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Walid A Alkeridy,1– 3 Arwa Aljasser,4 Khalid Mohammed Alayed,1 Saad M Alsaad,5 Amani S Alqahtani,6 Claire Ann Lim,7 Sultan H Alamri,8,9 Doaa Zainhom Mekkawy,1 Mohammed Al-Sofiani1,10 1Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Medicine, Geriatric Division, University of British Columbia, Vancouver, Canada; 3General Administration of Home Health Care, Therapeutic Affairs Deputyship, Riyadh, Saudi Arabia; 4Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 5Department of Family & Community medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Research department, Saudi Food and Drug Authority, Riyadh, Saudi Arabia; 7Department of Medical Rehabilitation, King Saud Medical City, Riyadh, Saudi Arabia; 8Department of Family Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 9Saudi Geriatrics Society, Riyadh, Saudi Arabia; 10Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University, Baltimore, MD, USACorrespondence: Walid A Alkeridy, West College of Medicine Building, 3rd Floor, Riyadh, Riyadh, 12372, Saudi Arabia, Tel +966118066802, Email walkeridy@ksu.edu.saObjective: This study aimed to 1) report the prevalence of chronic conditions among Saudi people receiving long-term home health care (HHC) services, 2) identify the predictors of mortality among individuals receiving long-term HHC services, and 3) study the association between frailty and poor health outcomes among HHC users.Design: Retrospective cross-sectional descriptive study.Setting and Participants: A total of 555 participants were recruited from HHC services at King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia. We collected the data from electronic health records (EHR), patient charts, and caregiver interviews for 555 participants included in HHC program from the year 2019 to 2022.Methods: Only individuals fulfilling the HHC program’s eligibility criteria were included to the study. A total of 555 participants were included in the analysis. We assessed the functional performance by the Katz activity of daily living and Bristol Activity of Daily Living Scale (BADLS). A trained health care provider assessed frailty using the Clinical Frailty Scale (CFS). We calculated the means and frequency to describe the prevalence of chronic conditions and variables of interest. A Chi-square test or independent-samples t-test was run to determine if there were differences between the alive and deceased individuals. A binary logistic regression model was performed to predict mortality of HHC service recipients.Results: The mean age for deceased individuals in HHC was 78.3 years. Over twenty percent of individuals receiving HHC services were readmitted to the hospital. We found that the strongest predictors for mortality were pressure ulcers with an odds ratio of 3.75 and p-value of < 0.0001, and the Clinical Frailty Scale, which had an odds ratio of 1.69 and p-value of 0.002, using multivariate regression analysis.Conclusions and Implications: In conclusion, our study found that pressure ulcers and frailty are the strongest predictors of mortality for individuals receiving home health care services.Keywords: home health care, Saudi Arabia, predictors of mortality

Abstract Disruption of alternative splicing frequently causes or contributes to human diseases and disorders. Consequently, there is a need for efficient and sensitive reporter assays capable of screening chemical libraries for compounds with efficacy in modulating important splicing events. Here, we describe a screening workflow employing dual Nano and Firefly luciferase alternative splicing reporters that affords efficient, sensitive, and linear detection of small molecule responses. Applying this system to a screen of ~95,000 small molecules identified compounds that stimulate or repress the splicing of neuronal microexons, a class of alternative exons often disrupted in autism and activated in neuroendocrine cancers. One of these compounds rescues the splicing of several analyzed microexons in the cerebral cortex of an autism mouse model haploinsufficient for Srrm4, a major activator of brain microexons. We thus describe a broadly applicable high-throughput screening system for identifying candidate splicing therapeutics, and a resource of small molecule modulators of microexons with potential for further development in correcting aberrant splicing patterns linked to human disorders and disease.

Abstract Background Dyslexia is a learning disability that is characterized by difficulties in the acquisition of reading and spelling skills independent of intelligence, motivation or schooling. Studies of western populations have suggested that DYX1C1 is a candidate gene for dyslexia. In view of the different languages used in Caucasian and Chinese populations, it is therefore worthwhile to investigate whether there is an association of DYX1C1 in Chinese children with dyslexia. Method and Results Eight single nucleotide polymorphisms (SNPs) were genotyped from three hundred and ninety three individuals from 131 Chinese families with two which have been reported in the literature and six tag SNPs at DYX1C1. Analysis for allelic and haplotypic associations was performed with the UNPHASED program and multiple testing was corrected using false discovery rates. We replicated the previously reported association of rs3743205 in Chinese children with dyslexia (pcorrected = 0.0072). This SNP was also associated with rapid naming, phonological memory and orthographic skills in quantitative trait analysis. Conclusion Our findings suggest that DYX1C1 is associated with dyslexia in people of Chinese ethnicity in Hong Kong.

Abstract Background For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg2+, one of the most versatile metal cofactors in cellular biochemistry. Even when Mg2+-proteins share insufficient sequence homology to identify Mg2+-specific sequence motifs, they may still share similarity in the Mg2+-binding site structure. However, no structural motifs characteristic of Mg2+-binding sites have been reported. Thus, our aims are (i) to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (ii) to apply it to Mg2+-proteins sharing 2+-structural motifs are identified as recurring structural patterns. Results The structural alphabet-based motif discovery method has revealed the structural preference of Mg2+-binding sites for certain local/secondary structures: compared to all residues in the Mg2+-proteins, both first and second-shell Mg2+-ligands prefer loops to helices. Even when the Mg2+-proteins share no significant sequence homology, some of them share a similar Mg2+-binding site structure: 4 Mg2+-structural motifs, comprising 21% of the binding sites, were found. In particular, one of the Mg2+-structural motifs found maps to a specific functional group, namely, hydrolases. Furthermore, 2 of the motifs were not found in non metalloproteins or in Ca2+-binding proteins. The structural motifs discovered thus capture some essential biochemical and/or evolutionary properties, and hence may be useful for discovering proteins where Mg2+ plays an important biological role. Conclusion The structural motif discovery method presented herein is general and can be applied to any set of proteins with known 3D structures. This new method is timely considering the increasing number of structures for proteins with unknown function that are being solved from structural genomics incentives. For such proteins, which share no significant sequence homology to proteins of known function, the presence of a structural motif that maps to a specific protein function in the structure would suggest likely active/binding sites and a particular biological function.

