THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder.

Covalent tRNA modifications play multi-faceted roles in tRNA stability, folding, and recognition, as well as the rate and fidelity of translation, and other cellular processes such as growth, development, and stress responses. Mutations in genes that are known to regulate tRNA modifications lead to a wide array of phenotypes and diseases including numerous cognitive and neurodevelopmental disorders, highlighting the critical role of tRNA modification in human disease. One such gene, THUMPD1, is involved in regulating tRNA N4-acetylcytidine modification (ac4C), and recently was proposed as a candidate gene for autosomal-recessive intellectual disability. Here, we present 13 individuals from 8 families who harbor rare loss-of-function variants in THUMPD1. Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism, and ophthalmological abnormalities. We demonstrate that the bi-allelic variants identified cause loss of function of THUMPD1 and that this defect results in a loss of ac4C modification in small RNAs, and of individually purified tRNA-Ser-CGA. We further corroborate this effect by showing a loss of tRNA acetylation in two CRISPR-Cas9-generated THUMPD1 KO cell lines. In addition, we also show the resultant amino acid substitution that occurs in a missense THUMPD1 allele identified in an individual with compound heterozygous variants results in a marked decrease in THUMPD1 stability and RNA-binding capacity. Taken together, these results suggest that the lack of tRNA acetylation due to THUMPD1 loss of function results in a syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss, and facial dysmorphism.

Microbially Induced Soil Colloidal Phosphorus Mobilization Under Anoxic Conditions.

Understanding the behavior of colloidal phosphorus (Pcoll) under anoxic conditions is pivotal for addressing soil phosphorus (P) mobilization and transport and its impact on nutrient cycling. Our study investigated Pcoll dynamics in acidic floodplain soil during a 30-day flooding event. The sudden oxic-to-anoxic shift led to a significant rise in pore-water Pcoll levels, which exceeded soluble P levels by more than 2.7-fold. Colloidal fractions transitioned from dispersed forms (<220 nm) to colloid-associated microaggregates (>220 nm), as confirmed by electron microscopy. The observed increase in colloidal sizes was paralleled by their heightened ability to form aggregates. Compared to sterile control conditions, anoxia prompted the transformation of initially dispersed colloids into larger particles through microbial activity. Curiously, the 16S rRNA and ITS microbial diversity analysis indicated that fungi were more strongly associated with anoxia-induced colloidal release than bacteria. These microbially induced shifts in Pcoll lead to its higher mobility and transport, with direct implications for P release from soil into floodwaters.

Development of new thieno[2,3-d]pyrimidines as dual EGFR and STAT3 inhibitors endowed with anticancer and pro-apoptotic activities.

In part due to the resilience of cellular feedback pathways that develop therapeutic resistance to targeting the EGFR alone, using EGFR inhibitors alone was demonstrated to be unsuccessful in clinical trials. The over-activation of the signal transducer/activator of transcription 3 (STAT3) during the administration of an EGFR inhibitor is expected to play a substantial part in the failure and resistance of EGFR inhibitor treatment. Therein, we proposed a hypothesis that induced STAT3-mediated resistance to EGFR inhibition therapy could be addressed by a dual inhibition of EGFR and STAT3 method. To this end, we tried to discover new thieno[2,3-d]pyrimidine derivatives "5a-o". Results from the screening on A549 and MCF7 cancer cell lines revealed that compounds 5j and 5k showed two-digit nanomolar with appropriate safety towards the WI-38 cell line. The best molecules, 5j and 5k, were subjected to γ-radiation, and their cytotoxic efficacy didn't change after irradiation, demonstrating that not having to use it avoided its side effects. Compounds 5j and 5k demonstrated the highest inhibition when their potency was tested as dual inhibitors on EGFR 67 and 41 nM, respectively, and STAT3 5.52 and 3.34 nM, respectively, proved with in silico molecular docking and dynamic simulation. In light of the results presented above, the capacity of both powerful compounds to alter the cell cycle and initiate the apoptotic process in breast cancer MCF7 cells was investigated. Caspase-8, Bcl-2, Bax and Caspase-9 apoptotic indicators were studied.

