functions and physical protein-protein interactions. On three key pharmacological tasks, the multiscale interactome predicts drug-disease treatment, identifies proteins and biological functions related to treatment, and predicts genes that alter a treatment's efficacy and adverse reactions. Our results indicate that physical interactions between proteins alone cannot explain treatment since many drugs treat diseases by affecting the biological functions disrupted by the disease rather than directly targeting disease proteins or their regulators. We provide a general framework for explaining treatment, even when drugs seem unrelated to the diseases they are recommended for.


An importance-performance analysis of teachers' perception of STEM engineering design education.
There is an increasing worldwide trend toward the development of science, technology, engineering, and mathematics (STEM) education using engineering design (ED) practice. Considering that teachers play pivotal roles in terms of student interest in STEM subjects and careers, it is important to explore teachers' perceptions of STEM-ED education. We analysed survey data from 184 technology teachers who participated in empowerment training (using a STEM-ED curriculum) in 2017, 2018, 2021, and 2022. We used an importance-performance analytical model to investigate the teachers' perceptions of STEM-ED itself, its impact on students, and the challenges experienced during implementation. The results showed that various improvements were required for STEM-ED promotion and for the preparation of STEM-ED lessons. Analysis of variance revealed that the age groups taught and the number of weekly teaching hours significantly affected the teachers' perceptions of STEM-ED. These findings will assist educational institutions worldwide in planning future education policies, designing teacher empowerment courses, and understanding teachers' needs in efforts to improve STEM-ED.


Chitosan Nanoparticles Containing Lipoic Acid with Antioxidant Properties as a Potential Nutritional Supplement.
The addition of the antioxidant α-lipoic acid (ALA) to a balanced diet might be crucial for the prevention of comorbidities such as cardiovascular diseases, diabetes, and obesity. Due to its low half-life and instability under stomach-like conditions, α-lipoic acid was encapsulated into chitosan nanoparticles (Ch-NPs). The resulting chitosan nanoparticles containing 20% w/w ALA (Ch-ALA-NPs) with an average diameter of 44 nm demonstrated antioxidant activity and stability under stomach-like conditions for up to 3 h. Furthermore, fluorescent Ch-ALA-NPs were effectively internalized into 3T3-L1 fibroblasts and were able to cross the intestinal barrier, as evidenced by everted intestine in vitro experiments. Thus, chitosan-based nanoparticles seem to be an attractive administration method for antioxidants, or other sensible additives, in food.


An arsenal of tools based on Kendrick mass defects to process congested electrospray ionization high-resolution mass spectra of polymers with multiple charging.
Electrospray ionization (ESI) favors the multiple charging of high molecular weight polymer samples and allows their high-resolution mass analysis in the low-mass range. It also induces the detection of numerous ion series at different charge states with different adducts complicating the interpretation of the mass spectrum which should be facilitated by an appropriate data processing. An arsenal of tools based on the Kendrick mass defect (KMD) is proposed to process congested ESI high-resolution mass spectra of poly(propylene oxide) (PPO) samples. The combination of regular, charge-dependent, and resolution-enhanced KMD plots in addition to a "remainders" plot and a new three-dimensional plot offers unrivaled capabilities of filtering for any minor series among thousands of points. The sequential data processing is conducted using Kendo, a spreadsheet developed in-house for an advanced KMD analysis. The charge-state distribution is easily evaluated by counting the parallel lines in a regular KMD plot. A charge-dependent resolution-enhanced KMD plot instantly reveals the variation of adducted ions at a given charge state, helping the user to choose the best analytical conditions. Ion series at different charge states from PPO oligomers carrying different end-groups are also efficiently extracted using several combinations of KMD and remainders plots and assigned using a new simulator tool. The innovative combination of existing and new KMD-related plots, selection tools, and simulator all combined in a single spreadsheet dramatically facilitates the processing and interpretation of complex ESI mass spectral data. The presented tools may be extended to any other class of homo-, co- and terpolymers.