Background: Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these landmark trials, sorafenib (SOR) served as the standard first-line treatment for a decade. Our study aimed to assess the outcomes of HCC patients treated during the SOR era (2008-2018) in contrast to those in the post-SOR era (2018-2021), of which the predominant first-line treatments were LEN or A + B., Methods: Inclusion criteria of the study were all HCC patients in the Canadian province of Alberta who started first-line systemic therapy at cancer centers between 1 January 2008 and 31 December 2021. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), along with clinician-assessed response rate (RR), were subject to retrospective analysis., Results: Of 372 total patients, 230 received treatment in the SOR era and 142 in the post-SOR era. The demographic and clinical characteristics for the SOR era and post-SOR era groups are as follows, respectively: the median age was 63 and 64 years, 80% and 81% were male, and 24% and 11% were of East Asian ethnicity. Before receiving systemic treatment, 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT in the two eras, respectively. In the post-SOR era, patients received A + B (23%), LEN (51%), and SOR (23%) as first-line treatment. There was a statistically significant improvement in RR (15% vs. 26%; p = 0.02), median PFS (3.8 months vs. 7.9 months; p < 0.0001), and median OS (9.8 months vs. 17.0 months; p < 0.0001)., Conclusions: In this retrospective multicenter real-world study, HCC patients treated in the post-SOR era, where LEN and A + B were commonly used first-line treatments, exhibited superior OS, PFS, and RR compared to patients treated in the SOR era. The findings of this study affirm the tangible progress achieved in the real world in enhancing outcomes for HCC patients through advancements in treatments over the past 15 years., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

(1) Background: This observational cohort study describes the frequency, content, and satisfaction with advance care planning (ACP) conversations with healthcare providers (HCPs), as reported by patients with advanced colorectal cancer. (2) Methods: The patients were recruited from two tertiary cancer centers in Alberta, Canada. Using the My Conversations survey with previously validated questions, the patients were asked about specific ACP elements discussed, with which HCPs these elements were discussed, their satisfaction with these conversations, and whether they had a goals of care designation (GCD) order. We surveyed and analyzed data from the following four time points: enrollment, months 1, 2, and 3. (3) Results: In total, 131 patients were recruited. At enrollment, 24% of patients reported discussing at least one ACP topic. From enrollment to month 3, patients reported a high frequency of discussions (80.2% discussed fears, 71.0% discussed prognosis, 54.2% discussed treatment preferences at least once); however, only 44.3% of patients reported discussing what is important to them in considering health care preferences. Patients reported having ACP conversations most often with their oncologists (84.7%) and cancer clinic nurses (61.8%). Patients reported a high level of satisfaction with their ACP conversations, with over 80% of patients reported feeling heard and understood. From enrollment to month 3, there was an increase in the number of patients with a GCD order from 53% to 74%. (4) Conclusions: Patients reported more frequent conversations compared to the literature and clinical documentation. While the satisfaction with these conversations is high, there is room for quality improvement, particularly in eliciting patients' personal goals for their treatment.

The PACIFIC trial led to a new standard of care for patients with locally advanced lung cancer, but real-world practice has demonstrated that immune checkpoint inhibitor (ICI) pneumonitis can lead to significant clinical complications. This study aimed to examine the clinical predictors, outcomes, and healthcare utilization data in patients who received consolidation durvalumab. Using the Alberta Immunotherapy Database, NSCLC patients who received durvalumab in Alberta, Canada, from January 2018 to December 2021 were retrospectively evaluated. We examined incidence and predictive values of severe pneumonitis, with overall survival (OS) and time-to-treatment failure (TTF) using exploratory multivariate analyses. Of 189 patients, 91% were ECOG 0-1 and 85% had a partial response from chemoradiation prior to durvalumab. Median TTF and OS were not reached; 1-year OS was 82%. An amount of 26% developed any grade of pneumonitis; 9% had ≥grade 3 pneumonitis. Male gender and a pre-existing autoimmune condition were associated with severe pneumonitis. V20 was associated with any grade of pneumonitis. Pneumonitis development was found to be an independent risk factor for worse OS ( p = 0.038) and TTF ( p = 0.007). Our results suggest clinical and dosimetric predictive factors of durvalumab-associated pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population.

Objectives: Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock., Methods: We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors., Results: Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4-12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7-8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8-9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66-100], specificity 38% [95% CI, 22-55])., Conclusions: Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To describe a single stage technique of reconstruction of full thickness lower eyelid defects using a lateral advancement flap and Z-plasty combined with a lateral periosteal strip., Methods: A retrospective case series of six patients who underwent reconstruction using this technique is presented documenting surgical technique, clinical photographs and postoperative outcomes., Results: All six patients demonstrated good eyelid position and cosmesis following reconstruction., Conclusion: A lateral advancement flap with Z-plasty combined with a periosteal strip is an effective technique to close lower eyelid defects of up to eighty percent of eyelid width, providing a good structural and aesthetic outcome.

