A comparison of psychometric properties of the smart balance master system and the postural assessment scale for stroke in people who have had mild stroke.
To compare the psychometric properties (including the test-retest reliability, responsiveness, and predictive validity) of the Smart Balance Master (SBM) system and the Postural Assessment Scale for Stroke patients (PASS) in patients with mild stroke. One repeated-measures design (at a 2-wk interval) was used to examine the test-retest reliability of the SBM and PASS, and another similar design was applied to investigate their responsiveness. Patients who participated in the responsiveness study were followed up approximately 1 year later, and the predictive validity of the SBM system and PASS were examined by assessing the patients' comprehensive activities of daily living (ADL) function. Three rehabilitation units in Taiwan. Twenty patients with chronic stroke in the reliability study; 40 and 32 patients who had recently had a stroke in the responsiveness and predictive validity studies, respectively. Not applicable. Three computerized tests of the SBM (the equilibrium score of the Sensory Organization Test, scores in rhythmic weight-shifting tests, and scores in the limits of stability test) and the PASS were used. The combination of the Barthel Index and Frenchay Activities Index was used to represent the comprehensive ADL function. For the SBM, all but the weight-shifting tests of the SBM had moderate to high reliability (intraclass correlation coefficient [ICC] range, .78-.91). The responsiveness of the equilibrium score and the limits of stability test were moderate (effect size [d], .63) and small (d range, .27-.33), respectively, whereas the responsiveness of the weight-shifting tests was limited (d range, .04-.29). All but the weight-shifting tests of the SBM in the second evaluation had acceptable predictive validity for comprehensive ADL function (r2 range, .15-.17). The PASS showed high reliability (ICC=.84) and small responsiveness (d=.41), and the PASS in the second evaluation had acceptable predictive validity (r2=.24). The PASS and the equilibrium score and limits of stability scores of the SBM had acceptable test-retest reliability, responsiveness, and predictive validity in patients with mild stroke, but the psychometric properties of the weight-shifting tests of the SBM should be further examined before consideration of their usage in patients with stroke.


Value of MR imaging in clinical evaluation of breast lesions.
To evaluate the value of dynamic MR imaging as an adjunctive tool to triple diagnosis (TD) (physical examination, mammography and fine needle aspiration cytology) in diagnosing breast lesions. Ninety-three consecutive patients with 114 palpable or mammographically detected breast lesions were examined with TD and MR imaging. The MR examination was performed dynamically using a dedicated breast coil. Five diagnostic groups were defined on a scale from 1=normal, to 5 = malignant, where groups 1-3 were defined as benign and groups 4-5 as malignant. All lesions were histopathologically examined. The sensitivity and specificity were calculated for mammography alone, TD, MR and the combination of MR and TD. Histopathology revealed 32 benign and 82 malignant lesions (73 invasive and 9 cancer in situ). The sensitivity/specificity was 84%/59% for mammography, 93%/41% for TD, 94%/47% for MR and 99%/19% for TD + MR. In the 32 mammographically dense breasts, mammography/TD/MR/TD + MR had a sensitivity of 72%/94%/94%/100% and a specificity of 79%/57%/36%/29%, respectively. MR imaging might be of value as an additive method to TD by increasing the sensitivity, but at the cost of decreasing specificity. Patients with mammographically dense parenchyma might have more benefit of the additive value, as the decrease in specificity in these patients was less pronounced in our study.


Phenyl-ring rotational disorder in the two-dimensional hydrogen-bonded structure of the 1:1 proton-transfer salt of the diazo-dye precursor 4-(phenyldiazenyl)aniline (aniline yellow) with L-tartaric acid.
In the structure of the 1:1 proton-transfer compound from the reaction of L-tartaric acid with the azo-dye precursor aniline yellow [4-(phenyldiazenyl)aniline], namely 4-(phenyldiazenyl)anilinium (2R,3R)-3-carboxy-2,3-dihydroxypropanoate, C(12)H(12)N(3)(+) x C(4)H(5)O(6)(-), the asymmetric unit contains two independent 4-(phenyldiazenyl)anilinium cations and two hydrogen L-tartrate anions. The structure is unusual in that all four phenyl rings of the two cations have identical rotational disorder with equal occupancy of the conformations. The two hydrogen L-tartrate anions form independent but similar chains through head-to-tail carboxyl-carboxylate O-H...O hydrogen bonds [graph set C(7)], which are then extended into a two-dimensional hydrogen-bonded sheet structure through hydroxy O-H...O hydrogen-bonded links. The anilinium groups of the 4-(phenyldiazenyl)anilinium cations are incorporated into the sheets and also provide internal hydrogen-bonded extensions, while their aromatic tails are layered in the structure without significant association except for weak pi-pi interactions [minimum ring centroid separation = 3.844 (3) A]. The hydrogen L-tartrate residues of both anions exhibit the common short intramolecular hydroxy-carboxylate O-H...O hydrogen bonds. This work provides a solution to the unusual disorder problem inherent in the structure of this salt, as well as giving another example of the utility of the hydrogen tartrate anion in the generation of sheet substructures in molecular assembly processes.


The use of porcine small intestinal submucosa as a prosthetic material for laparoscopic hernia repair in infected and potentially contaminated fields: long-term follow-up.
The treatment of hernias remains controversial, with multiple prosthetic meshes being exalted for a variety of their characteristics. In the event of incarcerated/strangulated hernias and other potentially contaminated fields the placement of prosthetic material remains controversial because of increased risk of recurrence and infection. Porcine small intestinal submucosa mesh (Surgisis, Cook Bloomington, IN) has been demonstrated safe and feasible in laparoscopic hernia repairs in this scenario. We present our 5-year experience, with placement of Surgisis mesh in potentially or grossly contaminated fields. From May 2000 to October 2006, 116 patients (52 male, 64 female) with 133 procedures were performed. Placement of Surgisis mesh for either incisional, umbilical, inguinal, femoral or parastomal hernia repairs in an infected or potentially contaminated setting were achieved, and studied in a prospective fashion. All procedures were laparoscopically with two techniques [intraperitoneal onlay mesh (IPOM) and two-layered "sandwich" repair]. Mean follow-up was 52 +/- 20.9 months. Thirty-nine cases were in an infected field and the rest in a potentially contaminated field. Ninety-one procedures were performed concurrently with a contaminated procedure. Twenty-five presented as intestinal obstruction, 16 strangulated hernias, and 17 required small bowel resection; 29 were inguinal hernias, 57 incisional, and 38 umbilical. In 13 patients more than two different hernias were repaired. Eighty-five percent 5-year follow-up was achieved, during which we identified 7 recurrences, 11 seromas (all resolved), and 10 patients reporting mild pain. Six second looks were performed and in all cases except one the mesh was found to be totally integrated into the tissue with strong scar tissue corroborated macro- and microscopically. In our experience the use of small intestine submucosa mesh in contaminated or potentially contaminated fields is a safe and feasible alternative to hernia repair with minimal recurrence rate and satisfactory results in long-term follow-up.


Telephone survey to investigate relationships between onychectomy or onychectomy technique and house soiling in cats.
OBJECTIVE To determine whether associations existed between onychectomy or onychectomy technique and house soiling in cats. DESIGN Cross-sectional study. SAMPLE 281 owners of 455 cats in Polk County, Iowa, identified via a list of randomly selected residential phone numbers of cat owners in that region. PROCEDURES A telephone survey was conducted to collect information from cat owners on factors hypothesized a priori to be associated with house soiling, including cat sex, reproductive status, medical history, and onychectomy history. When cats that had undergone onychectomy were identified, data were collected regarding the cat's age at the time of the procedure and whether a carbon dioxide laser (CDL) had been used. Information on history of house soiling behavior (urinating or defecating outside the litter box) was also collected. RESULTS Onychectomy technique was identified as a risk factor for house soiling. Cats for which a non-CDL technique was used had a higher risk of house soiling than cats for which the CDL technique was used. Cats that had undergone onychectomy and that lived in a multicat (3 to 5 cats) household were more than 3 times as likely to have house soiled as were single-housed cats with intact claws. CONCLUSIONS AND CLINICAL RELEVANCE Results of this cross-sectional study suggested that use of the CDL technique for onychectomy could decrease the risk of house soiling by cats relative to the risk associated with other techniques. This and other findings can be used to inform the decisions of owners and veterinarians when considering elective onychectomy for cats.


The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study.
A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Twenty three participants with mild or moderate Alzheimer's disease and twenty three with mild cognitive impairment were randomized to receive omega-3 PUFAs 1.8 g/day or placebo (olive oil). The data of 35 (76%) participants with at least one post-treatment visit was analyzed. There were no severe adverse effects in either group and it suggests that omega-3 PUFAs were well tolerable in this population. The treatment group showed better improvement on the Clinician's Interview-Based Impression of Change Scale (CIBIC-plus) than those in the placebo group over the 24 week follow-up (p=0.008). There was no significant difference in the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) change during follow-up in these two groups. However, the omega-3 fatty acids group showed significant improvement in ADAS-cog compared to the placebo group in participants with mild cognitive impairment (p=0.03), which was not observed in those with Alzheimer's disease. Higher proportions of eicosapentaenoic acid on RBC membranes were also associated with better cognitive outcome (p=0.003). Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment.