Initial experience of treating anal fistula with the Surgisis anal fistula plug.
Complex anal fistulas remain a challenge for the colorectal surgeon. The anal fistula plug has been developed as a simple treatment for fistula-in-ano. We present and evaluate our experience with the Surgisis anal fistula plug from two centres. Data were prospectively collected and analysed from consecutive patients undergoing insertion of a fistula plug between January 2007 and October 2009. Fistula plugs were inserted according to a standard protocol. Data collected included patient demographics, fistula characteristics and postoperative outcome. Forty-four patients underwent insertion of 62 plugs (27 males, mean age 45.6 years), 25 of whom had prior fistula surgery. Mean follow-up was 10.5 months Twenty-two patients (50%) had successful healing following the insertion of plug with an overall success rate of 23 out of 62 plugs inserted (35%). Nineteen out of 29 patients healed following first-time plug placement, whereas repeated plug placement was successful in 3 out of 15 patients (20%; p = 0.0097). There was a statistically significant difference in the healing rate between patients who had one or less operations prior to plug insertion (i.e. simple fistulas) compared with patients who needed multiple operations (18 out of 24 patients vs. 4 out of 20 patients; p = 0.0007). Success of treatment with the Surgisis anal fistula plug relies on the eradication of sepsis prior to plug placement. Plugs inserted into simple tracts have a higher success rate, and recurrent insertion of plugs following previous plug failure is less likely to be successful. We suggest the fistula plug should remain a first-line treatment for primary surgery and simple tracts.


[Quality of life in patients with vestibular schwannoma].
Vestibular schwannoma (VS) is a disease which might affect health-related quality of life (HR-QOL) in a negative manner. For many years, only generic quality of life instruments such as SF-36 were available to measure HR-QOL. However, some years ago, the Penn Acoustic Neuroma Quality Of Life (PANQOL) tool, a disease-specific instrument, was developed and validated. It is expected that the application of this instrument will be able to better assess relevant aspects of the HR-QOL of VS patients in the future. A validated German version of the instrument does not exist yet. The disease-specific symptoms most frequently named by patients are headache and dizziness. The available literature shows that the therapeutic approaches affect HR-QOL differently. In particular, radiation therapy of small and medium-sized tumors has no pronounced negative effects on HR-QOL. However, restrictions after surgery become similar to those after radiotherapy over the course of several years. For large VS with a diameter >3 cm, no guiding data on this aspect are currently available. To clarify the outstanding issues, future prospective studies with long-term follow-up of 10 years and more are desirable.


The association between household biomass fuel use and leukocyte telomere length among toddlers in Bhaktapur, Nepal.
Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults. To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18-23 months of age among 497 children from Bhaktapur, Nepal. In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models. Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with ≤2 rooms and without separate kitchen. Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings. Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a "biological marker" of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking. Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014).


Evidence for an intracellular action of platelet-activating factor in bovine cultured aortic endothelial cells.
Bovine culture endothelial cells (BAECs) generate platelet-activating factor (Paf) following activation by bradykinin (Bk 0.1 nM), the ionophore, A23187 (3 microM), and ATP (10 microM), but Paf is not released from the cells. These stimuli also elicit generation of prostacyclin (PGI2). The specific and competitive Paf receptor antagonists, WEB 2086 (0.1-1.0 microM) and CV 6209 (0.01-0.1 microM), inhibited Bk-, A23187- and, to a lesser extent, ATP-induced PGI2 generation but had no effect on basal PGI2 generation. These data suggest a role for intracellular Paf in signal transduction.


Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.
The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. Compared to no screening, biennial gFOBT screening between age 50-74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50-74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45-80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand.


Sarcoidosis and ocular disease in a young child. A case report and review of the literature.
Uveitis in the very young child may be a manifestation of sarcoidosis. A case of sarcoidosis with intraocular inflammation that occurred in a child 2 years 7 months old is reported. The diagnosis was supported by biopsy of uncommon bulbar conjunctival nodules. Knowledge by the ophthalmologists that this disease can occur in children younger than 5 years of age may be crucial to the establishment of proper diagnosis.


