The present study evaluated the ability of methanolic extract of Centella asiatica (Linn) Urban (Umbelliferae) to induce apoptosis in different cancer cell lines. MCF-7 cells emerged as the most sensitive cell line for in vitro growth inhibitory activity. C. asiatica extract induced apoptosis in MCF-7 cells as indicated by nuclear condensation, increased annexin staining, loss of mitochondrial membrane potential and induction of DNA breaks identified by TUNEL reactivity. It is possible that the use of C. asiatica extract as a component in herbal medicines could be justifiable.
Apoptosis; Cancer; Centella asiatica
To determine the appropriate wrist position in individuals with high-level paraplegia during the RAISE (relief of anatomical ischial skin embarrassment) maneuver.
Thirty individuals with high-level paraplegia were randomly selected; 15 individuals performed RAISE maneuver with extended wrist and 15 with neutral wrist. All the subjects who were at least 1 year post spinal cord injury were screened for positive carpal tunnel syndrome symptoms. All the subjects were allowed to participate in a trial of the Jebsen-Taylor Test of Hand Function to familiarize them with the test. Hand function was measured using the Jebsen-Taylor test.
During the RAISE maneuver, individuals with paraplegia weight bearing on their hands with wrists in the neutral position showed better hand function (P < .001) when compared to those weight bearing with their wrists in extension.
Weight bearing with the wrist in neutral position is advisable for paraplegics to prevent the deterioration in hand function due to carpal tunnel syndrome.
carpal tunnel syndrome; hand function; Jebsen-Taylor test; paraplegia
While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit is still unclear. The aim of the present study was to use fMRI to determine the effect of PAE on neuronal activation during a subtraction task.
Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n=17) and those with PAE, who were subdivided based on the presence (n=19) or absence of physical dysmorphic signs (n=18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population.
An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the non-dysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation.
Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.
prenatal alcohol; fMRI; arithmetic processing
TNF-Related Apoptosis Inducing Ligand (TRAIL) binds to and activates death receptors to stimulate caspase-8 and apoptosis with higher efficiency in cancer than normal cells but the development of apoptosis resistance has limited its clinical efficacy. We found that stable, but not transient knockdown of the ABL tyrosine kinase enhanced the apoptotic response to TRAIL. Re-expression of Abl, but not its nuclear import- or kinase-defective mutant, in the ABL-knockdown cells re-established apoptosis suppression. TRAIL is known to stimulate caspase-8 ubiquitination (Ub-C8), which can facilitate caspase-8 activation or degradation by the lysosomes. In the ABL-knockdown cells, we found a higher basal level of Ub-C8 that was not further increased by lysosomal inhibition. Re-expression of Abl in the ABL-knockdown cells reduced the basal Ub-C8, correlating with apoptosis suppression. We found that lysosomal inhibition by chloroquine (CQ) could also enhance TRAIL-induced apoptosis. However, this pro-apoptotic effect of CQ was lost in the ABL-knockdown cells but restored by Abl re-expression. Interestingly, kinase inhibition at the time of TRAIL stimulation was not sufficient to enhance apoptosis. Instead, persistent treatment for several days with imatinib, an ABL kinase inhibitor, was required to cause the enhanced and the CQ-insensitive apoptotic response to TRAIL. Together, these results show that persistent loss of nuclear ABL tyrosine kinase function can sensitize cells to TRAIL and suggest that long-term exposure to the FDA-approved ABL kinase inhibitors may potentiate apoptotic response to TRAIL-based cancer therapy.
Here, we report the 4.46-Mbp draft genome sequence of Bacillus sp. strain SB47, an extreme halophile isolated from a salt pan of the Little Rann of Kutch, India. Exploring the genome of this organism will facilitate the understanding and isolation of the gene(s) involved in its extreme osmotolerance.
We report the 4.52-Mbp draft genome sequence of Bacillus sp. strain NSP9.1, a moderately halophilic bacterium isolated from the salt marsh of the Great Rann of Kutch, India. Analysis of the genome of this organism will lead to a better understanding of the genes and metabolic pathways involved in imparting osmotolerance.
Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure, BMI, and HDL-C.
This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, where ancestry association evidence for hypertension, BMI or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1,733 unrelated African-Americans from the National Heart, Lung and Blood Institute’s (NHLBI) Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age2, sex, local marker ancestry, and BMI, as applicable. An individual’s African ancestry estimated from 2,507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification.
CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (p < 0.0006). F2RL1 (rs631465) on chromosome 5 was associated with BMI (p = 0.0005). Local ancestry in these regions was associated with the respective traits as well.
This study suggests that CXADR and F2RL1 likely play important roles in blood pressure and obesity variation, respectively; and these findings are consistent with other studies, so replication and functional analyses are necessary.
Blood pressure; Obesity; African Americans; Genetic Association Studies
•Grapheme–color synesthetes display superior color working memory than controls.•This effect is independent of color familiarity and color discrimination abilities.•Controls and synesthetes do not differ in grapheme working memory.•These results support enhanced color processing in synesthesia.•They also support research linking sensory processing and working memory.
There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme–color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory.
Color-processing; n-Back; Grapheme-processing; Synesthesia; Visual; Working memory
Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients.
SeHCAT; C4; glycocholate; fecal; diarrhea
Verruciform Xanthoma (VX) is a relatively rare benign mucocutaneous lesion of unknown aetiology. VX occurs predominantly in oral cavity which also occasionally affects skin and genital mucosa. It was first reported in the oral cavity in 1971. This rare harmless lesion usually presents as sessile or pedunculated, appear as a papule or single plaque showing verrucous or papillomatous mucosal growth with variable color from reddish pink to gray. In majority of oral cases, it affects gingiva and alveolar mucosa that may be mistaken for benign, premalignant and malignant conditions. VX is diagnosed with certainly only on histopathologic examination. Histologically VX is characterized by the presence of parakeratinized epithelium showing papillary or verrucous growth with thin rete ridges and connective tissue papillae extending up to the surface. The papillae characteristically consist of foam cells also called xanthoma cells. Here we describe a case report of verruciform xanthoma occurring on the buccal mucosa in a 42–years old male patient along with its clinical, pathogenesis, histological features and treatment modalities discussed.
Verruciform xanthoma; Oral cavity; Pathogenesis; Xanthoma cells
Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population. Hypoxic stress created in the micro-environment of the photoreceptors is thought to be the underlying cause that results in the pathophysiology of AMD. However, association of AMD with alternative splicing mediated gene regulation is not well explored. Alternative Splicing is one of the primary mechanisms in humans by which fewer protein coding genes are able to generate a vast proteome. Here, we investigated the expression of a known stress response gene and an alternative splicing factor called Serine-Arginine rich splicing factor 10 (Sfrs10). Sfrs10 is a member of the serine-arginine (SR) rich protein family and is 100% identical at the amino acid level in most mammals. Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and chicken retinae showed pan-retinal expression. However, SFRS10 was not detected in normal human retina but was observed as distinct nuclear speckles in AMD retinae. This is in agreement with previous reports that show Sfrs10 to be a stress response gene, which is upregulated under hypoxia. The difference in the expression of Sfrs10 between humans and lower mammals and the upregulation of SFRS10 in AMD is further reflected in the divergence of the promoter sequence between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR protein speckles or the HSF1+ stress granules. In all, our data suggests that SFRS10 is upregulated and forms distinct stress-induced speckles and might be involved in AS of stress response genes in AMD.
Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.
Excessive mucin degradation by intestinal bacteria may contribute to inflammatory bowel diseases because access of luminal antigens to the intestinal immune system is facilitated. This study investigated how the presence of a mucin degrading commensal bacterium affects the severity of an intestinal Salmonella enterica Typhimurium-induced gut inflammation. Using a gnotobiotic C3H mouse model with a background microbiota of eight bacterial species (SIHUMI) the impact of the mucin-degrading commensal bacterium Akkermansia muciniphila (SIHUMI-A) on inflammatory and infectious symptoms caused by S. Typhimurium was investigated. Presence of A. muciniphila in S. Typhimurium-infected SIHUMI mice caused significantly increased histopathology scores and elevated mRNA levels of IFN-γ, IP-10, TNF-α, IL-12, IL-17 and IL-6 in cecal and colonic tissue. The increase in pro-inflammatory cytokines was accompanied by 10-fold higher S. Typhimurium cell numbers in mesenteric lymph nodes of SIHUMI mice associated with A. muciniphila and S. Typhimurium (SIHUMI-AS) compared to SIHUMI mice with S. Typhimurium only (SIHUMI-S). The number of mucin filled goblet cells was 2- to 3- fold lower in cecal tissue of SIHUMI-AS mice compared to SIHUMI-S, SIHUMI-A or SIHUMI mice. Reduced goblet cell numbers significantly correlated with increased IFN-γ mRNA levels (r2 = −0.86, ***P<0.001) in all infected mice. In addition, loss of cecal mucin sulphation was observed in SIHUMI mice containing both A. muciniphila and S. Typhimurium compared to other mouse groups. Concomitant presence of A. muciniphila and S. Typhimurium resulted in a drastic change in microbiota composition of SIHUMI mice: the proportion of B. thetaiotaomicron in SIHUMI-AS mice was 0.02% of total bacteria compared to 78% – 88% in the other mouse groups and the proportion of S. Typhimurium was 94% in SIHUMI-AS mice but only 2.2% in the SIHUMI-S mice. These results indicate that A. muciniphila exacerbates S. Typhimurium-induced intestinal inflammation by its ability to disturb host mucus homeostasis.