Early discontinuation of endocrine therapy for breast cancer: who is at risk in clinical practice?
Despite evidence supporting at least five years of endocrine therapy for early breast cancer, many women discontinue therapy early. We investigated the impact of initial therapy type and specific comorbidities on discontinuation of endocrine therapy in clinical practice. We identified women in a population-based cohort with a diagnosis of early breast cancer and an incident dispensing of anastrozole, letrozole or tamoxifen from 2003-2008 (N = 1531). Pharmacy and health service data were used to determine therapy duration, treatment for pre-existing and post-initiation comorbidities (anxiety, depression, hot flashes, musculoskeletal pain, osteoporosis, vaginal atrophy), demographic and other clinical characteristics. Time to discontinuation of initial, and any, endocrine therapy was calculated. Cox regression determined the association of different characteristics on early discontinuation. Initial endocrine therapy continued for a median of 2.2 years and any endocrine therapy for 4.8 years. Cumulative probability of discontinuing any therapy was 17% after one year and 58% by five years. Initial tamoxifen, pre-existing musculoskeletal pain and newly-treated anxiety predicted shorter initial therapy but not discontinuation of any therapy. Early discontinuation of any therapy was associated with newly-treated hot flashes (HR = 2.1, 95% CI = 1.3-3.3), not undergoing chemotherapy (HR = 1.4, 95% CI = 1.1-1.8) and not undergoing mastectomy (HR = 1.5, 95% CI = 1.2-1.8). Less than half of women completed five years of endocrine therapy. Women at greatest risk of stopping any therapy early were those with newly-treated hot flashes, no initial chemotherapy, or no initial mastectomy. This suboptimal use means that the reductions in recurrence demonstrated in clinical trials may not be realised in practice.


[Human alpha 2-macroglobulin and its analogs in animals].
Biochemical and immunochemical properties of human alpha 2-macroglobulin and its analogues from cattle, horse, rabbit, guinea pig, rat, mouse, hen and perch have been investigated. It was found that all analogues have the identical molecular mass and structure, being different in their isoelectric point and carbohydrate composition. It was shown that some antigenic properties of macroglobulins remained constant during evolution, whereas other ones were strictly differentiated at the level of families and species. These data allow to classify macroglobulins as proteins which appeared in vertebrates at early stages of evolution revealing only relatively slight changes during the latter.


Introduced Scotch broom (Cytisus scoparius) invades the genome of native populations in vulnerable heathland habitats.
Cytisus scoparius is a global invasive species that affects local flora and fauna at the intercontinental level. Its natural distribution spans across Europe, but seeds have also been moved among countries, mixing plants of native and non-native genetic origins. Hybridization between the introduced and native gene pool is likely to threaten both the native gene pool and the local flora. In this study, we address the potential threat of invasive C. scoparius to local gene pools in vulnerable heathlands. We used nuclear single nucleotide polymorphic (SNP) and simple sequence repeat (SSR) markers together with plastid SSR and indel markers to investigate the level and direction of gene flow between invasive and native heathland C. scoparius. Analyses of population structures confirmed the presence of two gene pools: one native and the other invasive. The nuclear genome of the native types was highly introgressed with the invasive genome, and we observed advanced-generation hybrids, suggesting that hybridization has been occurring for several generations. There is asymmetrical gene flow from the invasive to the native gene pool, which can be attributed to higher fecundity in the invasive individuals, measured by the number of flowers and seed pods. Strong spatial genetic structure in plastid markers and weaker structure in nuclear markers suggest that seeds spread over relatively short distances and that gene flow over longer distances is mainly facilitated by pollen dispersal. We further show that the growth habits of heathland plants become more vigorous with increased introgression from the invaders. Implications of the findings are discussed in relation to future management of invading C. scoparius.


Energy compensation and nutrient displacement following regular consumption of hazelnuts and other energy-dense snack foods in non-obese individuals.
Regular nut consumption reduces cardiovascular disease risk, partly from improvements to dietary quality. Examining how individuals make dietary changes when consuming nuts may reveal key behavioural eating patterns beneficial for the development of dietary interventions. We examined the effects of nuts in comparison with other energy-dense snacks on energy compensation, nutrient displacement, and food group patterns. This was a 12-week randomised, controlled, parallel study with four arms: ~1100 kJ/day for each of hazelnuts (42 g), chocolate (50 g), potato crisps (50 g), or no added snack food. Diet records, body composition, and physical activity were measured at baseline and week 12, in 102 non-obese participants. Significant improvements in diet quality were observed in the hazelnut group, particularly when consumed as snacks. Intakes of monounsaturated fat (MUFA) and vitamin E were significantly higher (all P < 0.05), whereas saturated fat and carbohydrate were significantly lower (both P ≤ 0.022) in the hazelnut group compared to the other groups. Partial energy compensation did not differ significantly between groups, but nutrient displacement values for MUFA and fibre differed significantly. Within the hazelnut group, there was nearly complete displacement for fibre, partial displacement for energy, protein, total fat, MUFA, PUFA, potassium, folate, and vitamin E, and overcompensation for carbohydrate and sugar. Our results demonstrate that energy compensation occurs for all three intervention snacks in this non-obese population. Regular nut consumption significantly improves nutrient profiles compared to other snacks with changes occurring at the snack level.


Establishing a nurse-managed center: a community approach.
Documentation of need, designing and implementing services to meet the need, networking with and referral to other community providers, practice agreements, and mechanisms for reimbursement and billing are just a few issues that must be addressed when establishing a community-based health care unit. This article will discuss essentials of establishing a nurse-managed, community-based health care center, based on the author's experience in developing and managing the Outreach Health Care Unit.


Child- and Family-Focused Cognitive Behavioral Therapy for Pediatric Bipolar Disorder: Applications for Suicide Prevention.
Despite high rates of suicide ideation (SI) and behavior in youth with pediatric bipolar disorder (PBD), little work has examined how psychosocial interventions impact suicidality among this high-risk group. The current study examined SI outcomes in a randomized clinical trial comparing Child- and Family-Focused Cognitive Behavioral Therapy (CFF-CBT) for PBD versus psychotherapy treatment-as-usual (TAU). Although not designed for suicide prevention, CFF-CBT addresses child and family factors related to suicide risk and thus was hypothesized to generalize to the treatment of suicidality. Participants included 71 youth aged 7-13 years (M = 9.17, SD = 1.60) with DSM-IV-TR bipolar I, II, or not otherwise specified randomly assigned, with parent(s), to receive CFF-CBT or TAU. Both treatments consisted of 12 weekly and 6 monthly booster sessions. Suicide ideation was assessed via clinician interview at baseline, posttreatment, and 6-month follow-up. Results indicated that SI was prevalent pretreatment: 39% of youth reported current suicidal thoughts. All youth significantly improved in the likelihood and intensity of ideation across treatment, but group differences were not significant. Thus, findings suggest that early intervention for these high-risk youth may reduce SI, and at this stage of suicidality, youth may be responsive to even nonspecialized treatment.


Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma.
Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.


Humanised models of cancer in molecular medicine: the experimental control of disanalogy.
This paper explores the epistemology of extrapolation from model organisms to humans in molecular medicine. We take into account two common views on the issue, the homology view and the disanalogy view. In response to both interpretations, we argue that the foundational basis of extrapolations cannot simply be provided by homology and that relevant disanalogies can, thanks to the techniques of molecular biology, be experimentally controlled and exploited to allow useful and reliable extrapolations. The case of "humanised mice" in the context of cancer stem cell research provides evidence of how animal models can be construed to approximate bona fide causal analogue models of human diseases. To supplement this view we show how the epistemology of model organisms needs to take into account the engineering side of molecular medicine. Model organisms are often manipulated to create analogies or remove disanalogies with the target system. We maintain that highlighting this feature is fundamental to explain what warrants extrapolation in the search for the molecular causes of disease.


Cyclic decomposition explains a photosynthetic down regulation for Chlamydomonas reinhardtii.
The regulation of metabolic networks has been shown to be distributed and shared through the action of metabolic cycles. Biochemical cycles play important roles in maintaining flux and substrate availability for multiple pathways to supply cellular energy and contribute to dynamic stability. By understanding the cyclic and acyclic flows of matter through a network, we are closer to understanding how complex dynamic systems distribute flux along interconnected pathways. In this work, we have applied a cycle decomposition algorithm to a genome-scale metabolic model of Chlamydomonas reinhardtii to analyse how acetate supply affects the distribution of fluxes that sustain cellular activity. We examined the role of metabolic cycles which explain the down regulation of photosynthesis that is observed when cells are grown in the presence of acetate. Our results suggest that acetate modulates changes in global metabolism, with the pentose phosphate pathway, the Calvin-Benson cycle and mitochondrial respiration activity being affected whilst reducing photosynthesis. These results show how the decomposition of metabolic flux into cyclic and acyclic components helps to understand the impact of metabolic cycling on organismal behaviour at the genome scale.


