In order to define the undifferentiated transcriptional factors present in neurogenesis of pancreatic β-islet cells, we studied the
effect of Pdx1 in embryonic stem cell derived endocrine lineage. There are undifferentiated transcriptional progenitors
Pdx1+/Ptf1a+/Cpa1+ tracking the growth of acini, ducts, α and β-islet cells. The upregulated transcriptional factors Pdx1 and
ngn3 specify consequences of cell cycle regulation in early gut endocrine cells. The undifferentiated transcriptional factors basic
helix loop helix (bHLH) protein regulate Ptf1a+/Cpa1+ in acini, ducts and it also regulate ngn3 to decrease expression of insulin
and other pancreas secretions. The Pdx1+ and other unknown gene mutations show abnormal growth of neurogenesis in endocrine
lineages. Using microarray based gene expression analysis to determine undifferential gene ontology in tissue specific gene
regulation and disease progression that common in both metabolic and biological signaling pathways. The data expression profiles
of ngn3 of wild- type pancreatic islet and islet derived tumor stem cells provide information on endocrine specific ngn3 genes.
Therefore, 3755 genes were significantly regulated by Ngn3 induced pancreatic islet cell development. Moreover 317 upregulated
and 175 downregulated, 757 genes deemed as undifferential expressions in endocrine cell. Furthermore to predict signaling
pathways that associates with diabetes is highlighted.
Pancreatic regeneration; neurogenesis; ngn3; bHLH; Notch Pathway; Embryonic stem cells; islet cells; pancreatic beta cells; diabetes; microarray
A multiplex PCR was designed to detect Escherichia coli O104:H4, a hybrid pathotype of Shiga toxigenic and enteroaggregative E. coli, in cattle feces. A total of 248 fecal samples were tested, and 20.6% were positive for serogroup O104. The O104 isolates did not carry genes characteristic of the virulent hybrid strain.
Cross-sectional studies have shown that low vitamin D (25-hydroxyvitamin D (25(OH)D)) is associated with increased systemic lupus erythematosus (SLE) activity. This study is the first to assess the temporal relationship between 25(OH)D levels and onset of SLE flare. This assessment was made possible because of the specimen bank and database of the Ohio SLE Study (OSS), a longitudinal study of frequently relapsing SLE that involved regular bimonthly patient follow-up. We identified for this study 82 flares from 46 patients that were separated by at least 8 months from previous flares. Serum 25(OH)D levels were measured at 4 and 2 months before flare, and at the time of flare (a flare interval). We found that for flares occurring during low daylight months (LDM, Oct-Mar), 25(OH)D levels were decreased at the time of flare, but only in non-African American (non-AA) patients (32% decrease at flare, compared to 4 months prior, p < 0.001). To control for seasonal effects, we also measured 25(OH)D levels in the LDM “no-flare” intervals, which were intervals that matched to the same calendar months of the patients’ LDM flare intervals, but that didn’t end in flare (n = 24). For these matches, a significant decrease occurred in 25(OH)D levels during the flare intervals (18.1% decrease, p < 0.001), but not during the matching no-flare intervals (6.2% decrease, p = 0.411). For flares occurring during high daylight months (HDM), 25(OH)D levels changed only in non-AA patients, increasing slightly (5.6%, p = 0.010). Analysis of flare rates for the entire OSS cohort (n = 201 flares) revealed a tendency for higher flare rates during LDM compared to HDM, but again only in non-AA patients (p = 0.060). Flare rates were lower during HDM for non-AA patients compared to AA patients (p = 0.028). In conclusion, in non-AA SLE patients, unusually large declines in 25(OH)D during LDM may be mechanistically related to SLE flare, whereas relatively high 25(OH)D levels during HDM may protect against flare.
