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Abstract This study aimed to determine whether punitive state alcohol policies targeting pregnant women who drink alcohol are associated with decreased alcohol consumption among pregnant women over time. This study used data from the Pregnancy Risk Assessment Monitoring System (15 states) between 1990 and 2015. A difference-in-difference (DiD) approach was employed to determine whether passage of state laws changed alcohol consumption rates among pregnant women, while controlling for state and time fixed effects. The study specifically examined punitive state alcohol policies that clarify the admissibility of evidence in child welfare proceedings related to prenatal alcohol exposure, focusing on allegations of child abuse, child neglect, child deprivation, or child dependence, as well as proceedings seeking termination of parental rights. Punitive state alcohol policies were not significantly associated with decreased rates of alcohol consumption among pregnant women (+ 1.54%, 95% CI, -1.47-4.55), within 3 years of implementation. State alcohol policies that adopted a punitive stance toward pregnant women who drink alcohol did not result in the reduction of drinking during pregnancy. Given that punitive policies may not effectively reduce alcohol consumption during pregnancy, our findings highlight the need for reevaluation and potential reform to better address maternal/child health outcomes.

Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication.

ABSTRACTHepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.IMPORTANCEThe hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as “Deltacron.” We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

Abstract Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb). Here, we present a plasmid-based viral genome assembly and rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.

The present study examines import determinants of Pakistan with the top 28 trade partners from 2002 to 2018. To achieve this objective, the augmented gravity model of trade has been applied by incorporating both time-variant and time-invariant variables. In addition, the analysis quantifies the impact of free trade agreements (FTA) signed by Pakistan with China and other trade partners. The results show that along with income and distance, FTA, common language, and common border plays an essential role in imports of Pakistan with its main trade partners. In addition to identifying trade determinants, the impact of adherence to a particular trade agreement was also examined. The results indicate that FTA signed by Pakistan with China and other trade partners has created trade opportunities for participating countries, highlighting the importance of trade liberalization for the long-run development of the country.

Structural systems for tall buildings have gone through an evolutionary process. The rigid frame became popular in the first half of the 20th century but proved to be structurally inefficient beyond a certain height of tall buildings. The invention of the tubular structure in the 1960s allowed buildings to be built taller with low material consumption. Due to the obstructive nature of the closely spaced exterior columns of framed tubes and bracings of braced tubes, the core-outrigger system gained acceptance by the architects as it allowed them to freely articulate the façade design. However, the conventional tubular structures continued to retain their use for tall buildings to a lesser degree and later underwent a resurgence in modified forms. These and other advanced tubular forms in cutting-edge structural systems developed later continue to find application in modern times. This study presents a detailed narrative of different structural systems for tall buildings that is expected to assist structural engineers and architects to collaboratively select appropriate structural systems for tall buildings.

Background: Severe maternal morbidity (SMM) is considered as a near miss for maternal death, therefore it is crucial to identify and prevent SMM. Medical insurance claims can be used to identify SMM. There was a national transition from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to International Classification of Diseases, 10th Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) in October 2015. Objective: This study investigates the impact of transition from ICD-9-CM to ICD-10-CM on the rates of SMM in the state of Arkansas using birth certificates linked with insurance claims data in the Arkansas All-Payer Claims Database (APCD). Study Design: Birth certificates between January 1, 2013, and December 31, 2017, were linked to insurance claims data from the APCD. SMM was defined using the algorithm provided by the Centers for Disease Control and Prevention, using ICD-9 codes for births before October 1, 2015, and ICD-10-CM codes for births on or after October 1, 2015. Results: The incidence of SMM increased after transition to the ICD-10-CM system in Arkansas. The relatively higher rate of SMM in ICD-10-CM versus ICD-9-CM was greater in magnitude on the delivery day and throughout the 42-day postpartum period (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.20?1.42) compared with the rate on the day of delivery (OR: 1.20; 95% CI: 1.06?1.36). When excluding blood transfusions, the higher rate of SMM during the ICD-10 era was even greater both in the delivery day and 42-day postpartum period (OR: 1.66; 95% CI: 1.49?1.85) and on the day of delivery (OR: 1.58; 95% CI: 1.31?1.90).

