[Diabetic retinopathy and pregnancy].
Pregnancy is an important independent risk factor for diabetic retinopathy. This risk is increased with diabetes duration, bad metabolic control, diastolic hypertension, renal disease, anemia, rapid reduction of Hb A1c level and severity of baseline retinopathy. Retinal examination must be done at onset of pregnancy and every 3 months thereafter until 3 months after delivery. Eye fundus will be controlled every month if retinopathy occurs in patients with risk factors. Laser treatment is as efficient during pregnancy as usually.


Anal and rectal cancer in Crohn's disease.
Several epidemiological studies have been published regarding the risk of Crohn's disease- associated colorectal cancer. The findings are, however, contradictory and it has been particularly difficult to obtain indisputable information on the incidence of cancer limited to the rectum and the anus. During 1987-2000 rectal or anal cancer was diagnosed in 335 patients in Sweden (153 males, 182 females). In other words, approximately 3 Crohn patients per million inhabitants were diagnosed with rectal or anal cancer every year during that time period which is 1% of the total number of cases. At diagnosis of cancer 36% were aged below 50 years and 58% below 60 years. Corresponding figures for all cases of anal and rectal cancer were 5% and 18%, respectively. Present knowledge from the literature implies that there is an increased risk of rectal and anal cancer only in Crohn's disease patients with severe proctitis or severe chronic perianal disease. However, the rectal remnant must also be considered a risk factor. Multimodal treatment is similar to that in sporadic cancer but proctectomy and total or partial colectomy is added depending on the extent of the Crohn's disease. The outcome is the same as in sporadic cancer at a corresponding stage but the prognosis is often poor due to the advanced stage of cancer at diagnosis. We suggest that six high-risk groups should be recommended annual surveillance after a duration of Crohn's disease of 15 years including extensive colitis, chronic severe anorectal disease, rectal remnant, strictures, bypassed segments and sclerosing cholangitis.


[The effect of vitamin administration to sows during weaning on the weaning-estrus interval and on the number of live piglets in the next litter].
The effect of injection of additional vitamins in sows during weaning on the weaning-oestrus interval and on the number of piglets born alive in the next litter was studied in 735 sows. On five commercial farms, a total of 735 sows were divided into 3 groups. The first group was injected with 10 ml of a preparation of AD3E. The second group was injected with 10 ml multivitamin. The third group was not treated. It is concluded that injection of additional vitamins did not have any effect on the weaning-oestrus interval and on the number of piglets born alive in the next litter.


Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation.
A composite collagen hydrogel containing protein encapsulated alginate microspheres was developed for ocular applications. Bovine serum albumin (BSA) served as a drug model. The composite hydrogel retained optical clarity and mechanical robustness of control hydrogels without microspheres. A sustained release of BSA was achieved during an 11-day period in neutral phosphate buffer. The composite hydrogel supported human corneal epithelial cell growth and had adequate mechanical strength and excellent optical clarity for possible use as therapeutic lens for drug delivery and/or use as corneal substitute for transplantation into patients who have corneal diseases.


The Effect of Hormonal Therapy on the Behavioral Outcomes in 47,XXY (Klinefelter Syndrome) between 7 and 12 Years of Age.
47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal aneuploidy (SCA). Hormonal replacement therapy (HRT) has been associated with improved neurodevelopmental capabilities in boys with 47,XXY, although studies investigating HRT's possible positive effect on behavioral outcomes are scarce. This study explores the association between behavioral outcomes and HRT in boys ages 7-12. Patients were divided into 4 groups based on HRT status: untreated, early hormonal treatment (EHT), hormonal booster therapy (HBT), and both EHT and HBT. Analysis of Variance (ANOVA) and Kruskal-Wallis tests were conducted to determine group differences on the Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF). The treated groups were found to have better scores in emotional control, initiative, organization of materials, behavioral rating index, metacognition index, and global executive composite than the untreated group on the BRIEF. On the CBCL, the treated groups presented better scores for somatic complaints, social problems, thought problems, attention problems, aggressive behavior, internalizing problems, total problems, affective problems, somatic problems, ADHD problems, oppositional defiant problems, and sluggish problems in comparison to the untreated group. These results offer evidence that HRT, specifically the combination of both EHT and HBT, may be successful in mitigating some undesirable behavioral outcomes. Further research is necessary to determine the efficacy of the combination of EHT and HBT regarding dosage, specific ages, and long-term benefits.


Impact of obesity on mortality and complications in trauma patients.
To examine the association between obesity and outcomes in injured patients. The United States is facing an obesity epidemic affecting 1 in 3 adult Americans. Very little is known about the role of obesity in acute illness. Optimal care of obese trauma patients can only be achieved once we gain a better understanding of the impact of severe obesity on trauma outcomes. We conducted a retrospective cohort study of 147,680 patients admitted to 28 level I and level II Pennsylvania trauma centers between 2000 and 2009. Logistic regression was used to examine the association between obesity and in-hospital mortality and major complications, adjusting for injury severity, age, gender, mechanism of injury, systolic blood pressure, and the motor component of the Glasgow Coma Scale, comorbidities, and year of admission. Patients were grouped into predefined weight categories: underweight (<1st percentile), reference (1st-74th percentile), grade 1 obesity (75th-90th percentile), grade 2 obesity (91th-95th percentile), grade 3 obesity (96th-99th percentile), and grade 4 obesity (>99th percentile). Body mass index was not calculated because height data was not available. After adjusting for injury severity and other risk factors, male patients with severe obesity-grade 3 obesity [adjusted odds ratio (AOR) 1.28; 95% confidence interval (CI): 1.00, 1.64; P = 0.052] or grade 4 obesity (AOR 2.30; 95% CI: 1.48, 3.58; P < 0.001)-were more likely to die than nonobese patients. Severe obesity was associated with an approximately twofold higher risk of major complications: male patients with grade 3 obesity (AOR 1.71; 95% CI: 1.48, 1.97; P < 0. 001) or grade 4 obesity (AOR 2.14; 95% CI: 1.83, 2.51; P < 0.001). Similar results were obtained for female patients. Male and female patients with severe obesity had a 2.5- to 4-fold higher risk of developing acute renal failure. Severely obese females had 2.5- to 4.5-fold higher risk of developing wound complications, and a 4-to 8-fold higher risk of developing decubiti. Severely obese trauma patients were at least 30% more likely to die and approximately twice as likely to have a major complication compared with nonobese patients.


Stable isotopes reveal diet shift from pre-extinction to reintroduced Przewalski's horses.
The Przewalski's horse (Equus ferus przewalskii), the only remaining wild horse within the equid family, is one of only a handful of species worldwide that went extinct in the wild, was saved by captive breeding, and has been successfully returned to the wild. However, concerns remain that after multiple generations in captivity the ecology of the Przewalski's horse and / or the ecological conditions in its former range have changed in a way compromising the species' long term survival. We analyzed stable isotope chronologies from tail hair of pre-extinction and reintroduced Przewalski's horses from the Dzungarian Gobi and detected a clear difference in the isotopic dietary composition. The direction of the dietary shift from being a mixed feeder in winter and a grazer in summer in the past, to a year-round grazer nowadays, is best explained by a release from human hunting pressure. A changed, positive societal attitude towards the species allows reintroduced Przewalski's horses to utilize the scarce, grass-dominated pastures of the Gobi alongside local people and their livestock whereas their historic conspecifics were forced into less productive habitats dominated by browse.


Sensitive analysis of multiple low-molecular-weight thiols in a single human cervical cancer cell by chemical derivatization-liquid chromatography-mass spectrometry.
Low-molecular-weight (LMW) thiols are important small molecules that regulate or maintain redox homeostasis in physiological and pathological processes. Assessing the concentrations of LMW thiols in biological systems may provide valuable information regarding physiological processes and the early diagnosis of some diseases. Here, we developed a method to simultaneously determine the concentrations of multiple LWM thiols in single cells by chemical derivatization assisted liquid chromatography-mass spectrometry (LC-MS). In this method, we synthesized a pair of stable isotope reagents, N-(acridin-9-yl)-2-bromoacetamide (AYBA) and N-(1,2,3,4-[2H4]-acridin-9-yl)-2-bromoacetamide ([2H4]AYBA). AYBA was used to derivatize LWM thiols in human cervical cancer (HeLa) cells, while [2H4]AYBA was used to derivatize standard LWM thiols to prepare internal standards for the LC-MS method development. The proposed AYBA derivatization greatly enhanced the detection sensitivity of LWM thiols by LC-MS, and thereby achieved the simultaneous detection of multiple LWM thiols by LC-MS in ∼1000 HeLa cells. Finally, the developed method was successfully utilized for the quantitative analysis of multiple LWM thiols in a single HeLa cell and the content changes of LWM thiols in a single HeLa cell before and after oxidative stress treatment. Accordingly, six LMW thiols were detected, including cysteamine, cysteine, glutathione, homocysteine, hydrogen sulfide, and pantetheine.


