Comparative Evaluation of Sorption and Solubility of Core Buildup Materials in Different pH Media: An In-Vitro Study.

AIM: To evaluate and compare the sorption and solubility of two different core buildup materials in different pH media for periods of one day, one week, and one month. MATERIALS AND METHOD: Sixty samples were prepared and divided into Group A (30 resin-based samples) and Group B (30 glass ionomer cement (GIC)-based samples). The sorption and solubility of the different materials were calculated by weighing the samples before and after desiccation and media immersion for periods of one day, one week, and one month. Groups were compared using the Mann-Whitney U test, and for different media, the intragroup significance of the mean difference was performed using the Friedmann test and Wilcoxon signed rank test at a significance level of p<0.05. RESULTS: After immersion for different time periods, the resin-based core buildup material (Core X flow) showed less sorption and solubility as compared to the glass ionomer-based core buildup material (Secure Core Z) for all time periods, with a significant difference seen for a time period of one week and one month and being nonsignificant for a time period of one day. CONCLUSION: Core X flow had lower sorption and solubility values when compared to Secure Core Z, as per the International Organization for Standardization (ISO) 4049 standards, except for a one-month time period in alkaline media.

Intranasal Vaccination with a Respiratory-Syncytial-Virus-Based Virus-like Particle Displaying the G Protein Conserved Region Induces Severe Weight Loss and Pathology upon Challenge with Wildtype Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease worldwide, and a pediatric vaccine is not available. We generated a filamentous RSV-based virus-like particle (VLP) that presents the central conserved region of the attachment protein G. This was achieved by co-expressing the matrix protein, phosphoprotein, nucleoprotein, and a hybrid fusion protein in which the F ectodomain was replaced with the G central region (GCR). The latter is relatively conserved and contains a receptor binding site and hence is a logical vaccine target. The immunogenicity and efficacy of the resulting VLP, termed VLP-GCR, were examined in mice using intranasal application without adjuvant. VLP-GCR induced substantial anti-N antibody levels but very low anti-G antibody levels, even after three vaccinations. In contrast, a VLP presenting prefusion-stabilized fusion (preF) protein instead of GCR induced both high anti-F and anti-nucleoprotein antibody levels, suggesting that our GCR antigen was poorly immunogenic. Challenge of VLP-GCR-vaccinated mice caused increased weight loss and lung pathology, and both VLPs induced mucus in the lungs. Thus, neither VLP is suitable as a vaccine for RSV-naive individuals. However, VLP-preF enhanced the proportion of preF antibodies and could serve as a multi-antigen mucosal booster vaccine in the RSV-experienced population.

Midterm outcomes of one anastomosis gastric bypass for patients with BMI < 35 kg/m2 from a large single center.

BACKGROUND: One-anastomosis gastric bypass (OAGB) is gaining more attention in patients with severe obesity and recently is used for patients with body mass index (BMI) < 35 kg/m2. In this 5-year single center experience we aim to report our outcomes of using OAGB for patients with BMI < 35 kg/m2. METHODS: This is a retrospective analysis of prospectively collected data recorded in to our national obesity registry database. Variables including age, sex, weight, BMI, any associated disease, blood levels of metabolic markers, nutrients, and vitamins before and after surgery were extracted and analyzed. RESULTS: 173 patients with mean age and BMI of 41 ± 10 years and 33 ± 1 kg/m2 underwent OAGB and at least one of the obesity-associated medical problems was found in 88 (50.5%) of them preoperatively. The mean duration of surgery and length of hospital stay were 60.7 ± 7.4 min and 1.3 ± 1.4 days. 78% and 70% of patients had available data at 24 and 60 months, respectively. The mean BMI was 23.9 ± 2.2 kg/m2 1 year after surgery and each year after that till 5 years was 24 ± 2, 24.4 ± 2.6, 25.1 ± 2.7, and 25.5 ± 2.7 kg/m2. Significant improvement in levels of fasting blood glucose, lipid profile, and liver enzymes were observed. CONCLUSION: OAGB for BMI < 35 kg/m2 has significant effects in weight loss, helps remit diabetes and hypertension in the majority of cases, improves lipid profile, and has no increased burden of postoperative problems or deficiency in nutritional factors rather than what is known and predictable.

Safety and feasibility pilot study of continuous low-dose maternal supplemental oxygen in fetal single ventricle heart disease.