Abstract Complement activation plays a critical role in the pathogenesis of Guillain-Barré syndrome (GBS), a debilitating immune-mediated neuropathy. Mannose-binding lectin (MBL) is a complement activation factor of lectin pathway which as genetic host factor may influence the susceptibility or severity of GBS. We investigated the frequency of MBL2 promoter (− 550H/L and − 221X/Y) and functional region (exon 1 A/O) polymorphisms and their association with disease susceptibility, clinical features and serum MBL among GBS patients (n = 300) and healthy controls (n = 300) in Bangladesh. The median patient age was 30 years (IQR: 18–42; males, 68%). MBL2 polymorphisms were not significantly associated with GBS susceptibility compared to healthy controls. HL heterozygosity in GBS patients was significantly associated with mild functional disability at enrolment (P = 0.0145, OR, 95% CI 2.1, 1.17–3.82). The HY, YA, HA and HYA heterozygous haplotypes were more common among mildly affected (P = 0.0067, P = 0.0086, P = 0.0075, P = 0.0032, respectively) than severely affected patients with GBS. Reduced serum MBL was significantly associated with the LL, OO and no HYA variants and GBS disease severity. No significant association was observed between MBL2 polymorphisms and electrophysiological variants, recent Campylobacter jejuni infection or anti-ganglioside (GM1) antibody responses in GBS. In conclusion, MBL2 gene polymorphisms are related to reduced serum MBL and associated with the severity of GBS.

Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1's diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2–pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.

Design priorities for tall and supertall buildings have for some time shifted to achieving more energy efficiency to address the energy needs of the increasing global population. Engineers and architects aim to achieve energy conservation through active and passive approaches, pursuing technological innovations and adopting climate-responsive design. Because of the green movement currently dominating the building industry, tall buildings that need a massive amount of energy to build and operate, and the practical desire to switch from non-renewable to clean renewable energy resources, intense attention has been given to the energy efficiency of tall buildings in the recent past. Due to the vast array of energy-efficient design features, equipment, and applications available now, it is timely to examine the pros and cons of these issues. This review paper is an attempt to comprehensively present and deliberate these issues. It illustrates and discusses the concepts and applications through a few case studies from several continents worldwide. The review shows that the design of tall buildings focusing on energy conservation is an evolutionary process and there is a need for further research about how to face the associated challenges to improve energy efficiency by developing creative solutions and strategies, as well as applying additional innovative technologies.

Muhammad Umer, Murtaza Najabat Ali, Aamir Mubashar, Mariam Mir Biomedical Engineering & Sciences Department (BMES), School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad, PakistanCorrespondence: Murtaza Najabat AliBiomedical Engineering & Sciences Department, School of Mechanical and Manufacturing Engineering (SMME) National University of Sciences and Technology (NUST), Sector H-12, Islamabad, PakistanTel +929 085 6053Email murtaza_bme@hotmail.comIntroduction and purpose: For the implantation of a small mechanical supporting device such as a stent, angioplasty is a more reliable technique to regain the perfusion along the heart vessel. This research work demonstrates a relative study for two different stent models during implantation in coronary artery. The purpose of this analysis was to explore the clinical efficiency of a balloon expandable stent deployment employing the finite element method.Methods: The two different models included are the Cypher Bx Velocity® (Bx_Velocity; Johnson & Johnson Corporation, New Brunswick, NJ, USA) and Savior (ST Flex Pro; National Engineering and Scientific Commission, Islambad, Pakistan). As the majority of stents are deployed using an angioplasty balloon guided by a catheter-shaft, in this study, the delivery of stents was governed by a sophisticated balloon of a trifolded pattern, attached to the catheter-shaft. This configuration has often been neglected in the past due to the complexity of interaction and the limitation of computational power.Results: The use of a trifolded semi-compliant balloon gives more promising results for quantification with experimental data available from the manufacturer’s compliance charts. This type of relative study allows us not only to improve the design of the available stent model, but also helps in probing the integrity of newly suggested models and reduces certain risks associated with the angioplasty technique. The following factors, such as stent expansion, foreshortening, dog-boning, elastic recoil, and the distribution of equivalent stresses were used to compare and improve the clinical outcome of the available stent models.Conclusion: The validation of numerical study for the Bx_Velocity stent was made with the manufacturer’s compliance chart data and for the Savior Stent with a report of experimental work data from NESCOM. Finally, some suggestions were made for good deliverability and reliability based on the above design criteria.Keywords: stent, finite element method, trifolded balloon, foreshortening, open-deployment, confined-deployment