Healthcare professional preferences in the health and fitness assessment and optimization of older patients facing colorectal cancer surgery.
There are few age- and fitness-specific, evidence-based guidelines for colorectal cancer surgery. The uptake of different assessment and optimization strategies is variable. The aim of this study was to explore healthcare professional opinion about these issues using a mixed methods design. Semi-structured qualitative interviews were undertaken with healthcare professionals from a single UK region involved in the treatment, assessment and optimization of colorectal surgery patients. Interviews were analysed using the framework approach. An online questionnaire survey was subsequently designed and disseminated to UK surgeons to quantitatively assess the importance of interview themes. Descriptive statistics were used to analyse questionnaire data. Thirty-seven healthcare professionals out of 42 approached (response rate 88%) were interviewed across five hospitals in the south Yorkshire region. Three broad themes were developed: attitudes towards treatment of the older patient, methods of assessment of suitability and optimization strategies. The questionnaire was completed by 103 out of an estimated 256 surgeons (estimated response rate 40.2%). There was a difference in opinion regarding the role of major surgery in older patients, particularly when there is coexisting dementia. Assessment was not standardized. Access to optimization strategies was limited, particularly in the emergency setting. There is wide variation in the process of assessment and provision of optimization strategies in UK practice. Lack of evidence-based guidelines, cost and time constraints restrict the development of services and pathways. Differences in opinion between surgeons towards patients with frailty or dementia may account for some of the variation in colorectal cancer outcomes.


[Diabetes mellitus and Addison's disease)].
The authors diagnosed diabetes mellitus together with Addison's disease in a 38 year-old male patient. They are discussing therapeutic difficulties arising from the biglandular hypofunctional condition and the problems of the pathogenesis.


A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-alpha are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFalpha effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis. Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a nuclear factor-kappaB (NF-kappaB) reporter assay and in vivo in streptococcal cell wall-induced arthritis (SCW) and collagen-induced arthritis (CIA). Adenoviruses were administered before onset of CIA, and the effect of TNFR1 targeting on the clinical development of arthritis, histology, quantitative polymerase chain reaction (qPCR), cytokine analyses and T-cell assays was evaluated. Systemic delivery of Ad5.CMV-eGFP predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver, spleen and draining lymph nodes. In vitro, HpTNFR1 reduced the TNFR1 mRNA expression by three-fold resulting in a 70% reduction of TNFalpha-induced NF-kappaB activation. Local treatment with HpTNFR1 markedly reduced mRNA and protein levels of interleukin (IL)-1beta and IL-6 in SLC during SCW arthritis and ameliorated CIA. Systemic targeting of TNFR1 in RES of liver and spleen by systemic delivery of Ad5 virus encoding for a small hairpin RNA against TNFR1 markedly ameliorated CIA and simultaneously reduced the mRNA expression of IL-1beta, IL-6 and Saa1 (75%), in the liver and that of Th1/2/17-specific transcription factors T-bet, GATA-3 and RORgammaT in the spleen. Flow cytometry confirmed that HpTNFR1 reduced the numbers of interferon (IFN)gamma (Th1)-, IL-4 (Th2)- and IL-17 (Th17)-producing cells in spleen. TNFR1-mediated signaling in both synovial lining cells and the reticuloendothelial system independently played a major pro-inflammatory and immunoregulatory role in the development of experimental arthritis.


Measurement of Minute Cellular Forces by Traction Force Microscopy.
The ability of living cells to exert forces on their surrounding environment, such as the extracellular matrix (ECM) or neighboring cells, plays an important role in numerous biological processes. This chapter describes a simple protocol to measure forces exerted by living cells using traction force microscopy. This approach is based on the measurement of the deformation of compliant substrates using fluorescent fiducials. It can be implemented using widefield or confocal fluorescent microscopes, and open-source software. This chapter describes a step-by-step protocol to measure forces exerted by focal adhesions bound to the ECM protein fibronectin. However, this framework is versatile and can be easily adapted to a multitude of ligands and cellular processes in which cells exert forces, including the formation of an immunological synapse or a phagocytic cup. Technical considerations, limitations of the approach, and practical advice are discussed.


