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This document is an editorial published in Frontiers in Neuroscience titled "Data-driven clinical biosignatures and treatment for neurodegenerative diseases, volume II." The editorial discusses the importance of reliable and effective biosignatures for the early diagnosis of neurodegenerative diseases (NDD) and highlights recent advancements in this field. It mentions studies that have identified novel biomarkers for Alzheimer's Disease (AD) and the role of the glymphatic system in NDD. The editorial also includes papers on speech analysis for early diagnosis, neurobiological markers in NDD, and digital therapy progress. Overall, the editorial provides valuable insights into the diagnosis and treatment of NDD. [Extracted from the article]

Introduction: Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective. Methods: We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness ofWKS13 was evaluated in a hamstermodel. Results: Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant. Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants. [ABSTRACT FROM AUTHOR]

Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with poor prognosis and resistance to hormone therapy, which has limited therapeutic approaches. Therefore, this study aimed to identify a novel treatment for NEPC and provide evidence of its inhibitory effects. Methods: We performed a high-throughput drug screening and identified fluoxetine, originally an FDA-approved antidepressant, as candidate therapeutic agent for NEPC. We carried out both in vitro and in vivo experiments to demonstrate the inhibitory effects of fluoxetine on NEPC models and its mechanism in detail. Results: Our results demonstrated that fluoxetine effectively curbed the neuroendocrine differentiation and inhibited cell viability by targeting the AKT pathway. Preclinical test in NEPC mice model (PBCre4: Ptenf/f; Trp53f/f; Rb1f/f) showed that fluoxetine effectively prolonged the overall survival and reduced the risk of tumor distant metastases. Discussion: This work repurposed fluoxetine for antitumor application, and supported its clinical development for NEPC therapy, which may provide a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. Methods: The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. Results: A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and ß-sitosterol were obtained from the analysis of the key targets. Conclusions: Ursolic acid, anethole and ß-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways. [ABSTRACT FROM AUTHOR]

Although coccidioidomycosis in Arizona and California has been well-characterized, much remains unknown about its epidemiology in states where it is not highly endemic. We conducted enhanced surveillance in 14 such states in 2016 by identifying cases according to the Council of State and Territorial Epidemiologists case definition and interviewing patients about their demographic characteristics, clinical features, and exposures. Among 186 patients, median time from seeking healthcare to diagnosis was 38 days (range 1-1,654 days); 70% had another condition diagnosed before coccidioidomycosis testing occurred (of whom 83% were prescribed antibacterial medications); 43% were hospitalized; and 29% had culture-positive coccidioidomycosis. Most (83%) patients from nonendemic states had traveled to a coccidioidomycosis-endemic area. Coccidioidomycosis can cause severe disease in residents of non-highly endemic states, a finding consistent with previous studies in Arizona, and less severe cases likely go undiagnosed or unreported. Improved coccidioidomycosis awareness in non-highly endemic areas is needed. [ABSTRACT FROM AUTHOR]

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population. [ABSTRACT FROM AUTHOR]