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS). We sought to evaluate the impact of ECOG PS on clinical outcomes and health care utilization in patients with NSCLC treated with ICIs in real-world practice., Methods: Patients with advanced NSCLC who received at least one dose of pembrolizumab or nivolumab were retrospectively identified from the Alberta Immunotherapy Database. The primary outcome was median overall survival, as stratified by ECOG PS. Secondary outcomes included median time-to-treatment failure and metrics of health care utilization, including emergency department visits, hospitalizations, and death in hospital., Results: A total of 790 patients were included, with 29.2% having poor ECOG PS at initiation of ICI. These patients had significantly lower median overall survival (3.3 versus 13.4 mo) and median time-to-treatment failure (1.4 versus 4.9 mo) compared with those with favorable ECOG PS ( p < 0.0001 for both outcomes). Patients with poor ECOG PS were also more likely to present to the emergency department, be admitted to the hospital, and die in the hospital during their first admission (risk ratio = 1.6, 2.3-2.7, p < 0.001)., Conclusions: Patients with NSCLC with poor ECOG PS treated with ICI had significantly worse survival outcomes and were significantly more likely to use health care services than those with favorable ECOG PS. The large proportion of patients with poor ECOG PS further justifies the urgent need for randomized trials evaluating the efficacy of ICI in this high-risk population., (© 2023 The Authors.)

The aim of this study is to assess the Internet usage pattern amongst glioma patients and to characterize its impact in their decision-making and clinical interactions. Glioma patients attending a tertiary cancer center between June and December 2019 were invited to participate in this study. A 26-item survey consisting of closed and open-ended questions was distributed with a unique identifier. Quantitative data were analyzed with descriptive statistics using SPSS Statistical package, and qualitative data with grounded theory approach. Thirty-two patients completed the survey. Demographics varied in age, time since diagnosis, glioma type, and level of education. Eighty-one percent were identified as "Internet users" who sought online glioma information. Google was the most popular search engine (96%), with "glioma" being the most frequent search term. The selection of websites often relied on perceived credibility and top search hits. The most searched topic was prognosis (73%). The majority of patients found that online information was easy to understand, and this did not vary significantly amongst age groups. Website quality was always assessed by 60% of patients. Only 62% patients found the Internet a useful resource, and 70% patients found it facilitated their understanding. Most patients discussed their Internet findings with a physician, largely regarding concerns about reliability. There is variable glioma information available online. Patients with glioma use the Internet as a resource, with variable impact on their interactions and decision-making. This information can be used by physicians, educators, and website developers to support glioma patients' needs., (© 2021. American Association for Cancer Education.)

Objective: Differences in clinical manifestations between strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This retrospective descriptive study compares the clinical and demographic characteristics of all confirmed coronavirus disease (COVID-19) cases admitted to the National Isolation Centre (NIC) in the first wave and at the beginning of the second wave of the pandemic in Brunei Darussalam., Methods: All COVID-19 cases admitted to the NIC between 9 March and 6 May 2020 (first wave) and 7-17 August 2021 (second wave) were included. Data were obtained from NIC databases and case characteristics compared using Student's t -tests and χ 2 tests, as appropriate., Results: Cases from the first wave were significantly older than those from the second wave (mean 37.2 vs 29.7 years, P  < 0.001), and a higher proportion reported comorbidities (30.5% vs 20.3%, P  = 0.019). Cases from the second wave were more likely to be symptomatic at admission (77.7% vs 63.1%, P  < 0.001), with a higher proportion reporting cough, anosmia, sore throat and ageusia/dysgeusia; however, myalgia and nausea/vomiting were more common among symptomatic first wave cases (all P  < 0.05). There was no difference in the mean number of reported symptoms (2.6 vs 2.4, P  = 0.890)., Discussion: Our study showed clear differences in the profile of COVID-19 cases in Brunei Darussalam between the first and second waves, reflecting a shift in the predominating SARS-CoV-2 strain. Awareness of changes in COVID-19 disease manifestation can help guide adjustments to management policies such as duration of isolation, testing strategies, and criteria for admission and treatment., ((c) 2022 The authors; licensee World Health Organization.)

Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but emerging syndrome related to SARS-CoV-2 infection. While the presentation of MIS-C is generally delayed after exposure to the virus that causes coronavirus 2019, both MIS-C and Kawasaki disease (KD) share similar clinical features. Multisystem inflammatory syndrome in children poses a diagnostic and therapeutic challenge given the lack of definitive diagnostic tests and a paucity of evidence regarding treatment modalities. We review the clinical presentation, diagnostic evaluations, and management of MIS-C and compare its clinical features to those of KD.

Objectives: Inaccurate weight estimation is a contributing factor to medical error in pediatric emergencies, especially in the prehospital setting. Current American Heart Association guidelines recommend the use of length-based weight estimation tools such as the Broselow tape. We developed the AiRDose smartphone application that uses augmented reality to provide length-based weight estimates, as well as medication dosing, defibrillation energy, and equipment sizing recommendations; AiRDose was programmed to use Broselow conversions to obtain these estimates. The primary objective was to compare the length estimated by AiRDose with the actual length obtained by the standard tape measure. The secondary objectives were to compare the estimated weights and critical medication doses from AiRDose with current established methods., Methods: In this prospective validation study, lengths and estimated weights were obtained for children presenting to 2 emergency departments using AiRDose, Broselow, and a standard tape measure; actual weight was recorded from the patient chart. Using the AiRDose estimated weights, hypothetical doses of epinephrine and lorazepam were calculated and compared with doses recommended via Broselow and to actual weight-based doses. Spearman rank correlation coefficients were calculated. We defined an acceptable difference of 20% between AiRDose and standard measurements as clinically relevant., Results: Five hundred forty-nine children (mean age, 4.8 years; standard deviation [SD], 2.9 years) were recruited. There were 99.6% of AiRDose lengths within a 20% difference of tape-measure lengths. There was a significant correlation between AiRDose and tape-measure length measurements (r = 0.989, P < 0.0001), and between AiRDose and Broselow weights (r = 0.983, P < 0.0001) and AiRDose and actual weights (r = 0.886, P < 0.0001). AiRDose lorazepam and epinephrine doses correlated significantly with Broselow lorazepam (r = 0.963, P < 0.0001) and epinephrine (r = 0.966, P < 0.0001) doses., Conclusions: Anthropometric estimates and medication dose recommendations provided by AiRDose strongly correlate with established techniques. Further study will establish the feasibility of using AiRDose to accurately obtain weight estimates and medication doses for pediatric patients in the prehospital setting., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We report a rare case of stage IV pulmonary combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma (ACA), both demonstrating anaplastic lymphoma kinase ( ALK ) rearrangement by IHC and FISH. This 61-year-old lifelong nonsmoking Asian woman presented with a cough, and after diagnosis and surgical treatment, completed four cycles of adjuvant cisplatin and etoposide chemotherapy. She subsequently developed recurrence with bony metastases of exclusively ALK -positive LCNEC. Alectinib was started, and the patient experienced a partial response.