Autologous Iris transplant as plug for macular hole retinal detachment in highly myopic eyes.
To describe the anatomic and visual outcomes of eyes undergoing autologous iris transplantation for macular hole retinal detachment. Seven consecutive patients with macular hole retinal detachment were enrolled in a single-arm prospective study. All patients underwent pars plana vitrectomy with autologous iris transplantation placed in the subretinal space as a plug to close the macular hole; in one case, a posterior retinal break was also closed with the same technique. Seven patients (2 males and 5 females) with a mean age of 69.14 ± 7.79 years (range 58-80 years) were followed up for a period of six months. The best-corrected visual acuity improved from 2.44 ± 0.48 logMAR (20/2000) preoperatively to 1.90 ± 0.26 logMAR (20/800) 6 months after surgery. Optical coherence tomography analysis showed retinal adhesion around the iris plug, and the retina remained dry in the follow-up period. In this series of macular hole retinal detachments, autologous iris transplantation placed as a plug over the retinal pigment epithelium facing the macular hole opening or directly over the bare sclera achieved anatomical success with improvement in visual function.


Pure neuritic leprosy in India: an appraisal.
Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. To study the epidemiological characteristics of PNL in India. A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.


Juvenile rheumatoid arthritis.
The early diagnosis of JRA rests on the recognition of three distinct modes of onset that are important in preventing deformity, blindness, and even death. Systemic onset is characterized by typical systemic manifestations, particularly high spiking fever and the rheumatoid rash, polyarticular onset is noted by arthritis of more than four joints, and pauciarticular onset is distinguished by involvement of four joints or less, most often a knee initially. In JRA, fundamental to the heart of successful management is patient and parental education regarding both the nature of the disease and goals of therapy. Whereas the NSAIDs are adequate for the control of active disease in most patients, two key issues must be resolved. First, it is important to recognize that the choice of drug for the individual patient is frequently a matter of trial and error. Second, it is critical to prescribe antiinflammatory quantities of a given drug. The slow-acting (remittive) agents, such as intramuscular or oral gold, are reserved for patients with prolonged active polyarthritis, which affects 15 per cent of all patients with JRA. There are several drawbacks to the use of remittive agents. They must be tried for several months, often in the presence of rapidly developing joint limitation and erosions on radiograph, before their effectiveness can be determined. Also, when using these drugs, one must often follow a meticulously graduated dosage regimen, while carefully monitoring the patient for toxic and potentially lethal side effects. It follows, therefore, to never use these agents unless you are familiar with their administration and potential toxicity and to seek help from a specialist.


Patterns and Disparities in Telehealth Usage During the COVID-19 Pandemic Across Surgical Specialties.
Background: The COVID-19 pandemic has accelerated telehealth usage. This study aims to understand the impact of sociodemographic factors on telehealth usage during COVID-19 among surgical specialties. Methods: Our data contain surgical outpatient visits at an academic center from five periods between 2019 and 2020. A difference-in-differences regression model was used to examine the effect of exposure variables on virtual visit proportions between prepandemic and postpandemic time periods. Results: Compared with white patients, non-Medicare beneficiaries, and English-proficient patients, the rate of uptake in telehealth visits from prepandemic to postpandemic periods was lower for black patients, Medicare beneficiaries, and non-English-speaking patients, respectively. Surgical subspecialties saw varied usage of telehealth. A strong preference for phone visits by black patients, Medicare beneficiaries, and non-English-speaking patients existed. Conclusion: Phone visits are an important resource for marginalized communities. Understanding disparities in telemedicine usage may inform policy that could alleviate inequities in health care access.


Mood, eating behaviour and attention.
Obesity is a growing health problem, but most people find dieting unsuccessful. Three studies examine possible reasons for the difficulty and the extent to which dieting-related reductions in cognitive function are associated with mood and well-being. In Study One, 49 female dieters were compared with a control group of 31 matched non-dieters on measures of well-being, mood, eating behaviour (Dutch Eating Behaviour Questionnaire), and attention. Study Two examined two measures of restraint to examine why previous studies find high restrainers are prone to react to emotion. Study Three experimentally manipulated mood using music and the standard Velten Induction Procedure to examine attention in restrainers and emotional eaters. Dieting was found to be associated with deficits in sustained attention. This finding was further supported by the demonstration of a significant impairment in performance following a negative mood induction in high emotional eaters whereas high restrainers were relatively unaffected by the mood challenge. We suggest that different aspects of eating behaviour have dissociable effects on cognitive-affective function. Trait tendencies to restrained eating are associated with attentional deficits, but are not further affected by mood disruption. It is the long-term tendency to eat when emotional that combines with current emotional state to trigger cognitive deficits.


Genome Based Meta-QTL Analysis of Grain Weight in Tetraploid Wheat Identifies Rare Alleles of GRF4 Associated with Larger Grains.
The domestication and subsequent genetic improvement of wheat led to the development of large-seeded cultivated wheat species relative to their smaller-seeded wild progenitors. While increased grain weight (GW) continues to be an important goal of many wheat breeding programs, few genes underlying this trait have been identified despite an abundance of studies reporting quantitative trait loci (QTL) for GW. Here we perform a QTL analysis for GW using a population of recombinant inbred lines (RILs) derived from the cross between wild emmer wheat accession 'Zavitan' and durum wheat variety 'Svevo'. Identified QTLs in this population were anchored to the recent Zavitan reference genome, along with previously published QTLs for GW in tetraploid wheat. This genome-based, meta-QTL analysis enabled the identification of a locus on chromosome 6A whose introgression from wild wheat positively affects GW. The locus was validated using an introgression line carrying the 6A GW QTL region from Zavitan in a Svevo background, resulting in >8% increase in GW compared to Svevo. Using the reference sequence for the 6A QTL region, we identified a wheat ortholog to OsGRF4, a rice gene previously associated with GW. The coding sequence of this gene (TtGRF4-A) contains four single nucleotide polymorphisms (SNPs) between Zavitan and Svevo, one of which reveals the Zavitan allele to be rare in a core collection of wild emmer and completely absent from the domesticated emmer genepool. Similarly, another wild emmer accession (G18-16) was found to carry a rare allele of TtGRF4-A that also positively affects GW and is characterized by a unique SNP absent from the entire core collection. These results exemplify the rich genetic diversity of wild wheat, posit TtGRF4-A as a candidate gene underlying the 6A GW QTL, and suggest that the natural Zavitan and G18-16 alleles of TtGRF4-A have potential to increase wheat yields in breeding programs.


The otolaryngological manifestations of mitochondrial disease and the risk of neurodegeneration with infection.
To report the nature and extent of hearing loss and other otolaryngological problems in patients with mitochondrial disease, and to document the risk of neurodegeneration with infection. Medical chart review and telephone interview of 40 patients with documented mitochondrial disease. An international referral center for the diagnosis and management of mitochondrial disorders. We describe 40 patients with a definitive diagnosis of mitochondrial disease. Thirty-three (82%) were younger than 15 years. Hearing loss was the most common clinical finding associated with mitochondrial disease. Twenty-eight (80%) of the 35 patients undergoing testing had hearing loss or significant auditory dysfunction. In 20 (57%) of these, brainstem conduction abnormalities were identified. Eight (30%) of the 27 patients had an abnormal number of recurrent upper respiratory tract infections, and 4 (50%) of these had life-threatening or neurodegenerative sequelae. Mitochondrial disease followed an episodic course, with periods of stasis or slow developmental progress, punctuated by neurodegenerative events in 18 (60%) of 30 patients. Intercurrent infection was recognized as a precipitant of neurodegenerative events in 13 (72%) of 18 patients with a history of episodic degeneration. Children and adults with mitochondrial disorders are at high risk for hearing loss and life-threatening complications of intercurrent infections. A constellation of audiologic abnormalities, multiorgan system involvement, and history of neuromuscular setbacks with infection strongly suggests mitochondrial disease. Knowledge of these features can lead to more rapid diagnosis and improved medical and surgical management for this special group of patients with fundamental defects in bioenergy metabolism.


Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 5-HT3 and 5-HT2 receptors by different mechanisms.
The mechanisms of action of two different serotonin receptors, found in a neuronal cell line (neuroblastoma X glioma hybrid cells) and in a non-excitable glioma cell line, were explored. In both cell lines, serotonin induced a dose-dependent, transient rise of cytosolic Ca2+ activity (measured by fura-2 or indo-1 fluorescence). Ca2+ channel blockers (Ni2+ and La3+, not nifedipine) suppressed the Ca2+ response to serotonin in the hybrid cells but not in the glioma cells. After application of Ca2+ ionophores (ionomycin and A23187) in order to short-circuit internal Ca2+ stores, serotonin was still able to induce a Ca2+ response in the hybrid cells but not in the glioma cells. Serotonin dose-dependently stimulated the rate of 45Ca2+ uptake several-fold in the hybrid cells, but hardly at all in the glioma cells. Thus, in the neuronal cell line cytosolic Ca2+ activity is raised through enhancement of Ca2+ entry into the cells from the extracellular environment via 5-HT3 receptors (blocked by ICS 205-930, MDL 72222 and GR 38032 F). The depolarization response caused by serotonin in the hybrid cells is due to activation of cation conductance(s), obviously allowing entry of extracellular Ca2+. In contrast to the neuronal cell line, in the glial cell line the rise of Ca2+ activity is mediated by ketanserin-susceptible 5-HT2 receptors (not affected by treatment with pertussis toxin) mainly liberating Ca2+ from internal stores. In the glioma cells the release of Ca2+ from internal stores leads to opening of Ca2+-dependent K+ channels, responsible for the hyperpolarizing response. Thus, the neuronal and the glial cell lines might provide suitable systems in which to study the diverse cellular functions triggered by the rise of cytosolic Ca2+ activity, which is caused by different serotonin receptors.


Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells.
Iron deficiency is the most common nutritional disorder worldwide, whereas pathologic elevations of body iron stores can occur under certain circumstances due to genetic abnormalities or in association with other diseases. The intestine is the exclusive locus of homeostatic regulation of body iron stores, which is accomplished by changes in iron absorption efficiency by largely unknown molecular mechanisms in response to alterations in body iron stores. Recently, a number of novel genes involved in iron metabolism, such as the iron uptake transporter DMT1/DCT1/Nramp2 and the iron export transporter IREG1/ferroportin1/MTP1, have been identified, providing important insights about molecular aspects of intestinal iron absorption and its regulation. The aim of this study was to investigate the effects of iron treatment on DMT1 and IREG1 mRNA expression in Caco-2 cells, a human intestinal cell line. Exposure of the cells to iron (200 micromol/L ferric nitrilotriacetic acid for 72 h) significantly decreased transferrin receptor mRNA (80%), DMT1 mRNA (57%) and IREG1 mRNA (52%). These observations are consistent with the notion of parallel regulation of these iron-responsive genes in vivo to protect the enterocyte from iron toxicity and mediate a decreased efficiency of intestinal iron absorption to prevent iron overload.


Just one click: a content analysis of advertisements on teen web sites.
The current study provides a comprehensive analysis of the content of advertisements on Web sites targeted at adolescents, with a particular focus on the female beauty ideal. Advertisements (N = 631) from 14 Web sites popular with adolescents were analyzed with respect to product advertised, characteristics of people presented, and emphasis on appearance and the thin beauty ideal. Although a wide variety of products were featured, advertisements for cosmetics and beauty products were the most frequent. Further, many of the products advertised (e.g., dating services, weight loss products, gambling games) might be considered inappropriate for the intended audience (i.e., teenagers) of the Web site. People who were a part of advertisements were generally female, young, thin, and attractive. Advertisements for games, weight loss products, and cosmetic and beauty products strongly focused on appearance and laid emphasis on the thin ideal. Like advertisements in mainstream media, advertising on the Internet perpetuates the stereotypical ideal of feminine beauty. Adolescents using the Internet are likely to be exposed to numerous advertisements that reinforce the importance of beauty and thinness, which could have a detrimental impact on how they feel about their bodies.


A Case of New-onset Immune-mediated Necrotizing Myopathy and Trigeminal Neuropathy after SARS-CoV-2 mRNA Vaccination in a Patient with Rheumatoid Arthritis and Sjögren's Syndrome.
We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after SARS-CoV-2 mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.


Occupational Health Risk Assessment in the Electronics Industry in China Based on the Occupational Classification Method and EPA Model.
The awareness of occupational health risk management in the electronics industry is weak in China, and many Chinese occupational health management regulations have not been effectively implemented. China's current occupational hazards classification method and the Environmental Protection Agency (EPA) inhalation risk assessment model recognized internationally were used to perform health risk assessments for a chip manufacturing company in the electronics industry in order to determine the existing problems and put forward the optimization proposals of the occupational hazards classification method in China. The results showed that the detected concentrations of toxic and harmful chemicals in all testing points did not exceed the occupational health exposure limits in China. According to the EPA inhalation risk assessment model, the highest values of non-carcinogenic risks of ammonia, chlorine, fluoride, sulfuric acid, hydrogen chloride, ethylene glycol, phosphine, boron trifluoride, isopropanol, benzene, and xylene were 5.10, 67.12, 1.71, 45.98, 1.83, 1.43, 160.35, 46.56, 2.52, 5.55, and 5.37, respectively, which means workers in electronic chip manufacturing companies exposed to these chemicals have higher occupational health risks. However, on the basis of the occupational hazards classification method, the occupational health risks of exposure to the toxic and hazardous chemicals are relatively harmless operations. The evaluation results of the EPA inhalation risk assessment model are generally higher than those of the occupational hazards classification method. It's recommended to refine the value of occupational exposure limit B, taking more characteristics of the hazard factors into account and fuzzifying the parameters to optimize the occupational hazards classification method. At the same time, it is suggested that the electronic chip manufacturing company should conduct anti-virus risk management covering in three aspects: increasing the awareness of occupational hazards, enhancing system ventilation, and improving personal health management measures.


Applications of Near-Infrared Fluorescence Imaging and Angiography of Inferior Vesical Artery in Laparoscopic Lateral Lymph Node Dissection: A Prospective Nonrandomized Controlled Study.
Near-infrared imaging with indocyanine green has been used to guide lateral lymph node dissection, yet its efficacy and benefits need further investigation. To investigate the efficacy and feasibility of near-infrared fluorescence imaging and angiography of the inferior vesical artery in laparoscopic lateral lymph node dissection. A prospective nonrandomized controlled study. Single-center study. Patients with lower rectal cancer who underwent total mesorectal excision plus lateral lymph node dissection. A cohort of 108 patients was enrolled. After propensity score matching, 29 patients in the near-infrared group and 50 patients in the non-near-infrared group were matched. The total number of harvested lateral lymph nodes, positive lateral lymph nodes, inferior vesical artery preservation, and postoperative urinary function were compared. After propensity score matching, both groups had similar baseline characteristics. The total number of harvested lateral lymph nodes in the near-infrared group was significantly higher (12 vs 9, p = 0.013), but positive lateral lymph nodes were similar between the 2 groups (1 vs 1, p = 0.439). The inferior vesical artery preservation ratio was significantly increased with the aid of indocyanine green angiography (93.1% vs 56.0%, p < 0.001). The non-near-infrared group required more days for urinary catheter removal than the near-infrared group (5 vs 4, p = 0.046). Urinary recatheterization tended to occur more frequently in the non-near-infrared group, with a marginally significant trend (16% vs 0%, p = 0.059). The non-near-infrared group tended to have more cases with residual urine volume ≥50 mL than the near-infrared group (20.0% vs 3.4%, p = 0.087), especially in the bilateral dissection subgroup (41.2% vs 0%, p = 0.041). Small sample size. Near-infrared imaging increased the number of harvested lateral lymph nodes, whereas real-time indocyanine green fluorescence angiography ensured the preservation of the inferior vesical artery and tended to improve postoperative urinary function.


Crosstalk between Endothelial Cells and Tumor Cells: A New Era in Prostate Cancer Progression.
Prostate cancer stands as one of the most prevalent malignancies afflicting men worldwide. The tumor microenvironment plays a pivotal role in tumor progression, comprising various cell types including endothelial cells, tumor-associated fibroblasts, and macrophages. Recent accumulating evidence underscores the indispensable contribution of endothelial cells to prostate cancer development. Both endothelial cells and tumor cells release a multitude of factors that instigate angiogenesis, metastasis, and even drug resistance in prostate cancer. These factors serve as regulators within the tumor microenvironment and represent potential therapeutic targets for managing prostate cancer. In this review, we provide an overview of the crucial functions of endothelial cells in angiogenesis, metastasis, and drug resistance, and their prospective therapeutic applications in combating this disease.


Consensus by democracy. Using meta-analyses of microarray and genomic data to model the cold acclimation signaling pathway in Arabidopsis.
The whole-genome response of Arabidopsis (Arabidopsis thaliana) exposed to different types and durations of abiotic stress has now been described by a wealth of publicly available microarray data. When combined with studies of how gene expression is affected in mutant and transgenic Arabidopsis with altered ability to transduce the low temperature signal, these data can be used to test the interactions between various low temperature-associated transcription factors and their regulons. We quantized a collection of Affymetrix microarray data so that each gene in a particular regulon could vote on whether a cis-element found in its promoter conferred induction (+1), repression (-1), or no transcriptional change (0) during cold stress. By statistically comparing these election results with the voting behavior of all genes on the same gene chip, we verified the bioactivity of novel cis-elements and defined whether they were inductive or repressive. Using in silico mutagenesis we identified functional binding consensus variants for the transcription factors studied. Our results suggest that the previously identified ICEr1 (induction of CBF expression region 1) consensus does not correlate with cold gene induction, while the ICEr3/ICEr4 consensuses identified using our algorithms are present in regulons of genes that were induced coordinate with observed ICE1 transcript accumulation and temporally preceding genes containing the dehydration response element. Statistical analysis of overlap and cis-element enrichment in the ICE1, CBF2, ZAT12, HOS9, and PHYA regulons enabled us to construct a regulatory network supported by multiple lines of evidence that can be used for future hypothesis testing.


Genetic spectrum and distinct evolution patterns of SARS-CoV-2.
Four signature groups of frequently occurred single-nucleotide variants (SNVs) were identified in over twenty-eight thousand high-quality and high-coverage SARS-CoV-2 complete genome sequences, representing different viral strains. Some SNVs predominated but were mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguishable evolution patterns over time. A few hundred patients were detected with multiple viral strain-representing mutations simultaneously, which may stand for possible co-infection or potential homogenous recombination of SARS-CoV-2 in environment or within the viral host. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tended to switch between bat RaTG13 coronavirus sequence and Wuhan-Hu-1 genome, indicating the higher genetic instability or tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.