Patient-centered communication, ratings of care, and concordance of patient and physician race.
African-American patients who visit physicians of the same race rate their medical visits as more satisfying and participatory than do those who see physicians of other races. Little research has investigated the communication process in race-concordant and race-discordant medical visits. To compare patient-physician communication in race-concordant and race-discordant visits and examine whether communication behaviors explain differences in patient ratings of satisfaction and participatory decision making. Cohort study with follow-up using previsit and postvisit surveys and audiotape analysis. 16 urban primary care practices. 252 adults (142 African-American patients and 110 white patients) receiving care from 31 physicians (of whom 18 were African-American and 13 were white). Audiotape measures of patient-centeredness, patient ratings of physicians' participatory decision-making styles, and overall satisfaction. Race-concordant visits were longer (2.15 minutes [95% CI, 0.60 to 3.71]) and had higher ratings of patient positive affect (0.55 point, [95% CI, 0.04 to 1.05]) compared with race-discordant visits. Patients in race-concordant visits were more satisfied and rated their physicians as more participatory (8.42 points [95% CI, 3.23 to 13.60]). Audiotape measures of patient-centered communication behaviors did not explain differences in participatory decision making or satisfaction between race-concordant and race-discordant visits. Race-concordant visits are longer and characterized by more patient positive affect. Previous studies link similar communication findings to continuity of care. The association between race concordance and higher patient ratings of care is independent of patient-centered communication, suggesting that other factors, such as patient and physician attitudes, may mediate the relationship. Until more evidence is available regarding the mechanisms of this relationship and the effectiveness of intercultural communication skills programs, increasing ethnic diversity among physicians may be the most direct strategy to improve health care experiences for members of ethnic minority groups.


Relaxation of canine saphenous vein following brief transmural nerve stimulation.
The ability of electrical stimulation to cause relaxation in the canine saphenous vein was evaluated. Rings of vein were studied isometrically in organ chambers containing physiological salt solution. Prostaglandin F2 alpha produced stable contractions, during which brief periods of electrical stimulation caused further contraction. With cessation of the electrical stimulation, tension transiently decreased to a level below that observed prior to the stimulation (undershoot). This poststimulation undershoot was blocked by tetrodotoxin, phentolamine, ouabain, and potassium-free solution; it was not affected by atropine, cimetidine, indomethacin, ketanserin, methysergide, propranolol, pyrilamine, or removal of the endothelium. Undershoot did not occur following electrical stimulation during contractions evoked by norepinephrine. During superfusion with PGF2 alpha, a brief exposure to exogenous norepinephrine caused a transient contraction followed by a subsequent undershoot. These results suggest that 1) the interaction of norepinephrine with postjunctional alpha-adrenoceptors on vascular smooth muscle leads to an increase in the activity of Na+-K+-ATPase, and 2) increased activity of Na+-K+-ATPase is responsible for the poststimulation undershoot.


[Mortality and disablement as criteria in the evaluation of ecological situation].
A uniform study analyzed criteria for evaluation of ecologic jeopardy of some territories. Mortality and disablement appeared to be inadequate for that evaluation. The authors suggest specific parameters for cities neighbouring to major chemical enterprises.


The role of laparoscopy in newborns affected by NEC.
For many years, laparoscopic procedures have been reported in the literature in pediatrics also. In this article, we report their experiences of the use of gasless laparoscopy in 8 newborns affected by necrotizing enterocolitis (NEC). From January 2007 to May 2008, 8 patients affected by stage 1-2 NEC were treated at the Department of Pediatric Surgery, Fondazione Policlinico Milan (Milan, Italy). Of those, 3 patients presented with a birth weight below 1.5 kg. All patients were submitted at gasless laparoscopy. In 6 of 8 patients, a covered perforation was detected; in 5 cases, the perforation was on the posterior wall of the ascending colon, and in 1, a perforation of the transverse colon was detected. In these 6 of 8 patients, the procedure was converted to formal laparotomy, with colonic resection and primary anastomosis. In 2 of 8 patients, a diffuse necrotizing enteritis of the small bowel was reported, without evidence of perforation; two drains were placed and continued abdominal washout with antibiotics solution was maintained for 48 hours, associated with systemic therapy. All patients were maintained on systemic antibiotic therapy for 7 days with regression of sepsis; all patients survived and were discharged in good general condition. At follow-up of 3 months, none of the patients presented with complications. We believe that the decision to perform a laparoscopy, despite the very low weight of the patient, was crucial in the management of nondetected perforation at X-ray. Retrospectively, laparoscopy would be the best option to define the presence of NEC without a perforation, which may only require washout of the cavity that can be also managed with this technique. We believe that laparoscopy can be easily managed also in newborns and small for gestational age neonates, reducing the morbidity of laparotomy for suspicion of perforation in patients affected by NEC who do not respond to medical treatment.


Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers.
Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.


High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial.
High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months).Significance: This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. Cancer Discov; 7(6); 586-95. ©2017 AACR.See related commentary by Schram and Hyman, p. 552This article is highlighted in the In This Issue feature, p. 539.


Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis.
Chronic stress is associated with hormonal changes that are known to affect multiple systems, including the immune and endocrine systems, but the effects of stress on cancer growth and progression are not fully understood. Here, we demonstrate that human ovarian cancer cells exposed to either norepinephrine or epinephrine exhibit lower levels of anoikis, the process by which cells enter apoptosis when separated from ECM and neighboring cells. In an orthotopic mouse model of human ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth by activating focal adhesion kinase (FAK). These effects involved phosphorylation of FAKY397, which was itself associated with actin-dependent Src interaction with membrane-associated FAK. Importantly, in human ovarian cancer patients, behavioral states related to greater adrenergic activity were associated with higher levels of pFAKY397, which was in turn linked to substantially accelerated mortality. These data suggest that FAK modulation by stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in patients with ovarian cancer and may point to potential new therapeutic targets for cancer management.


Acitretin Use in Dermatology.
Acitretin has been used for the treatment of severe psoriasis for over 20 years. The current project was conceived to optimise patient care by recognising the role acitretin can play in the treatment of patients with psoriasis and those with other disorders of keratinisation. A literature review was conducted to explore the role of acitretin and to assess its value for dermatologic disorders other than severe psoriasis. A panel of Canadian dermatologists developed a clinical pathway using a case-based approach, focusing on specific patient features. The clinical pathway covers plaque psoriasis with hyperkeratotic plantar disease, palmoplantar pustulosis, hyperkeratotic hand dermatitis, lichen planus, lamellar ichthyosis, and hidradenitis suppurativa. The recommendations in our clinical pathway reflect the current use of acitretin in Canada for severe psoriasis and other disorders of keratinisation.


Hyaluronic acid fillers: Hylaform and Captique.
Although hyaluronic acids are relatively new treatment for facial lines and wrinkles, they have provided numerous advances in the area of cosmetic surgery. This article discusses the inherent properties of hyaluronic acid fillers that make them ideal for treatment of facial lines. It encompasses a review of the current literature on US Food and Drug Administration-approved hyaluronic acid fillers and the role that each of these fillers currently has in facial cosmetics. This article also discusses the potential pitfalls and adverse effects that can be associated with using hyaluronic acids for filling facial lines. Finally, it serves as an overview of current techniques for clinical assessment of patients and administration and treatment of facial lines and wrinkles.


MicroRNA expression profile in human macrophages in response to Leishmania major infection.
Leishmania (L.) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages. They cause leishmaniasis, a heterogeneous group of worldwide-distributed affections, representing a paradigm of neglected diseases that are mainly embedded in impoverished populations. To establish successful infection and ensure their own survival, Leishmania have developed sophisticated strategies to subvert the host macrophage responses. Despite a wealth of gained crucial information, these strategies still remain poorly understood. MicroRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs, are described to participate in the regulation of almost every cellular process investigated so far. They regulate the expression of target genes both at the levels of mRNA stability and translation; changes in their expression have a profound effect on their target transcripts. We report in this study a comprehensive analysis of miRNA expression profiles in L. major-infected human primary macrophages of three healthy donors assessed at different time-points post-infection (three to 24 h). We show that expression of 64 out of 365 analyzed miRNAs was consistently deregulated upon infection with the same trends in all donors. Among these, several are known to be induced by TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA-targeted genes revealed that several pathways and molecular functions were disturbed upon parasite infection. Finally, following parasite infection, miR-210 abundance was enhanced in HIF-1α-dependent manner, though it did not contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3 regulation. Our data suggest that alteration in miRNA levels likely plays an important role in regulating macrophage functions following L. major infection. These results could contribute to better understanding of the dynamics of gene expression in host cells during leishmaniasis.