Objectives: Delirium is a well-described complication of critical illness, with occurrence rates of >25% in the PICU, and associated morbidity. Infants in the NICU are likely at risk. There have been no previous screening studies to quantify delirium rates in the neonatal population. We hypothesized that delirium was prevalent in term neonates in the NICU. In this pilot study, our objective was to estimate prevalence using a validated pediatric delirium screening tool, which has not yet been tested in NICUs., Methods: In this point prevalence study, all term or term-corrected infants admitted to the NICU on designated study days were screened for delirium using the Cornell Assessment of Pediatric Delirium., Results: A total of 149 infants were eligible for screening over 8 study days. A total of 147 (98.6%) were successfully screened with the Cornell Assessment of Pediatric Delirium. Overall, 22.4% ( n = 33) screened positive for delirium. Delirium was more commonly detected in children on invasive mechanical ventilation (67% vs 17%, P < .01) and those with underlying neurologic disorders (64% vs 13%, P < .01). A multivariate logistic regression revealed that neurologic disability and mechanical ventilation were both independently associated with a positive delirium screen (aOR: 12.3, CI: 4.5-33.6 and aOR: 9.3, CI: 2.5-34.6, respectively)., Conclusions: Our results indicate that delirium likely occurs frequently in term-equivalent infants in the NICU. Further research is necessary to establish feasibility, validity, and interrater reliability of delirium screening in this population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

The widespread evolution of glyphosate-resistant (GR) Bassia scoparia in the U.S. Great Plains poses a serious threat to the long-term sustainability of GR sugar beet. Glyphosate resistance in B. scoparia is due to an increase in the EPSPS (5-enolpyruvyl-shikimate-3-phosphate) gene copy number. The variation in EPSPS gene copies among individuals from within a single GR B. scoparia population indicated a differential response to glyphosate selection. With the continued use of glyphosate in GR sugar beet, the effect of increasing glyphosate rates (applied as single or sequential applications) on the fitness of GR B. scoparia individuals with variable EPSPS gene copies was tested under field conditions. The variation in EPSPS gene copy number and total glyphosate rate (single or sequential applications) did not influence any of the reproductive traits of GR B. scoparia, except seed production. Sequential applications of glyphosate with a total rate of 2214 g ae ha -1 or higher prevented seed production in B. scoparia plants with 2-4 (low levels of resistance) and 5-6 (moderate levels of resistance) EPSPS gene copies. Timely sequential applications of glyphosate (full recommended rates) can potentially slow down the evolution of GR B. scoparia with low to moderate levels of resistance (2-6 EPSPS gene copies), but any survivors (highly-resistant individuals with ≥ 8 EPSPS gene copies) need to be mechanically removed before flowering from GR sugar beet fields. This research warrants the need to adopt ecologically based, multi-tactic strategies to reduce exposure of B. scoparia to glyphosate in GR sugar beet., (© 2021. The Author(s).)

Objectives: To evaluate the impact of a 12-month multi-modal public health intervention programme for treating and preventing anaemia among children aged 6 months to 4 years in an underserved community in Peru., Methods: The intervention included nutritional education, use of a Lucky Iron Fish ® cooking tool, and dietary supplementation. The primary outcome measure was anaemia resolution. Secondary outcomes included absolute changes in haemoglobin, change in knowledge survey scores and adherence to interventions. Chi-square test and Mann-Whitney U-test were employed to identify associations between anaemia and intervention-related measures. Variables found to be significantly associated in bivariate analysis or of clinical importance were included in a logistic regression model., Results: Of the 406 children enrolled, 256 (63.1%) completed the programme. Of those, 34.0% had anaemia at baseline; this decreased to 13.0% over 12 months. The mean haemoglobin for all ages at baseline was 11.3 g/dL (SD 0.9). At 12 months, the mean was 11.9 g/dL (SD 0.8), with a mean increase of 0.5 g/dL (95% CI 0.4-0.6). Children with anaemia at baseline saw an increase of 1.19 g/dL at the 12-month follow-up (95% CI 1.12-1.37). Parents correctly answered 79.0% of knowledge assessment questions at baseline, which increased to 86.6% at 12 months., Conclusions: We observed a reduction in the prevalence of mild to moderate anaemia among study participants in this vulnerable population and conclude that multi-modal intervention programmes providing nutrition education in conjunction with low-cost iron supplementation and easy-to-use Lucky Iron Fish ® cooking tools may reduce and prevent anaemia in children., (© 2021 John Wiley & Sons Ltd.)

Background: Preparation of del-Nido cardioplegia and its delivery technique can cause significant hemodilution. The resultant effects from hemodilution are largely proportionate to the use of a dual circuit. We opted for a custom-disposable single cardioplegia circuit instead of a dual circuit., Methods: We describe an alternative technique of del-Nido cardioplegia delivery and initial clinical experience with it at National University Hospital, Singapore. This is a retrospective analysis of data from January 2017 to April 2019, comprising of 177 patients of heart surgery and reflecting a single center database survey under the National Health Care Group., Results: Of the 177 patients who underwent surgery with del-Nido cardioplegia, 76 (42.9%) were valve-only procedures and 5 (2.8%) were coronary artery bypass graft-only procedures. Ultrafiltration was utilized in 132 (62.6%) patients, whereas filtrate volume was 2200 [150-9500] mL. The alternative technique of del-Nido cardioplegia delivery adopted by National University Hospital advocates for a single pump, single circuit system. The retrospective institutional data highlighted safe delivery of del-Nido cardioplegia using this technique in a range of procedures., Conclusion: Besides the safe delivery of del-Nido cardioplegia, the National University Hospital Technique reduces hemodilution and provides other technical benefits including a steeper temperature gradient, modification of circuit configuration to deliver another cardioplegia while on bypass, as well as re-configuration of clamps to spike the base solution.