Electroactive Brevundimonas diminuta consortium mediated selenite bioreduction, biogenesis of selenium nanoparticles and bio-electricity generation.

In this study, highly selenite-resistant strains belonging to Brevundimonas diminuta (OK287021, OK287022) genus were isolated from previously operated single chamber microbial fuel cell (SCMFC). The central composite design showed that the B. diminuta consortium could reduce selenite. Under optimum conditions, 15.38 Log CFU mL-1 microbial growth, 99.08% Se(IV) reduction, and 89.94% chemical oxygen demand (COD) removal were observed. Moreover, the UV-visible spectroscopy (UV) and Fourier transform infrared spectroscopy (FTIR) analyses confirmed the synthesis of elemental selenium nanoparticles (SeNPs). In addition, transmission electron microscopy (TEM) and scanning electron microscope (SEM) revealed the formation of SeNPs nano-spheres. Besides, the bioelectrochemical performance of B. diminuta in the SCMFC illustrated that the maximum power density was higher in the case of selenite SCMFCs than those of the sterile control SCMFCs. Additionally, the bioelectrochemical impedance spectroscopy and cyclic voltammetry characterization illustrated the production of definite extracellular redox mediators that might be involved in the electron transfer progression during the reduction of selenite. In conclusion, B. diminuta whose electrochemical activity has never previously been reported could be a suitable and robust biocatalyst for selenite bioreduction along with wastewater treatment, bioelectricity generation, and economical synthesis of SeNPs in MFCs.

Effect of prosthetic management of congenital cleft lip and palate on the middle ear function of infants: A clinical trial.

STATEMENT OF PROBLEM: Infants with a cleft palate often experience middle ear disease, a condition of great significance, and early prosthetic management of these infants is essential. However, any correlation between prosthetic palatal obturation and middle ear function is unclear. PURPOSE: The purpose of this clinical trial was to assess whether prosthetic palatal obturation with a feeding appliance prevented or improved middle ear problems in infants with a cleft lip and palate. MATERIAL AND METHODS: Ten infants with congenital cleft lip and palate (20 ears) were referred to the Prosthodontics department immediately after birth. Assessment of the middle ear function by tympanometry as well as hearing quality by auditory brainstem response (ABR) was conducted before the prosthetic treatment (control readings). The middle ear function and hearing quality was followed up after the prosthetic treatment every month until surgical palatal closure (tenth month). The Friedman test was applied to compare data from the various study periods. When the results were significant, the Dunn post hoc test was conducted to compare the control first week readings with those of the later periods (α=.05 for all tests). RESULTS: The preprosthetic readings of tympanometry in the first week were 90% Type A and 10% Type B for both right and left ears. Readings starting from the first to the fifth month revealed no statistically significant differences compared with the first week readings (P>.05). However, tympanometry readings starting from the sixth month (20% Type A and 80% Type B) until the tenth month (90% Type B and 10% Type C) for both ears represented a statistically significant difference compared with the first week readings (P≤.05). The preprosthetic readings of ABR in the first week showed that 90% of ears had normal hearing status and 10% had mild hearing loss. Readings starting from the first until the fifth month revealed no statistically significant differences compared with the first week readings (P>.05). However, ABR readings starting from the sixth month (20% normal hearing, 70% mild hearing loss, and 10% moderate hearing loss) until the tenth month (0% normal hearing, 80% mild hearing loss, and 20% moderate hearing loss) for both ears revealed a statistically significant difference compared with the first week readings (P≤.05). CONCLUSIONS: Prosthetic palatal obturation with a feeding appliance plays a role in delaying rather than preventing the occurrence of otitis media with effusion in infants with a cleft lip and palate and could reduce the need for ventilation tubes.