Vitamin D; systemic lupus erythematosus; disease flare
Mindful eating offers promise as an effective approach for weight management and glycemic control in people with diabetes. Diabetes self-management education (DSME) is an essential component of effective self-care. Yet, little research has compared the effect of mindful eating to DSME-based treatment. This study compared the impact of these two interventions in adults with type 2 diabetes mellitus (T2DM). A prospective randomized controlled trial with two parallel interventions was employed. Participants included adults aged 35–65 with T2DM for ≥ 1 year, body mass index (BMI) ≥ 27.0, and A1c ≥ 7.0% who were randomly assigned to a 3-month mindful eating (MB-EAT-D; n=27) or Smart Choices (SC) DSME-based (n=25) intervention. Follow-up occurred 3-months following intervention completion. Dietary intake, physical activity, weight, glycemia, and fasting insulin were assessed using repeated measures ANOVA with contrast analysis. There was no significant difference between groups in the change in weight or glycemia at study end. Significant difference occurred between groups in the change in dietary intake/1000 kcal of trans fats, total fiber, and sugars (all P<0.05). Mean (±SE) reduction in weight (−2.92 ± 0.54 kg for SC vs. −1.53 ± 0.54 kg for MB-EAT-D) and A1c (−0.67 ± 0.24% for SC and −0.83 ± 0.24% for MB-EAT-D) were significant (P<0.01). Significant reduction in energy intake and glycemic load occurred (all P<0.0001) for both groups. Training in mindful eating and diabetes self-management facilitate improvement in dietary intake, modest weight loss, and glycemic control. The availability of effective treatments allows diabetes patients choices in meeting their self-care needs.
type 2 diabetes mellitus; meditation; patient education; randomized controlled trial
Oral infections have a strong ethnic predilection; suggesting that ethnicity is a critical determinant of oral microbial colonization. Dental plaque and saliva samples from 192 subjects belonging to four major ethnicities in the United States were analyzed using terminal restriction fragment length polymorphism (t-RFLP) and 16S pyrosequencing. Ethnicity-specific clustering of microbial communities was apparent in saliva and subgingival biofilms, and a machine-learning classifier was capable of identifying an individual’s ethnicity from subgingival microbial signatures. The classifier identified African Americans with a 100% sensitivity and 74% specificity and Caucasians with a 50% sensitivity and 91% specificity. The data demonstrates a significant association between ethnic affiliation and the composition of the oral microbiome; to the extent that these microbial signatures appear to be capable of discriminating between ethnicities.
Breakdown of the blood-brain barrier (BBB) is present in several neurological disorders such as stroke, brain tumors, and multiple sclerosis. Non-invasive evaluation of BBB breakdown is important for monitoring disease progression and evaluating therapeutic efficacy in such disorders. One of the few techniques available for non-invasively and repeatedly localizing and quantifying BBB damage is magnetic resonance imaging (MRI). This usually involves the intravenous administration of a gadolinium-containing MR contrast agent such as Gd-DTPA, followed by dynamic contrast-enhanced MR imaging (DCE-MRI) of brain and blood, and analysis of the resultant data to derive indices of blood-to-brain transfer. There are two advantages to this approach. First, measurements can be made repeatedly in the same animal; for instance, they can be made before drug treatment and then again after treatment to assess efficacy. Secondly, MRI studies can be multiparametric. That is, MRI can be used to assess not only a blood-to-brain transfer or influx rate constant (Ki or K1) by DCE-MRI but also complementary parameters such as: 1) cerebral blood flow (CBF), done in our hands by arterial spin-tagging (AST) methods; 2) magnetization transfer (MT) parameters, most notably T1sat, which appear to reflect brain water-protein interactions plus BBB and tissue dysfunction; 3) the apparent diffusion coefficient of water (ADCw) and/or diffusion tensor, which is a function of the size and tortuosity of the extracellular space; and 4) the transverse relaxation time by T2-weighted imaging, which demarcates areas of tissue abnormality in many cases. The accuracy and reliability of two of these multiparametric MRI measures, CBF by AST and DCE-MRI determined influx of Gd-DTPA, have been established by nearly congruent quantitative autoradiographic (QAR) studies with appropriate radiotracers. In addition, some of their linkages to local pathology have been shown via corresponding light microscopy and fluorescence imaging. This chapter describes: 1) multiparametric MRI techniques with emphasis on DCE-MRI and AST-MRI; 2) the measurement of the blood-to-brain influx constant and CBF; and 3) the role of each in determining BBB permeability.