Regulation of ATP-induced calcium release in COS-7 cells by calcineurin.
Experiments were conducted to examine the role of calcineurin in regulating Ca(2+) fluxes in mammalian cells. In COS-7 cells, increasing concentrations (1-10 microM) of ATP triggered intracellular Ca(2+) release in a dose-dependent manner. Treatment of the cells with calcineurin inhibitors such as cyclosporin A (CsA), deltamethrin and FK506 resulted in an enhancement of ATP-induced intracellular Ca(2+) release. Measurement of calcineurin-specific phosphatase activity in vitro demonstrated a high level of endogenous calcineurin activities in COS-7 cells, which was effectively inhibited by the addition of deltamethrin or CsA. The expression of constitutively active calcineurin (CnADeltaCaMAI) inhibited the ATP-induced increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), in both the presence and the absence of extracellular Ca(2+). These results suggest that the constitutively active calcineurin prevented Ca(2+) release from the intracellular stores. In the calcineurin-transfected cells, treatment with CsA restored the calcineurin-mediated inhibition of intracellular Ca(2+) release. Protein kinase C-mediated phosphorylation of Ins(1,4,5)P(3) receptor [Ins(1,4,5)P(3)R] was partly inhibited by the extracts prepared from the vector-transfected cells and completely inhibited by those from cells co-transfected with CnADeltaCaMAI and calcineurin B. On the addition of 10 microM CsA, the inhibited phosphorylation of Ins(1,4,5)P(3)R was restored in both the vector-transfected cells and the calcineurin-transfected cells. These results show direct evidence that Ca(2+) release through Ins(1, 4,5)P(3)R in COS-7 cells is regulated by calcineurin-mediated dephosphorylation.


Evaluating an interprofessional disease state and medication management review model.
There is lack of literature data reporting an incorporation of medication management reviews in students' interprofessional education (IPE) and practice programs in aged care settings. This pilot study reports how an interprofessional disease state and medication management review program (DSMMR) was established in a residential aged care facility in Perth, Western Australia. Students from the professions of nursing, pharmacy and physiotherapy focused on a wellness check in the areas of cognition, falls and continence while integrating a medication management review. Students' attitudes were explored using a pre- and post-placement questionnaire. Students indicated positive experience with the IPE DSMMR program which also resulted in their positive attitudinal shift towards IPE and practice. These findings indicated that aged care can be a suitable setting for student interprofessional programs focusing on DSMMR.


Maturation of finger-synchronization skills.
The ability to move two fingers at the same time was measured in young and older adults. This study measured the accuracy with which 45 normally developing children (23 boys, 22 girls; mean ages 8.4 and 8.3 years respectively) and 49 young adults (25 males, 24 females; mean ages 19.8 and 20.5 years respectively) could synchronize movements of two fingers when making or breaking contact with circular metal discs. A portable electronic instrument displayed the timings. To measure 'in-phase' skills, attempts were made to contact both discs simultaneously with the two index fingers or to break both contacts; asynchrony was only a few milliseconds and differences between children and adults were insignificant. To measure 'antiphase' skills, attempts were made with the index and middle fingers to make contact simultaneously with one disc while breaking contact with the other; asynchrony was larger. Usually one contact was made and later the other was broken; for a while both fingers touched (overlap). Rarely one contact was broken before the other was made; for a while neither finger touched (gap). Boys' periods of overlap were longer than those of men and women; on both sides these differences were highly significant statistically (p<0.0001). Boys' errors on the right side were also significantly greater than those of girls. On both sides, mean errors of girls were higher than those of men and women: three of the four sets of data reached statistical significance. While boys' performance improved with age, that of girls was static. Children achieved an essentially adult level of control for in-phase skills but with antiphase skills the children, and especially the boys, had clearly poorer performances.


Usability of a CKD educational website targeted to patients and their family members.
Web-based technology is critical to the future of healthcare. As part of the Safe Kidney Care cohort study evaluating patient safety in CKD, this study determined how effectively a representative sample of patients with CKD or family members could interpret and use the Safe Kidney Care website (www.safekidneycare.org), an informational website on safety in CKD. Between November of 2011 and January of 2012, persons with CKD or their family members underwent formal usability testing administered by a single interviewer with a second recording observer. Each participant was independently provided a list of 21 tasks to complete, with each task rated as either easily completed/noncritical error or critical error (user cannot complete the task without significant interviewer intervention). Twelve participants completed formal usability testing. Median completion time for all tasks was 17.5 minutes (range=10-44 minutes). In total, 10 participants had greater than or equal to one critical error. There were 55 critical errors in 252 tasks (22%), with the highest proportion of critical errors occurring when participants were asked to find information on treatments that may damage kidneys, find the website on the internet, increase font size, and scroll to the bottom of the webpage. Participants were generally satisfied with the content and usability of the website. Web-based educational materials for patients with CKD should target a wide range of computer literacy levels and anticipate variability in competency in use of the computer and internet.


Case-mix differences between teaching and nonteaching hospitals.
It has been suggested that teaching hospitals as a group have done well financially under Medicare's prospective payment system. If so, is this because teaching hospitals have reduced inefficiencies or because their case mix is not as severe as presumed? In this study, we used Disease Staging and diagnosis related groups (DRGs) to isolate case mix attributed to given patient populations from that attributed to hospital treatment standards. We also analyzed differences among types of teaching hospitals. We found few case-mix differences between teaching and nonteaching hospitals when the weighting system was independent of resource consumption (i.e., Disease Staging). However, when resources were used to weight case-mix measurement (i.e., DRGs), teaching hospitals were found to have a more serious case mix. We conclude that although teaching hospitals typically do not have a more severe case mix than nonteaching hospitals, they do use more resources to treat their patient mix under DRGs.


Inexperienced preys know when to flee or to freeze in front of a threat.
Using appropriate antipredatory responses is crucial for survival. While slowing down reduces the chances of being detected from distant predators, fleeing away is advantageous in front of an approaching predator. Whether appropriate responses depend on experience with moving objects is still an open question. To clarify whether adopting appropriate fleeing or freezing responses requires previous experience, we investigated responses of chicks naive to movement. When exposed to the moving cues mimicking an approaching predator (a rapidly expanding, looming stimulus), chicks displayed a fast escape response. In contrast, when presented with a distal threat (a small stimulus sweeping overhead) they decreased their speed, a maneuver useful to avoid detection. The fast expansion of the stimulus toward the subject, rather than its size per se or change in luminance, triggered the escape response. These results show that young animals, in the absence of previous experience, can use motion cues to select the appropriate responses to different threats. The adaptive needs of young preys are thus matched by spontaneous defensive mechanisms that do not require learning.


[Mixed drink consisting of guava (Psidium guajava. L) and forrageira palm (Opuntia fícus-indica): development and acceptability].
Nowadays, in the beverage industry, the mixture of products became an alternative to increase the nutritional value or even to develop new flavors in the formulation of mixed drinks. The objective of this work was to develop a mixed drink of forrageira palm with guava. Four formulations with different palm concentrations and soluble solids were evaluated, keeping the concentration of guava stable. The products were submitted to chemical characterization (pH, soluble solids, titratable acidity, vitamin C) sensory evaluation (flavor, color, body and global acceptance) and microbiological analysis (total coliforms and thermotolerants, Salmonella and Estaphylococcus aureus). All the samples were well accepted in the sensory aspect and did not present any significant difference (p < 0.5) among them. And the level of acceptance ranged from "I liked it slightly." to "I liked it moderately." for all the evaluated features. The formulated mixed drink was according to the chemical and microbiological patterns set by Brazilian laws, except for the pH that was above the ideal level for industrialized products. In respect of the microbiological analysis, none of the formulations presented microorganisms. The results showed that the elaborated product is in accordance with the identity and quality standards established for beverages. It also has a good sensory acceptance, which makes it a product with high potential for industrialization.


The hydrating effect of a cream and white petrolatum measured by optothermal infrared spectrometry in vivo.
Optothermal infrared spectrometry (OTIS) is a novel way of measuring the water content of stratum corneum non-invasively. This principle has been used in the present study to evaluate the hydrating effect of a one-week treatment of human skin twice a day with either white petrolatum or a cream (o/w emulsion). Forty-two females volunteered for the study, which comprised one control pretreatment week, one treatment week, and one post-treatment week. White petrolatum was greasy and did not produce any hydrating effect at any point in time when the hydration was measured 10 h after application, whereas the cream produced a clear hydration that became statistically significant from day one of treatment and was maintained for at least 2 days after the treatment was stopped. The hydrating effect amounted to an about 80% increase in those volunteers who had initial values below the mean OTIS value of 23.5%. It is concluded that saturation of the stratum corneum with appropriate lipids and emulsifiers as in the cream leads to hydration of the stratum corneum to about 35% water as measured by the OTIS technique.