Glycogen Storage Disease (GSD) type III, glycogen debranching enzyme deficiency, causes accumulation of glycogen in liver, skeletal, and cardiac muscle. Some patients develop increased left ventricular (LV) thickness by echocardiography, but the rate of increase and its significance remain unclear.
We evaluated 33 patients with GSD type III, 23 with IIIa and 10 with IIIb, ages 1 month – 55.5 yrs, by echocardiography for wall thickness, LV mass, shortening and ejection fractions, at 1 time point (n = 33) and at 2 time points in patients with more than 1 echocardiogram (13 of the 33).
Of 23 cross-sectional patients with type IIIa, 12 had elevated LV mass, 11 had elevated wall thickness. One type IIIb patient had elevated LV mass but 4 had elevated wall thickness. For those with multiple observations, 9 of 10 with type IIIa developed increased LV mass over time, with 3 already increased at first measurement. Shortening and ejection fractions were generally normal.
Elevated LV mass and wall thickness is more common in patients with type IIIa but develops rarely in type IIIb, though ventricular systolic function is preserved. This suggests serial echocardiograms with attention to LV thickness and mass are important for care of these patients.
Glycogen Storage Disease Type III; left ventricular hypertrophy; ventricular function; left ventricular mass
The gold standard for surgical correction of both uni- and bilateral coronal synostosis remains to this day, the “standardised bilateral fronoto-orbital advancement and reshaping” based on the “tongue in groove” technique developed by Tessier. It consists of bilateral frontal craniotomy for suture release and decompression, combined with creation of a “supraorbital bar” as a bilateral orbital complex by osteotomising the orbital roof (anterior cranial base), supraorbital ridge and upper lateral orbital rims bilaterally. This is followed by a bilateral advancement and remodelling of the frontal region as well as the orbital region bilaterally which is then rigidly fixed in position, the supraorbital bar to the face (at the fronto-zygomatic region and the fronto-nasal region) and the reconstructed forehead to the supraorbital bar. In this study, a slightly modified procedure was employed for correction of the right sided unilateral coronal synostosis, using a bifrontal craniotomy combined with unilateral orbital osteotomy (creating a unilateral supraorbital bar/bandeau), followed by radial osteotomies/kerfing, reshaping and advancement of the bifrontal calvarial segment. This was followed by the “tongue in groove” advancement of the right orbital segment (unilaterally). We preferred to spare osteotomising the contralateral (that is, the left) orbital region as it was not involved by compensatory growth deformity, and the frontal bossing/bulging was restricted to the upper forehead region alone. A gratifying aesthetic outcome and perfect symmetry was achieved using this technique. There were also no complications like wound infection or dehiscence, CSF leak, bone loss from resorption, damage to orbital contents or brain, recurrence of the dysmorphology or residual deformities or asymmetrics of the orbital region or forehead. Gratifying cosmetic results were seen using this modified technique and it was found that bilateral frontal reshaping and unilateral orbital advancement together with kerfing the frontal segment followed by fixation using resorbable implants is an effective strategy to not only permit remodelling of the skull and face thus correcting the cosmetic deformity, but also to increase the intracranial volume within the anterior cranial vault, without the need for any graft placement.
