Improvement in Care and Maintenance of Port-A-Cath Following the Introduction of Care" Bundle.

Background: Port-a-cath is a type of indwelling central venous catheter used to manage pediatric patients who require long-term intravenous therapy. Objectives: The objective of this study was to improve the care and maintenance of port-a-cath among the nursing staff by introducing a care bundle. Materials and Methods: Pretraining and posttraining designs using PDSA (Plan, Do, Study, Act.) model were followed. We observed two sets of 30 procedures for accessing of port-a-cath by the nursing staff. Following the initial 30 observations of port-a-cath handling, a "care bundle" was designed as per the set standards of the maintenance of port-a-cath. It involved education and training and live audio-visual sessions. Two months after the initiation of the care bundle, the second set of 30 procedures was observed. Results: Following the introduction of the care bundle, the observed efficacy on obtaining verbal consent improved to 100% from 83%, arrangement of drugs and instruments before insertion to 100% from 90%, not touching the needle while inserting from 60%, administration of adequate amount saline flush from 83.3% (25/30), heparin administration from 71.1%, and looking out for signs of extravasation to 100% from 80%. Two nursing staff involvement improved from 23% to 63%. A 100% efficacy in the management of nonbleeding back scenarios was observed. The cross-checking of drug expiry improved from an initial 26.6% to 89.3%. The port-a-cath infections have significantly come down (3 vs. 0) (P < 0.05). Conclusion: Implementation of a "care bundle" has significantly improved the quality of handling of port-a-cath and reduction in infections.

Nutrient sensing.

PURPOSE OF REVIEW: Sensing of nutrients is foundational for life and allows for cellular adaption to environmental stress. The aim of this review is to provide a basic background and overview of new data on cellular nutrient sensing. RECENT FINDINGS: We focus on sensing of energy by adenosine monophosphate-activated protein kinase, sensing of amino acids via general amino acid control nonderepresible 2 and regulation of cellular metabolism via mammalian target of rapamycin pathways. Over the last 5 years, new data has elucidated how these pathways are both interconnected and regulated by amino acids. SUMMARY: Regulation of these pathways is complex and tightly orchestrated in order to provide unified cellular responses that meet environmental demands. Amino acids provide key cues for the regulation of mammalian target of rapamycin pathways, in particular.

Clinical and Ultrasonic Evaluation of the Thumb: Comparison of Young Adults With and Without Thumb Pain With Text Messaging.

OBJECTIVE: The aim of this study was to compare clinical and ultrasound findings of thumb joints in young adults with and without thumb pain associated with text messaging. METHODS: In this case-control study, 117 students with thumb pain associated with text messaging were evaluated clinically and with ultrasound analysis of the thumb. Age- and sex-matched controls received ultrasound evaluation to note any subclinical changes. RESULTS: Clinical examination in the cases identified tenderness most commonly in the metacarpophalangeal joints, followed by the carpometacarpal joints, and then the interphalangeal joints. Tenderness was noted in the web space and the anatomic snuff box. Hypermobility on the Beighton scale was recorded as 2. Grind tests were positive in 21% of participants. Grip strength did not differ, but lateral and tip pinch strength were significantly reduced in the cases compared with controls. Fluid was detected in the metacarpal joints by ultrasound but not in the carpometacarpal or interphalangeal joints. No changes were detected in the controls. CONCLUSION: Clinical examination indicated involvement of all joints of the thumb, but ultrasound evaluation could identify changes only in metacarpal joints, indicating signs of possible subclinical changes taking place in the thumb in these participants as a result of repetitive use.