The most apparent practical advantage of del Nido cardioplegia (DNC) is that it allows the surgeon a longer arrest period before a subsequent dose is needed, as opposed to the conventional St. Thomas' cardioplegia solution where the recommended ischemic time is ∼15-20 minutes. In this study, we explored the incidence of arrhythmia after cross-clamp removal as a surrogate for a safe myocardial ischemic time with the use of DNC in adult heart surgery. A total of 113 patients who had undergone heart valve repair and/or replacement surgery at the National University Hospital, Singapore, were investigated. This single-center retrospective study was conducted on a population where DNC had been used for myocardial protection between January 2017 and April 2019. Cardioplegia ischemic time interval groups were not significant predictors of postoperative arrhythmia, defibrillation, and intraoperative intra-aortic balloon pump usage. Crude comparison of postoperative outcomes showed no significant differences in any other postoperative variables, including mortality and total hospital stay. From the results of the present study, it appears that there is no optimal ischemic time interval for the administration of DNC within a 120-minute time period. It is likely that DNC has a redosing interval of, and may provide adequate myocardial protection, for up to 120 minutes., (© Copyright 2020 AMSECT.)

Background: Meningiomas are the most common primary central nervous system tumors and patients face difficulty evaluating resources available online. The purpose of this study is to systematically evaluate the educational resources available for patients seeking meningioma information on the Internet., Methods: A total of 127 meningioma websites were identified by inputting the term "meningioma" on Google and two meta-search engines. A structured rating tool developed by our research group was applied to top 100 websites to evaluate with respect to accountability, interactivity, readability, and content quality. Responses to general and personal patient questions were evaluated for promptness, accuracy, and completeness. The frequency of various social media account types was analyzed., Results: Of 100 websites, only 38% disclosed authorship, and 32% cited sources. Sixty-two percent did not state date of creation or modification, and 32% provided last update less than 2 years ago. Websites most often discussed the definition (99%), symptoms (97%), and treatment (96%). Prevention (8%) and prognosis (47%) were most often not covered. Only 3% of websites demonstrated recommended reading level for general population. Of 84 websites contacted, 42 responded, 32 within 1 day., Conclusions: Meningioma information is readily available online, but quality varies. Sites often lack markers for accountability, and content may be difficult to comprehend. Information on specific topics are often not available for patients. Physicians can direct meningioma patients to appropriate reliable online resources depicted in this study. Furthermore, future web developers can address the current gaps to design reliable online resources., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

After a decades-long reduction in vaccine-preventable illnesses worldwide, there has been a reappearance of childhood illnesses once thought to be eradicated. This resurgence in illnesses such as polio and measles is a consequence of multifactorial events leading to decreased vaccination rates. A lack of resources in poor and war-torn countries, coupled with increasing global travel, and decisions to delay or defer vaccinations because of inaccurate studies further emphasized by media have combined to result in current state of frequent local and widespread epidemics, specifically the current outbreak of measles. As providers in the pediatric emergency department, we are often the first to encounter children manifesting these diseases. It is imperative that we understand the circumstances leading to these encounters, so that we can have engaged conversations with families, gain an understanding of their motivations, dispel any misinformed beliefs, and encourage positive health behaviors for their children.

Background: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted., Objective: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function., Methods: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro., Results: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased., Conclusion: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Objectives: This study aimed to assess the oral health and the prevalence of pre-existing oral colonization with respiratory pathogens in dependent elderly, and whether these factors influence pneumonia development., Materials and Methods: Participants residing in a long-term care facility received bedside oral examinations, and information on their oral health (caries status, calculus index and debris index) was obtained. Samples from the tongue and teeth were collected at baseline and at time of pneumonia development. Sputum was collected at the time of pneumonia diagnosis. Samples were assessed for Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae by polymerase chain reaction., Results: This was a 1-year longitudinal study of 60 dependent elderly (mean age: 64.2 ± 14.1 years). Seventeen patients (28.3%) developed pneumonia. The mean Decayed, Missing and Filled Teeth and Simplified Oral Hygiene Index were 22.8 ± 9.2 and 4.0 ± 1.0, respectively. At baseline, 48.3% were orally colonized with ≥1 respiratory pathogens. The presence of H. influenzae (P = .002) and P. aeruginosa (P = .049) in the sputum was significantly associated with their colonization on the tongue at baseline. In the bivariate analyses, pneumonia development was associated with naso-gastric feeding tube (P = .0001), H. influenzae (P = .015) and P. aeruginosa (P = .003) tongue colonization at baseline and calculus index (P = .002). Multivariate analyses revealed that calculus index (P = .09) and the presence of tracheostomy (P = .037) were associated with pneumonia., Conclusions: The calculus amount and tongue colonization with respiratory pathogens are risk factors for pneumonia development. Oral hygiene measures to remove tongue biofilm and calculus may reduce pneumonia development., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The articular surface replacement (ASR) was recalled in 2010 because of higher than expected revision rates. Patients reported symptoms of neurologic dysfunction including poor vision. This cohort study, using objective measurements, aimed to establish whether a higher incidence of visual function defects exists in ASR patients., Methods: Thirty-three ASR patients and 33 non-ASR controls (control 1) were recruited. Data were compared with normative population data from the visual electrophysiology database (control 2). Patients underwent investigations for serum cobalt levels, psychophysical visual tests, and extensive electrophysiological visual testing., Results: After excluding 2 subjects with pre-existing eye disease, data from 33 ASR patients were compared with the 2 control cohorts. The median serum cobalt level in the ASR group (median, 52 nmol/L [interquartile range, 14-151 nmol/L]) was significantly higher than that in the control 1 cohort (median, 7 nmol/L [interquartile range, 5-14 nmol/L]; P < .0001). The photoreceptor function of patients with an ASR of the hip showed significantly larger electroretinography mixed rod-cone b-wave amplitudes than both control 1 and control 2 cohorts (P = .0294 and .0410, respectively). Abnormalities in macular function as reflected by multifocal and scotopic electroretinography were more prevalent in control 1 (P = .0445 and .0275, respectively). Optic nerve pathway measurements using visual-evoked potential latency was significantly longer in the ASR group compared with those in the control 2 cohort (P = .0201). There were no statistical differences in visual acuity., Conclusion: A statistically significant disturbance in visual electrophysiology was found in the ASR group when compared with the control groups. These differences did not translate to identifiable clinical visual deficits. Orthopedic surgeons need to be aware of the possibility of visual dysfunction in patients with ASR and other metal-on-metal hip arthroplasties; however, routine visual testing is not recommended., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We present a case of an adolescent patient with multiple mandibular fractures diagnosed by point-of-care ultrasound in the pediatric emergency department. Sonographic findings consistent with fracture were identified in our patient, and early consultation expedited interdepartmental coordination and disposition. The role of ultrasound in identifying various traumatic orthopedic and maxillofacial injuries is discussed.