The clinical efficacy of microsurgical neck clipping for the treatment of cerebral aneurysm rupture and its effect on serum nuclear factor κ-light-chain-enhancer of activated ß cells (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and matri-x metalloproteinase-9 (MMP-9)levels were investigated. A total of 56 patients with first occurrence of cerebral aneurysm rupture were enrolled from June 2015 to June 2016. These patients were divided into control (25 patients) and observation groups (31 patients) according to treatment received. The patients in the control group were treated with interventional embolization and extraventricular drainage, while the patients in the observation group were treated with microsurgical neck clipping. Serum NF-κB, MCP-1 and MMP-9 levels were measured by ELISA prior to the operation and at 6 h post-operation. Clinical effects were compared at the 6-month follow-up. There was no significant difference in the success rate of the operation between the two groups (p>0.05). The incidence of complications in the observation group was significantly lower than that in the control group (p<0.05). The Glasgow Outcome Scale score was significantly improved in the observation group (p<0.05) compared with the control group. Serum NF-κB, MMP-9 and MCP-1 were significantly decreased in both groups at 6 and 24 h after operation, but the observational group showed significantly lower levels for all three proteins than the control group (p<0.05). The application of early microsurgical neck clipping for the treatment of cerebral aneurysm rupture can reduce complications and improve clinical prognosis, and this may be related to a decrease in serum inflammatory response-related factors (NF-κB and MCP-1) and MMP-9. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML).Design: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews. Medication possession ratio (MPR) was used to measure drug adherence.Setting: A large, community-based, integrated health plan in Southern California.Participants: The cohort consisted of 245 adult patients (≥18 years old) with Philadelphia positive chronic phase CML diagnosed from 2001 to 2012 and followed through 2013.Main Outcome Measures: In survival analyses, we examined the association of TKI adherence (MPR) and polymerase chain reaction (PCR) monitoring test frequency with the composite clinical outcome, progression to accelerated phase disease-blast crisis or mortality (progression-free survival). The cohort was followed for a maximum of 13 years (median 4.6 years).Results: Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and the mean MPR was 88% (SD 18%). Virtually all patients (96%) started on imatinib. The rates of progression to accelerated phase-blast crisis and mortality were lower in patients with greater TKI adherence (20.4/1000 person-years) versus lower adherence (27.0/1000 person-years). Patients who underwent PCR monitoring had a significantly reduced risk of progression or mortality, which was seen in patients with high and low TKI adherence status from both the groups (hazard ratio [HR] 0.07 [95% CI 0.03-0.19 if MPR >90%] and HR 0.70 [95% CI 0.02-0.21 if MPR<90%]).Conclusion: Our results suggest that close clinical monitoring, which includes PCR monitoring in patients with high and low TKI drug adherence, is associated with a lower risk of progression or mortality. [ABSTRACT FROM AUTHOR]

Uveitis, defined as inflammation of the uveal tract, may cause blindness in both young and middle-aged people. Approximately 10–15% of blindness in the West is caused by uveitis. Therefore, a comprehensive investigation to determine the disease pathogenesis is urgent, as it will thus be possible to design effective treatments. Identification of the disease genes that cause uveitis is an important requirement to achieve this goal. To begin to answer this question, in this study, a computational method was proposed to identify novel uveitis-related genes. This method was executed on a large protein–protein interaction network and employed a popular ranking algorithm, the RandomWalk with Restart (RWR) algorithm. To improve the utility of the method, a permutation test and a procedure for selecting core genes were added, which helped to exclude false discoveries and select the most important candidate genes. The five-fold cross-validation was adopted to evaluate the method, yielding the average F1-measure of 0.189. In addition, we compared our method with a classic GBA-based method to further indicate its utility. Based on our method, 56 putative genes were chosen for further assessment. We have determined that several of these genes (e.g., CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis. [ABSTRACT FROM AUTHOR]

Background Optimal management of complicated chronic type B dissection with involvement of the distal aortic arch is controversial. Late complications related to thoracic endovascular aortic repair (TEVAR) are much more common than those using open aortic surgery. We reviewed our experience of left subclavian artery (LSCA) transposition with implantation of a stented elephant trunk for complicated chronic type B dissection with involvement of the distal aortic arch. Materials and Methods From January 2011 to June 2015, 20 patients with complicated chronic type B dissection with involvement of the distal aortic arch underwent LSCA transposition with implantation of a stented elephant trunk via a median sternotomy under hypothermic cardiopulmonary bypass with selective antegrade cerebral perfusion (SACP). Preoperative renal dysfunction was observed in three patients, left heart failure in one patient, and spinal cord ischemia in one patient. Results There was one (5.0%, 1/20) in-hospital death. All but one patient required mechanical ventilation for < 24 hours. Mean duration of mechanical ventilation and mean duration of stay in the intensive care unit was 16 ± 4 and 35 ± 16 hours, respectively. No severe complications occurred. There was one death because of unknown cause during follow-up. One case received thoracoabdominal aortic replacement 9 months after surgery. Conclusion Acceptable surgical outcomes were obtained using LSCA transposition with implantation of a stented elephant trunk. This method is an alternative to TEVAR for complicated chronic type B dissection with involvement of the distal aortic arch. [ABSTRACT FROM AUTHOR]