RNA binding protein RBM3 increases ß-catenin signaling to increase stem cell characteristics in colorectal cancer cells.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. It arises from loss of intestinal epithelial homeostasis and hyperproliferation of the crypt epithelium. In order to further understand the pathogenesis of CRC it is important to further understand the factors regulating intestinal epithelial proliferation and more specifically, regulation of the intestinal epithelial stem cell compartment. Here, we investigated the role of the RNA binding protein RBM3 in stem cell homeostasis in colorectal cancers. Using a doxycycline (Dox) inducible RBM3 overexpressing cell lines HCT 116 and DLD-1, we measured changes in side population (SP) cells that have high xenobiotic efflux capacity and increased capacity for self-renewal. In both cell lines, RBM3 induction showed significant increases in the percentage of side population cells. Additionally, we observed increases in spheroid formation and in cells expressing DCLK1, LGR5 and CD44Hi . As the Wnt/ß-catenin signaling pathway is important for both physiologic and cancer stem cells, we next investigated the effects of RBM3 overexpression on ß-catenin activity. RBM3 overexpression increased levels of nuclear ß-catenin as well as TCF/LEF transcriptional activity. In addition, there was inactivation of GSK3ß leading to decreased ß-catenin phosphorylation. Pharmacologic inhibition of GSK3ß using (2'Z,3'E)-6-Bromoindirubin-3'-oxime (BIO) also recapitulates the RBM3 induced ß-catenin activity. In conclusion, we see that RNA binding protein RBM3 induces stemness in colorectal cancer cells through a mechanism involving suppression of GSK3ß activity thereby enhancing ß-catenin signaling. © 2015 Wiley Periodicals, Inc.

Honokiol inhibits melanoma stem cells by targeting notch signaling.

Melanoma is an aggressive disease with limited therapeutic options. Here, we determined the effects of honokiol (HNK), a biphenolic natural compound on melanoma cells and stemness. HNK significantly inhibited melanoma cell proliferation, viability, clonogenicity and induced autophagy. In addition, HNK significantly inhibited melanosphere formation in a dose dependent manner. Western blot analyses also demonstrated reduction in stem cell markers CD271, CD166, Jarid1b, and ABCB5. We next examined the effect of HNK on Notch signaling, a pathway involved in stem cell self-renewal. Four different Notch receptors exist in cells, which when cleaved by a series of enzymatic reactions catalyzed by Tumor Necrosis Factor-α-Converting Enzyme (TACE) and γ-secretase protein complex, results in the release of the Notch intracellular domain (NICD), which then translocates to the nucleus and induces target gene expression. Western blot analyses demonstrated that in HNK treated cells there is a significant reduction in the expression of cleaved Notch-2. In addition, there was a reduction in the expression of downstream target proteins, Hes-1 and cyclin D1. Moreover, HNK treatment suppressed the expression of TACE and γ-secretase complex proteins in melanoma cells. To confirm that suppression of Notch-2 activation is critical for HNK activity, we overexpressed NICD1, NICD2, and performed HNK treatment. NICD2, but not NICD1, partially restored the expression of Hes-1 and cyclin D1, and increased melanosphere formation. Taken together, these data suggest that HNK is a potent inhibitor of melanoma cells, in part, through the targeting of melanoma stem cells by suppressing Notch-2 signaling.

Endovascular treatment of sporadic renal angiomyolipoma presenting with Wunderlich syndrome.

Angiomyolipomas are benign renal hamartomas with - fat, smooth muscle, and abnormal blood vessel (tortuous, dysmorphic) components. The risk of hemorrhage is related to size of the tumor, presence of aneurysm, associations with tuberous sclerosis. In this case report we review the case of a 42-year-old woman presenting with acute flank pain and decreased hemoglobin, who was diagnosed with AML with right renal artery pseudo aneurysm on CT. Subsequent coil embolization of feeding vessels and using PVA particles was successfully done. Selective embolization remains a minimally invasive, attractive option, and a nephron sparing approach.

Evidence of functional cross talk between the Notch and NF-κB pathways in nonneoplastic hyperproliferating colonic epithelium.