Older adults' experiences of self-determination when needing homecare services-an interview study.
Self-determination has been shown to be an important factor in mental health and wellbeing, but from the homecare recipients' point of view, autonomy and self-determination is not fully integrated into homecare services. The aim of this study was to explore older adults' experiences of self-determination when needing homecare services. In 2018, a qualitative descriptive study was conducted and a convenience sample of 15 older adults from 3 homecare service facilities were invited to participate in individual interviews. Data were analysed using qualitative content analyse. The theme Transitioning from self-determination as independence towards self-determination as shared decision-making emerged through the older adults' narratives. This 'transition' is one in which older adult's understanding of self-determination and self-esteem was transitioning towards the acceptance of shared decision-making. The person's inner strength and willingness to make decisions was promoting to enact and preserve independence. Accepting one's dependence on others and being in a positive atmosphere were described as promoting self-determination and shared decision-making, and vice versa. The above overarching theme permeated all subthemes, which included: mobilising inner strength to enact independence; accepting increasing dependence on others; and being influenced by the atmosphere. The study contributes increased understanding of older adults' experiences of self-determination. The results can act as a guide when planning future person-centred care interventions in the context of homecare services and help improve homecare services' ability to meet the needs of older adults. To summarise, older adults' reflections on their own self-determination highlighted relationships with other people as important for shared decision-making, which could help preserve older adults' autonomy and self-esteem.


The International Society of Thrombosis and Hemostasis (ISTH) criteria in intensive care units.
Disseminated Intravascular Coagulation (DIC) has been assessed by the International Society of Thrombosis and Hemostasis (ISTH) 2001 and the ISTH 2018-modified version. More investigations are needed to assess usability and visibility of those DIC scoring systems in the intensive care units (ICU). This study investigated the predictive performance of the ISTH-Overt DIC versions of 28-day mortality in ICUs compared to SOFA as a gold standard assessment tool of sepsis. A retrospective design (2015-2017) included 220 adult patients enrolled from medical and surgical ICUs in two major hospitals in Jordan. We calculated ISTH-Overt DIC scores and SOFA score on time of DIC diagnosis. Overt DIC was categorized based on a score of ≥ five for ISTH DIC 2001; and ≥ 4 for ISTH DIC 2018. Provided, a score > 12 was categorized as Multiple-Organ- Dysfunction-Syndrome (MODS) for Sequential Organ Failure Assessment (SOFA) score. Then, 28-day mortality follow-up was performed. More than half of sample died before 28-days of follow-up. The analysis of Receiver Operating Characteristic (ROC) showed that higher scores of ISTH DIC 2001(≥ 5), ISTH DIC 2018 (≥ 4), and SOFA score (>12) were highly associated with 28-day mortality. The ISTH DIC 2001 and SOFA score were superior on the modified ISTH 2018 in predicting 28-day mortality, with an Area Under the Curve (AUC) of (0.724 vs. 0.822 vs. 0.507, respectively). Yet, the accuracy of the SOFA score was better than the ISTH DIC 2001. This study suggests that ISTH DIC 2001 score is helpful when applied on medical and surgical ICU Jordanian populations. It showed better results compared to the Modified ISTH DIC 2018 in mortality prediction, regardless of the underlying diseases.


CT angiography in the examination of patients with aneurysm clips.
The use of CT angiography is described in three patients for the evaluation of intracranial clips after surgery for an aneurysm. A postprocessing technique is described in which shaded-surface-display models were superimposed on maximum intensity projection CT angiograms. CT angiograms showed residual aneurysmal filling adjacent to a clip, patency of a vessel thought to be compromised by recent clip placement, and errant position of a clip, which required repeat surgery.


The effectiveness of modified vertical dome division technique in reducing nasal tip projection in rhinoplasty.
The technique of vertical dome division or tip defining, involves incising the lateral crura and vestibular skin at or lateral to the dome or tip defining point. The incision divides the lower lateral cartilage into a lateral segment and a medial segment, which are advanced anteriorly and sutured together to increase tip projection. The present study aimed at assessing a new vertical dome division, which is a modified version of vertical dome technique to decrease nasal tip projection, and increase or decrease nasal tip rotation and other tip deformities. The medical files of patients undergone rhinoplasty from 2003 to 2008 were retrospectively analyzed. The files were selected from a computerized rhinoplasty database of patients, who had been operated using a modified vertical dome technique and followed-up for one year or more after the surgery. A total of 3756 patients were operated. Complications related to the nasal tip such as bossae, bifidity, persistent tip projection or tip asymmetry was seen in 81 patients (2.1%). Revisions for tip-related problems were performed in 42 patients (1.1%). The findings suggest that the modified vertical dome technique is an effective method for nasal tip deprojection and narrowing via an open approach. The length of follow-up and the large sample size support effectiveness of the technique.


Phosphorylation of serine 337 of NF-kappaB p50 is critical for DNA binding.
It has been demonstrated that phosphorylation of the p50 subunit of NF-kappaB is required for efficient DNA binding, yet the specific phospho-residues of p50 have not been determined. In this study, we substituted all of the serine and conserved threonine residues in the p50 Rel homology domain and identified three serine residues, Ser65, Ser337, and Ser342, as critical for DNA binding without affecting dimerization. Although substitution with negatively charged aspartic acid at each of these positions failed to restore DNA binding, substitution with threonine, a potential phospho-acceptor, retained DNA binding for residues 65 and 337. In particular, Ser337, in a consensus site for protein kinase A (PKA) and other kinases, was shown to be phosphorylated both in vitro and in vivo. Importantly, phosphorylation of Ser337 by PKA in vitro dramatically increased DNA binding of p50. This study shows for the first time that the DNA binding ability of NF-kappaB p50 subunit is regulated through phosphorylation of residue Ser337, which has implications for both positive and negative control of NF-kappaB transcription.


[Detection, quantitative calculation and identification of bacteria of the Proteus genus in objects of the environment].
The author suggests a complex of nutrient media which aid in detection, quantitative recording and identification of bacteria belonging to Proteus genus and also of the species included into this genus, as well as of the biochemically similar bacteria. The complex of the media constitutes a complete cycle of study: the first stage-fluid enrichment medium, the second stage-isolation and preliminary identification on a hard differential medium with a narrow directed action, and the third stage-determination of the reference of the isolated culture by 9 signs in three integrated media.


A comparison of extended spectrum β-lactamase producing Escherichia coli from clinical, recreational water and wastewater samples associated in time and location.
Extended spectrum β-lactamase producing Escherichia coli (ESBL-EC) are excreted via effluents and sewage into the environment where they can re-contaminate humans and animals. The aim of this observational study was to detect and quantify ESBL-EC in recreational water and wastewater, and perform a genetic and phenotypic comparative analysis of the environmental strains with geographically associated human urinary ESBL-EC. Recreational fresh- and saltwater samples from four different beaches and wastewater samples from a nearby sewage plant were filtered and cultured on differential and ESBL-selective media. After antimicrobial susceptibility testing and multi-locus variable number of tandem repeats assay (MLVA), selected ESBL-EC strains from recreational water were characterized by whole genome sequencing (WGS) and compared to wastewater and human urine isolates from people living in the same area. We detected ESBL-EC in recreational water samples on 8/20 occasions (40%), representing all sites. The ratio of ESBL-EC to total number of E. coli colony forming units varied from 0 to 3.8%. ESBL-EC were present in all wastewater samples in ratios of 0.56-0.75%. ST131 was most prevalent in urine and wastewater samples, while ST10 dominated in water samples. Eight STs and identical ESBL-EC MLVA-types were detected in all compartments. Clinical ESBL-EC isolates were more likely to be multidrug-resistant (p<0.001). This study confirms that ESBL-EC, including those that are capable of causing human infection, are present in recreational waters where there is a potential for human exposure and subsequent gut colonisation and infection in bathers. Multidrug-resistant E. coli strains are present in urban aquatic environments even in countries where antibiotic consumption in both humans and animals is highly restricted.


Familial resemblance for body composition measures: the HERITAGE Family Study.
A sex-specific familial correlation model was used to assess the heritable contributions to several measures of body composition in 86 sedentary white families participating in the HERITAGE Family Study. For this study, sedentary families were recruited, tested for a battery of measures, endurance exercise trained for 20 weeks, and remeasured. This sample is unique in that activity level was controlled for in these families at baseline measurement. In this report, three body composition variables measured at baseline were analyzed, two indexing adiposity (total subcutaneous fat based on eight skinfold measurements [SF8] and percent body fat measured by underwater weighing techniques [%BF]) and one assessing fat free mass ([FFM] derived from underwater weighing). The maximal heritabilities for SF8 (34%) and %BF (62%) were consistent with those reported in previous studies. There were no sex nor generation differences in the familial correlations, and the spouse correlation was significant, consistent with the hypothesis that the familial aggregation reflects genetic and familial environmental factors. However, the results for FFM were very different. The most parsimonious pattern of familial resemblance was consistent with mitochondrial inheritance (i.e., mother-offspring and sibling correlations were equal and were larger than those for spouse and father-offspring pairs). Under the mitochondrial hypothesis, 39% of the variance was accounted for by familial/genetic effects. However, under a nonmitochondrial hypothesis, which could not be ruled out, 65% of the FFM phenotypic variance was accounted for by familial/genetic factors. This high heritability level, as compared with results from previous studies, is consistent with the hypothesis that activity may constitute an important environmental determinant of FFM. These alternative hypotheses for FFM warrant further investigation using complex multilocus-multitrait segregation models, which allow for major genetic, polygenic, and environmental sources of variance, as well as interactions among them.