Previous studies have evaluated the marginal effect of various factors on the risk of severe maternal morbidity (SMM) using regression approaches. We add to this literature by utilizing a Bayesian network (BN) approach to understand the joint effects of clinical, demographic, and area-level factors. We conducted a retrospective observational study using linked birth certificate and insurance claims data from the Arkansas All-Payer Claims Database (APCD), for the years 2013 through 2017. We used various learning algorithms and measures of arc strength to choose the most robust network structure. We then performed various conditional probabilistic queries using Monte Carlo simulation to understand disparities in SMM. We found that anemia and hypertensive disorder of pregnancy may be important clinical comorbidities to target in order to reduce SMM overall as well as racial disparities in SMM.

Study DesignIn vitro biomechanical investigation.PurposeTo compare the biomechanics of integrated three-screw and four-screw anterior interbody spacer devices and traditional techniques for treatment of degenerative disc disease.Overview of LiteratureBiomechanical literature describes investigations of operative techniques and integrated devices with four dual-stacked, diverging interbody screws; four alternating, converging screws through a polyether-ether-ketone (PEEK) spacer; and four converging screws threaded within the PEEK spacer. Conflicting reports on the stability of stand-alone devices and the influence of device design on biomechanics warrant investigation.MethodsFourteen cadaveric lumbar spines were divided randomly into two equal groups (n=7). Each spine was tested intact, after discectomy (injured), and with PEEK interbody spacer alone (S), anterior lumbar plate and spacer (AP+S), bilateral pedicle screws and spacer (BPS+S), circumferential fixation with spacer and anterior lumbar plate supplemented with BPS, and three-screw (SA3s) or four-screw (SA4s) integrated spacers. Constructs were tested in flexion-extension (FE), lateral bending (LB), and axial rotation (AR). Researchers performed one-way analysis of variance and independent t-testing (p≤0.05).ResultsInstrumented constructs showed significantly decreased motion compared with intact except the spacer-alone construct in FE and AR (p≤0.05). SA3s showed significantly decreased range of motion (ROM) compared with AP+S in LB (p≤0.05) and comparable ROM in FE and AR. The three-screw design increased stability in FE and LB with no significant differences between integrated spacers or between integrated spacers and BPS+S in all loading modes.ConclusionsIntegrated spacers provided fixation statistically equivalent to traditional techniques. Comparison of three-screw and four-screw integrated anterior lumbar interbody fusion spacers revealed no significant differences, but the longer, larger-diameter interbody spacer with three-screw design increased stabilization in FE and LB; the diverging four-screw design showed marginal improvement during AR.

Study DesignResearchers created a proper type II dens fracture (DF) and quantified a novel current posterior fixation technique with spacers at C1–C2. A clinical case study supplements this biomechanical analysis.PurposeResearchers explored their hypothesis that spacers combined with posterior instrumentation (PI) reduce range of motion significantly, possibly leading to better fusion outcomes.Overview of LiteratureLiterature shows that the atlantoaxial joint is unique in allowing segmental rotary motion, enabling head turning. With no intervertebral discs at these joints, multiple ligaments bind the axis to the skull base and to the atlas; an intact odontoid (dens) enhances stability. The most common traumatic injury at these strong ligaments is a type II odontoid fracture.MethodsEach of seven specimens (C0–C3) was tested on a custom-built six-degrees-of-freedom spine simulator with constructs of intact state, type II DF, C1–C2 PI, PI with joint capsulotomy (PIJC), PI with spacers (PIS) at C1–C2, and spacers alone (SA). A bending moment of 2.0 Nm (1.5°/sec) was applied in flexion-extension (FE), lateral bending (LB), and axial rotation (AR). One-way analysis of variance with repeated measures was performed.ResultsDF increased motion to 320%, 429%, and 120% versus intact (FE, LB, and AR, respectively). PI significantly reduced motion to 41%, 21%, and 8%. PIJC showed negligible changes from PI. PIS reduced motion to 16%, 14%, and 3%. SA decreased motion to 64%, 24%, and 54%. Reduced motion facilitated solid fusion in an 89-year-old female patient within 1 year.ConclusionsType II odontoid fractures can lead to acute or chronic instability. Current fixation techniques use C1–C2 PI or an anterior dens screw. Addition of spacers alongside PI led to increased biomechanical rigidity over intact motion and may offer an alternative to established surgical fixation techniques.