The Notch and NF-κB signaling pathways regulate stem cell function and inflammation in the gut, respectively. We investigate whether a functional cross talk exists between the two pathways during transmissible murine colonic hyperplasia (TMCH) caused by Citrobacter rodentium (CR). During TMCH, NF-κB activity and subunit phosphorylation in colonic crypts of NIH Swiss mice at days 6 and 12 were associated with increases in downstream target CXC chemokine ligand (CXCL)-1/keratinocyte-derived chemokine (KC) expression. Blocking Notch signaling acutely for 5 days with the Notch blocker dibenzazepine (DBZ) failed to inhibit crypt NF-κB activity or CXCL-1/KC expression. Chronic DBZ administration for 10 days, however, blocked Notch and NF-κB signaling in the crypts and abrogated hyperplasia. Intriguingly, chronic Notch inhibition was associated with significant increases in IL-1α, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and KC in the crypt-denuded lamina propria or whole distal colon, with concomitant increases in myeloperoxidase activity. In core-3(-/-) mice, which are defective in intestinal mucin, DBZ administration replicated the results of NIH Swiss mice; in Apc(Min/+) mice, which are associated with CR-induced elevation of NF-κB-p65(276) expression, DBZ reversed the increase in NF-κB-p65(276), which may have blocked rapid proliferation of the mutated crypts. DBZ further blocked reporter activities involving the NF-κB-luciferase reporter plasmid or the Toll-like receptor 4/NF-κB/SEAPorter HEK-293 reporter cell line, while ectopic expression of Notch-N(ICD) reversed the inhibitory effect. Dietary bael (Aegle marmelos) extract (4%) and curcumin (4%) restored Notch and NF-κB cross talk in NIH Swiss mice, inhibited CR/DBZ-induced apoptosis in the crypts, and promoted crypt regeneration. Thus functional cross talk between the Notch and NF-κB pathways during TMCH regulates hyperplasia and/or inflammation in response to CR infection.

Epidemiology and biology of early onset colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in men or women in the United States. Average-risk screening that begins at age 50 years has reduced incidence and mortality of CRC in those over 50 years of age, whereas CRC incidence in those under age 50 years (early onset colorectal cancer (eoCRC)) has recently and dramatically increased. In this review, we summarize the recent literature including risk factors for eoCRC, differences in clinicopathologic presentation and outcomes in eoCRC, and emerging evidence regarding the molecular pathways that are altered in eoCRC compared to later onset CRC (loCRC). Epidemiologic studies of eoCRC show predominance in distal colon and rectum, and association with several modifiable risk factors, including diabetes, obesity, diet, sedentary time, alcohol consumption and smoking. Data regarding potential risk factors of prior antibiotic exposure and microbiome alterations or direct carcinogen exposure are still emerging. Aggressive clinicopathologic features of eoCRC at presentation may be due to delay in diagnosis or more aggressive tumor biology. EoCRC outcomes are similar to loCRC when matched for stage, but overall mortality is greater due to higher frequency of advanced disease at a younger presentation, with more life-years lost. There are only few molecular evaluations of eoCRC to date, with findings of potential increase in TP53 and CTNNB1 somatic mutation and decrease in APC, KRAS and BRAF somatic mutation, compared to loCRC. Other findings include LINE-1 hypomethylation, absence of microsatellite instability (MSI-H), presence of chromosomal instability (CIN) or microsatellite and chromosomal stability (MACS). These studies are only now emerging and have not yet identified a specific molecular signature defining eoCRC. Further research evaluating genetic and molecular differences as well as environmental triggers for eoCRCs should provide a clearer understanding to inform targeted screening for pre-symptomatic at-risk younger individuals.

Colorectal Cancer in Young Adults.