Geographic patterns of craniofacial variation in pre-Hispanic populations from the Southern Cone of South America.
In this study we analyzed the relationships and patterns of spatial variation from morphological cranial variability of 17 population samples representing the ancient inhabitants of the central territory of Argentina (archaeologically known as "Sierras Centrales") and other pre-Hispanic populations from different ecological and geographic regions of the Southern Cone of South America (Argentina and Uruguay), based on the analysis of 10 craniofacial measurements. Results obtained from D2 distances can be interpreted as evidence of a similar biological history for the populations that inhabited the Sierras Centrales and the population of Santiago del Estero. Matrix correlation analysis demonstrated that craniometric variation is significantly influenced by geography, suggesting that populations that lived at lower geographical distance share more biological similarity. Global spatial autocorrelation analysis suggests a clinal pattern for the biological variation, although Moran's I estimates calculated for each variable demonstrate that only nasal height and breadth show this spatial pattern of variation. Results from spatial regression techniques show a significant effect of altitude modeling nasal shape, in agreement with previous studies suggesting that nasal morphology is strongly influenced by environment variables.


Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding.
The opportunistic pathogen Pseudomonas aeruginosa, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.


Endothelial dysfunction, intima-media thickness, ankle-brachial pressure index, and pulse pressure in young post-myocardial infarction patients with various expressions of classical risk factors.
Coronary risk assessment based on the presence of classical risk factors may be insufficient. Several markers of arterial function and morphology, such as endothelial dysfunction (ED), intima-media thickness (IMT), ankle-brachial pressure index (ABPI), and pulse pressure (PP) may be useful in coronary risk estimation. To investigate their usefulness, we compared them in young post-myocardial infarction (MI) patients with various expressions of classical risk factors. Young male patients (on average 44 years old) in the stable phase after MI were included in the study. Twenty patients had high and 21 patients low expression of risk factors, while 25 healthy age-matched males served as controls. Endothelial dysfunction (estimated by ultrasound measurement of the flow-mediated dilation [FMD] of the brachial artery), IMT (of common carotid arteries), ABPI, and PP were compared between both groups of patients and controls. Compared with the control group, endothelial function and IMT were significantly impaired in both groups of patients, whereas ABPI was significantly reduced only in high-risk patients, and PP was similar in patients and controls. In all subjects, the level of FMD was significantly negatively related to IMT (r = -0.38, P = 0.01). Our study showed that endothelial function and IMT (but not ABPI and PP) are impaired in young post-MI patients independently of presence or absence of classical risk factors. Thus, we conclude that in young patients ED and IMT better assess coronary disease than classical risk factors, and are probably better markers of coronary risk.


Unacceptable complications following intra-articular injection of yttrium 90 in the ankle joint for diffuse pigmented villonodular synovitis.
Simple resection of diffuse pigmented villonodular synovitis of the ankle joint is associated with local recurrence rates as high as 50%. Thus, adjuvant treatment modalities, such as radiation or intra-articular isotope injection, are sometimes used after tumor resection. Our initial and highly satisfactory experience with the injection of radioactive yttrium 90 to treat pigmented villonodular synovitis of the ankle joint eroded with time so much so that we discontinued its use in the ankle and believe that it is important to alert our colleagues to the complications that we observed. Between 1989 and 2006, we treated seven patients who had diffuse pigmented villonodular synovitis of the ankle joint with subtotal synovectomy followed by intra-articular injection of 15 mCi of yttrium 90. Two of the study patients had full-thickness skin necrosis develop around the injection site, necessitating free muscle flap transfer within three months of treatment, and a third patient had development of a draining sinus that was associated with chronic severe pain. The other four patients reported pain after the injection that was reasonably controlled by the use of nonsteroidal anti-inflammatory drugs. At the most recent follow-up evaluation, no study patient had recurrent disease. Because of the unacceptably high rate of serious complications associated with the injection of yttrium 90 into the ankle joint following subtotal synovectomy, we discontinued its use as a local adjuvant in the management of diffuse pigmented villonodular synovitis of the ankle.


EBSeq-HMM: a Bayesian approach for identifying gene-expression changes in ordered RNA-seq experiments.
With improvements in next-generation sequencing technologies and reductions in price, ordered RNA-seq experiments are becoming common. Of primary interest in these experiments is identifying genes that are changing over time or space, for example, and then characterizing the specific expression changes. A number of robust statistical methods are available to identify genes showing differential expression among multiple conditions, but most assume conditions are exchangeable and thereby sacrifice power and precision when applied to ordered data. We propose an empirical Bayes mixture modeling approach called EBSeq-HMM. In EBSeq-HMM, an auto-regressive hidden Markov model is implemented to accommodate dependence in gene expression across ordered conditions. As demonstrated in simulation and case studies, the output proves useful in identifying differentially expressed genes and in specifying gene-specific expression paths. EBSeq-HMM may also be used for inference regarding isoform expression. An R package containing examples and sample datasets is available at Bioconductor. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Functionalized Graphene Oxide Thin Films for Anti-tumor Drug Delivery to Melanoma Cells.
Since Graphene discovery, their associated derivate nanomaterials, Graphene Oxide (GO) and reduced-GO were in the forefront of continuous developments in bio-nano-technology due to unique physical-chemical properties. Although GO nano-colloids (GON) were proposed as drug release matrix for targeting cancer cells, there is still a concern regarding its cytotoxicity issues. In this study, we report on the fabrication of functional GON bio-coatings by Matrix-Assisted Pulsed Laser Evaporation (MAPLE) to be used as drug carriers for targeting melanoma cells. We first performed a thorough in vitro cytotoxicity assay for comparison between GON and protein functionalized GON coatings. As functionalization protein, Bovine Serum Albumin (BSA) was non-covalently conjugated to GO surface. Safe concentration windows were identified in cytotoxicity tests by live/dead staining and MTS assays for five different human melanoma cell lines as well as for non-transformed melanocytes and human dermal fibroblasts. Hybrid GON-BSA nano-scaled thin coatings incorporating Dabrafenib (DAB) and Trichostatin A (TSA) inhibitors for cells bearing BRAFV600E pathway activating mutation were assembled on solid substrates by MAPLE technique. We further demonstrated the successful immobilization for each drug-containing GON-BSA assembling systems by evaluating cellular BRAF activity inhibition and histone deacetylases activity blocking, respectively. DAB activity was proven by the decreased ERK phosphorylation in primary melanoma cells (SKmel28 BRAFV600E cell line), while TSA effect was evidenced by acetylated histones accumulation in cell's nuclei (SKmel23 BRAF WT cell line). In addition, melanoma cells exposed to GON-BSA coatings with compositional gradient of inhibitors evidenced a dose-dependent effect on target activity. Such functional bio-platforms could present high potential for cell-biomaterial interface engineering to be applied in personalized cancer therapy studies.


Effect of Low Concentration of Nitroxides on SH-SY5Y Cells Transfected with the Tau Protein.
Nitroxides, stable synthetic free radicals, are promising antioxidants, showing many beneficial effects both at the cellular level and in animal studies. However, the cells are usually treated with high millimolar concentrations of nitroxides which are not relevant to the concentrations that could be attained in vivo. This paper aimed to examine the effects of low (≤10 μM) concentrations of three nitroxides, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), 4-hydroxy-TEMPO (TEMPOL) and 4-amino-TEMPO (TEMPAMINE), in pure chemical systems and on SH-SY5Y cells transfected with the human tau protein (TAU cells), a model of chronic cellular oxidative stress, and transfected with the empty plasmid (EP cells). All nitroxides were active in antioxidant-activity tests except for the 2,2'-azinobis-(3-ethylbenzthiazolin-6-sulfonate) radical (ABTS•) decolorization assay and reduced Fe3+, inhibited autoxidation of adrenalin and pyrogallol and oxidation of dihydrorhodamine123 by 3-morpholino-sydnonimine SIN-1. TEMPO protected against fluorescein bleaching from hypochlorite, but TEMPAMINE enhanced the bleaching. Nitroxides showed no cytotoxicity and were reduced by the cells to non-paramagnetic derivatives. They decreased the level of reactive oxygen species, depleted glutathione, and increased mitochondrial-membrane potential in both types of cells, and increased lipid peroxidation in TAU cells. These results demonstrate that even at low micromolar concentrations nitroxides can affect the cellular redox equilibrium and other biochemical parameters.


Asymmetrical Flow Field-Flow Fractionation Coupled to ICP-MS for Characterization of Trace Metal Species in the Environment from Macromolecular to Nano-Assemblage Forms: Current Challenges for Quantification.
Asymmetrical flow field-flow fractionation (AF4) is a powerful technique employed for the separation of macromolecules, nanoparticles, and their assemblages according to their hydrodynamic behavior. It is well known that at this size range, complex interactions can occur between components (e.g. surface adsorption, aggregation) controlling the fate of trace metals (TMs) bound to them. AF4 coupling to inductively coupled plasma mass spectrometry (ICP-MS) allows the quantification of metal-containing species at trace levels present in environmental and biological systems on a size-composition basis. The combination of AF4-ICP-MS with other online detectors provides additional information that allows the assessment of the origin of analytes present in mixtures and complex matrixes with minimal sample preparation, which is crucial for understanding the behavior of trace metal contaminants. Despite the increasing use of AF4-ICP-MS in environmental contexts, we acknowledge that the quantification of inorganic species using such combined techniques requires further development of standardized procedures and need certified reference materials. In this review, we also discuss critical endpoints within the ICP-MS instrument coupled to AF4 that need to be controlled before quantitative measurements can be validated. Then, we illustrate how the combination of different online detectors in addition to ICP-MS offers an integrated picture of natural components states, thus providing key information on the changes in behavior of trace metal species and metallic nanoparticles (MNPs) as observed in both environmental samples and biofluids.