Evaluation of soft tissue prediction accuracy for orthognathic surgery with skeletal class III malocclusion using maxillofacial regional aesthetic units.
This study aimed to evaluate the soft tissue prediction accuracy of patients undergoing orthognathic surgery to correct skeletal class III malocclusion using maxillofacial regional aesthetic units. Pre- and postoperative cone-beam computed tomography (CBCT) and 3D facial scans were taken for 58 patients who had undergone orthognathic surgery. The preoperative 3D facial scan was integrated with the preoperative CBCT using ProPlan CMF software. The software simulated the surgery and generated postoperative soft tissue prediction. The simulated 3D facial scan was then compared with the actual 3D facial scan obtained at least 6 months after the surgery by the maxillofacial regional aesthetic units and the facial soft tissue landmark points. The anatomical regions of the upper lip, lower lip, chin, right external buccal and left external buccal prediction were above 2.0 mm. As for the soft tissue landmarks, at chl, chr, ls, stm and li, the position of predicted scan was higher than that of the actual postoperative scan. The accuracy of 3D soft tissue predictions using ProPlan CMF software in Skeletal III patients was clinically satisfactory according to maxillofacial regional aesthetic units combined with facial soft tissue landmark points. However, the accuracy of prediction still needed improvement in some areas. The accuracy of soft tissue prediction can be analyzed more clearly through maxillofacial regional aesthetic units so that clinicians have a deeper understanding of the use of the software to predict soft tissue change after orthognathic surgery.


Substituted indanylacetic acids as PPAR-alpha-gamma activators.
A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.


Identification of X-chromosomal genes that drive sex differences in embryonic stem cells through a hierarchical CRISPR screening approach.
X-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signaling pathway, and delaying differentiation. To identify the genetic basis of these sex differences, we use a two-step CRISPR screening approach to comprehensively identify X-linked genes that cause the female pluripotency phenotype in murine embryonic stem cells. A primary chromosome-wide CRISPR knockout screen and three secondary screens assaying for different aspects of the female pluripotency phenotype allow us to uncover multiple genes that act in concert and to disentangle their relative roles. Among them, we identify Dusp9 and Klhl13 as two central players. While Dusp9 mainly affects MAPK pathway intermediates, Klhl13 promotes pluripotency factor expression and delays differentiation, with both factors jointly repressing MAPK target gene expression. Here, we elucidate the mechanisms that drive sex-induced differences in pluripotent cells and our approach serves as a blueprint to discover the genetic basis of the phenotypic consequences of other chromosomal effects.


Fibroma of the cecum: report of a case.
A woman suffering from recurrent attacks of abdominal pain was found at operation to have a fibroma of the cecum. The clinical, operative and pathologic findings are described. The medical literature was reviewed and the lesion was found to be uncommon. The importance of specific histologic stains to distinguish the true fibroma from other spindle-cell tumors is stressed.


Biochemical and Nutritional Changes during Food Processing and Storage.
Domestic food processing goes a long way back in time, for example, heat for cooking was used 1 [...].


Intestinal mucus components and secretion mechanisms: what we do and do not know.
Damage to the colon mucus barrier, the first line of defense against microorganisms, is an important determinant of intestinal diseases such as inflammatory bowel disease and colorectal cancer, and disorder in extraintestinal organs. The mucus layer has attracted the attention of the scientific community in recent years, and with the discovery of new mucosal components, it has become increasingly clear that the mucosal barrier is a complex system composed of many components. Moreover, certain components are jointly involved in regulating the structure and function of the mucus barrier. Therefore, a comprehensive and systematic understanding of the functional components of the mucus layer is clearly warranted. In this review, we summarize the various functional components of the mucus layer identified thus far and describe their unique roles in shaping mucosal structure and function. Furthermore, we detail the mechanisms underlying mucus secretion, including baseline and stimulated secretion. In our opinion, baseline secretion can be categorized into spontaneous Ca2+ oscillation-mediated slow and continuous secretion and stimulated secretion, which is mediated by massive Ca2+ influx induced by exogenous stimuli. This review extends the current understanding of the intestinal mucus barrier, with an emphasis on host defense strategies based on fortification of the mucus layer.