PURPOSE OF REVIEW: Routine screening for colorectal cancer (CRC) in adults > 50 years of age has led to overall reductions in CRC incidence and CRC-related mortality. Yet CRC incidence among young adults age < 50 continues to increase without a clear explanation. This review examines the changing epidemiology of CRC and emerging evidence regarding the influence of genetic and lifestyle factors on risk for colorectal neoplasia. RECENT FINDINGS: Young-onset CRC (yCRC), defined as CRC diagnosed in individuals younger than age 50, is a heterogeneous disease. Approximately, one in every five individuals affected with yCRC carries a pathogenic germline variant in genes associated with predisposition to cancer. However, most have no clinically identifiable risk factors. Analyses of birth cohorts estimate CRC risk among millennials to be 2-4 times higher than their grandparents', suggesting that changes in health behaviors and environmental factors are having an impact on CRC risk. Young individuals with CRC tend to be diagnosed at later stages and often present with metastatic disease. yCRC tumors arise predominantly in the distal colon and are more likely than older-onset tumors to exhibit microsatellite and chromosome stable (MACS) phenotypes. Although yCRC patients are more likely than their older counterparts to be treated with multimodality chemotherapy regimens, more aggressive treatments have not yielded measurable survival gains. Since one in ten new CRC diagnoses involve individuals age < 50, recent guidelines have proposed lowering the age for average risk CRC screening from 50 to 45; however, further studies are needed to evaluate testing strategies based on individuals' age and risk. Significant shifts in CRC epidemiology and diversity of tumor phenotypes support genetic and environmental factors as modifiers of cancer risk. Emerging data correlating tumor molecular features with outcomes justify further investigation into mechanisms of carcinogenesis to elucidate how specific factors (inherited and/or acquired) might stimulate young-onset colorectal neoplasia.

Extensor Pollicis Longus Injury in Addition to De Quervain's with Text Messaging on Mobile Phones.

OBJECTIVE: To do a clinical and ultrasonic evaluation of subjects with thumb pain with text messaging. BACKGROUND: Thumbs are commonly used for text messaging, which are not as well designed for fine manipulative or dexterous work. Repetitive use as in text messaging can lead to the injury to the tendons of the thumb. MATERIALS AND METHODS: Ninety eight students with symptoms of Repetitive Strain Type of injuries of the thumb were selected from a survey and evaluated both clinically and by ultrasound analysis of the musculotendinous unit of the thumb to note changes due to excessive use of the mobile phone. Age and sex matched controls were also subjected to ultrasound evaluation. RESULTS: Clinical examination showed positive Finkelstein test in 40% of the cases, significant reduction in the lateral and tip pinch strengths in the cases. Ultrasound detected changes in the first and the third compartments in 19% of the cases. CONCLUSION: Isolated cases of pain in the thumb have been reported but this study noted changes both clinically and by ultrasound in the tendons of the thumb. These changes should be taken as warning signs of possible subclinical changes taking place in the soft tissues of the thumb in these subjects due to repetitive use of mobile phones and thus, making them prone for developing painful Musculoskeletal Disorders. APPLICATION: Repetitive use of mobile phones for text messaging can lead to the damage of Extensor pollicis longus of the thumb in addition to the tendons of the first compartment of the wrist.

Effectiveness of progressive resistance strength training versus traditional balance exercise in improving balance among the elderly - a randomised controlled trial.

INTRODUCTION: Falls are important health issues among the elderly people. Most falls in elderly result from abnormal balance control mechanisms. Balance and muscle force generation are directly related, and are associated with age related muscular changes. Studies addressing fall prevention have focused on various group and individualised strength training. However, evidence on strengthening of key muscles necessary for maintaining balance and postural control is lacking. OBJECTIVES: To evaluate the effectiveness of individualised progressive resistance strength training (PRT) programme in improving balance for forward limits of stability in elderly with balance impairment, compared to traditional balance exercise (TBE), and combination of both (COMBI). MATERIALS AND METHODS: This randomised controlled trial included three groups; 18 subjects in each aged ≥ 65 years, from the elderly care centres of Mangalore city in Southern India (between June 2008 and December 2012). Block randomisation technique was used and allocation concealment was done using sequentially arranged sealed opaque envelopes. The TBE group received 8 component traditional balance exercise; 4 times a week for 6 months. The PRT group received resistance training for the key muscles of lower extremities, using DeLormes and Watkins protocol. The COMBI group received PRT and TBE alternately (2 days of PRT and 2 days of TBE per week). Functional reach test (FRT) was used for measurement of forward limits of stability. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 15. RESULTS: For functional reach, PRT group had steady progression from baseline to 6 months (p<0.001). The TBE and COMBI groups showed considerable initial improvement; beyond 3 months, moderate improvement was seen. The changes in scores of FRT were significantly better for PRT than TBE. CONCLUSION: Individualised PRT intervention targeting the key muscles of lower limbs is more effective than TBE in improving forward limits of stability among non-frail elderly aged ≥65 years.