Plagiocephaly; Craniosynostosis; Fronto-orbital advancement; Biodegradeable implants
A rare case report of a plexiform unicystic ameloblastoma in a 3-year-old girl stimulated us to conduct a review of literature to understand the correlation of this tumor with various factors such as that of age, sex, histopathological correlation, and its incidence rates pertaining to children and adolescent population. This is a case report of ameloblastoma in a 3-year-old patient, along with a literature review of ameloblastoma in relation to age. A computerized literature search using Medline was conducted for published articles on treatment of ameloblastoma. MeSH phrases used in search were ameloblastoma AND age; ameloblastoma AND children. The search was restricted to published articles from 1970 to 2010, as the histological features were not clearly defined until 1st edition of WHO histological classification of odontogenic tumors of 1971, search parameter was also set to select literatures under English language only. An additional systematic hand search was also conducted simultaneously to identify other published articles, considering similar parameters as used for Medline search. Most of search result yielded literatures in which primary importance were given to treatment patterns and prognosis of intervention, there were not much specific article or meta analysis which reviewed on the affected age range of ameloblastoma exclusively. We reviewed the identified literatures with patients' age, case numbers, incidence, sex, location, and histopathology. The statistical data collected were exported to SPSS 16.0 for windows software which performed a descriptive analysis giving an average mean age of 14.1 years (range from 4 to 20); with maximum mean age being 16.0 and minimum mean age being 10.8 with standard deviation of 1.60. Majority of lesions 91.86% (327 of 356) were found between the age group of 11 and 20 years, only 8.14% (29 of 356) were below the age of 10 years. This rare case report highlights occurrence of plexiform unicystic ameloblastoma in maxilla of a 3-year-old girl, which is very much incongruent with the various review of literature on ameloblastoma in children and adolescents. We have emphasized the significance of patient's age and histopathological pattern of the tumor as it has its influence on the treatment plan. However, there is much of research needed with focus in respect to age, histological pattern, and treatment outcomes.
ameloblastoma; pediatrics; children; adolescents; literature review
Sphingobium chinhatense strain IP26T is a conducive hexachlorocyclohexane (HCH) degrader isolated from a heavily contaminated (450 mg HCH/g soil) HCH dumpsite. IP26T degrades α-, β-, γ-, and δ-HCH, which are highly persistent in the environment. Here we report the draft genome sequence (~5.8 Mbp) of this strain.
AIM: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).
METHODS: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.
RESULTS: One hundred and twenty patients with SSAs were identified: 61% were distal and 39% were proximal SSAs. Proximal SSAs were more likely to be flat than distal (100% vs 78% respectively; P = 0.0001). Proximal SSAs were more likely to occur in smokers (OR = 2.63; 95%CI: 1.17-5.90; P = 0.02) and in patients with family history of colorectal cancer (OR = 4.72; 95%CI: 1.43-15.55; P = 0.01) compared to distal. Proximal SSAs were statistically more likely to be ≥ 6 mm in size (OR = 2.94; P = 0.008), and also more likely to be large (≥ 1 cm) (OR = 4.55; P = 0.0005) compared to the distal lesions. Smokers were more likely to have proximal (P = 0.02), flat (P = 0.01) and large (P = 0.007) SSAs compared to non-smokers. Compared to proximal tubular adenomas, proximal SSAs were more likely to be large and occur in smokers.
CONCLUSION: Proximal SSAs which accounted for two-fifths of all SSAs were more likely to present as flat lesions, larger SSAs, and were more likely to occur in smokers and in patients with family history of colorectal cancer. Our data has implications for colorectal cancer screening.
Proximal; Sessile; Serrated; Adenoma; Colonoscopy; Colorectal cancer; Smoking
Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients who are at high risk of mortality from infection. We conducted a population-based case-control study to determine risk factors and predictors for candidemia in the PICU.
Candida species are the leading cause of invasive fungal infections in hospitalized children and are the third most common isolates recovered from pediatric healthcare-associated bloodstream infection in the US . Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients.
We conducted a population-based case-control study of PICU patients at Children's Hospital of Philadelphia (CHOP) from 1997-2004. Cases were identified using laboratory records, controls were selected from PICU rosters. Controls were matched to cases by incidence density sampling, adjusting for time at risk. Following conditional multivariate analysis, we performed weighted multivariate analysis to determine predicted probabilities for candidemia given certain risk factor combinations.