Effect of prosthetic management and its timing on otological and audiological outcomes in infants with cleft lip and palate: A clinical trial.

PURPOSE: To evaluate how prosthetic management affects the otological and audiological state of infants with cleft lip and palate by preventing or treating otitis media (OM). MATERIALS AND METHODS: Thirty infants with cleft lip and palate (L/P) were assigned to three equal groups according to the age of prosthetic intervention; Group I: immediately after birth, Group II: 2 months old, Group III: 5 months old. Assessment of middle ear function by tympanometry and hearing quality by auditory brainstem response (ABR) under natural sleep was conducted before and after prosthetic treatment every month till 10 months of age. Data from the study groups were compared. RESULTS: No statistically significant differences were found between Gp I and Gp II in the 2nd, 3rd, and 4th months for right and left ears (p > 0.05). In the 5th month, statistically significant differences between the three groups were found in tympanometry for right (p = 0.011) and left (p = 0.024) ears also, in ABR for right (p = 0.007) and left (p = 0.011) ears. Tympanometric readings starting from the 6th till the 10th month showed no statistically significant differences between the three groups (p >0.05). The final ABR outcomes of the 10th month indicated statistically significant differences between the three groups for both ears (p = 0.027). CONCLUSIONS: Early prosthetic care could delay the development of OM, so it could potentially improve the otological and audiological state in infants with cleft L/P. However, prosthetic treatment may not be able to completely prevent or eliminate middle ear disorders.

Expression and purification of the mitochondrial transmembrane protein FAM210A in Escherichia coli.

The protein Family with sequence similarity 210 member A (FAM210A) is a mitochondrial inner membrane protein that regulates the protein synthesis of mitochondrial DNA encoded genes. However, how it functions in this process is not well understood. Developing and optimizing a protein purification strategy will facilitate biochemical and structural studies of FAM210A. Here, we developed a method to purify human FAM210A with deleted mitochondrial targeting signal sequence using the MBP-His10 fusion in Escherichia coli. The recombinant FAM210A protein was inserted into the E. coli cell membrane and purified from isolated bacterial cell membranes, followed by a two-step process using Ni-NTA resin-based immobilized-metal affinity chromatography (IMAC) and ion exchange purification. A pulldown assay validated the functionality of purified FAM210A protein interacting with human mitochondrial elongation factor EF-Tu in HEK293T cell lysates. Taken together, this study developed a method for purification of the mitochondrial transmembrane protein FAM210A partially complexed with E.coli derived EF-Tu and provides an opportunity for future potential biochemical and structural studies of recombinant FAM210A protein.

Statistical optimization of waste molasses-based exopolysaccharides and self-sustainable bioelectricity production for dual chamber microbial fuel cell by Bacillus piscis.

BACKGROUND: The application of exopolysaccharide-producing bacteria (EPS) in dual chamber microbial fuel cells (DCMFC) is critical which can minimize the chemical oxygen demand (COD) of molasses with bioelectricity production. Hence, our study aimed to evaluate the EPS production by the novel strain Bacillus piscis by using molasses waste. Therefore, statistical modeling was used to optimize the EPS production. Its structure was characterized by UV, FTIR, NMR, and monosaccharides compositions. Eventually, to highlight B. piscis' adaptability in energy applications, bioelectricity production by this organism was studied in the BCMFC fed by an optimized molasses medium. RESULTS: B. piscis OK324045 characterized by 16S rRNA is a potent EPS-forming organism and yielded a 6.42-fold increase upon supplementation of molasses (5%), MgSO4 (0.05%), and inoculum size (4%). The novel exopolysaccharide produced by Bacillus sp. (EPS-BP5M) was confirmed by the structural analysis. The findings indicated that the MFC's maximum close circuit voltage (CCV) was 265 mV. The strain enhanced the performance of DCMFC achieving maximum power density (PD) of 31.98 mW m-2, COD removal rate of 90.91%, and color removal of 27.68%. Furthermore, cyclic voltammetry (CV) revealed that anodic biofilms may directly transfer electrons to anodes without the use of external redox mediators. Additionally, CV measurements made at various sweep scan rates to evaluate the kinetic studies showed that the electron charge transfer was irreversible. The SEM images showed the biofilm growth distributed over the electrode's surface. CONCLUSIONS: This study offers a novel B. piscis strain for EPS-BP5M production, COD removal, decolorization, and electricity generation of the optimized molasses medium in MFCs. The biosynthesis of EPS-BP5M by a Bacillus piscis strain and its electrochemical activity has never been documented before. The approach adopted will provide significant benefits to sugar industries by generating bioelectricity using molasses as fuel and providing a viable way to improve molasses wastewater treatment.