Differences in traffic judgements between young and old adult pedestrians.
Older pedestrians have been shown to be over-involved in casualty crashes, compared to younger pedestrians, in recent reports. This study set out to investigate whether older pedestrians' road crossing behaviour might render them more vulnerable to crashes because of declines in their physical, sensory, perceptual or cognitive abilities. An initial 'blackspot' accident analysis highlighted the types of crashes in which older (and younger) adult pedestrians were involved and likely crossing actions. Road crossing behaviour was then systematically measured from unobtrusive video recordings of individual road crossings for a sample of younger and older pedestrians at several urban locations. On two-way undivided roads, older pedestrians crossed more frequently when there was closer moving traffic and generally adopted less safe road crossing strategies than their younger counterparts. On one-way divided roads, their crossing behaviour was considerably more safe and similar to that of younger pedestrians. The findings suggest that age-related perceptual and cognitive deficits may play a substantial role in many of the crashes involving older pedestrians.


Dynamic stabilization for degenerative spondylolisthesis and lumbar spinal instability.
Lumbar interbody fusion is a widely accepted surgical procedure for patients with lumbar degenerative spondylolisthesis and lumbar spinal instability in the active age group. However, in elderly patients, it is often questionable whether it is truly necessary to construct rigid fixation for a short period of time. In recent years, we have been occasionally performing posterior dynamic stabilization in elderly patients with such lumbar disorders. Posterior dynamic stabilization was performed in 12 patients (6 women, 70.9 ± 5.6 years old at the time of operation) with lumbar degenerative spondylolisthesis in whom % slip was less than 20% or instability associated with lumbar disc herniation between March 2011 and March 2013. Movement occurs through the connector linked to the pedicle screw. In practice, 9 pairs of D connector system where the rod moves in the perpendicular direction alone and 8 pairs of Dynamic connector system where the connector linked to the pedicle screw rotates in the sagittal direction were installed. The observation period was 77-479 days, and the mean recovery rate of lumbar Japanese Orthopedic Association (JOA) score was 65.6 ± 20.8%. There was progression of slippage due to slight loosening in a case with lumbar degenerative spondylolisthesis, but this did not lead to exacerbation of the symptoms. Although follow-up was short, there were no symptomatic adjacent vertebral and disc disorders during this period. Posterior dynamic stabilization may diminish the development of adjacent vertebral or disc disorders due to lumbar interbody fusion, especially in elderly patients, and it may be a useful procedure that facilitates decompression and ensures a certain degree of spinal stabilization.


Multivariate chemometrics for the forensic discrimination of blue ball-point pen inks based on their Vis spectra.
Fifty blue ball-point pen inks of five different brands were examined on the basis of the Vis spectrum of their ethanolic solutions with a view to achieving good discrimination between them. Samples were dissolved in absolute ethanol and their absorbance values in the range of 400-750 nm, after appropriate transformations, were used as variables in the multivariate statistical techniques of cluster analysis (CA), principal component analysis (PCA) and discriminant analysis (DA). These techniques were used successively so that an effective and meaningful discriminant model was calculated in the final step. The initial 351 variables (log10 transformed ink absorption values at each wavelength) were subjected to a K-means CA over the objects (samples) and only 20 variables were retained. Principal component analysis was used to detect any outliers (four samples were removed) and the remaining samples were re-subjected to PCA to decide how many variables to enter into DA and whether original variables or components should be used. It was found that the first three principal components (in accordance with the Kaiser criterion) were good descriptors of the 20 original variables (96.97% of the data variance was explained) and their use as latent variables in DA lead to low average variable redundancy (33.6%) in the discriminant model. The calculated model had a Wilks' lambda of 8.98 x 10(-5) and was statistically significant at the P = 0.05 level. The post hoc classification of the training dataset was 100% correct. From the DA results and the component loadings it was found that discrimination was achieved on the basis of differences in the shape of the absorption bands as well as their relative intensities. The method was therefore deemed appropriate for supporting exclusionary forensic purposes.


Enzyme-linked immunosorbent assay for detection of antibodies to Pseudomonas aeruginosa exoproteins.
Enzyme-linked immunosorbent assays were developed with four purified Pseudomonas aeruginosa extracellular proteins (exotoxin A, elastase, alkaline protease, and phospholipase C) to determine antibody levels in sera from healthy subjects and the serological response in patients colonized or infected with Pseudomonas aeruginosa. Five of 39 burn patients with wounds colonized by Pseudomonas aeruginosa had elevated antibody titers to alkaline protease. Response to the other antigens was found in only a few patients. Pseudomonas aeruginosa infections (septicemia, osteitis, pneumonia etc.) resulted in increased antibody levels to exotoxin A or phospholipase C in 15 of 22 patients. These findings suggest that repeated determinations of antibodies to Pseudomonas aeruginosa exotoxin A and phospholipase C might be used to monitor therapy in certain patients with osteitis and other deep Pseudomonas infections.


Organelle targeting: third level of drug targeting.
Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.


Gene profiling after knocking-down expression of nucleostemin in Hela cells using oligonucleotide DNA microarray.
Nucleostemin (NS) is preferentially and exclusively expressed in the stem cells and cancer cells, but not in differentiated adult tissues and cells. NS is likely to take part in controlling the proliferation and differentiation switch in stem cells and progenitor cells. Its deregulation in cancer also contributes to the elevated proliferation and undifferentiation of cancer cells. However, the mechanisms by which NS helps to maintain both cancer and stem cells in undifferentiated state remain unclear. In this study, we carried out gene profilings using oligonucleotide DNA microarray after knocking down the expression of NS in Hela cells. Of the 21,329 genes, 200 genes were found differentially expressed in NS silenced Hela cells with > 2 fold ratio (either > 2 or < 0.5). Category analysis indicated these differential genes were mainly related with cancer pathogenesis, cell death, cell growth and proliferation. NS related gene pathway analysis suggested NS was mostly involved in the networks of cell cycle and differentiation controls. p53 may not be the only partner of NS in its regulated pathways. c-Myc may directly or indirectly interact with it to control the proliferation and differentiation switch in cancer cells. Our study provides a general view of the NS-target genes, and indicates the possible pathways in which NS plays its role in proliferation control.


Tracking the evolution of cancer cell populations through the mathematical lens of phenotype-structured equations.
A thorough understanding of the ecological and evolutionary mechanisms that drive the phenotypic evolution of neoplastic cells is a timely and key challenge for the cancer research community. In this respect, mathematical modelling can complement experimental cancer research by offering alternative means of understanding the results of in vitro and in vivo experiments, and by allowing for a quick and easy exploration of a variety of biological scenarios through in silico studies. To elucidate the roles of phenotypic plasticity and selection pressures in tumour relapse, we present here a phenotype-structured model of evolutionary dynamics in a cancer cell population which is exposed to the action of a cytotoxic drug. The analytical tractability of our model allows us to investigate how the phenotype distribution, the level of phenotypic heterogeneity, and the size of the cell population are shaped by the strength of natural selection, the rate of random epimutations, the intensity of the competition for limited resources between cells, and the drug dose in use. Our analytical results clarify the conditions for the successful adaptation of cancer cells faced with environmental changes. Furthermore, the results of our analyses demonstrate that the same cell population exposed to different concentrations of the same cytotoxic drug can take different evolutionary trajectories, which culminate in the selection of phenotypic variants characterised by different levels of drug tolerance. This suggests that the response of cancer cells to cytotoxic agents is more complex than a simple binary outcome, i.e., extinction of sensitive cells and selection of highly resistant cells. Also, our mathematical results formalise the idea that the use of cytotoxic agents at high doses can act as a double-edged sword by promoting the outgrowth of drug resistant cellular clones. Overall, our theoretical work offers a formal basis for the development of anti-cancer therapeutic protocols that go beyond the 'maximum-tolerated-dose paradigm', as they may be more effective than traditional protocols at keeping the size of cancer cell populations under control while avoiding the expansion of drug tolerant clones. This article was reviewed by Angela Pisco, Sébastien Benzekry and Heiko Enderling.


Driving Hierarchical Collagen Fiber Formation for Functional Tendon, Ligament, and Meniscus Replacement.
Hierarchical collagen fibers are the primary source of strength in musculoskeletal tendons, ligaments, and menisci. It has remained a challenge to develop these large fibers in engineered replacements or in vivo after injury. The objective of this study was to investigate the ability of restrained cell-seeded high density collagen gels to drive hierarchical fiber formation for multiple musculoskeletal tissues. We found boundary conditions applied to high density collagen gels were capable of driving tenocytes, ligament fibroblasts, and meniscal fibrochondrocytes to develop native-sized hierarchical collagen fibers 20-40 μm in diameter. The fibers organize similar to bovine juvenile collagen with native fibril banding patterns and hierarchical fiber bundles 50-350 μm in diameter by 6 weeks. Mirroring fiber organization, tensile properties of restrained samples improved significantly with time, reaching ~1 MPa. Additionally, tendon, ligament, and meniscal cells produced significantly different sized fibers, different degrees of crimp, and different GAG concentrations, which corresponded with respective juvenile tissue. To our knowledge, these are some of the largest, most organized fibers produced to date in vitro. Further, cells produced tissue specific hierarchical fibers, suggesting this system is a promising tool to better understand cellular regulation of fiber formation to better stimulate it in vivo after injury.