The psychological impact on patients with memory disorders and their caregivers during COVID-19.
COVID-19 is erupting globally. Mass quarantine had been implemented all around China which could influence the psychological status of patients with memory disorders and their caregivers. To investigate the psychological impact of mass quarantine on patients with memory disorders and their caregivers in China. We completed a cross-sectional study in 787 patients and their caregivers registered from 2010 to 2019 in Memory Clinic, The First Affiliated Hospital of Chongqing Medical University, by telephone interviews. The performance in neuropsychiatric symptoms (NPSs), sleep, nutrition, chronic diseases of patients, and the burden of care, anxiety and depression of caregivers was assessed by six assessment scales (MNA-SF, PSQI, NPI, RSS, PHQ-9 and GAD-7). Only 68 (8.6%) patients worried about the outbreak of COVID-19. The prevalence of NPSs among all subjects was nearly 60.0%. Approximately 50.0% of the caregivers reported distress. More than 70.0% of patients remained stable in NPSs. However, anxiety, depression, aberrant motor disorder and delusion were exacerbated (22.9%, 18.6%, 17.1% and 16.8%, respectively). Appetite and eating disorder led alleviation rate by 25.8% while disappearing rate of agitation led by 5.8%. 7.5% of caregivers manifested depressive symptoms while 4.9% expressed anxiety symptoms, and 40.8% showed care burden. The coefficients of RSS and PHQ-9, RSS and GAD-7, RSS and NPI-D, PHQ-9 and GAD-7 were 0.7, 0.5, 0.5 and 0.6, respectively (p < 0.01). Changes in NPSs during COVID-19 were observed in some patients with memory disorders and their caregivers, and adherence to medication contributed to the stabilization of NPSs.


Cingulate cortex morphology impacts on neurofunctional activity and behavioral performance in interference tasks.
Inhibitory control is the capacity to withhold or suppress a thought or action intentionally. The anterior Midcingulate Cortex (aMCC) participates in response inhibition, a proxy measure of inhibitory control. Recent research suggests that response inhibition is modulated by individual variability in the aMCC sulcal morphology. However, no study has investigated if this phenomenon is associated with neurofunctional differences during a task. In this study, 42 participants performed an Attention Network Task and a Numerical Stroop task in an MRI scanner. We investigated differences in brain activity and response inhibition efficiency between individuals with symmetric and asymmetric aMCC sulcal patterns. The results showed that aMCC morphological variability is partly associated with inhibitory control, and revealed greater activation in individuals with symmetric patterns during the Stroop task. Our findings provide novel insights into the functional correlates of the relationship between aMCC morphology and executive abilities.


The effect of the conformer state and the model size chosen on the force field of the polypeptide backbone.
We have attempted to check the validity of our previously calculated ab initio force field for the polypeptide backbone, for the variance with conformer state and model size chosen. For the previous problem we applied our usual ab initio Hartree-Fock SQM method, also used at the original development of the force field, while for the latter we utilized the semiempirical MNDO CO-gradient method. It is shown that the in-plane force field is reasonably stable for change of conformational state, while the out-of-plane force field can be assigned good average guess values. The effect of the model size is shown to be moderate upon introducing a dipeptide into a polymer chain.


Extracorporeal complexation and haemodialysis for the treatment of cadmium poisoning. I. Effects of four chelators on the in vitro elimination of cadmium from human blood.
The effect of ethylenediamine tetraacetic acid (EDTA), glutathione (GSH), citrate and 2,3-dimercaptosuccinic acid (DMSA) on the elimination of cadmium (Cd) from human blood, by complexing haemodialysis, was investigated in vitro. A significant increase in elimination rate was observed with all four chelators compared to that observed without chelators. EDTA was found to be the most effective agent, which at a level of 0.01M in the dialysate facilitated elimination of 80% of the blood Cd originally present.