Novel 4-(2-arylidenehydrazineyl)thienopyrimidine derivatives as anticancer EGFR inhibitors: Design, synthesis, biological evaluation, kinome selectivity and in silico insights.

The current study discovered fifteen new thieno[2,3-d]pyrimidine derivatives with potential anticancer action, including 5a-l, 6, and 7a-b. Results from the NCI screening revealed that compounds 5f-i and 7a significantly inhibited the proliferation of MDA-MB-468 cells at mean GI% and GI50 levels. Compared to staurosporine, these compounds (5f-i and 7a) demonstrated better safety towards typical WI-38 cells. Compounds 5g and 7a demonstrated the highest inhibition (two-digit nanomolar) when compared to erlotinib when their potency was tested on EGFR kinase. Considering the outcomes above, 5g was examined for its ability to disrupt the cell cycle with trigger apoptosis in breast cancer MDA-MB-468 cell lines. The apoptosis markers Bax, Bcl-2, Caspase-8, and Caspase-9, were detected. In silico molecular docking and dynamic simulation were used to explainthe biological activities of the most potent compound.

The prevalence of thyroid dysfunction in Jordan: a national population-based survey.

BACKGROUND: The objectives of this study are to assess the prevalence of clinical and subclinical hypo- and hyperthyroidism and their associated factors among Jordanian adults. METHODS: In a cross-sectional population-based survey, a representative sample that included 3753 Jordanian adults was selected from the 12 governorates that represent the three regions of the country, in the year 2017. Sociodemographic and clinical data were obtained and blood samples were collected from all participants. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were measured to evaluate the thyroid function. RESULTS: The overall prevalence of thyroid dysfunction was 11.9%. Around 76% of patients with thyroid dysfunction were previously undiagnosed. The prevalence of hypothyroidism and subclinical hypothyroidism was 3.1 and 5.3%, respectively. The prevalence of hyperthyroidism and subclinical hyperthyroidism was 1.0 and 2.5%, respectively. Female preponderance which was mainly related to hypothyroid disorders was evident. The prevalence of positive TPOAb and TgAb in the study population was 14.9 and 15.3%, respectively. The prevalence of detectable TPOAb and TgAb in the euthyroid participants was10.3 and 11.9%, respectively. Logistic regression analysis revealed that female sex, age ≥ 50 years and the presence of TgAb and TPOAb were strongly associated with hypothyroidism. Hyperthyroidism was significantly associated with the presence of TPOAb and age ≥ 50 years. CONCLUSION: The prevalence of unrecognized thyroid dysfunction is high among Jordanians. A public health policy of screening high risk groups particularly those ≥50 years of age is recommended.

Facial Asymmetry in Children With Unilateral Congenital Ptosis.