Managing alcohol and drug abuse in the nursing profession.
Annual increases in indices which reflect the extent of alcohol and drug abuse in society result in a considerable cost to industry. Nurses as a professional group have not generally been identified as having a significantly high incidence of staff with problems of alcohol or drug abuse, although there is some evidence that they are more likely than other workers to attend treatment agencies. The role of nurse management in the early recognition and handling of problems can be vital and training material has been developed to encourage appropriate involvement. A brief description and preliminary evaluation of management training is given. Guidelines and policies which clarify the roles of management, trade unions, occupational health and specialist treatment agencies should facilitate the rehabilitation of the nurse with a drink or drug problem and, in doing so, have potential economic as well as personal benefit to the parties involved.


Association between hypertension and hearing impairment in health check-ups among Japanese workers: a cross-sectional study.
Prevention of hearing impairment (HI) is important because recovery of hearing is typically difficult. Epidemiological studies have examined the risk factors for HI. However, the association between hypertension and HI remains unclear. We aimed to clarify the association between hypertension and HI. Cross-sectional study. Japanese workers in an information and communication technologies company. Of 24 823 employees of the same company, we recruited 13 475 participants who underwent hearing testing by audiometry in annual health check-ups and did not have missing data regarding body measurement, blood test results and drinking/smoking status (mean age: 49.4 years; males: 86.4%). Hearing tests were performed at two frequencies (1 kHz, 4 kHz). We defined the inability of participants to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate HI. We also defined moderate HI at 1 or 4 kHz as an abnormal finding at 1 or 4 kHz. We defined hypertension as ≥140 mm Hg systolic blood pressure and/or ≥90 mm Hg diastolic blood pressure and/or taking medication for hypertension. We examined the association between hypertension and HI after adjusting for age, sex, body mass index, smoking/drinking status, diabetes mellitus, hyperlipidaemia and proteinuria. Moderate HI was identified in 980 participants (7.3%). Of these, 441 participants (3.3%) exhibited moderate HI at 1 kHz, and 787 participants (5.8%) exhibited moderate HI at 4 kHz. Subjects with hypertension showed a higher prevalence of any HI. The prevalence of overall moderate HI, moderate HI at 1 kHz and moderate HI at 4 kHz among subjects with hypertension was 8.7%, 4.3% and 6.8%, while those among subjects without hypertension was 6.9%, 3.0% and 5.6% (p<0.01, p<0.01 and p=0.01, respectively). Hypertension was associated with moderate HI in Japanese workers.


Ascorbic Acid in the Nutrition of Plant-Feeding Insects.
Bollworms, Heliothis zea (Boddie), and salt-marsh caterpillars, Estigmene acrea (Drury) gradually decreased in ascorbic acid content as they matured, even in its presence. Cotton leafworms, Alabama argillacea (Hübner), also lost ascorbic acid, although a dietary need for the vitamin was not proved. Pink bollworms, Pectinophora gossypiella (Saunders), reared without the vitamin, increased in ascorbic acid content as they matured, an indication that the vitamin was synthesized by the insect.


Molecular Mechanism of Stabilizing the Helical Structure of Huntingtin N17 in a Micellar Environment.
Huntington's disease is a deadly neurodegenerative disease caused by the fibrilization of huntingtin (HTT) exon-1 protein mutants. Despite extensive efforts over the past decade, much remains unknown about the structures of (mutant) HTT exon-1 and their enigmatic roles in aggregation. Particularly, whether the first 17 residues in the N-terminal (HTT-N17) adopt a helical or a coiled structure remains unclear. Here, with the rigorous study of molecular dynamics simulations, we explored the most possible structures of HTT-N17 in both dodecylphosphocholine (DPC) micelles and aqueous solution, using three commonly applied force fields (OPLS-AA/L, CHARMM36, and AMBER99sb*-ILDNP) to examine the underlying molecular mechanisms and rule out potential artifacts. We show that local environments are essential for determining the secondary structure of HTT-N17. This is evidenced by the insertion of five hydrophobic residues of HTT-N17 into the DPC micelle, which promotes the formation of an amphipathic helix, whereas such amphipathic helices unfold quickly in aqueous solution. A relatively low free-energy barrier (∼3 kcal/mol) for the secondary structure transformation was also observed for all three force fields from their respective folding-free-energy landscapes, which accounts for possible HTT-N17 conformational changes upon environmental shifts such as membrane binding and protein complex aggregation.


[Cost effectiveness of workplace smoking policies].
This study reviews the motivations of companies to set out a policy for controlling smoking, the economic benefits for the company resulting from such a policy and the costs, broken down by European Union countries. The literature on the costs of implementing a policy related to smoking at the workplace is reviewed. The main objective of policies related to smoking at the workplace is that of safeguarding employees from environmental tobacco smoke. Other reasons are cutting costs, improving the company image, and reducing absenteeism, occupational accidents, internal quarrels and extra costs due to cigarette smoking, protection against environmental tobacco smoke does not entail any higher costs for companies, and economic advantages are visible. The benefits are by far greater than the costs involved, particularly on a long-range basis, and seem to be greater when smoking at the workplace is completely prohibited and no smoking areas are set.


Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators in Drosophila epithelial tumorigenesis.
The deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib) and overexpression of the BTB-ZF protein Abrupt (Ab). Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.


Does a feline leukemia virus infection pave the way for Bartonella henselae infection in cats?
Domestic cats serve as the reservoir hosts of Bartonella henselae and may develop mild clinical symptoms or none after experimental infection. In humans, B. henselae infection can result in self-limiting cat scratch disease. However, immunocompromised patients may suffer from more-severe courses of infection or may even develop the potentially lethal disease bacillary angiomatosis. It was reasoned that cats with immunocompromising viral infections may react similarly to B. henselae infection. The aim of our study was to investigate the influence of the most important viruses known to cause immunosuppression in cats-Feline leukemia virus (FeLV), Feline immunodeficiency virus (FIV), and Feline panleukopenia virus (FPV)-on natural B. henselae infection in cats. Accordingly, 142 cats from animal shelters were necropsied and tested for B. henselae and concurrent infections with FeLV, FIV, or FPV by PCR and immunohistochemistry. A significant association was found between B. henselae and FeLV infections (P = 0.00028), but not between B. henselae and FIV (P = 1.0) or FPV (P = 0.756) infection, age (P = 0.392), or gender (P = 0.126). The results suggest that susceptibility to B. henselae infection is higher in cats with concurrent FeLV infections, regardless of whether the infection is latent or progressive. Histopathology and immunohistochemistry for B. henselae failed to identify lesions that could be attributed specifically to B. henselae infection. We conclude that the course of natural B. henselae infection in cats does not seem to be influenced by immunosuppressive viral infections in general but that latent FeLV infection may predispose cats to B. henselae infection or persistence.


Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden).
With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46 v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.


Clinicopathologic significance of claudin-6, occludin, and matrix metalloproteinases -2 expression in ovarian carcinoma.
Tight junctions (TJs) are mainly composed of claudins, occludin, and tight junction adhesion molecules (JAM). The invasive and metastatic phenotype of highly invasive cancer cells has been related to abnormal structure and function of TJs, and with expression of activated matrix metalloproteinases (MMPs). The relevance of these mechanisms responsible for the invasion and metastasis of ovarian carcinoma is unclear. Similarly, it is not known if the expression of claudin-6, occludin and MMP2 is related with the clinical properties of these tumors. Expression of claudin-6, occludin, and MMP2 was detected in samples of human ovarian cancer tissues by immunohistochemistry and correlated with the clinical properties of the tumors. The positive expression rates of claudin-6 and MMP-2 were higher in ovarian papillary serous carcinomas than n ovarian serous adenomas (P < 0.05). There were no differences in the expression of occludin (P > 0.05). The expression of claudin-6 and occludin in ovarian cancer was not correlated with patient age, pathological grade, clinical stage, and metastasis (P > 0.05). MMP-2 expression was enhanced with increased clinical stage and metastasis (P < 0.05), but was unrelated to patient age or tumor grade (P > 0.05). There were no apparent correlations between expression of claudin-6, occludin and MMP-2 in ovarian cancer tissue (P > 0.05). Our data suggest, for the first time, that the claudin-6 and MMP-2 are up-regulated in ovarian papillary serous carcinomas, MMP-2 expression was enhanced with increased clinical stage and metastasis. Claudin-6 and MMP-2 may play a positive role in the invasion and metastasis of ovarian cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1775628454106511.