Dyke-Davidoff-Masson syndrome.

Dyke-Davidoff-Masson syndrome refers to atrophy of one cerebral hemisphere (hemiatrophy) due to an insult to the brain in fetal or early childhood period. This is an uncommon condition. We present a case of a nine month- old female presented with seizure and weakness of the right upper and lower extremities and subsequently computed tomography was performed and showed hemiatrophy of the left fronto-parietal lobe with degenerative changes in the left cerebral peduncle.

Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance.

Recently, we demonstrated that extracts of bitter melon (BME) can be used as a preventive/therapeutic agent in colon cancers. Here, we determined BME effects on anticancer activity and bioavailability of doxorubicin (DOX) in colon cancer cells. BME enhanced the effect of DOX on cell proliferation and sensitized the cells toward DOX upon pretreatment. Furthermore, there was both increased drug uptake and reduced drug efflux. We also observed a reduction in the expression of multidrug resistance conferring proteins (MDRCP) P-glycoprotein, MRP-2, and BCRP. Further BME suppressed DOX efflux in MDCK cells overexpressing the three efflux proteins individually, suggesting that BME is a potent inhibitor of MDR function. Next, we determined the effect of BME on PXR, a xenobiotic sensing nuclear receptor and a transcription factor that controls the expression of the three MDR genes. BME suppressed PXR promoter activity thereby suppressing its expression. Finally, we determined the effect of AMPK pathway on drug efflux because we have previously demonstrated that BME affects the pathway. However, inhibiting AMPK did not affect drug resistance, suggesting that BME may use different pathways for the anticancer and MDR modulating activities. Together, these results suggest that BME can enhance the bioavailability and efficacy of conventional chemotherapy.

Association between bipolar affective disorder and thyroid dysfunction.

BACKGROUND: Bipolar affective disorder may be associated with alterations in thyroid function. A comprehensive thyroid assessment is important for assessing clinical and sub-clinical imbalances linked to a variety of mood disorders like bipolar affective disorder. AIM: To find out the association between bipolar affective disorder and thyroid dysfunction. MATERIALS AND METHOD: The present cross-sectional study was conducted at Government District Wenlock Hospital, Mangalore (GDWH), India. A total of 50 newly diagnosed bipolar affective disorder patients and 50 age and sex matched controls without bipolar affective disorder as confirmed by the application of Bipolar Spectrum Diagnostic Scale were included in the study. Thyroid function was assessed among the patients and control group to study the association between bipolar affective disorder and thyroid dysfunction. Odds ratio was calculated to find out the strength of association between thyroid gland dysfunction and bipolar affective disorder. RESULTS: The mean Bipolar Spectrum Diagnostic Scale score among patients diagnosed with bipolar affective disorder was 20.84 and that of the control group was 1.98. The proportion of thyroid dysfunction among bipolar affective disorder patients and among control group was 14% and 6% respectively. The odds ratio was calculated to be 2.55. Mean T3 values were higher in the bipolar affective disorder patients than the control group and this association was found to be statistically significant (p=0.031). Mean T4 and TSH values were higher among the bipolar affective disorder patients but did not show any significant differences when compared with the control group. CONCLUSION: The present study concludes that a statistically significant association exists between elevated T3 hormone and bipolar affective disorder and observes that the patients with bipolar affective disorder are 2.55 times more commonly associated with thyroid dysfunction.