Background: Conflicting reports on the efficacy of intra-aortic balloon pump (IABP) during percutaneous coronary intervention (PCI) incited us to evaluate the utility of IABP in patients with acute myocardial infarction (AMI).Methods: Randomized clinical trials comparing patients, who received IABP vs. control (no IABP) during PCI, were hand-searched from MEDLINE, Cochrane, and EMBASE databases using the terms "intra-aortic balloon pump, percutaneous coronary intervention, myocardial infarction, acute coronary syndrome". Mortality rate (30-day and 6-month mortality) was the primary outcome, while the secondary outcomes included 30-day bleeding rate, reinfarction rate, revascularization rate and stroke rate.Results: Pooled results of the seven trials identified indicated that the 30-day and 6-month mortality rate were not significantly different between the IABP and control groups. However, in patients with MI, but without cardiogenic shock (CS), IABP was associated with lower odds of 30-day mortality (OR = 0.35, p = 0.015) and 6-month mortality (OR = 0.41, p = 0.020). The pooled results of 30-day bleeding rate was not significantly higher in patients with IABP than the control group, but for the patients with high risk PCI without CS, it was higher in patients with IABP than the control group (OR = 1.58, p = 0.009). The re-infarction, revascularization, and the stroke rate at 30 days of follow-up were not significantly different between the two groups.Conclusions: The present results do not favor the clinical utility of IABP in patients suffering high-risk PCI without CS and AMI complicated with CS. However, in patients with AMI, but without CS, IABP may reduce the 30-day and 6-month mortality rate. [ABSTRACT FROM AUTHOR]

Spontaneous subarachnoid hemorrhage (SAH) is the most common cerebrovascular disease. The conventional treatment for SAH is usually associated with high mortality. The present study aims to assess the prognosis of microsurgical treatment for patients with poor-grade aneurysm (Hunt and Hess grades IV-V) associated with intracerebral hematoma. A total of 18 consecutive patients who were diagnosed with poor-grade aneurysm accompanied with intracerebral hematoma were retrospectively recruited. All patients underwent microsurgical treatment between April 2010 and June 2013 at The 101st Hospital of Chinese People's Liberation Army (Wuxi, China). Among them, 15 cases underwent microsurgery within 24 h of SAH, and 3 cases underwent microsurgery 24 h following SAH. All 18 cases were examined by computed tomography angiography (CTA). The outcome was assessed during a follow-up time of 6-36 months. According to the Glasgow Outcome Scale, 4 patients experienced a good recovery, 6 were dissatisfied with the outcome, 4 were in vegetative state and 4 succumbed to disease. Poor outcome occurred in patients with an aneurysm diameter >10 mm, exhibited >50 ml volume of intracerebral hematoma or presented cerebral hernia prior to the surgical operation. The outcome of ultra-early surgery (within 24 h of SAH) was improved, compared with that of surgery following 24 h of SAH (P=0.005). Among 7 patients who accepted extraventricular drainage, good outcomes were achieved in 4 of them, whereas dissatisfaction and mortality occurred in 2 and 1 patients, respectively. Therefore, ultra-early microsurgery (within 24 h of SAH) combined with extraventricular drainage may improve the prognosis of patients with poor-grade aneurysm. [ABSTRACT FROM AUTHOR]

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferatoractivated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppressesAMPARexpression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. [ABSTRACT FROM AUTHOR]

Background: Wingspan stenting for the treatment of complex intracranial atherosclerotic stenosis (ICAS), i.e., that involving tortuous vascular pathways, long (>15 mm) lesions or arterial bifurcations, has a relatively high risk of complications. This retrospective study assessed the safety and efficacy of undersized balloon angioplasty followed by deployment of the more flexible Enterprise stent for the treatment of complex symptomatic ICAS.Methods: Forty-four patients on combined antiplatelet therapy and intensive risk factor management and a symptomatic 70-99% stenosis of a major intracranial artery in complex settings that was treated with balloon angioplasty and Enterprise stent deployment between July 2009 and August 2013 were enrolled. Primary outcome was occurrence of ischemic or hemorrhagic stroke or death within 30 days after intervention. Secondary outcomes included procedural success (defined as achievement of <50% immediate residual stenosis), and follow-up clinical and angiographic outcomes.Results: With a procedural success rate of 100%, stenosis was reduced from 79.3 ± 8.1-14.9 ± 2.3%. Three (6.8%) ischemic and 1 (2.2%) hemorrhagic strokes occurred during the periprocedural period, with no further transient ischemic attacks or strokes in the 42 patients available at median 25.6 (range, 12-57) months follow-up. Of the 38 (86.4%) patients who underwent angiographic follow-up, 3 (6.81%) developed >50% in-stent restenosis after mean 22 months follow-up.Conclusion: In this retrospective, single-center experience, undersized balloon angioplasty followed by Enterprise stent deployment appears technically feasible with a relatively low rate of complications for the treatment of complex symptomatic ICAS. Prospective, multicenter, randomized controlled trials against optimal medical management are warranted. [ABSTRACT FROM AUTHOR]