Salmonella Typhi genomics: envisaging the future of typhoid eradication.
Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.


An analysis of equity in Brazilian health system financing.
Health care in Brazil is financed from many sources--taxes on income, real property, sales of goods and services, and financial transactions; private insurance purchased by households and firms; and out-of-pocket payments by households. Data on household budgets and tax revenues allow the burden of each source except firms' insurance purchases for their employees to be allocated across deciles of adjusted per capita household income, indicating the progressivity or regressivity of each kind of payment. Overall, financing is approximately neutral, with progressive public finance offsetting regressive payments. This last form of finance pushes some households into poverty.


Bilateral thoracic paravertebral block: potential and practice.
Paravertebral nerve blocks (PVBs) can provide excellent intraoperative anaesthetic and postoperative analgesic conditions with less adverse effects and fewer contraindications than central neural blocks. Most published data are related to unilateral PVB, but its potential as a bilateral technique has been demonstrated. Bilateral PVB has been used successfully in the thoracic, abdominal, and pelvic regions, sometimes obviating the need for general anaesthesia. We have reviewed the use of bilateral PVB in association with surgery and chronic pain therapy. This covers 12 published studies with a total of 538 patients, and with varied methods and outcome measures. Despite the need for relatively large doses of local anaesthetics, there are no reports of systemic toxicity. The incidence of complications such as pneumothorax and hypotension is low. More studies on the use of bilateral PVB are required.


Patterns of dietary intake and relation to respiratory disease, forced expiratory volume in 1 s, and decline in 5-y forced expiratory volume.
The independent effect of individual foods on the risk of respiratory disease is difficult to establish because intakes of specific foods are generally strongly correlated. To date, few studies have examined the relation between dietary food patterns and forced expiratory volume in 1 s (FEV(1)) or respiratory symptoms. The objective was to investigate the relation between dietary patterns and FEV(1), FEV(1) decline, and respiratory health in a general population sample. Data were collected from the cross-sectional study in 12,648 adults from the Netherlands [MORGEN-EPIC (Monitoring Project on Risk Factors and Chronic Diseases in the Netherlands-European Prospective Investigation into Cancer and Nutrition)]. Principal components analysis was used to derive dietary patterns, and multivariate regression analyses were conducted to investigate these patterns with FEV(1) or respiratory health. We also investigated these dietary patterns in relation to lung function decline over 5 y in a subpopulation. A more traditional diet (high intake of meat and potatoes and lower intake of soy and cereal) was associated with a lower FEV(1) (fifth compared with first quintile: -94.4 mL; 95% CI: -123.4, -65.5 mL; P for trend < 0.001) and a higher prevalence of chronic obstructive pulmonary disease. An increased trend through quintiles was seen with a cosmopolitan diet (higher intakes of vegetables, fish, and chicken) for asthma and wheeze. The results suggest that a traditional diet has adverse effects on lung function and chronic obstructive pulmonary disease and that a more cosmopolitan diet was associated with increased risk of wheeze and asthma. However, none of the dietary patterns appear to be related to lung function decline.


Transformation of human cultured fibroblasts with plasmids carrying dominant selection markers and immortalizing potential.
The disadvantages of using human cultured cells for biochemical and genetic studies are their limited lifespan in vitro and their lack of chemical selection markers. These problems are now overcome by transfecting human cultured fibroblasts with the pSV3-gpt and pSV3-neo plasmid DNA which carry genes coding for the immortalizing SV40 large T-antigen and dominant selection markers. Transformed human fibroblasts were obtained at a frequency of about 10(-5) with both selection systems. These transformed cells showed a twofold increase in growth rate and three to tenfold increase in cell number at confluence. The improved growth characteristics were associated with the expression of the SV40 T-antigen detected with immunoprecipitation. These cell lines also changed from their usual spindle shapes to an epithelioid morphology characteristic of transformed cells. From 60 to 100% of the cells transfected with pSV3 plasmid DNA demonstrated numerical and structural abnormalities in their karyotypes. Cells transfected with DNA from a similar plasmid, pSV2-neo, which differed from the pSV3-neo plasmid only by missing the sequence encoding the complete early region of SV40, neither expressed T-antigen nor showed any change in morphology, improvement in growth characteristics or abnormalities in karyotype. However, they were still selectable with the aminoglycoside G-418. Therefore, by appropriate choice of vector plasmids, dominant selection markers and improved growth characteristics can be imparted separately or simultaneously to human fibroblasts. The morphological, biochemical and chromosomal changes resulting from such transformations must be recognized in using this approach for biochemical and genetic studies.


Genomic organization and evolutionary analysis of Ly49 genes encoding the rodent natural killer cell receptors: rapid evolution by repeated gene duplication.
Ly49 genes regulate the cytotoxic activity of natural killer (NK) cells in rodents and provide important protection against virus-infected or tumor cells. About 15 Ly49 genes have been identified in mice, but only a few genes have been reported to date in rats. Here we studied all Ly49 genes in the entire rat genome sequence and identified 17 putative functional and 16 putative non-functional genes together with their genomic locations in a 1.8-Mb region of chromosome 4. Phylogenetic analysis of these genes indicated that the Ly49 gene family expanded rapidly in recent years, and this expansion was mediated by both tandem and genomic block duplication. The joint phylogenetic analysis of mouse and rat genes suggested that the most recent common ancestor of the two species had at least several Ly49 genes, but that the majority of current duplicate genes were generated after divergence of the two species. In both species Ly49 genes are apparently subject to birth-and-death evolution, but the birth and death rates of Ly49 genes are higher in rats than in mice. The rate of gene expansion in the Ly49 gene family in rats is one of the highest among all mammalian multigene families so far studied. The biochemical function of Ly49 genes is essentially the same as that of KIR genes in primates, but the molecular structures of the two groups of NK cell receptors are very different. A hypothesis was presented to explain the origin of the differential use of Ly49 and KIR genes in rodents and primates.


Imbalanced dietary profile, anthropometry, and lipids in urban Asian Indian adolescents and young adults.
To analyze the macronutrient, micronutrient, food intake pattern, anthropometry, and lipid profile of urban Asian Indian adolescents and young adults and compare it with the nutrient profile of rural Asian Indian and American adolescents. This was a cross-sectional, epidemiologic descriptive study. Body mass index (BMI), percentage body fat, waist and hip circumferences, skinfold thickness, serum lipids, and dietary intake were assessed in 1236 subjects (607 males, 629 females) aged 13-25 years from schools and colleges of a metropolitan city of India. The mean age and BMI of study subjects were 17.6 +/- 2.4 years (range 13-25 years) and 19.8 +/- 3.3 kg/m(2) (range 11.9-35.9 kg/m(2)), respectively. The mean daily percentages of total energy contributed by carbohydrates, total fats, proteins, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), omega-3 PUFAs, omega-6 PUFAs, and trans-fatty acids for all subjects were 53%, 34%, 11%, 11%, 10%, 9%, 1%, 8%, and 0.3%, respectively. The absolute daily intake of total fat was 84 +/- 29 g/d in males and 72 +/- 21 g/d in females, which was approximately 4 times the recommended dietary allowance for Asian Indians (20-22 g/d). Among food groups, a high intake of milk, milk products, roots, and tubers was observed. In these young individuals, the prevalence of hypercholesterolemia (males > or =169 mg/dl; females > or =181 mg/dl) and overweight (BMI > or =23.1 kg/m(2)) was 14.4% and approximately 16%, respectively. On comparison with rural Asian Indian adolescents, an inappropriately high intake of total fat was observed in our subjects. On the other hand, the percentage of energy intake of SFAs in Asian Indian and American adolescents was at par. High total fat and SFA intake and a low intake of MUFAs and omega-3 PUFAs showed imbalanced nutrition, which could be responsible for the increasing prevalence of obesity and insulin resistance in urban Asian Indian adolescents and young adults. Nutritional strategies for reducing SFA intake and balancing the omega-3/omega-6 PUFAs ratio should be urgently applied in Asian Indian adolescents and are also presented in this paper.


Achalasia mimicking peptic esophageal stricture.
Peptic stricture of the esophagus and achalasia both cause dysphagia. They are not always readily distinguished by history. The usual workup with upper gastrointestinal x ray and endoscopy may also fail to differentiate the two disorders. Two cases are presented wherein antireflux procedures were mistakenly performed when achalasia was present rather than peptic stricture. Dysphagia was unrelieved and extensive further procedures were required. In a third patient referred for a peptic stricture, manometry revealed the correct diagnosis and heller myotomy provided relief. It is recommended that manometry be performed as a part of the preoperative workup in patients in whom there is any element of dysphagia.