Epidemiological studies and proposed preventive measures in the fight against human salmonellosis.
A large number of countries annually report high numbers of Salmonella infections in man. Since it is estimated that these reported cases only represent 1 to 10% of the real incidence of this disease, it must be concluded that human salmonellosis is a serious problem all over the world. The major source for human salmonellosis is caused by farm animals, which may frequently be intestinal carriers of the organism. Particularly pigs and poultry are incriminated in this respect, and, to a lesser degree, cattle and sheep. Because generally no symptoms of disease can be observed, these animals usually pass veterinary slaughterhouse inspection without restrictions. During slaughter however, intestinal material, often containing Salmonella bacteria, pollutes the surface of carcasses, which in later stages may lead to extensive Salmonella contamination of meat and meat products. Additionally, milk may also be contaminated by faecal material during collection, while eggs may be externally contaminated by faecal material or internally infected by way of transovarial transmission. Cross-contamination in slaughterhouses, in butchers' shops and in the kitchen may add to the problem. Human infection occurs when animal products are improperly handled during final preparation. This may happen at home, but also in large kitchens of restaurants, hospitals, institutions and factories. In most instances infection is related to cross-contamination from meat to foods that are to be consumed without further treatment, such as bread, salads and fruits, to improper heating of the animal products themselves, as for instance with eggs, or even to the consumption of raw animal products, as may be the case with meat and milk. The faecal excretion of Salmonella by human patients, wild and domesticated animal carriers, as well as the disposal of slaughter offal, sludge, slurry and manure contributes to an overall Salmonella spread in the environment. This may lead, by way of contamination of surface waters and colonisation of birds, rodents and insects, to the contamination of animal feeds or directly contribute to the re-colonisation of farm animals. In order to solve the problem of human salmonellosis, measures should be taken simultaneously on several levels. Since there are so many transmission ways, particularly in the environment and on the farm, isolated actions, such as the decontamination of animal feed, will never give lasting results. Likewise, the sole responsibility for the problem should never lie with the consumer.(ABSTRACT TRUNCATED AT 400 WORDS)


Two children with lethargy and intussusception.
The cases of two patients with lethargy as the predominant symptom of intussusception are described. The first patient was admitted to the pediatric ICU with unexplained lethargy. The diagnosis of intussusception was made after he developed right lower quadrant abdominal tenderness and heme-positive stool. The second patient was diagnosed after presenting to the emergency department with intermittent lethargy, right lower quadrant abdominal tenderness, and heme-positive stool. The presence of gastrointestinal symptoms or signs in association with lethargy should alert the physician to the possibility of an intussusception.


Health anxiety and illness-related fears across diverse chronic illnesses: A systematic review on conceptualization, measurement, prevalence, course, and correlates.
Patients with chronic diseases commonly report fears of illness or symptoms recurring or worsening. These fears have been addressed from an illness-specific perspective (e.g., fear of cancer recurrence), a generic illness perspective (e.g., fear of progression), and a psychiatric perspective (DSM-5 illness anxiety disorder and somatic symptom disorder). The broader concept of health anxiety (HA) can also be applied to patients with a chronic disease. This review was conducted to investigate the conceptual, theoretical, measurement-overlap, and differences between these distinct perspectives. We also aimed to summarize prevalence, course, and correlates of these fears in different chronic illnesses. We used PsycINFO, PubMED, CINAHL, Web of Science, SCOPUS, and PSYNDEX to conduct a systematic review of studies pertaining to these fears in chronic illness published from January 1996 to October 2017. A total of 401 articles were retained. There were commonalities across different conceptualizations and diseases: a high prevalence of clinical levels of fears (>20%), a stable course over time, and a deleterious impact on quality of life. Reviewed studies used definitions, models, and measures that were illness-specific, with only a minority employing a psychiatric perspective, limiting cross-disease generalizability. There appears to be some applicability of DSM-5 disorders to the experience of fear of illness/symptoms in patients with a chronic illness. While conceptualizing HA on a continuum ranging from mild and transient to severe may be appropriate, there is a lack of agreement about when the level of fear becomes 'excessive.' The definitions, models, and measures of HA across chronic illnesses involve affective, cognitive, behavioral, and perceptual features. The concept of HA may offer a unifying conceptual perspective on the fears of illness/symptoms worsening or returning commonly experienced by those with chronic disease.


Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy.
The study was designed to determine whether invasion of the tumor capsule, in the absence of vascular invasion (VI), was significant in predicting cause-specific mortality in follicular thyroid carcinoma (FTC). Seventy-two patients with FTC were treated by us during 1971 through 1985. In 65 cases the tumors could be classified as either showing capsular invasion (CI) alone (20) or VI, with or without CI, (45). Median follow-up of 45 survivors was 11 years; 12 patients died of FTC. The 10-year occurrence rates for cause-specific mortality and distant metastases were 28% and 19%, respectively, for patients with VI. Comparable rates for the patients with CI were 0% (p = 0.019) and 0% (p = 0.052), respectively. By univariate analysis, higher rates of cause-specific mortality were significantly associated with distant metastases at diagnosis (p < 0.0001), the presence of VI (p = 0.019), and moderate or marked microinvasion (p = 0.019). In stepwise multivariate analyses, only distant metastases at diagnosis had independent prognostic significance (p < 0.0001) in the prediction of cause-specific mortality. In a Cox model, adjusting for distant metastases at diagnosis, the presence of VI was of borderline significance (p = 0.06) in predicting cause-specific mortality. FTC, diagnosed on the basis of CI alone, did not result in either distant metastases or cancer-related death. The dominant determinant of cause-specific mortality was the presence of distant metastases at diagnosis.


Community-based projects in rural internships: an alternative approach.
Supervision of medical interns posted to various primary health centres and rural health training centres by specialists in preventive and social medicine and other clinical disciplines is becoming less and less effective for a number of unavoidable reasons. Because of lack of proper and timely guidance, interns feel that during the 6-month rural internship they do not get enough experience of rural life. In order to provide them with learning experiences in community medicine and orient them in the social dynamics of the community, a new approach involving interns in small community-based projects, probably for the first time, was tried on a pilot basis at the Rural Health Training Centre (RHTC), Sirur, a field practice area of B.J. Medical College, Pune, Maharashtra, India. Interns working at RHTC Sirur completed these community-based projects successfully. Identification of problems, study design analysis and drawing conclusions, based on observation, were all undertaken by the interns under the guidance of the staff of the Department of Preventive and Social Medicine, B.J. Medical College. The opinion poll at the end of the rural internship revealed that 76% of interns considered this experience valuable for improving their knowledge and skills, and 56% though that interaction during these projects was beneficial to the community as well. This experience with community-based projects for interns during their rural posting provides them with an opportunity for interaction with the community.


Bridging the gap: Spinal cord fusion as a treatment of chronic spinal cord injury.
Despite decades of animal experimentation, human translation with cell grafts, conduits, and other strategies has failed to cure patients with chronic spinal cord injury (SCI). Recent data show that motor deficits due to spinal cord transection in animal models can be reversed by local application of fusogens, such as Polyethylene glycol (PEG). Results proved superior at short term over all other treatments deployed in animal studies, opening the way to human trials. In particular, removal of the injured spinal cord segment followed by PEG fusion of the two ends along with vertebral osteotomy to shorten the spine holds the promise for a cure in many cases.


Advances in quantitative biology methods for studying replicative aging in Saccharomyces cerevisiae.
Aging is a complex, yet pervasive phenomenon in biology. As human cells steadily succumb to the deteriorating effects of aging, so too comes a host of age-related ailments such as neurodegenerative disorders, cardiovascular disease and cancer. Therefore, elucidation of the molecular networks that drive aging is of paramount importance to human health. Progress toward this goal has been aided by studies from simple model organisms such as Saccharomyces cerevisiae. While work in budding yeast has already revealed much about the basic biology of aging as well as a number of evolutionarily conserved pathways involved in this process, recent technological advances are poised to greatly expand our knowledge of aging in this simple eukaryote. Here, we review the latest developments in microfluidics, single-cell analysis and high-throughput technologies for studying single-cell replicative aging in S. cerevisiae. We detail the challenges each of these methods addresses as well as the unique insights into aging that each has provided. We conclude with a discussion of potential future applications of these techniques as well as the importance of single-cell dynamics and quantitative biology approaches for understanding cell aging.