ABSTRACT Zika virus (ZIKV) infection of neural progenitor cells (NPCs) in utero is associated with neurological disorders, such as microcephaly, but a detailed molecular understanding of ZIKV-induced pathogenesis is lacking. Here we show that in vitro ZIKV infection of human cells, including NPCs, causes disruption of the nonsense-mediated mRNA decay (NMD) pathway. NMD is a cellular mRNA surveillance mechanism that is required for normal brain size in mice. Using affinity purification-mass spectrometry, we identified multiple cellular NMD factors that bind to the viral capsid protein, including the central NMD regulator up-frameshift protein 1 (UPF1). Endogenous UPF1 interacted with the ZIKV capsid protein in coimmunoprecipitation experiments, and capsid expression posttranscriptionally downregulated UPF1 protein levels, a process that we confirmed occurs during ZIKV infection. Cellular fractionation studies show that the ZIKV capsid protein specifically targets nuclear UPF1 for degradation via the proteasome. A further decrease in UPF1 levels by RNAi significantly enhanced ZIKV infection in NPC cultures, consistent with a model in which NMD restricts ZIKV infection in the fetal brain. We propose that ZIKV, via the capsid protein, has evolved a strategy to lower UPF1 levels and dampen antiviral activities of NMD, which in turn contributes to neuropathology in vivo. IMPORTANCE Zika virus (ZIKV) is a significant global health threat, as infection has been linked to serious neurological complications, including microcephaly. Using a human stem cell-derived neural progenitor model system, we find that a critical cellular quality control process called the nonsense-mediated mRNA decay (NMD) pathway is disrupted during ZIKV infection. Importantly, disruption of the NMD pathway is a known cause of microcephaly and other neurological disorders. We further identify an interaction between the capsid protein of ZIKV and up-frameshift protein 1 (UPF1), the master regulator of NMD, and show that ZIKV capsid targets UPF1 for degradation. Together, these results offer a new mechanism for how ZIKV infection can cause neuropathology in the developing brain.

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication.

ImportanceThe hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.

People with autism spectrum disorder (ASD) experience high rates of psychotropic medication utilization and barriers to psychosocial services, yet limited literature explores use of these services and the association between a mental health condition (MH) and use. Using national multipayer claims data, this study estimates a multinomial logistic regression model to discern psychotropic medication and psychosocial service use among transition age youth (TAY) with ASD (12-26 years; N = 52,083) compared to a matched cohort of those without ASD (12-26 years; N = 52,083). Approximately one-third of TAY with ASD and no MH condition receive only psychotropic medication and the likelihood of using both psychosocial services and medication is higher only when TAY with ASD have a co-occurring MH condition.

The tall building is the most dominating symbol of the cities and a human-made marvel that defies gravity by reaching to the clouds. It embodies unrelenting human aspirations to build even higher. It conjures a number of valid questions in our minds. The foremost and fundamental question that is often asked: Why tall buildings? This review paper seeks to answer the question by laying out arguments against and for tall buildings. Then, it provides a brief account of the historic and recent developments of tall buildings including their status during the current economic recession. The paper argues that as cities continue to expand horizontally, to safeguard against their reaching an eventual breaking point, the tall building as a building type is a possible solution by way of conquering vertical space through agglomeration and densification. Case studies of some recently built tall buildings are discussed to illustrate the nature of tall building development in their respective cities. The paper attempts to dispel any discernment about tall buildings as mere pieces of art and architecture by emphasizing their truly speculative, technological, sustainable, and evolving nature. It concludes by projecting a vision of tall buildings and their integration into the cities of the 21st century.