Effect of acute sympathetic activation on leg vasodilation before and after endurance exercise.
Vascular conductance (VC) regulation involves a continuous balance between metabolic vasodilation and sympathetic vasoconstriction. Endurance exercise challenges the sympathetic control on VC due to attenuated sympathetic receptor responsiveness and persistence of muscle vasodilation, especially in endurance athletes, predisposing them to blood pressure control dysfunctions. This study assessed whether acute handgrip-mediated sympathetic activation (SYMP) restrains sudden leg vasodilation before and after a half-marathon. Prior to, and within the 20 min following the race, 11 well-trained runners underwent two single passive leg movement (SPLM) tests to suddenly induce leg vasodilation, one without and the other during SYMP. Leg blood flow and mean arterial pressure were measured to assess changes in leg VC. Undertaking 60 sec of SYMP reduced the baseline leg VC both before (4.0 ± 1.0 vs. 3.3 ± 0.7 ml/min/mmHg; P=0.01; NO SYMP vs. SYMP, respectively) and after the race (4.6 ± 0.8 vs. 3.9 ± 0.8 ml/min/mmHg; P=0.01). However, SYMP did not reduce leg peak vasodilation immediately after the SPLM either before (11.5 ± 4.0 vs. 12.2 ± 3.8 ml/min/mmHg; P=0.35) or after the race (7.2 ± 2.0 vs. 7.3 ± 2.6 ml/min/mmHg; P=0.96). Furthermore, SYMP did not blunt the mean leg vasodilation over the 60 sec after the SPLM before (5.1 ± 1.7 vs. 5.9 ± 2.5 ml/min/mmHg; P=0.14) or after the race (4.8 ± 1.3 vs. 4.2 ± 1.5 ml/min/mmHg; P=0.26). This data suggest that the release of local vasoactive agents effectively opposes any preceding handgrip-mediated augmented vasoconstriction in endurance athletes before and after a half-marathon. Handgrip-mediated SYMP might improve normal vasoconstriction while athletes are still, but not necessarily while they move, as movements can induce a release of vasoactive molecules.


Interaction between HSP70 homolog and filamentous virions of the Beet yellows virus.
An HSP70 homolog (HSP70h), encoded by the Closterovirus Beet yellows virus (BYV), functions in viral movement from cell to cell. A previous study revealed that in infected cells, HSP70h colocalizes with the masses of BYV filamentous virions. Here we demonstrate that HSP70h forms a physical complex with BYV virions. This conclusion is based on both the comigration of HSP70h with BYV virions in sucrose density gradients and the coimmunoprecipitation of the HSP70h and BYV capsid protein using anti-HSP70h serum. The HSP70h-virion complex is stable at high concentrations of sodium chloride; its dissociation using sodium dodecyl sulfate, lithium chloride, or alkaline pH was accompanied by virion disassembly. However, the complex formation does not involve covalent bonds between HSP70h and virion components. Each BYV virion contains approximately 10 molecules of HSP70h. The possible role of HSP70h interaction with the virions in cell-to-cell movement of BYV is discussed.


Age-specific accuracy of initial versus subsequent mammography screening: results from the Ghent breast cancer-screening programme.
The aim of this study was to determine whether age-related differences in the accuracy of mammography breast cancer screening decrease with repeated examination. Data from the first 8 years (May 1992 to April 1999) of the Ghent breast cancer-screening programme were used for analysis. In total, 28 944 mammography examinations were included. The referral rate, cancer detection rate, positive predictive value, sensitivity and specificity were chosen as performance indicators. Values were calculated for women aged 40-49, 50-59 and 60-69 years, at initial versus subsequent examinations, respectively. For first examinations, overall, performance was much lower for the women in their forties than for the older age groups. On subsequent screening, the effect of age disappeared, as expected, or was even reversed for the positive predictive value and sensitivity of the examination. In the light of the ongoing debate over the eligible age for mammography screening, these results support a universal recommendation beginning at the age of 40 years.


A validated HPTLC method for estimation of moxifloxacin hydrochloride in tablets.
A simple HPTLC method having high accuracy, precision and reproducibility was developed for the routine estimation of moxifloxacin hydrochloride in the tablets available in market and was validated for various parameters according to ICH guidelines. moxifloxacin hydrochloride was estimated at 292 nm by densitometry using Silica gel 60 F254 as stationary phase and a premix of methylene chloride: methanol: strong ammonia solution and acetonitrile (10:10:5:10) as mobile phase. Method was found linear in a range of 9-54 nanograms with a correlation coefficient >0.99. The regression equation was: AUC = 65.57 × (Amount in nanograms) + 163 (r(2) = 0.9908).


[Allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia].
To explore the optimal time of allogeneic hematopoietic stem cell transplantation (allo-HSCT) applied in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and the optimum order of donor selection. From Mar 2000 to Jul 2004, 32 patients with Ph+ ALL were treated by Allo-HSCT, and the follow up ended at Dec 30.2004 with medium of 13 months. Of whom, 24 were male, and 8 were female. Twenty-three patients have been transplanted in CR1, 9 patients beyond CR1 (1 in CR2, 8 in refractory or relapse status). Twelve cases received HSCT from identical sibling donor, 4 unrelated Cord Blood Transplantation (CBT), 3 HSCT from matched unrelated donor (MUD), and 13 HSCT from mismatched related donor (MMRD), of which, 6 cases were M(BCR/ABL) subtype, and 20 m(BCR/ABL) subtype. The Kaplan-Meier method was used to estimate the probabilities of leukemia-free survival (LFS), overall survival (OS) and relapse incidence (RI), and the factors were compared by means of the Log-rank test. Simultaneous effect of multiple covariates were estimated with Cox model. Of all the 32 cases engrafted, 4-year OS was 57.19%, LFS 37.09%, and RI 56.36%. In univariate prognostic analysis model, the OS was higher in CR1 group pre-HSCT than that in non-CR1 group (74.50% vs 22.22%, P=0.0046), LFS was higher (49.06% vs 11.11%, P=0.0057), RI was lower (44.80% vs 84.76%, P=0.0157); the OS was higher in M(BCR/ABL) group than that in m(BCR/ABL) group (100% vs 40.91%, P=0.0318), LFS was higher (75% vs 17.72%, P=0.0057), RI was lower (25% vs 77.88, P=0.0116); OS was similar in HLA MM RD group to that in HLA identical group (52.65% vs 55.56%, P=0.6247), LFS was similar (45.12% vs 30.00%, P=0.8315), and RI was also similar (50.77% vs 60.62%, P=0.8217). In multiple covariate analysis model, the BCR/ABL type was the risk factor of LFS [P=0.005, Exp(B)=9.971] and RI (P=0.006, Exp(B)=9.488), the status of disease pre-HSCT and BCR/ABL subtype was the risk factor of OS [P was 0.010 and 0.038, Exp(B) was 4.532 and 37.537 respectively]. We had better do HSCT in CR1 to treat Ph+ ALL, if patient is refractory to chemotherapy, we can try STI571, and HSCT should be done as soon as possible if the patients get CR. Mismatched related donor is considered as regular donor for Ph+ ALL patients without identical donors. We should pay more attention to monitoring and prophylaxis of relapse in m(BCR/ABL) patients after HSCT.


Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events.
The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.


Neural markers of remission in first-episode schizophrenia: a volumetric neuroimaging study of the hippocampus and amygdala.
The temporolimbic region has been implicated in the pathophysiology in schizophrenia. More specifically, significantly smaller hippocampal volumes but not amygdala volumes have been identified at onset in first-episode schizophrenia (FES) patients. However, volumetric differences (namely, in the hippocampus) exhibit an ambiguous relationship with long-term outcome. So, we examined the relationship between hippocampus and amygdala volumes and early remission status. We compared hippocampus and amygdala volumes between 40 non-remitted and 17 remitted FES patients and 57 healthy controls. Amygdala and hippocampus were manually traced with the hippocampus additionally segmented into three parts: body, head, and tail. Remission was defined as mild or less on both positive and negative symptoms over a period of 6 consecutive months as per the 2005 Remission in Schizophrenia Working Group criteria. A significant [group x structure x side] interaction revealed outcome groups differed in hippocampus tail volumes; significantly on the left (non-remitted=694+/-175 mm(3); remitted=855+/-133 mm(3); p=0.001) with a trend difference on the right (non-remitted=723+/-162 mm(3); remitted=833+/-126 mm(3); p=0.023). Groups did not differ in body, head, or amygdala volumes bi-laterally. A smaller hippocampal tail volume may represent a neural marker in FES patients who do not achieve early remission after the first 6 months of treatment. The early identification of patients with poor outcome with respect to the hippocampus tail may encourage the search for new, more target-specific, medications in hope of improving outcome and moving us towards a better understanding of the pathophysiology of schizophrenia.