We identified 101 cases of candidemia(incidence,3.5/1,000 PICU admissions). Factors independently associated with candidemia included presence of a central venous catheter(OR 30.4;CI,7.7,119.5), malignancy(OR 4.0;CI,1.23,13.1), use of vancomycin for >3 days in the prior two weeks(OR 6.2;CI,2.4,16), and receipt of agents with activity against anaerobic organisms for >3 days in the prior two weeks(OR 3.5;CI, 1.5,8.4). Predicted probability of various combinations of the factors above ranged from 10.7%-46%. The 30-day mortality rate was 44% in cases compared to 14% in controls (OR 4.22;CI,2.35,7.60).
To our knowledge, this is the first study to evaluate independent risk factors and to determine a population of children in PICUs at high risk for developing candidemia. Future efforts should focus on validation of these risk factors identified in a different PICU population and development of interventions for prevention of candidemia in critically ill children.
Candidemia; Pediatrics; Risk factors; Intensive Care
Context. Usnea ghattensis G. Awasthi (Usneaceae) endemic fruticose lichen found growing luxuriantly in Northern Western Ghats of India, it also contains Usnic acid as a major chemical and tested against some human pathogenic bacteria. Objective. To explore antimicrobial properties of Usnea ghattensis against some human pathogenic bacteria. Materials and Methods. The lichen was extracted in acetone, methanol, and ethanol. In vitro antimicrobial activity was tested initially by Kirby-Bauer technique of disc diffusion method and was confirmed by minimum inhibitory concentration using Broth microdilution method according to the NCCLS guidelines. Results. Ethanol extract was most effective against Bacillus cereus and Pseudomonas aeruginosa with a zone of inhibition 29.8 ± 0.6 mm and 12.3 ± 0.5 mm diameters at a concentration of 0.2 mg/mL. Acetone and methanol extract demonstrated almost similar activity against Staphylococcus aureus and the zone of inhibition was 24.6 ± 0.5 and 24.7 ± 0.4 mm. Only methanol extract was showing activity against Streptococcus faecalis with a 13.5 ± 0.8 mm zone. MIC value noted against Staphylococcus aureus and Streptococcus faecalis was 6.25 μg/mL and 25 μg/mL, whereas against Bacillus cereus and Pseudomonas aeruginosa, MIC calculated was 3.125 μg/mL and 200 μg/mL, respectively. Conclusion. The present study demonstrates the relatively higher activity of this lichen against not only gram (+) but significantly also against gram (−) bacteria. This indicates that this lichen might be a rich source of effective antimicrobial agents.
Community health centers (CHCs) seek effective strategies to address obesity. MidWest Clinicians’ Network partnered with [an academic medical center] to test feasibility of a weight management quality improvement (QI) collaborative. MidWest Clinicians’ Network members expressed interest in an obesity QI program. This pilot study aimed to determine whether the QI model can be feasibly implemented with limited resources at CHCs to improve weight management programs. Five health centers with weight management programs enrolled with CHC staff as primary study participants; this study did not attempt to measure patient outcomes. Participants attended learning sessions and monthly conference calls to build QI skills and share best practices. Tailored coaching addressed local needs. Topics rated most valuable were patient recruitment/retention strategies, QI techniques, evidence-based weight management, motivational interviewing. Challenges included garnering provider support, high staff turnover, and difficulty tracking patient-level data. This paper reports practical lessons about implementing a weight management QI collaborative in CHCs.
Obesity; weight management; Quality Improvement Collaborative; community health centers; primary care
Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a condition known as non-syndromic EVA. A significant number of patients with Pendred syndrome and non-syndromic EVA show only one mutation in SLC26A4. Two genes, KCNJ10, encoding an inwardly rectifying potassium channel and FOXI1, a transcriptional factor gene, are thought to play a role in the disease phenotypes.
Using Polymerase Chain Reaction and Sanger sequencing, sixty-eight patients with monoallelic mutations of SLC26A4 were tested for mutations in KCNJ10 and FOXI1.
Two variants were observed in the KCNJ10 gene, p.Arg271Cys in three patients and p.Arg18Gln in one patient; only one variant, p.Arg123Trp was observed in the FOXI1 gene in a single patient. Both p.Arg271Cys and p.Arg18Gln are likely to be polymorphisms as judged by their frequency in the general population.