Background: Alopecia areata (AA) is an autoimmune skin disease difficult to manage and treat. The pathogenesis of AA features a T-cell-associated autoimmune process, and systemic immunosuppressive therapy is prescribed widely for AA., Objective: To evaluate the efficacy and tolerance of systemic low-dose methotrexate (LD-MTX) therapy in treatment of recalcitrant AA multiplex., Methods: In a retrospective, non-controlled study, we evaluated 29 patients with recalcitrant AA treated with LD-MTX and assessed the therapeutic response according to severity of disease, disease duration, cumulative dose of MTX, and drug safety., Results: MTX was administered twice weekly, and the mean maximum weekly dose was 14.48 mg. The response was A5 (regrowth=100.0%) in 14 (48.3%) patients and A4 (regrowth of 75%~90%) in 12 (41.4%) patients. Three patients had poor response to LD-MTX treatment (A2: n=2 [6.9%], A1: n=1 [3.4%]). All three of the patients showing a poor response had disease durations exceeding 24 months. Relapse was observed in 31% of patients with more than 75% regrowth. Common side-effects were elevated liver enzyme levels and gastrointestinal discomfort., Conclusion: LD-MTX appears to be an effective and well-tolerated treatment for recalcitrant AA multiplex., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Micro-needle patches have been recently used to increase skin permeability, which improves drug delivery, and for cosmetic purposes. However, these patches may often have limited efficacy due to insufficient skin penetration and reduced compliance caused by discomfort., Objective: We evaluated the efficacy and the safety of soluble micro-spicule containing epidermal growth factor (MS-EGF) for the treatment of periocular wrinkles., Methods: Twenty healthy volunteers aged 33 to 54 years were enrolled in a randomized, controlled, split-face study. For 4 weeks, a periocular wrinkle was treated daily with either a soluble MS-EGF cream or a cream containing EGF alone. All subjects underwent 8 weeks of follow-up. Efficacy was assessed using an ultrasonic measurement of dermal depth and density, digital skin image analysis, 5-point photonumeric scale for periocular wrinkles and subjective satisfaction., Results: MS-EGF group showed statistically significant increase of dermal depth and density compared to EGF alone group after 4 and 8 weeks. In addition, there was a marked improvement shown in clinical and 3-dimensional skin image in MS-EGF group. The treatments were well-tolerated; no significant side-effect was noted., Conclusion: The MS-EGF formulation may represent an effective and biocompatible advance in the treatment of periocular wrinkles., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Purpose: To review the epidemiology and management of facial fractures in a pediatric population., Materials and Methods: This study was a retrospective review of patients younger than 18 years who presented to a pediatric emergency department during a 5-year period in an urban, academic, level 1 designated trauma center., Results: Of the 156 patients identified, most were boys (87%) and the mean age was 13.5 years (standard deviation, 4.9 yr; interquartile range, 12 to 17 yr). The most common mechanism of injury was assault (48.1%). Mandibular fractures (40.7%) were most common. Multiple fractures occurred in 26.9% of patients. Concomitant injuries occurred in 73.7% of patients, most commonly concussions (39.1%). Intracranial hemorrhages were associated with panfacial (P = .005), frontal (P = .001), and orbital (P = .04) fractures. Most patients (91.7%) were admitted, and nonoperative repair was undertaken in 57.1%. There was an independent association of surgical intervention with age older than 14 years and with mandibular fractures (P < .01)., Conclusions: Assault was the most common mechanism of injury and mandibular fracture was the most commonly encountered. Concomitant nonfacial injuries occurred in most patients. Patients sustaining panfacial, frontal, and orbital fractures should provoke an evaluation for other intracranial injuries. Children older than 14 years and those with mandibular fractures should prompt mobilization of resources for operative repair., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Ischaemum rugosum Salisb. (Saramolla grass) is a noxious weed of rice that is difficult to control by chemical or mechanical means once established. A study was conducted to determine the effect of light, temperature, salt, drought, flooding, rice residue mulch, burial depth, and pre-emergence herbicides on seed germination and emergence of I. rugosum. Germination was stimulated by light and inhibited under complete darkness. Optimum temperature for germination was 30/20°C (97.5% germination). Germination reduced from 31 to 3.5% when the osmotic potential of the growing medium decreased from -0.1 to -0.6 MPa and no germination occurred at -0.8 MPa. Germination was 18 and 0.5% at 50 and 100 mM NaCl concentrations, respectively, but was completely inhibited at 150 mM or higher. Residue application at 1-6 t ha-1 reduced weed emergence by 35-88% and shoot biomass by 55-95%. The efficacy of pre-emergence herbicides increased with increasing application rates and decreased with increasing rice residue mulching. The efficacy of herbicides was in the order of oxadiazon> pendimethalin> pretilachlor. At 6 t ha-1, all herbicides, regardless of rates, did not differ from the control treatment. I. rugosum seeds buried at 2 cm or deeper did not emerge; however, they emerged by 4.5 and 0.5% at 0.5 and 1 cm depths, respectively, compared to the 39% germination for soil surface seeding. Flooding at 4 DAS or earlier reduced seedling emergence and shoot biomass while flooding at 8 DAS reduced only seedling emergence. The depth and timing of flooding independently reduced root biomass. Flooding at 4 and 6 cm depths reduced the root biomass. Relative to flooding on the day of sowing, flooding at 8 DAS increased root biomass by 89%. Similarly, flooding on the day of sowing and at 2 DAS reduced the root-shoot biomass ratio. Under the no-flood treatment, increasing rates of pretilachlor from 0.075 to 0.3 kg ai ha-1 reduced weed emergence by 61-79%. At the flooding depth of 2-4 cm, pretilachlor reduced weed emergence and shoot and root biomass, but the differences across rates were non-significant. Information generated in this study will be helpful in developing integrated weed management strategies for managing this weed.