Symptomatic carotid near-occlusion with full collapse might cause a very high risk of stroke.
The risk of early stroke recurrence amongst patients with symptomatic carotid near-occlusion with and without full collapse is unknown. Therefore, the aim of this study was to analyse the 90-day risk of recurrent ipsilateral ischaemic stroke in patients with symptomatic carotid near-occlusion both with and without full collapse. This study was a secondary analysis of the Additional Neurological SYmptoms before Surgery of the Carotid Arteries: a Prospective study (ANSYSCAP). We prospectively analysed 230 consecutive patients with symptomatic 50-99% carotid stenosis or near-occlusion. Based on the combination of several imaging modalities, 205 (89%) patients were classified as having 50-99% carotid stenosis, and 10 (4%) and 15 (7%) as having near-occlusion with and without full collapse, respectively. The 90-day risk of recurrent ipsilateral ischaemic stroke was compared between these three groups. Only events that occurred before carotid endarterectomy were analysed. The 90-day risk of recurrent stroke was 18% [95% confidence interval (CI) 12-25%; n = 29] for patients with 50-99% carotid stenosis, 0% for patients with near-occlusion without full collapse and 43% (95% CI 25-89%; n = 4) for patients with near-occlusion with full collapse (P = 0.035, log-rank test). The increased risk of recurrent ipsilateral ischaemic stroke for patients with symptomatic near-occlusion with full collapse remained significant after multivariable adjustment for age, sex and type of presenting event. Patients with symptomatic carotid near-occlusion with full collapse might have a very high risk of stroke recurrence. Carotid endarterectomy could be considered for these patients.


Knowing.
The author, a third-year medical school student, talks about her mother's treatment for cancer. As her mother moved through the phases of her treatment, she struggled to reconcile what she should know as a family member with what she needed to know as a medical student. She was far enough along in her training to be familiar with all the heavy, often daunting, details of diseases and their treatments but not far enough along to know how to handle the weight of this knowledge. The author had already known the importance of understanding the chief complaint and the history of present illness. Through her mother's cancer journey, however, she has seen how much more there is to a patient's story. As she prepares for her third-year clinical rotations, her mother's cancer journey and its lessons for her have come just in time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Current smoking as a predictor of chronic musculoskeletal pain in young adult twins.
Chronic pain is common during adolescence and young adulthood and is associated with poor quality of life, depression, and functional disability. Recognizing that chronic pain has significant consequences, it is important to identify modifiable health behaviors that may place young adults at risk for chronic pain. This study examines associations between chronic musculoskeletal pain and smoking in young adult twins (n = 1,588, ages 18-30) participating in a statewide twin registry. Twins completed questionnaires assessing smoking, mood (anxiety, depressive symptoms, and stress), and chronic musculoskeletal pain. Analyses examined associations between chronic pain and smoking, particularly the role of genetics/shared familial factors and psychological symptoms. As predicted, results revealed a near-2-fold increased risk for chronic musculoskeletal pain in twins who currently smoked compared to nonsmokers, even when accounting for psychological factors. Results of within-pair analyses were only minimally attenuated, suggesting that associations between smoking and chronic musculoskeletal pain are better accounted for by nonshared factors than by shared familial factors/genetic effects. Future twin research is needed to identify what nonshared factors (eg, attitudes, direct effects of smoking on pain) contribute to these associations to further understand comorbidity. Longitudinal studies and recruitment of participants prior to smoking initiation and chronic pain onset will better identify causal associations. This article describes associations between musculoskeletal pain and smoking in young adult twins, taking into account psychological symptoms. Findings highlight the importance of nonshared factors in associations between pain and smoking and the need to explore the roles of lifestyle, individual attitudes, and direct effects of smoking on pain.


Mechanical evaluation of fracture fixation augmented with tricalcium phosphate bone cement in a porous osteoporotic cancellous bone model.
The purpose of this study was to examine the effects of resorbable bone cement on screw and plate-screw fracture fixation in a porous osteoporotic bone model. Experiment 1: Screw pullout strength was assessed for 4 sets of 4.5-mm cortical screws inserted into a synthetic osteoporotic cancellous bone model, including screws inserted without cement augmentation (control), screws augmented with tricalcium phosphate (TCP) bone cement (Norian SRS; Synthes USA, Paoli, PA), and screws augmented with polymethylmethacrylate. Experiment 2: The effects of cement augmentation on plate-screw fixation strength were examined by performing cantilever bending tests on 4 sets of 8 plate-screw constructions, including nonaugmented and TCP-augmented standard and locked screw-plate constructions in a similar bone model. Experiment 1: Cement augmentation with both TCP and polymethylmethacrylate increased screw pullout strength from a porous osteoporotic cancellous bone model by about 4-fold (P < 0.05), and there was no significant difference between the 2 cements (P > 0.1). Experiment 2: Fixation strength was 1.5 times higher for locked plates compared with standard plates when neither was augmented with cement (P = 0.07). Cement augmentation with TCP improved fixation strength by 3.6 times for a standard plate-screw construction (P < 0.05) and 3.3 times for a locked plate-screw construction (P < 0.05). The most stable construction was the TCP-augmented locked plate, in which a 5-fold increase was observed compared with that of standard plates without TCP (P < 0.05). This study indicates augmenting screws with TCP cement during osteosynthesis improves fixation strength in an osteoporotic cancellous bone model. : In fracture situations in which osteoporotic bone makes screw and screw-plate fixation tenuous, screw augmentation with TCP cement should be considered as adjunct treatment.


A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.
A five-generation Hispanic pedigree with autosomal dominant zonular pulverulent cataract was studied to identify the causative mutation in connexin 46 (Cx46), a gap junction protein responsible for maintaining lens homeostasis. Twenty-six individuals from the family were comprehensively clinically examined. DNA was extracted from their peripheral blood samples. The DNA was used for automated genotyping with fluorescently labeled microsatellite markers and for mutation detection by automated sequencing. A novel D3Y missense mutation in GJA3 segregated with autosomal dominant (AD) zonular pulverulent cataract throughout the family. The mutation was absent in the unaffected individuals in the family and in 230 control chromosomes. A novel mutation causing AD zonular pulverulent cataract has been identified in a Hispanic Central American family. This is the first report of a mutation in GJA3 causing autosomal dominant congenital cataract (ADCC) in this ethnic group. It is also the first reported cataract-causing mutation in the NH2-terminal region of the Cx46 protein.


Physiologically based pharmacokinetic modeling 1: predicting the tissue distribution of moderate-to-strong bases.
Tissue-to-plasma water partition coefficients (Kpu's) form an integral part of whole body physiologically based pharmacokinetic (WBPBPK) models. This research aims to improve the predictability of Kpu values for moderate-to-strong bases (pK(a) > or = 7), by developing a mechanistic equation that accommodates the unique electrostatic interactions of such drugs with tissue acidic phospholipids, where the affinity of this interaction is readily estimated from drug blood cell binding data. Additional model constituents are drug partitioning into neutral lipids and neutral phospholipids, and drug dissolution in tissue water. Major assumptions of this equation are that electrostatic interactions predominate, drugs distribute passively, and non-saturating conditions prevail. Resultant Kpu predictions for 28 moderate-to-strong bases were significantly more accurate than published equations with 89%, compared to 45%, of the predictions being within a factor of three of experimental values in rat adipose, bone, gut, heart, kidney, liver, muscle, pancreas, skin, spleen and thymus. Predictions in rat brain and lung were less accurate probably due to the involvement of additional processes not incorporated within the equation. This overall improvement in prediction should facilitate the further application of WBPBPK modeling, where time, cost and labor requirements associated with experimentally determining Kpu's have, to a large extent, deterred its application.


Caffeine dependence in schoolchildren?
Schoolchildren (N = 289) kept a log and calculated their habitual caffeine consumption (principally in soft drinks). On 2 successive days, they completed a 20-item checklist adapted from the Profile of Moods Scale. On Day 2, they abstained from caffeine. Complete data were obtained for 175 children. A low-consumption group (10 mg or less daily) was compared with a high-consumption group (50 mg or more daily). The high-consumption group reported more stimulation than did the low-consumption group on Day 1 and more dysphoric symptoms during abstinence on Day 2. The results of this open-label pilot trial suggest that a large-scale double-blind placebo-controlled trial would be worthwhile.


Discrete surface Ricci flow.
This work introduces a unified framework for discrete surface Ricci flow algorithms, including spherical, Euclidean, and hyperbolic Ricci flows, which can design Riemannian metrics on surfaces with arbitrary topologies by user-defined Gaussian curvatures. Furthermore, the target metrics are conformal (angle-preserving) to the original metrics. A Ricci flow conformally deforms the Riemannian metric on a surface according to its induced curvature, such that the curvature evolves like a heat diffusion process. Eventually, the curvature becomes the user defined curvature. Discrete Ricci flow algorithms are based on a variational framework. Given a mesh, all possible metrics form a linear space, and all possible curvatures form a convex polytope. The Ricci energy is defined on the metric space, which reaches its minimum at the desired metric. The Ricci flow is the negative gradient flow of the Ricci energy. Furthermore, the Ricci energy can be optimized using Newton's method more efficiently. Discrete Ricci flow algorithms are rigorous and efficient. Our experimental results demonstrate the efficiency, accuracy and flexibility of the algorithms. They have the potential for a wide range of applications in graphics, geometric modeling, and medical imaging. We demonstrate their practical values by global surface parameterizations.