Apparent diffusion coefficient; Arterial spin tagging; Blood-brain barrier; Cerebral blood flow; Cerebral ischemia; Gd-DTPA; Hemorrhagic transformation; Influx constant; Look-Locker; Magnetic resonance contrast agents; Magnetization transfer; Patlak plot; Quantitative autoradiography; Rat; T1; T1sat; T1WI; T2; TOMROP
Bacteria use a number of small basic proteins for organization and compaction of their genomes. By their interaction with DNA, these nucleoid-associated proteins (NAPs) also influence gene expression. Rv3852, a NAP of Mycobacterium tuberculosis, is conserved among the pathogenic and slow-growing species of mycobacteria. Here, we show that the protein predominantly localizes in the cell membrane and that the carboxy-terminal region with the propensity to form a transmembrane helix is necessary for its membrane localization. The protein is involved in genome organization, and its ectopic expression in Mycobacterium smegmatis resulted in altered nucleoid morphology, defects in biofilm formation, sliding motility, and change in apolar lipid profile. We demonstrate its crucial role in regulating the expression of KasA, KasB, and GroEL1 proteins, which are in turn involved in controlling the surface phenotypes in mycobacteria.
Cardioversion (CV) and radiofrequency catheter ablation (RFA) are often used to restore sinus rhythm in patients with atrial fibrillation (AF). These procedures are associated with a risk for stroke. The use of transesophageal echocardiography (TEE) to guide the management of AF is a validated strategy for patients in whom CV is planned, as well patients before RFA. For patients in whom the initial procedure fails, repeat TEE is often performed before repeat CV or RFA. The aim of this study was to test the hypothesis that patients with initial negative results on TEE would be unlikely to have thrombi detected on subsequent TEE and thus may avoid repeat procedures.
A total of 2,999 patients with AF were identified via retrospective review who had undergone TEE before CV or RFA, and 418 of these individuals underwent repeat TEE. After excluding patients who underwent repeat TEE >365 days from the initial study (n= 135) and those with thrombi on initial TEE (n= 20), 263 patients who had underwent two or more examinations were identified and analyzed.
Of 263 eligible patients, two (0.8%; 95% confidence interval,0.21–2.7%)had thrombion subsequent TEE.
Fewer than 1% of patients with AF with negative results on baseline TEE had thrombi detected on repeat TEE before subsequent CV or RFA. Thus, it may be possible to selectively screen patients to identify those at low risk for developing thrombi subsequent to negative results on initial TEE, especially if patients are in sinus rhythm. These results suggest the need for a prospective trial to definitively answer the question regarding repeat TEE in low-risk patients. (J Am Soc Echocardiogr 2012;25:1106-12.)
Atrial fibrillation; Atrial flutter; Electrical cardioversion; Transesophageal echocardiography
PLAC1 (placenta-specific 1) is a gene that is placenta specific and transcribed very little, if at all, in any somatic tissue. It is nevertheless expressed in many cancer cell lines. To understand how cancer cells may activate the gene in nonexpressing cells, we found that a model is provided by classical transformation of normal fibroblasts by SV40 T antigen. T antigen derepressed the PLAC1 P1 promoter, with Tp53 and RB exerting critical and opposing actions and nuclear receptors, retinoid X receptor and liver X receptor, sharply increasing the level of expression.
large T antigen; transcription; NCOA2; RXRα; LXR; chromatin
One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART.
A review of records routinely maintained under the National AIDS Control Programme (NACP) was carried out in six districts of Karnataka. HIV-positive persons diagnosed during the months from January to June 2011 in 233 public HIV-testing sites were followed up until December 2011 based on the pre-ART registers. A chi-square test was used to assess statistical significance.
Of 2291 HIV-positive persons diagnosed (52% male; mean age of 35 years), 1829 (80%) reached ART centres. Of the latter, 1166 (64%) were eligible for ART, and 959 (82%) were initiated on treatment. Overall losses (attrition) on the road between HIV diagnosis and ART initiation were 669 (29%). Deaths, migration and not willing to go to the ART centres were cited as the main known reasons for not reaching ART centres. For ART-eligible individuals who did not initiate ART, the most common known reasons for non-initiation included dying before initiation of ART and not being willing to start ART.