Minoo Mahshid,1 Aboulfazl Saboury,1 Ali Fayaz,1 Seyed Jalil Sadr,1 Friedrich Lampert,2 Maziar Mir2,31Department of Prosthodontics, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Conservative Dentistry, Aachen RWTH Hospital, Aachen, Germany; 3Beckman Laser Institute, UCI, Irvine, CA, USABackground: Mechanical torque devices (MTDs) are one of the most commonly recommended devices used to deliver optimal torque to the screw of dental implants. Recently, high variability has been reported about the accuracy of spring-style mechanical torque devices (S-S MTDs). Joint stability and survival rate of fixed implant supported prosthesis depends on the accuracy of these devices. Currently, there is limited information on the steam sterilization influence on the accuracy of MTDs. The purpose of this study was to assess the effect of steam sterilization on the accuracy (±10% of the target torque) of spring-style mechanical torque devices for dental implants.Materials and methods: Fifteen new S-S MTDs and their appropriate drivers from three different manufacturers (Nobel Biocare, Straumann [ITI], and Biomet 3i [3i]) were selected. Peak torque of devices (5 in each subgroup) was measured before and after autoclaving using a Tohnichi torque gauge. Descriptive statistical analysis was used and a repeated-measures ANOVA with type of device as a between-subject comparison was performed to assess the difference in accuracy among the three groups of spring-style mechanical torque devices after sterilization. A Bonferroni post hoc test was used to assess pairwise comparisons.Results: Before steam sterilization, all the tested devices stayed within 10% of their target values. After 100 sterilization cycles, results didn't show any significant difference between raw and absolute error values in the Nobel Biocare and ITI devices; however the results demonstrated an increase of error values in the 3i group (P < 0.05). Raw error values increased with a predictable pattern in 3i devices and showed more than a 10% difference from target torque values (maximum difference of 14% from target torque was seen in 17% of peak torque measurements).Conclusion: Within the limitation of this study, steam sterilization did not affect the accuracy (±10% of the target torque) of the Nobel Biocare and ITI MTDs. Raw error values increased with a predictable pattern in 3i devices and showed more than 10% difference from target torque values. Before expanding upon the clinical implications, the controlled and combined effect of aging (frequency of use) and steam sterilization needs more investigation.Keywords: accuracy, steam sterilization, mechanical torque devices, spring-style, dental implants

New developments of tall buildings of ever-growing heights have been continuously taking place worldwide. Consequently, many innovations in structural systems have emerged. This paper presents a retrospective survey of the main structural systems for tall buildings with emphasis on the advancements of recent, emerging, and potentially emerging systems. A structural systems chart that was previously developed by the authors has been updated in this paper to recognize, categorize and add the more recent structural systems. Recent trends of tubular structural systems in modified forms including the braced megatubes and diagrids are presented. Core-outrigger structural systems are discussed with emphasis on their adaptability. The potential of employing superframes for stand-alone and conjoined megatall buildings is predicted. As a means to solve today’s various project-specific complex design requirements, different mixed structural systems for supertall and megatall buildings are presented. This paper also discusses the widespread application of composite structural systems and recent trends of concrete cores for contemporary tall buildings. Finally, the future of tall buildings is predicted as the race for height continues.

Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

Background: Nasogastric tube (NG tube) usage was first described in 1921 by Levin. Surgeons routinely use NG tube in most esophageal resections. Considering the numerous complications caused by this tube, the uncertainty about its usefulness and the scarcity of studies conducted on the subject, particularly in esophageal cancer patients, we investigated the necessity of the NG tube in these cases.Methods: This clinical trial was performed at the Cancer Institute of Imam Khomeini Hospital. Esophageal cancer patients were randomized into groups either with or without postoperative NG tube; the latter group was also prescribed metoclopramide. Postoperative obstruction was the exclusion criteria. The operation was done by a team of surgeons using the surgical techniques of McKeown or Orringer. All patients received ranitidine, heparin and antibiotics postoperatively. All patients received postoperative chest X-ray and chest physiotherapy. The NG tube was inserted or reinserted for those with abdominal distention and/or repeated vomiting. The NG tube was pulled out after return of bowel movements. The variables recorded for each patient included the first day of flatus, the first day of defecation, the first day of bowel sound (BS) upon auscultation, duration of post-operative hospitalization, nausea and vomiting, abdominal distension, pulmonary complications, wound complications, anastomotic leakage and the need for placing/replacing the NG tube. Statistical analysis was performed using SPSS, v. 11.5.Results: After randomization, the NG tube was inserted for 22 patients, and 18 patients had no NG tube. The incidence of anastomotic leakage was significantly higher in the NG-tube group. No significant differences between the two groups were found for other complications. The mean times until first passage of flatus, defecation and BS upon auscultation and the duration of post-operative hospitalization were not significantly different. The need for placing/replacing the NG tube was the same for both groups. There was no difference in the perioperative death rates between the two groups.Conclusions: We conclude that the routine use of NG tubes after surgery is not recommended for all patients. NG tube should be used according to the specific needs of each patient. This protocol will protect patients from undesired complications.

Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1's diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.

Informations regarding 152 patients of cancer of tongue in cancer institute from 1978 to 1998 was collected and analyzed. From these cases, 53.3 percent were male with a mean age of 54.49 years (SD=16.23) and the mean age of female was 2.5 years more than of male. Positive lymphadenopathy in men was positive and significantly more than that of female (P

In this paper, factors affecting the result of prophylactic lymph node dissection in 125 patients with skin melanoma during the period between 1987-1992 in the cancer institute were evaluated and prognostic parameters ascertained. The result showed prevalence of head and neck melanoma in men were two times more than in women with a preponderance of regional and lymphatic recurrence. Majority of patients presented with advanced clark levels (76.8 Pct). Clinical and histologic evaluation of the regional lymph nodes failed to show any meaningful relation.

The purpose of the study is to explore the relationship between individuals' perceptions of their weight-status, self-reported height and weight, and measured weight status.A national survey of 9,248 adolescents (47% male) between the ages of 11 and 27 is analyzed to determine whether inaccuracies in reporting are caused by misperception or conscious intent, and whether there tends to be a systematic bias in how individuals self-report. Self-esteem was used as an example of an important outcome variable in order to illustrate the magnitudes of the biases that may arise when using different measures of body size.Our results indicate that measured obesity status is associated with the reduction in Rosenberg Self-Esteem (RSE) of 0.30 points (p-value 0.005) among adolescents and 0.20 points (p-value 0.002) among young adults; in addition, using self-reported height and weight as opposed to measured height and weight does not result in a statistically detectable difference in the estimates.Individuals' self-reports of height and weight are not as unreliable as we might have expected. Although estimates from measured height and weight are preferred, in the absence of such measures, self-reported measures would likely be a reliable alternative. The differences in self-perception of weight status, however, imply that it is not comparable to measured weight categories.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains extensive sequence changes relative to the earlier-arising B.1, B.1.1, and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (VLPs), we examined mutations in all four structural proteins and found that Omicron and Delta showed 4.6-fold higher luciferase delivery overall relative to the ancestral B.1 lineage, a property conferred mostly by enhancements in the S and N proteins, while mutations in M and E were mostly detrimental to assembly. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in eight out of eight subjects compared to one out of eight preboosting. Furthermore, the monoclonal antibody therapeutics casirivimab and imdevimab had robust neutralization activity against B.1 and Delta VLPs but no detectable neutralization of Omicron VLPs, while newly authorized bebtelovimab maintained robust neutralization across variants. Our results suggest that Omicron has similar assembly efficiency and cell entry compared to Delta and that its rapid spread is due mostly to reduced neutralization in sera from previously vaccinated subjects. In addition, most currently available monoclonal antibodies will not be useful in treating Omicron-infected patients with the exception of bebtelovimab.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

Inhibitors of bromodomain and extraterminal domain (BET) proteins are possible anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here we show that BET proteins should not be inactivated therapeutically because they are critical antiviral factors at the post-entry level. Depletion of BRD3 or BRD4 in cells overexpressing ACE2 exacerbates SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection and not before. Viral replication and mortality are also enhanced in BET inhibitor-treated mice overexpressing ACE2. BET inactivation suppresses interferon production induced by SARS-CoV-2, a process phenocopied by the envelope (E) protein previously identified as a possible "histone mimetic." E protein, in an acetylated form, directly binds the second bromodomain of BRD4. Our data support a model where SARS-CoV-2 E protein evolved to antagonize interferon responses via BET protein inhibition; this neutralization should not be further enhanced with BET inhibitor treatment.