Subcellular localization of the five members of the human steroid 5α-reductase family.
In humans the steroid 5alpha-reductase (SRD5A) family comprises five integral membrane enzymes that carry out reduction of a double bond in lipidic substrates: Δ4-3-keto steroids, polyprenol and trans-enoyl CoA. The best-characterized reaction is the conversion of testosterone into the more potent dihydrotestosterone carried out by SRD5A1-2. Some controversy exists on their possible nuclear or endoplasmic reticulum localization. We report the cloning and transient expression in HeLa cells of the five members of the human steroid 5α-reductase family as both N- and C-terminus green fluorescent protein tagged protein constructs. Following the intrinsic fluorescence of the tag, we have determined that the subcellular localization of these enzymes is in the endoplasmic reticulum, upon expression in HeLa cells. The presence of the tag at either end of the polypeptide chain can affect protein expression and, in the case of trans enoyl-CoA reductase, it induces the formation of protein aggregates.


Two π-Conjugated Covalent Organic Frameworks with Long-Term Cyclability at High Current Density for Lithium Ion Battery.
Organic lithium ion batteries (LIBs) are considered as one of the next-generation green electrochemical energy storage (EES) devices. However, obtaining both high capacity and long-term cyclability is still the bottleneck of organic electrode materials for LIBs because of weak structural and chemical stability and low conductivity. Covalent organic frameworks (COFs) show potential to overcome these problems owing to its good stability and high capacity. Herein, the synthesis and characterization of two π-conjugated COFs, derived from the Schiff-base reaction of 2,4,6-triaminopyrimidne (TM) respectively with 1,4-phthalaldehyde (PA) and 1,3,5-triformylbenzene (TB) by a mechanochemical process are presented. As anode materials for LIBs, the COFs exhibit favorable electrochemical performance with the highest reversible discharge capacities of up to 401.3 and 379.1 mAh g-1 at a high current density (1 A g-1 ), respectively, and excellent long-term cyclability with 74.8 and 72.7 % capacity retention after 2000 cycles compared to the initial discharge capacities.


Patients' opinion on the use of 2 generations of power-driven water flossers and their impact on gingival inflammation.
To assess patients' opinion on the use of 2 generations of power-driven water flossers and their impact on gingival inflammation. In the present prospective cohort study 24 periodontitis patients under regular supportive periodontal therapy used daily 2 generations of a power-driven water flosser (Sonicare AirFloss [SAF] and Sonicare AirFloss Ultra [SAFU]) for 12 weeks each. Patients were instructed to position the nozzle interproximally from the buccal aspect at each interproximal space. Patients' opinion was assessed by a questionnaire and interproximal bleeding on probing (BoP) was recorded. Overall satisfaction with SAF/SAFU was rated high, by about 80% of the patients. About 66% of the patients preferred SAF/SAFU compared to their previous interdental cleaning device and indicated that they would continue using SAF/SAFU after the study; none of the patients reported any discomfort or pain. Compared to only tooth brushing, daily use of SAF/SAFU caused a significant reduction of interproximal BoP values, which were well maintained over 6 months; that is, BoP at interproximal buccal and oral sites (pooled), as well as at interproximal buccal and oral sites separately, was proportionately reduced by 29.1%, 41.2%, and 24.8%, respectively (pooled: p = 0.027; buccal sites: p = 0.030; oral sites: p = 0.030). Patients were very fond of the power-driven water flossers tested herein, and daily use of the devices for 6 months (i.e., each device was used for 3 months) resulted in a significant reduction of gingival inflammation interproximally.


Reaction times of four year old children to monaurally presented verbal stimuli: some evidence for right-hemisphere linguistic function.
Previous studies of cerebral dominance in children have provided information about the relative superiority of the left hemisphere over the right for language processing. The present study, however, assessed the absolute capacity of each hemisphere's ability for analyzing auditory-verbal stimuli in a group of young children (mean age = 4.0). Twenty-four normally developing children (12 males and 12 females) responded to monaurally presented verbal stimuli with their right and left hands at separate times. The results were consistent with an efficiency model of neurolinguistic organization, suggesting that the childrens' minor hemisphere was actively processing verbal information in the presence of a dominant left hemisphere.