PURPOSE: To analyze facial asymmetry in children with unilateral congenital ptosis. METHODS: This is a retrospective review of pediatric patients undergoing ptosis repair between January 1, 2017, and December 31, 2020. Charts were reviewed to ensure a diagnosis of idiopathic unilateral congenital ptosis. Sex, age, laterality, margin to reflex distance 1, levator function, and surgical intervention were collected.Clear preoperative photos without head turn were included. Using the ImageJ software ( nih.gov ), landmarks of the periorbital region, midface, and lower face were marked, and measurements between these landmarks were taken.Two-tailed Student t tests were used to compare measurements between the ptotic and non-ptotic sides. Relationships between different measurements on the same side of the face were analyzed using paired-variable regressions. RESULTS: Forty-four patients with unilateral congenital ptosis were included. The surgical management consisted of Mullerectomy in 9 of 44 (20%), levator resection in 15 of 44 (34%), and frontalis suspension in 20 of 44 (46%) patients. The side of the face with blepharoptosis was found to more often have smaller margin to reflex distance 1 ( p < 0.001), smaller margin to reflex distance 2 ( p < 0.005), smaller horizontal palpebral fissure ( p < 0.05), shorter midface height ( p < 0.001), and a more inferiorly displaced lateral canthus (canthal angle, p < 0.001) relative to the non-ptotic side of the face. The mean head tilt of patients with right sided ptosis (1.37° right tilt) was statistically significantly different from those with left sided ptosis (0.85° left tilt; p = 0.04). CONCLUSIONS: In children with unilateral congenital ptosis, the ptotic side of the face was found to be the nondominant side of the face. Patients were also found to have ipsilateral head tilt.

Performance of loop-mediated isothermal amplification (LAMP) for detection of Schistosoma mansoni infection compared with Kato-Katz and real-time PCR.

The performance of loop-mediated isothermal amplification (LAMP) for detection of Schistosoma mansoni DNA from stool and urine samples in comparison with Kato-Katz and real-time polymerase chain reaction (PCR) was studied. After obtaining informed consent, 50 children participated in the present study and agreed to submit stool and urine samples. Stool samples were examined by Kato-Katz. Both real-time PCR and LAMP techniques were applied on stool and urine samples. The overall prevalence of S. mansoni was 46% in stool and urine samples as detected by the employed techniques, and 90% of cases had light infection intensity. The highest percentage of infection was diagnosed by real-time PCR (44%), followed by Kato-Katz (42%) and LAMP in the stool (36%), while the lowest percentages of infection were diagnosed by real-time PCR and LAMP in urine samples (24% and 14%, respectively). Kato-Katz, real-time PCR and LAMP showed 100% specificity where the sensitivity was 91.3%, 95.7% and 78.3%, respectively, in stool samples. Real-time PCR and LAMP showed lower sensitivity in urine samples. The LAMP assay is a promising technique for S. mansoni diagnosis in endemic countries of moderate and high-intensity infection. Yet, it needs further optimization, particularly in urine samples.

The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract.

MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1ß and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.

Variations in radioiodine ablation: decision-making after total thyroidectomy.

BACKGROUND: The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today. METHODS: We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018.

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.

The Effect of Gonadotropin-Releasing Hormone Analogue on Final Adult Height in Children with Idiopathic Short Stature.

OBJECTIVE: To assess final adult height (FAH) in children with short stature treated with gonadotropin-releasing hormone analogue (GnRHa). METHODS: All patients with idiopathic short stature (ISS) with normally timed puberty and a Tanner stage between 2 and 3, who achieved their FAH between 2005 and 2015, were included in this clinical historical cohort study. Height gain, FAH, and mid-parental height of 28 children with ISS who received GnRHa treatment for 1.8 ± 1.0 years to delay their puberty were compared to 31 untreated children. RESULTS: The FAHs of the treated and the untreated girls were 151.3 ± 5.1 and 146.8 ± 3.8 cm (p = 0.01), respectively. The FAHs of the treated and the untreated boys were 156.4 ± 4.7 and 152.3 ± 5.7 cm (p = 0.111), respectively. The height gain in the treated and the untreated girls was 1.6 ± 7.8 and -3.6 ± 5.7 cm (p = 0.036), respectively. Height gain in the treated and the untreated boys was -5.1 ± 13.6 and -11.5 ± 8.4 cm (p = 0.171), respectively. CONCLUSION: GnRHa therapy has a modest effect in improving FAH in adolescent females with ISS but not in boys.