Therefore we found no evidence for a significant association between mutations of KCNJ10 and FOXI1 with SLC26A4. It was also observed that the variant, p.Arg271Cys in KCNJ10, previously thought to have a protective effect against seizure susceptibility, was found in a patient with Pendred syndrome with co-existing epilepsy.
Deafness; Enlarged vestibular aqueducts; Epilepsy; EVAS; FOXI1; Hearing impairment; KCNJ10; Pendred syndrome; SLC26A4
Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person’s lifetime risk of cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and in persons with a genetic variant near IL28B, the genetic basis is not well understood.
To evaluate the host genetic basis for spontaneous resolution of HCV infection.
Two-stage genome wide association study (GWAS).
13 international multicenter study sites.
919 individuals with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 individuals with serum HCV antibodies and RNA (persistence).
Frequencies of 792,721 SNPs.
Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL28B and included rs12979860 (overall per-allele OR = 0.45, P = 2.17 × 10−30) and 10 additional SNPs spanning 55,000 bases. On chromosome 6, allele frequency differences localized near genes for class II human leukocyte antigens (HLA) and included rs4273729 (overall per-allele OR= 0.59, P = 1.71 × 10−16) near DQB1*03:01 and an additional 116 SNPs spanning 1,090,000 base pairs. The associations in chromosomes 19 and 6 were independent, additive, and explain an estimated 14.9% (95% CI: 8.5–22.6%) of the variation in HCV resolution in those of European-Ancestry, and 15.8% (95% CI:4.4–31.0%) in individuals of African-Ancestry. Replication of the chromosome 6 SNP, rs4272729 in an additional 746 individuals confirmed the findings (p=0.015).
Epigenetic effects were not studied.
IL28B and HLA class II are independently associated with spontaneous resolution of HCV infection and SNPs marking IL28B and DQB1*03:01 may explain ~15% of spontaneous resolution of HCV infection.
Rhabdomyosarcomas (RMS) are highly malignant pediatric sarcomas. We have discovered that the gene encoding the major histocompatibilty complex class II transactivator, CIITA, is silenced in cells representing both major subtypes of RMS. Silencing of CIITA prevents the IFN-γ inducible expression of MHC class II genes in these cells. Overexpression of CIITA in these cells can restore MHC expression. We have found that IFN-γ signaling is intact in these cells, but pSTAT1 and IRF1 do not bind to the CIITA PIV promoter. The CIITA promoter is not hypermethylated in RD (ERMS) cells, but does show a modestly enhanced methylation status in SJRH30 (ARMS) cells. We have found that histone acetylation, which normally increases on the CIITA PIV promoter following IFN-γ treatment, is blocked in both types of RMS cells. In RD cells, treatment with a histone deacetylase inhibitor (TSA) reverses the silencing of CIITA. In SJRH30 cells, treatment with DNA methyltransferase inhibitors and TSA cooperatively restores CIITA expression. Surprisingly, we have also shown that the expression of two components of the immunoproteasome, which are embedded in the class II locus, is stimulated by IFN-γ in certain RMS cells in the absence of stimulation by CIITA. CIITA overexpression can also activate the expression of these genes, indicating that the immunoproteasome genes LMP2 and LMP7 can be activated by both CIITA dependent and CIITA independent pathways.
Background. Secondary hospital-acquired fungal infections are common in critically-ill patients and mortality remains high despite antimicrobial therapy. Interleukin-7 (IL-7) is a potent immunotherapeutic agent that improves host immunity and has shown efficacy in bacterial and viral models of infection. This study examined the ability of IL-7, which is currently in multiple clinical trials (including hepatitis and human immunodeficiency virus), to improve survival in a clinically relevant 2-hit model of fungal sepsis.
Methods. Mice underwent cecal ligation and puncture to induce peritonitis. Four days later, surviving mice had intravenous injection with Candida albicans. Following Candida infection, mice were treated with IL-7 or saline control. The effect of IL-7 on host immunity and survival was recorded.
Results. IL-7 ameliorated the loss of immune effector cells and increased lymphocyte functions, including activation, proliferation, expression of adhesion molecules, and interferon-γ production. These beneficial effects of IL-7 were associated with an increase in global immunity as reflected by an enhanced delayed type hypersensitivity response and a 1.7-fold improvement in survival.
Conclusions. The present findings showing that IL-7 improves survival in fungal sepsis, together with its previously reported efficacy in bacterial and viral infectious models, further supports its use as a novel immunotherapeutic in sepsis.