RIP mutated ITS genes in populations of Ophiocordyceps sinensis and their implications for molecular systematics.
Different hypotheses have been proposed to interpret the observed unusual ITS (internal transcribed spacer) sequences in Ophiocordyceps sinensis. The coexistence of diverged ITS paralogs in a single genome was previously shown by amplifying the ITS region from mono-ascospore isolates using specific primers designed for different ITS paralog groups. Among those paralogs, are AT-biased ITS sequences which were hypothesized to result from repeat-induced point mutation (RIP). This is a process that detects and mutates repetitive DNA and frequently leads to epigenetic silencing, and these mutations have been interpreted as pseudogenes. Here we investigate the occurrence and frequency of ITS pseudogenes in populations of O. sinensis using large-scale sampling, and discusses the implications of ITS pseudogenes for fungal phylogenetic and evolutionary studies. Our results demonstrate a wide distribution of ITS pseudogenes amongst different geographic populations, and indicate how ITS pseudogenes can contribute to the reconstruction of the evolutionary history of the species.


A compact point-of-use water purification cartridge for household use in developing countries.
Simple, low-cost household interventions are known to be effective in lowering the incidence of waterborne diseases in developing countries. However, high costs along with operational and maintenance issues have prevented the successful adoption of these interventions among the affected communities. To address these limitations, a cost-effective, gravity-driven water purification cartridge has been developed by employing the synergistic disinfection action of low concentrations of silver and chlorine on bacteria and viruses. The silver and chlorine treatment components within the cartridge have been developed using inexpensive materials and integrated with a life indicator and auto-shut-off-mechanism within a compact form factor. The antibacterial as well as antiviral performance of the cartridge was tested by using ground water spiked with Escherichia coli and MS2 bacteriophage. The results show that, although individually, the silver and chlorine treatment systems were unable to inactivate the test strains, the integrated cartridge inactivates both bacteria as well as viruses up to the log reduction requirement of the USEPA guide standard for microbiological water purifiers over its designated life of 2,000 liters.


Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy. Mechanisms and clinical consequences.
Symptoms and signs of myocardial ischemia are often found in patients with hypertrophic cardiomyopathy (HCM) despite angiographically normal coronary arteries. Myocardial ischemia is deemed responsible for some of the lethal complications of HCM including ventricular arrhythmias, sudden death, progressive left ventricular remodeling, and systolic dysfunction. In the past decade, a number of studies using positron emission tomography have demonstrated severe impairment of the vasodilator response to dipyridamole in the majority of HCM patients, not only in the hypertrophied septum but also in the non-hypertrophied left ventricular free wall. In the absence of coronary stenoses, this finding is indicative of diffuse microvascular dysfunction, in line with the autoptic evidence of widespread abnormalities of the intramural coronary arterioles. In turn, microvascular dysfunction represents a very likely substrate for recurrent ischemia. This may account for the fact that microvascular dysfunction has recently been shown to represent an early and powerful predictor of an unfavorable outcome in HCM. The aim of this article is to provide a concise overview of the available evidence of microvascular dysfunction and ischemia in HCM, and to speculate on the potential implications for management.


Treatment of the humeral shaft aseptic nonunion using plate or unilateral external fixator.
Although the use of a plate and bone graft is described as a well-known treatment for aseptic humeral shaft nonunion, unilateral external fixator can be alternative as a minimally invasive method. There has been no report comparing two methods of plate and external fixator for humeral shaft nonunion. Also, a few studies described humeral shaft aseptic nonunion treatment using unilateral external fixator. We retrospectively reviewed 31 patients (15 men and 16 women) with aseptic humeral shaft nonunion treated by plate (n = 20) and unilateral external fixator (n = 11). Patients were followed for a mean of 31.8 months. The right upper arm was involved in 19 patients (17 dominant) and left in 12 patients (2 dominant). The inclusion criteria were aseptic, middle shaft nonunion, without bone defects more than 2 cm. Four patients had hypertrophic, and 27 patients had atrophic nonunion. Solid union, as documented on plain radiographic views, was obtained in 28 (90.3%) patients without additional operation. The average operative time was 92.8 minutes in plate group and 47.8 minutes in external fixator group (p < 0.05). The average blood loss was 142.5 mL in plate group and it was 45.5 mL in external fixator group (p < 0.05). Average hospital stay was 10.9 days in plate group and 3.9 days for external fixator group (p < 0.05). Overall, healing time in the plate group was 4.4 months, compared with 3.6 months in the external fixation group (p < 0.05). The mean Constant and Murley score for plate group was 85.6 points and it was 74.3 points for the external fixator group. According to Stewart and Hundley criteria, 16 (80%) patients in the plate group and 6 (54.5%) patients in the external fixator group had good outcome. Two-pin track infection of the external fixator (18.2%) and two transient radial nerve palsy (10%) were recorded. In this retrospective study of the humeral shaft nonunion, unilateral external fixator tended to yield equally favorable treatment results as did plate fixation. Advantages of the plate are good stability on the nonunion site and comfortability for patient. On the contrary, the advantages of the unilateral external fixator are minimal exposure to the nonunion site with minimal surgical trauma to the soft tissue, easy application of the fixator and consecutively minimal blood loss and short operative time. Unilateral external fixator could be a valuable alternative to plate fixation in aseptic humeral shaft nonunions.


[Neuro-glio-vascular interaction in ischemic brains].
The brain contains glial cells (astrocytes, microglia, and oligodendrocytes) and endothelial cells in addition to neurons. Under various pathologic conditions, the invasion of leukocytes such as neutrophils, monocytes/macrophages, and lymphocytes is observed. Interactions among these cell types play crucial roles both in brain function and dysfunction. However, the molecular basis of such interactions remains unclear. Cytokines and chemokines were originally identified as essential mediators of inflammatory and immune responses. Enhanced production and release of cytokines/chemokines are observed also in the central nervous system under various pathologic conditions. There is growing evidence showing that brain cytokines/chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders and therefore are potential targets for the development of novel and effective therapeutics for central nervous system diseases. This article reviews the evidence for the involvement of cytokines/chemokines in ischemic brain injury and presents our data on introducing organotypic brain slice cultures and in vitro blood brain barrier models as useful tools to investigate neuro-glio-vascular interaction.


Mutating the highly conserved second membrane-spanning region 9' leucine residue in the alpha(1) or beta(1) subunit produces subunit-specific changes in the function of human alpha(1)beta(1) gamma-aminobutyric Acid(A) receptors.
The properties of the human alpha(1)beta(1) gamma-aminobutyric acid (GABA)(A) receptors were investigated after mutation of a highly conserved leucine residue at the 9' position in the second membrane-spanning region (TM2). The role of this residue in alpha(1) and beta(1) subunits was examined by mutating the 9' leucine to phenylalanine, tyrosine, or alanine. The mutations were in either the alpha(1) subunit (alpha*beta), the beta(1) subunit (alphabeta*), or in both subunits (alpha*beta*), and the receptors were expressed in Sf9 cells. Our results show that the rate of desensitization is increased as the size and hydrophobicity of the 9' residue in the alpha(1) subunit is increased: Y, F > L > A, T. Mutation of L9' in only the beta(1) subunit (alphabeta*) to either phenylalanine or tyrosine increased the EC(50) value for GABA at least 100 times, but the EC(50) was unchanged in alphabeta* alanine mutants. In the 9' alpha(1) mutants (alpha*beta, alpha*beta*) the GABA EC(50) was minimally affected. In alpha*beta and alpha*beta*, but not alphabeta*, the peak currents evoked by millimolar concentrations of GABA were greatly reduced. The reduction in currents could only be partially accounted for by decreased expression of the receptors These findings suggest different roles for the two types of subunits in GABA activation and later desensitization of alpha(1)beta(1) receptors. In addition, an increase in the resting membrane conductance was recorded in alanine but not in phenylalanine and tyrosine mutants, indicating that the side chain size at the 9' position is a major determinant of current flow in the closed conformation.


SIGMAR1 mutation associated with autosomal recessive Silver-like syndrome.
To describe the genetic and clinical features of a simplex patient with distal hereditary motor neuropathy (dHMN) and lower limb spasticity (Silver-like syndrome) due to a mutation in the sigma nonopioid intracellular receptor-1 gene (SIGMAR1) and review the phenotypic spectrum of mutations in this gene. We used whole-exome sequencing to investigate the proband. The variants of interest were investigated for segregation in the family using Sanger sequencing. Subsequently, a larger cohort of 16 unrelated dHMN patients was specifically screened for SIGMAR1 mutations. In the proband, we identified a homozygous missense variant (c.194T>A, p.Leu65Gln) in exon 2 of SIGMAR1 as the probable causative mutation. Pathogenicity is supported by evolutionary conservation, in silico analyses, and the strong phenotypic similarities with previously reported cases carrying coding sequence mutations in SIGMAR1. No other mutations were identified in 16 additional patients with dHMN. We suggest that coding sequence mutations in SIGMAR1 present clinically with a combination of dHMN and pyramidal tract signs, with or without spasticity, in the lower limbs. Preferential involvement of extensor muscles of the upper limbs may be a distinctive feature of the disease. These observations should be confirmed in future studies.