Aims/Introduction The role of the renal nitric oxide ( NO) system in the pathophysiology of diabetic nephropathy constitutes a very challenging and fertile field for future investigation. The purpose of the present study was to investigate whether NO donors can attenuate diabetic renal fibrosis and apoptosis through modulating oxidative- and nitrosative-stress, and Wnt signaling using in vivo diabetic models. Materials and Methods Diabetic rat was induced by a single intraperitoneal injection of streptozotocin. Rats in each group were intraperitoneally given 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (1 U/kg/day) and vehicle for 28 and 56 consecutive days. Expression of the oxidative- and nitrosative-stress, and Wnt signaling components were examined in kidneys from diabetic animals by quantitative reverse transcription polymerase chain reaction, western blot analysis and immunohistochemical staining. Results NO donor treatment significantly reduced the ratio of kidney weight to bodyweight and proteinuria. This treatment also significantly restored the suppressive effect of diabetes on urinary NO2 + NO3 levels. Immunohistochemistry showed that NO donor treatment significantly reduced transforming growth factor ( TGF)-β1, fibronectin, cleaved caspase-3 and triphosphate-biotin nick end-labeling expression in the glomeruli of diabetic rats. We found that diabetes promoted 8-hydroxy-2′-deoxyguanosine, and peroxynitrite expression coincided with reduced endothelial NO synthase expression in glomeruli. Interestingly, NO donor treatment completely removed oxidative stress and nitrosative stress, and restored endothelial NO synthase expression in diabetic renal glomeruli. Immunohistomorphometry results showed that NO donor treatment significantly restored suppressed Wnt5a expression and β-catenin immunoreactivities in glomeruli. Based on laser-captured microdissection for quantitative reverse transcription polymerase chain reaction, diabetes significantly increased TGF-β1, and fibronectin expression coincided with depressed Wnt5a expression. NO donor treatment reduced TGF-β1, fibronectin activation, and the suppressing effect of diabetes on Wnt5a and β-catenin expression in renal glomeruli. Conclusions NO donor treatment alleviates extracellular matrix accumulation and apoptosis in diabetic nephropathy in vivo by not only preventing the diabetes-mediated oxidative and nitrostative stress, but also restoring downregulation of endothelial NO synthase expression and Wnt/β-catenin signaling. These findings suggest that modulation of NO is a viable alternative strategy for rescuing diabetic renal injury. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether valproic acid (VPA) pretreatment enhances the therapeutic effectiveness of mesenchymal stem cells derived from bone marrow (BMSCs) transplanted into rats with an acute spinal cord injury (SCI). BMSCs were pretreated with VPA before transplantation and then intravenously injected 1 week after SCI. Before transplantation, levels of CXC chemokine receptor 4 (CXCR4) expression in BMSCs were tested using quantitative real-time PCR and Western blotting. Stromal derived factor-1 (SDF-1), the unique ligand of CXCR4, was quantified using RT-PCR and immunofluorescence. The locomotor function of rats with an SCI was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Fluorescence microscopy and hematoxylin-eosin (HE) staining were also performed to evaluate pathophysiological changes after transplantation. On day 7 after SCI, the level of SDF-1 expression peaked. CXCR4 expression increased significantly in BMSCs pretreated with VPA. After intravenous transplantation, BrdU-labeled BMSCs were noted at the spinal injury site, and this was especially true for BMSCs pretreated with VPA. More significant functional improvement was observed in rats receiving BMSCs pretreated with VPA than in other groups of rats. AMD3100 partially inhibited improvement. This study demonstrates that pretreatment with VPA before transplantation enhances the therapeutic benefits of BMSCs in terms of greater cell migration and better neurological outcomes after traumatic SCI. The mechanism of this enhancement may be related to the SDF-1/CXCR4 axis. Therefore, pretreatment of BMSCs with VPA warrants further study in relation to the treatment of traumatic SCI. [ABSTRACT FROM AUTHOR]