Sequencing, genome analysis and host range of a novel Ralstonia phage, RsoP1EGY, isolated in Egypt.

A novel Ralstonia phage was isolated from soil in Egypt. It was designated Ralstonia phage RsoP1EGY using our phage identifier naming approach to reflect the phage's bacterial host species, characteristics and origin. When tested, this phage specifically infected only race 3 biovar 2 phylotype IIB sequevar 1, and not non-race 3 biovar 2 strains of Ralstonia solanacearum. The phage has an icosahedral capsid of 60 ± 5 nm in diameter with a short tail of 15 ± 5 nm in length, typical of a podovirus. The genome of RsoP1EGY is 41,297 bp in size, containing 50 open reading frames, with no significant sequence identity to any other reported R. solanacearum or non-Ralstonia phages, except to the recently deposited but unreported and unclassified Ralstonia phage DU_RP_I. RsoP1EGY is the first sequenced and characterized R. solanacearum phage isolated in Egypt.

Prediction of Zika-confirmed cases in Brazil and Colombia using Google Trends.

Zika virus infection in humans has been linked to severe neurological sequels and foetal malformations. The rapidly evolving epidemics and serious complications made the frequent updates of Zika virus mandatory. Web search query has emerged as a low-cost real-time surveillance system to anticipate infectious diseases' outbreaks. Hence, we developed a prediction model that could predict Zika-confirmed cases based on Zika search volume in Google Trends. We extracted weekly confirmed Zika cases of two epidemic countries, Brazil and Colombia. We got the weekly Zika search volume in the two countries from Google Trends. We used standard time-series regression (TSR) to predict the weekly confirmed Zika cases based on the Zika search volume (Zika query). The basis TSR model - using 1-week lag of Zika query and using 1-week lag of Zika cases as a control for autocorrelation - was the best for predicting Zika cases in Brazil and Colombia because it balanced the performance of the model and the advance time in the prediction. Our results showed that we could use Google search queries to predict Zika cases 1 week earlier before the outbreak. These findings are important to help healthcare authorities evaluate the outbreak and take necessary precautions.

Cerebrospinal-fluid drain-related complications in patients undergoing open and endovascular repairs of thoracic and thoraco-abdominal aortic pathologies: a systematic review and meta-analysis.

BACKGROUND: Cerebrospinal-fluid (CSF) drainage is recommended by current guidelines for spinal protection during open and endovascular repairs of thoracic and thoraco-abdominal aortic aneurysms. In the published literature, great variability exists in the rate of CSF-related complications and morbidity. Herein, we perform a systematic review and meta-analysis on the incidence of CSF drainage-related complications, and compare the complication rates between open and endovascular repairs. METHODS: The systematic review was conducted according to the Meta-Analysis of Observational Studies in Epidemiology guidelines. Thirty-four studies (4714 patients) were included in the quantitative analysis. The CSF drainage-related complications were categorised as mild, moderate, and severe. Pooled event rates for each complication category were estimated using a random-effect model. Random-effect uni- and multivariable meta-regression analyses were used to assess the effect of aortic-repair approach (open vs endovascular) and the CSF drainage criteria on CSF drainage-related complications. RESULTS: The pooled event rates were 6.5% [95% confidence interval (CI): 4.3-9.8%] for overall complications, 2% (95% CI: 1.1-3.4%) for minor complications, 3.7% (95% CI: 2.5-5.6%) for moderate complications, and 2.5% (95% CI: 1.6-3.8%) for severe complications. The drainage-related-mortality pooled event rate was 0.9% (95% CI: 0.6-1.4%). The uni- and multivariable meta-regression analyses showed no difference in complication rates between the open and endovascular approaches, or between the different CSF drainage protocols. CONCLUSION: The complication rate for CSF drainage is not negligible. Our results help define a more accurate risk-benefit ratio for CSF drain placement at the time of repair of thoracic and thoraco-abdominal aneurysms.