Purpose: The effect of elevated serum cobalt on the human visual system has not yet been established. In light of recent reports of visual problems with elevated cobalt in association with hip prostheses, this review examines the literature for evidence regarding the effects of cobalt on human visual function., Methods: A systematic literature review was undertaken in July 2013. The electronic databases of PubMed (1955 to July week 1 2013), Cochrane Library and EMBASE were searched. Only human studies or case reports written in English were included., Results: Eight case reports were identified. Five case reports involved patients with metal hip arthroplasties, two cases involved patients exposed to environmental cobalt, and one case involved a patient treated medically for anaemia with cobalt chloride. No human prospective studies were identified., Conclusions: Several case reports showed that high serum cobalt may be associated with both irreversible and reversible visual loss, optic neuropathy and atrophy, electrophysiological evidence of abnormal retinal and retinal pigment epithelium function and fluorescein angiographic evidence of abnormal choroidal perfusion.

Objectives: Most medications administered to children are weight-based, and inaccurate weight estimation may contribute to medical errors. Previous studies have been limited to hypothetical patients and those in cardiopulmonary arrest. We aim to determine the accuracy of weight estimates by Emergency Medical Services (EMS) personnel of children receiving medications and to identify factors associated with accuracy., Methods: EMS records of children <18 years old receiving weight-based medications were merged with EMS staffing data and hospital records. The rate of accurate weight estimates, defined as a value within 20% of the actual weight, was evaluated as the primary outcome. Factors associated with patients and prehospital personnel were also evaluated., Results: 29233 transports occurring during the study period were reviewed, and 199 transports of 179 children were analyzed. The average experience of EMS personnel was 35.8 months (SD ±30.7). EMS personnel accurately estimated weights in 164/199 (82.4%) patients; estimated weights were within 10.8% (SD ±10.5) of the actual weights. Underestimated weights were associated with receiving doses outside of the therapeutic range. Inaccurate weight estimates were associated with age less than 10 years or cardiopulmonary arrest. There was a trend toward inaccurate weight estimates among children who presented with seizures., Conclusions: EMS personnel are generally accurate in estimating weights of children. There was an association between underestimated weights and inaccurate medication dosing. Younger children or those presenting with seizure or cardiopulmonary arrest were more likely to have inaccurate weight estimates., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Irritability in children has a broad differential diagnosis, ranging from benign processes to life-threatening emergencies. In children with comorbid conditions and developmental delay, the diagnostic process becomes more challenging. This case report describes a developmentally delayed 14-year-old boy who presented with pain and crying caused by a malfunction of a surgically implanted baclofen pump. We describe recommendations concerning the diagnostic evaluation, medical management, and surgical repair.

Breast cancer is the most common cancer among women worldwide. Breast cancer metastasis primarily happens through lymphatic system, where the extent of lymph node metastasis is the major factor influencing staging, prognosis and therapeutic decision of the disease. We aimed to study the protein expression changes in different N (regional lymph nodes) stages of breast cancer. Protein expression profiles of breast cancerous and adjacent normal tissues were mapped by proteomics approach that comprises of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and tandem mass spectrometry (LC-MS/MS) analysis. Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa glucose-regulated protein was found useful for N2 stage. In addition, significant up-regulation of PDI A3 was detected only in the metastasized breast cancer. The up-regulation expression of these proteins in cancerous tissues can potentially use as indicators for diagnosis, treatment and prognosis of different N stages of breast cancer.

Automated image processing is a critical and often rate-limiting step in high-content screening (HCS) workflows. The authors describe an open-source imaging-statistical framework with emphasis on segmentation to identify novel selective pharmacological inducers of autophagy. They screened a human alveolar cancer cell line and evaluated images by both local adaptive and global segmentation. At an individual cell level, region-growing segmentation was compared with histogram-derived segmentation. The histogram approach allowed segmentation of a sporadic-pattern foreground and hence the attainment of pixel-level precision. Single-cell phenotypic features were measured and reduced after assessing assay quality control. Hit compounds selected by machine learning corresponded well to the subjective threshold-based hits determined by expert analysis. Histogram-derived segmentation displayed robustness against image noise, a factor adversely affecting region growing segmentation.

Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely and maintain pluripotency. These properties require transcription factors that specify the gene expression programme of ES cells. It has been possible to reverse the highly differentiated state of somatic cells back to a pluripotent state with a combination of four transcription factors: Klf4 is one of the reprogramming factors required, in conjunction with Oct4, Sox2 and c-Myc. Maintenance of self-renewal and pluripotency of ES cells requires Oct4, Sox2 and c-Myc, but Klf4 is dispensable. Here, we show that Krüppel-like factors are required for the self-renewal of ES cells. Simultaneous depletion of Klf2, Klf4 and Klf5 lead to ES cell differentiation. Chromatin immunoprecipitation coupled to microarray assay reveals that these Klf proteins share many common targets of Nanog, suggesting a close functional relationship between these factors. Expression analysis after triple RNA interference (RNAi) of the Klfs shows that they regulate key pluripotency genes, such as Nanog. Taken together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression that is unique to ES cells.

NF-kappaB is a key mediator of inflammation. Here, we mapped the genome-wide loci bound by the RELA subunit of NF-kappaB in lipopolysaccharide (LPS)-stimulated human monocytic cells, and together with global gene expression profiling, found an overrepresentation of the E2F1-binding motif among RELA-bound loci associated with NF-kappaB target genes. Knockdown of endogenous E2F1 impaired the LPS inducibility of the proinflammatory cytokines CCL3(MIP-1alpha), IL23A(p19), TNF-alpha, and IL1-beta. Upon LPS stimulation, E2F1 is rapidly recruited to the promoters of these genes along with p50/RELA heterodimer via a mechanism that is dependent on NF-kappaB activation. Together with the observation that E2F1 physically interacts with p50/RELA in LPS-stimulated cells, our findings suggest that NF-kappaB recruits E2F1 to fully activate the transcription of NF-kappaB target genes. Global gene expression profiling subsequently revealed a spectrum of NF-kappaB target genes that are positively regulated by E2F1, further demonstrating the critical role of E2F1 in the Toll-like receptor 4 pathway.

Tight regulation of p53 is essential for maintaining normal cell growth. Here we report that BLIMP1 acts in an autoregulatory feedback loop that controls p53 activity through repression of p53 transcription. p53 binds to and positively regulates BLIMP1, which encodes for a known B cell transcriptional repressor. Knockdown of BLIMP1 by siRNA results in both apoptosis and growth arrest in human colon cancer cells and cell-cycle arrest in primary human fibroblasts. Interestingly, the levels of both p53 mRNA and protein are substantially increased after BLIMP1 depletion, which is accompanied by the induction of p53 target genes. Importantly, the apoptosis induced by BLIMP1 depletion in HCT116 cells is largely abrogated in cells lacking p53 or in cells depleted in p53 by siRNA. We further demonstrate that BLIMP1 binds to the p53 promoter and represses p53 transcription, and this provides a mechanistic explanation for the induction of p53 response in cells depleted of BLIMP1. Hence, suppression of p53 transcription is a crucial function of endogenous BLIMP1 and is essential for normal cell growth.

Several technologies that emerged in the post-genomic era have been particularly useful in dissecting the molecular mechanisms of complex biological processes through the systems approach. Here, we review how three of these technologies, namely transcriptional profiling, large-scale RNA interference (RNAi) and genome-wide location analysis of protein-DNA interactions, have been used in the study of ageing in metazoans. We also highlight recent developments of these three technologies and how these developments are applicable to ageing research.

Hematopoiesis is precisely orchestrated by lineage-specific DNA-binding proteins that regulate transcription in concert with coactivators and corepressors. Mutations in the zebrafish moonshine (mon) gene specifically disrupt both embryonic and adult hematopoiesis, resulting in severe red blood cell aplasia. We report that mon encodes the zebrafish ortholog of mammalian transcriptional intermediary factor 1gamma (TIF1gamma) (or TRIM33), a member of the TIF1 family of coactivators and corepressors. During development, hematopoietic progenitor cells in mon mutants fail to express normal levels of hematopoietic transcription factors, including gata1, and undergo apoptosis. Three different mon mutant alleles each encode premature stop codons, and enforced expression of wild-type tif1gamma mRNA rescues embryonic hematopoiesis in homozygous mon mutants. Surprisingly, a high level of zygotic tif1gamma mRNA expression delineates ventral mesoderm during hematopoietic stem cell and progenitor formation prior to gata1 expression. Transplantation studies reveal that tif1gamma functions in a cell-autonomous manner during the differentiation of erythroid precursors. Studies in murine erythroid cell lines demonstrate that Tif1gamma protein is localized within novel nuclear foci, and expression decreases during erythroid cell maturation. Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates., Competing Interests: The authors have declared that no conflicts of interest exist.

5' untranslated and partial core (C) region sequence of hepatitis C virus (HCV) in 21 Singaporean and 15 Indonesian isolates were amplified by reverse-transcription polymerase chain reaction and sequenced with the use of conserved primer sequences deduced from HCV genomes identified in other geographical regions. The HCV genotypes are predominantly that of Simmonds type 1 and less of type 2 and 3 with the latter genotype currently not detected in Indonesia. The 5' untranslated sequences are related to HCV-1. DK-7 (Denmark), US-11 (United States of America), HCV-J4, SA-10 (South Africa), T-3 (Taiwan), HCV-J6, HCV-J8, Eb-1 and Eb-8. When compared with the prototype HCV-1, insertions are found within the 5' untranslated region of Singaporean isolates and not in the Indonesians. There are Singaporean and Indonesian isolates that have sequences within the 5' untranslated region that differ slightly from each other. Microheterogeneity is observed in the core region of two Singaporeans and one Indonesian isolate. Finally, not all HCV isolates can be amplified with the conserved core sequence primers when compared with the ease with which these isolates can be amplified with 5' untranslated region conserved primers.