VEGF (vascular endothelial growth factor) is a potent proangiogenic cytokine, and vascular change is one of the characteristic features of airway remodelling. Since the glucocorticoids have shown antifibrosis properties, we sought to investigate whether budesonide, a widely used glucocorticoid in clinical practice, could attenuate TGF-β1 (transforming growth factor-β1)-induced VEGF production by HFL-1 (human lung fibroblasts). HFL-1 fibroblasts were treated with various concentrations of budesonide (10-11 M, 10-9 M and 10-7 M) in the absence or presence of TGF-β1. Postculture media were collected for ELISA of VEGF at the indicated times. The cell lysates were subjected to Western blotting analysis to test TGF-β1/Smad and MAP (mitogen-activated protein) kinase signalling activation, respectively. The results suggested that budesonide pretreatment reduced the significant increase of VEGF release induced by TGF-β1 in HFL-1 fibroblasts in a dose-dependent manner, and suppressed the increase of phospho-Smad3 and phosphor-ERK (extracellular signalregulated kinase) protein levels. In conclusion, budesonide may reduce TGF-β1-induced VEGF production in the lung, probably through the Smad/ERK signalling pathway and, thus, may provide new sight into the molecular mechanism underlying glucocorticoid therapy for airway inflammatory diseases. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground:Proton pump inhibitors (PPIs) are the most commonly used pharmacological treatment for gastroesophageal reflux disease (GERD).Objective:To examine the utilization patterns of PPIs and other GERD-related medications, satisfaction with PPI treatment and presence of GERD symptoms.Patients and methods:GERD patients using prescription PPIs were identified from a mixed-model HMO health plan. Utilization patterns of PPIs and other GERD medications, satisfaction with PPI treatment and presence of GERD symptoms were assessed using questionnaires.Results:Among the 617 patients who completed the survey, 71.0 used PPIs once a day (QD), 22.2 used twice a day (BID) and 6.8 more than twice a day or on an as-needed basis. Approximately 42.1 of all patients supplemented their prescription PPIs with other GERD medications, including over-the-counter medications and H2-receptor antagonists. Over 85 of the patients still experienced GERD symptoms and 82.7 nighttime symptoms. Overall, 72.8 of all patients were satisfied or very satisfied with their PPI treatment.Limitations:The study used self-reported data which may have been subject to recall bias. As the study was conducted in a specific region of the US, the results may have limited generalizability to other US regions or countries.Conclusions:Patients on PPI treatment often experience GERD symptoms and supplement their prescription PPIs with other GERD medications. A substantial proportion of GERD patients receiving PPI treatment are on a BID regimen. Furthermore, more than a quarter of the patients are not completely satisfied with their PPI treatment. [ABSTRACT FROM AUTHOR]

Background. Urethral catheterization is the method of choice for obtaining samples for urine culture and urine analysis in infants. Before the procedure, there is little certainty of the presence or amount of urine in the bladder. Consequently, this relatively invasive and uncomfortable procedure often needs to be repeated. The newly available technology of portable ultrasound may be useful in reducing the number of unsuccessful procedures. Objective. To investigate the utility of bedside ultrasound of the bladder performed by pediatric emergency medicine physicians before catheterization in reducing the number of unsuccessful attempts. Methods. A prospective, 2-phase study was performed in the setting of an urban pediatric emergency department from August 2003 to February 2004. Children who were between the ages of 0 and 24 months were enrolled. During the observation phase, the amount of urine obtained during the first catheterization was recorded for each patient. During the intervention period, a rapid bedside ultrasound of the bladder was performed by a pediatric emergency medicine physician immediately before urethral catheterization. When a sufficient amount of urine was seen, catheterization was conducted as usual. Otherwise, catheterization was deferred and repeated ultrasound was performed at 30-minute intervals until sufficient urine was identified. The amount of urine obtained was recorded. Results. During the observation phase, 136 infants underwent urethral catheterization. Overall, the rate of success during the first attempt, defined as obtaining >2 mL of urine, sufficient for culture and other routine studies, was 72% (95% confidence interval: 66%-78%). A total of 112 subjects were enrolled during the intervention phase. Sufficient urine was identified on the first ultrasound in 76% (n = 85) of the patients. Among these, 98% (n = 83) underwent successful urethral catheterization during the first attempt. Among those in whom... [ABSTRACT FROM AUTHOR]

The article discusses the medical case of New Delhi-metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae in a patient presented at an acute care hospital with carbapenem-resistant Enterobacteriaceae (CRE) in Washoe County, Nevada. It highlights important considerations in CRE control, which include uncommon isolates that are resistant to antimicrobials and recommendations by U.S. Centers for Disease Control and Prevention (CDC) to slow the spread of bacteria with resistance mechanism.