In a large state of India, eight in ten HIV-positive persons reached ART centres, and of those found ART eligible, 82% start treatment. Although this is an encouraging achievement, the programme needs to take further steps to improve the current performance by further reducing pre-ART attrition. We recommend online registering of diagnosed HIV-positive patients to track the patients more efficiently.
operational research; ART centres; loss to follow-up; India
Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent metal ions for DNA cleavage but not for binding. The active site of KpnI can accommodate metal ions of different atomic radii for DNA cleavage. Although Mg2+ ion higher than 500 μM mediates promiscuous activity, Ca2+ suppresses the promiscuity and induces high cleavage fidelity. Here, we report that a conservative mutation of the metal-coordinating residue D148 to Glu results in the elimination of the Ca2+-mediated cleavage but imparting high cleavage fidelity with Mg2+. High cleavage fidelity of the mutant D148E is achieved through better discrimination of the target site at the binding and cleavage steps. Biochemical experiments and molecular dynamics simulations suggest that the mutation inhibits Ca2+-mediated cleavage activity by altering the geometry of the Ca2+-bound HNH active site. Although the D148E mutant reduces the specific activity of the enzyme, we identified a suppressor mutation that increases the turnover rate to restore the specific activity of the high fidelity mutant to the wild-type level. Our results show that active site plasticity in coordinating different metal ions is related to KpnI promiscuous activity, and tinkering the metal ion coordination is a plausible way to reduce promiscuous activity of metalloenzymes.
Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India.
To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC.
Cross- sectional survey using semi-structured interviews.
Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine.
Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.
Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
To assess the efficacy and advantages of femtosecond laser enabled keratoplasty (FLEK) over conventional penetrating keratoplasty (PKP) in advanced keratoconus.
Materials and Methods:
Detailed review of literature of published randomized controlled trials of operative techniques in PKP and FLEK.
Fifteen studies were identified, analyzed, and compared with our outcome. FLEK was found to have better outcome in view of better and earlier stabilization uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and better refractive outcomes with low astigmatism as compared with conventional PKP. Wound healing also was noticed to be earlier, enabling early suture removal in FLEK.
Studies relating to FLEK have shown better results than conventional PKP, however further studies are needed to assess the safety and intraoperative complications of the procedure.
Femtosecond enabled keratoplasty; keratoconus; penetrating keratoplasty
Norepinephrine (NE) can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here, we identify Src as a key regulator of phosphoproteomic signaling networks activated in response to beta-adrenergic signaling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumor cell migration, invasion and growth. In human ovarian cancer samples, high tumoral NE levels were correlated with high pSrcY419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signaling in the tumor microenvironment.
We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).
Materials and Methods:
Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2nd), 4th, and 6th week of stroke.
Results: Affected hemisphere:
MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.
MEP was recordable in all patients at baseline, and reduced significantly over time (2nd week 43.52 ± 9.60, 4th week 38.84 ± 7.83, and 6th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.
The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.
Central motor conduction time; cortical excitability; ischemic stroke; plasticity; resting motor threshold; transcranial magnetic stimulation
Few studies have examined the effect of goal difficulty on behavioral change even though goal setting is widely used in diabetes education. The effect of a goal to consume either 6 or 8 servings/day of low glycemic index (LGI) foods was evaluated in this study.
Adults 40–65 years old with type 2 diabetes were randomly assigned to the 6 or 8 serving/day treatment group following a 5-week GI intervention. Perceived goal difficulty, commitment, satisfaction, and self-efficacy were evaluated, and four day food records assessed dietary intake.
Both groups increased consumption of LGI foods (P < 0.001); there were no significant differences in the change in consumption between groups. Participants who were more committed to the goal perceived the goal to be less difficult (P < 0.01). Those with greater efficacy beliefs were more committed to their goal, perceived the goal to be less difficult, and were more satisfied with their performance (all P < 0.05).
A specific goal regarding LGI foods can facilitate the adoption of a lower GI diet. Future research is needed to determine if goal commitment or goal difficulty mediate the process.
Clinicians should help clients set specific goals regarding dietary change.
Type 2 diabetes mellitus; Patient education; Health behavior; Goals; Nutrition assessment
Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn2+ finger motifs in the CTD. The Zn2+ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn2+ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn2+ fingers from the mycobacterial topoI could be associated with Zn2+ export and homeostasis.