Family SES Is Associated with the Gut Microbiome in Infants and Children.
While early life exposures such as mode of birth, breastfeeding, and antibiotic use are established regulators of microbiome composition in early childhood, recent research suggests that the social environment may also exert influence. Two recent studies in adults demonstrated associations between socioeconomic factors and microbiome composition. This study expands on this prior work by examining the association between family socioeconomic status (SES) and host genetics with microbiome composition in infants and children. Family SES was used to predict a latent variable representing six genera abundances generated from whole-genome shotgun sequencing. A polygenic score derived from a microbiome genome-wide association study was included to control for potential genetic associations. Associations between family SES and microbiome diversity were assessed. Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae spp. significantly loaded onto a latent factor, which was significantly predicted by SES (p < 0.05) but not the polygenic score (p > 0.05). Our results indicate that SES did not predict alpha diversity but did predict beta diversity (p < 0.001). Our results demonstrate that modifiable environmental factors influence gut microbiome composition at an early age. These results are important as our understanding of gut microbiome influences on health continue to expand.


Fish processing side streams are promising ingredients in diets for rainbow trout (Oncorhynchus mykiss) - Effects on growth physiology, appetite, and intestinal health.
Due to the growth of aquaculture and the finite supply of fishmeal and oil, alternative marine protein and lipid sources are highly sought after. Particularly promising is the use of side streams from the fish processing industry, allowing for the recovery and retention of otherwise lost nutrients in the food production chain. The aim of the present study was to evaluate the potential of three fish processing side streams as fish feed ingredients. The side streams originated from different stages of the production chain, were used without further processing, and included sprat trimmings (heads, frames, viscera), marinated herring (fillets) and mackerel in tomato sauce (fillets and sauce). The three side streams contained moderate levels of protein (28-32% dry matter) and high levels of lipid (34-43%). The sprat trimmings included ca. 29% ash and 1.5% phosphorous which may add value due to the high level of essential minerals but needs to be considered in feed formulations. Three diets were formulated to include 50% of each side stream replacing all fishmeal and ca. 80% of the fish oil of the control diet, which contained 35% fishmeal and 10% fish oil. The diets were evaluated in a 12-week feeding trial using rainbow trout (Oncorhynchus mykiss). Fish fed the sprat diet displayed the highest feed intake and growth, and showed no negative effects on the intestinal health. The mackerel side stream displayed a good digestibility but resulted in lower growth rates compared to the sprat trimmings. Fish fed the herring diet, displayed the lowest performance regarding growth, feed intake and digestibility. They further exhibited a reduction in nutrient uptake in both proximal and distal intestine, likely contributing to the observed lower digestibility and growth, and a reduction in plasma ghrelin levels. As part of a circular approach to increase marine lipid and protein production for fish feed, the tested sprat and mackerel side streams are promising raw materials however additional studies using more commercial-like feed formulations are encouraged.


The landscape of current research on pediatric diffuse midline glioma: a quantitative analysis of shifts, leaders, and future avenues.
Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.


Detection of Clostridium difficile infection clusters, using the temporal scan statistic, in a community hospital in southern Ontario, Canada, 2006-2011.
In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital. Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases. Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007-2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023). Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital personnel. The identification of time periods with decreased or increased CDI rates may have been a result of specific hospital events. Understanding the clustering of CDIs can aid in the interpretation of surveillance data and lead to the development of better early detection systems.


Development, characterization, and anti-microbial efficacy of hydroxyapatite-chlorhexidine coatings produced by surface-induced mineralization.
The surface-induced mineralization (SIM) technique was used to produce hydroxyapatite (HAP) coatings on external fixation pins with the antimicrobial agent, chlorhexidine, incorporated within the coating. The SIM process involved surface modification of the substrate with organic functional groups followed by immersion in aqueous supersaturated calcium phosphate solutions. X-ray diffraction spectra confirmed that hydroxyapatite coatings were formed. Chlorhexidine was incorporated into the coating by placing the substrate into various chlorhexidine solutions in between mineralization cycles. Total uptake was measured by dissolution of the coating into a 0.1 M nitric acid solution and measuring the chlorhexidine concentration using UV spectroscopy at 251 nm. Release rates were measured by submersion of coated substrates into saline solutions and measuring chlorhexidine UV absorbency at 231 nm as a function of time. Results show an initial rapid release followed by a period of slower sustained release. The anti-microbial efficacy of the HAP-chlorhexidine coatings was evaluated in vitro using a Staphylococcus aureus cell culture. Initial results show a large "inhibition zone" formed around the chlorhexidine/HAP coating vs. coatings with HAP only. This preliminary work clearly demonstrates that SIM HAP coatings have great potential to locally deliver antimicrobial agents such as chlorhexidine at implantation sites, which may greatly reduce the incidence of pin tract infection that occurs in external fixation.


Postoperative epidural injection of saline can shorten postanesthesia care unit time for knee arthroscopy patients.
The goal of this prospective, double-blind study was to ascertain if the postanesthesia care unit (PACU) stay of outpatients receiving epidural anesthesia for knee arthroscopy is decreased by injection of epidural saline at the end of the case. Twenty healthy patients undergoing knee arthroscopy received lumbar epidural anesthesia with 2% lidocaine. At the end of surgery, in a double-blind design, group 1 patients (intervention group) received 20 mL 0.9% saline injected into the epidural catheter. Patients in group 2 (control group) had 1 mL 0.9% saline injected into the epidural catheter. In the PACU, the epidural catheter was removed, and motor block was assessed at 15-minute intervals according to the Bromage scale. Standard discharge criteria for our ambulatory surgery center were followed. Patients who received 20 mL epidural 0.9% saline remained in phase I (intensive nursing) 83 +/- 8 minutes compared with control patients who stayed 110 +/- 8 minutes (P < .01). Nonmedical issues related to the unavailability of the patients transportation or waiting for medications to be issued from the pharmacy delayed discharge from phase II (non-nursing) in 70% of group 1 patients and 60% of group 2 patients. Time to actual hospital dismissal for group I was 119 +/- 14 minutes, compared with 159 +/- 13 minutes (P < .05) for group 2. Patients receiving epidural anesthesia for knee arthroscopy had a shorter PACU stay if they received an injection of saline into the epidural space at the end of surgery.


Flavonoid-responsive nodY-lacZ expression in three phylogenetically different Bradyrhizobium groups.
Previously, restriction fragment length polymorphism analysis using the nodD1YABC gene probe showed the genetic diversity of common nodD1ABC gene regions of Bradyrhizobium japonicum, Bradyrhizobium elkanii, and the Thai soybean Bradyrhizobium. The nodD1 sequences of representative strains of the 3 groups differed phylogenetically, suggesting that responses of NodD1 proteins of the 3 Bradyrhizobium groups to diverse flavonoids may differ. To confirm this hypothesis, 6 representative strains were chosen from the 3 Bradyrhizobium groups. Six reporter strains were constructed, all carrying the pZB32 plasmid, which contains a nod box and the nodY-lacZ fusion of B. japonicum USDA 110. Differences in nodY-lacZ expression among the strains in response to 37 flavonoid compounds at various concentrations were evaluated. Of those compounds, prunetin (4',5-dihydroxy-7-methoxyisoflavone) and esculetin (6,7-dihydroxycoumarin) were identified as Bradyrhizobium group-specific nod gene inducers. Esculetin showed nod gene induction activities unique to Thai Bradyrhizobium strains. The levels of nodY-lacZ induction among B. japonicum and Thai Bradyrhizobium strains increased with increasing concentration of prunetin, whereas, those in B. elkanii strains did not.


Specialized compartments of cardiac nuclei exhibit distinct proteomic anatomy.
As host to the genome, the nucleus plays a critical role as modulator of cellular phenotype. To understand the totality of proteins that regulate this organelle, we used proteomics to characterize the components of the cardiac nucleus. Following purification, cardiac nuclei were fractionated into biologically relevant fractions including acid-soluble proteins, chromatin-bound molecules and nucleoplasmic proteins. These distinct subproteomes were characterized by liquid chromatography-tandem MS. We report a cardiac nuclear proteome of 1048 proteins--only 146 of which are shared between the distinct subcompartments of this organelle. Analysis of genomic loci encoding these molecules gives insights into local hotspots for nuclear protein regulation. High mass accuracy and complementary analytical techniques allowed the discrimination of distinct protein isoforms, including 54 total histone variants, 17 of which were distinguished by unique peptide sequences and four of which have never been detected at the protein level. These studies are the first unbiased analysis of cardiac nuclear subcompartments and provide a foundation for exploration of this organelle's proteomes during disease.