Clinico-epidemiological profile of burn patients admitted in a tertiary care hospital in coastal South India.

Every year a substantial proportion of deaths in India occur due to burn injuries. Prolonged morbidity as well as temporary and permanent disability due to burns results in a heavy economic loss. The etiological factors of burn injuries vary considerably in different communities and regions and hence the need for detailed epidemiological studies to understand the problem status in different regions. This study was aimed to study the sociodemographic profile of burn patients and to evaluate the causes, manner, and place of occurrence of burns injuries along with its outcome. A registry-based retrospective study was conducted at a tertiary care hospital in coastal South India, and the medical records of all the patients admitted to the burns centre during the year 2009 were reviewed. The data were analyzed using SPSS version 11.5. A total of 101 burn patients were admitted during the study period. The burn patients were aged between 4 months and 80 years with a mean age of 32.11 (± 3.46) years. The overall male to female ratio was 0.83:1. Majority of the patients were Hindus and were married. Flame burns were the most common etiology for sustaining burns (82.2%). Most of the burn injuries were sustained at home (n = 81, 80.2%), and the manner was designated as accidental in 79.2% of the cases. The TBSA involvement in burns ranged from 5 to 100% and the mean TBSA was found to be 45.8 ± 24.7%. A higher TBSA involvement is associated with an increased risk of mortality and this association between TBSA and mortality was found to be statistically significant (P < .05). Mortality rate in our study was 40.9%. Septicemia (n = 24, 63.2%) was the most common cause of death followed by shock (n = 12, 31.6%). Higher mortality is found to be associated with female sex, suicides, and flame burns. This study identifies the epidemiological and clinical features associated with burn injuries in coastal South India. Majority of the burn victims in our study were married females of younger age group. Although the manner of sustaining burns was mostly accidental, females were proportionately more commonly the victims of suicides and homicides than males. Injuries and deaths due to burns are preventable, provided a community-specific preventive program is implemented with a strong educational component.

Bilateral calcified stylohyoid ligament: an incidental autopsy finding with medicolegal significance.

Eagle's syndrome occurs due to elongation of the styloid process or calcification of the stylohyoid ligament, which then may produce a pain sensation due to pressure exerted on various structures in the head and neck region. A case report of calcified stylohyoid ligament found incidentally at autopsy and further confirmed by computed tomography scan and histopathology is herein discussed with associated medicolegal significance.

Role of phenylalanine B10 in plant nonsymbiotic hemoglobins.

All plants contain an unusual class of hemoglobins that display bis-histidyl coordination yet are able to bind exogenous ligands such as oxygen. Structurally homologous hexacoordinate hemoglobins (hxHbs) are also found in animals (neuroglobin and cytoglobin) and some cyanobacteria, where they are thought to play a role in free radical scavenging or ligand sensing. The plant hxHbs can be distinguished from the others because they are only weakly hexcacoordinate in the ferrous state, yet no structural mechanism for regulating hexacoordination has been articulated to account for this behavior. Plant hxHbs contain a conserved Phe at position B10 (Phe(B10)), which is near the reversibly coordinated distal His(E7). We have investigated the effects of Phe(B10) mutation on kinetic and equilibrium constants for hexacoordination and exogenous ligand binding in the ferrous and ferric oxidation states. Kinetic and equilibrium constants for hexacoordination and ligand binding along with CO-FTIR spectroscopy, midpoint reduction potentials, and the crystal structures of two key mutant proteins (F40W and F40L) reveal that Phe(B10) is an important regulatory element in hexacoordination. We show that Phe at this position is the only amino acid that facilitates stable oxygen binding to the ferrous Hb and the only one that promotes ligand binding in the ferric oxidation states. This work presents a structural mechanism for regulating reversible intramolecular coordination in plant hxHbs.