A network of intracellular signaling pathways and complex intercellular interactions regulate calcium mobilization in vascular cells, arteriolar tone, and blood flow. Different endothelium-derived vasoreactive factors have been identified and the importance of myoendothelial communication in vasoreactivity is now well appreciated. The ability of many vascular networks to conduct signals upstream also is established. This phenomenon is critical for both short-term changes in blood perfusion as well as long-term adaptations of a vascular network. In addition, in a phenomenon termed vasomotion, arterioles often exhibit spontaneous oscillations in diameter. This is thought to improve tissue oxygenation and enhance blood flow. Experimentation has begun to reveal important aspects of the regulatory machinery and the significance of these phenomena for the regulation of local perfusion and oxygenation. Mathematical modeling can assist in elucidating the complex signaling mechanisms that participate in these phenomena. This review highlights some of the important experimental studies and relevant mathematical models that provide the current understanding of these mechanisms in vasoreactivity.
vascular tone; smooth muscle; endothelium; vasomotion; spreading responses
A lower glycaemic index (GI) diet is associated with a reduction in glycosylated Hb (HbA1c) in people with diabetes. Yet, little research has been conducted to determine the effects of specific goals regarding consumption of low GI (LGI) foods on diabetes outcomes. The present study evaluated a behavioural intervention on dietary intake, weight status and HbA1c, which included a goal to consume either six or eight servings of LGI foods daily.
A parallel two-group design was used. Following the 5-week intervention, participants were randomly assigned to the group of six (n 15) or eight (n 20) servings of LGI foods daily and followed up for 8 weeks. Dietary intake was assessed using the mean of 4 d food records.
A metropolitan community in the USA.
Individuals aged 40–65 years with type 2 diabetes of ≥1 year and HbA1c ≥ 7·0 % were eligible.
There was no significant difference between goal difficulty groups with regard to GI servings at the end of the study. However, mean consumption of LGI foods increased by 2·05 (se 0·47) and 1·65 (se 0·40) servings per 4184 kJ in the six (P< 0·001) and eight (P< 0·001) LGI serving groups, respectively. For all participants combined, there were significant decreases in mean HbA1c (−0·58 (se 0·21) %; P = 0·01), weight (−2·30 (se 0·78) kg; P = 0·01), BMI (−0·80 (se 0·29) kg/m2; P = 0·01) and waist circumference (−2·36 (se 0·81) cm; P = 0·01).
An intervention including a specific goal to consume six to eight servings of LGI foods daily can improve diabetes outcomes. Clinicians should help patients set specific targets for dietary change and identify ways of achieving those goals.
Type 2 diabetes mellitus; Patient education; Nutritional assessment; Behavioural change
The asymmetric unit of the title compound, C23H21N3, consists of two symmetry-independent and conformationally different molecules [the comparable dihedral angles between the imidazole ring and the three benzene rings being 38.5 (2)/61.5 (3)/3.37 (17) and 45.8 (2)/36.01 (19)/46.94 (17)°]. In the crystal, intermolecular imidazole N—H⋯N hydrogen-bonding interactions give a one-dimensional chain extending along .
Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.
With advances in the neuro-imaging modalities, diverse manifestations of the cerebral venous sinus thrombosis (CVT) are being recognized. There are very few reports of isolated cranial nerve palsies in CVT. In this case report, we describe a patient of lower motor neuron facial palsy with CVT who was successfully treated with anticoagulation, highlighting the atypical manifestation of the disease.
Anticoagulation; cranial nerve diseases; cerebral venous sinus thrombosis; facial paralysis; magnetic resonance venography; sinus thrombosis
Recurrent bacterial meningitis (RBM) in many instances is associated with identifiable anatomical defects. Presence of congenital deafness with recurrent meningitis should alert clinician for presence of middle and inner ear malformation. These defects can be demonstrated by various neuro imaging techniques and can be surgically corrected. In this case report we describe a child seen at our institute with congenital deafness and recurrent meningitis, discuss the approach to RBM and briefly describe inner ear malformation associated with the same and how to differentiate them.
Congenital deafness; cystic cochleovestibular anomaly; lumbar puncture; recurrent bacterial meningitis