OBJECTIVES: Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth but current evidence on dosing, candidacy, and outcomes are limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP. METHODS: This single-centre, open-label, pilot phase 1 safety and feasibility clinical trial included 25 pregnant individuals with a fetal diagnosis of SVP. Participants self-administered continuous supplemental oxygen using medical-grade oxygen concentrators for up to 24 hours per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation by echocardiography and late-gestational cardiovascular magnetic resonance, early outcomes including brain growth and pre-operative brain injury, and 18-month neurodevelopmental outcomes by the Bayley Scales of Infant and Toddler Development 3rd Edition compared to a contemporary fetal SVP cohort that received standard of care (SOC). RESULTS: Among 25 participants, the average maternal age at conception was 35 years, and fetal SVP diagnoses included 16 right ventricle dominant, 8 left ventricle dominant, and 1 indeterminant ventricular morphology. Participants started the trial at approximately 29.3 gestational weeks and took MSO for a median 16.1 hours per day for 63 days, cumulating a median 1029 hours of oxygen intake from enrollment until delivery. The only treatment-associated adverse events were nasal complications that were typically resolved by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio, nor head circumference to abdominal circumference ratio Z-scores over gestation compared to SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over gestation compared to SOC (p=0.02), this was likely due to initial baseline differences in placental resistance. At late-gestational cardiovascular magnetic resonance, MSO was not associated with any significant increase in umbilical vein oxygen saturation, fetal oxygen delivery, or fetal cerebral oxygen delivery. Similarly, we observed no differences in newborn outcomes including brain volume and pre-operative brain injury, nor mortality by 18 months of age, nor neurodevelopmental outcomes at 18 months of age. CONCLUSIONS: This pilot phase 1 clinical trial indicates low-dose maternal supplemental oxygen therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with any significant changes in fetal circulatory physiology or improvements in early neurologic or neurodevelopmental outcomes. This article is protected by copyright. All rights reserved.

Imaging Acute Myocarditis with 68Ga-DOTANOC PET/CT.

Somatostatin receptor (SSTR) imaging is a useful method in the diagnosis of acute myocarditis. We present a case of a 54-year-old male with a clinical diagnosis of acute myocarditis in whom, 68Ga-DOTANOC positron emission tomography/computed tomography PET/CT showed diffuse left ventricular myocardial uptake. SSTR imaging can act as a surrogate marker of active inflammation. SSTR imaging is useful in deciding site of biopsy, assessing response to therapy and for prognostication.

Highly stable, non-toxic and functionalized nanoemulsion for the early diagnosis and amelioration of cancer.

Aim: To overcome the limitations associated with conventional formulations for cancer treatment by the effective utilization of nanoemulsion with therapy and diagnosis through the single unit. Patent: US20210275687 describes the usage of functionalized various oil-in-water nanoemulsions as pharmacological vehicles with theranostic potential in cancer treatment. Materials & methods: Vitamin E, oleic acid, sphingomyelin, ligands for functionalization, contrast agents and therapeutic biomolecules. Results: The toxicity studies conducted on healthy mice did not show any apparent toxicity issues. The stability studies conducted at 40 °C and 75% relative humidity, which is mandatory for regulatory approval, indicated the adequate physical stability of the formulation. Conclusion: The studies exhibited the promising theranostic potential of the developed nanoemulsion for the effective management and diagnosis of cancer and metastatic diseases.

A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts.

The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.

Potential of novel self-assembled functionalized carbon nanotubes for selective tumor targeting.

Conventional cancer therapies are associated with toxicity toward healthy cells, which need to be addressed by novel therapeutic approaches. US2021/0230592 patent application discloses a carbon nanotube-based approach for tumor targeting, wherein a self-assembling single-wall nanotube complex has been developed and functionalized to deliver a molecule to a cancerous cell. The radiolabeled nanotubes exhibited markedly reduced toxicity as they did not depict any 'over toxicity' up to radioactivity value of 1350 nCi. The single-wall carbon nanotube conjugates were covalently connected to several chelators, therapeutic or diagnostic radionuclides, and showed promising results in the effective cancer management. Besides, this invention with further modifications paves an ideal pathway to researchers in effective diagnosis and treatment of cancer.

Sustained drug delivery strategies for treatment of common substance use disorders: Promises and challenges.

Substance use disorders (SUDs) are a leading cause of death and other ill health effects in the United States and other countries in the world. Several approaches ranging from detoxification, behavioral therapy, and the use of antagonists or drugs with counter effects are currently being applied for its management. Amongst these, drug therapy is the mainstay for some drug abuse incidences, as is in place specifically for opioid abuse or alcohol dependence. The severity of the havocs observed with the SUDs has triggered constant interest in the discovery and development of novel medications as well as suitable or most appropriate methods for the delivery of these agents. The chronic need of such drugs in users warrants the need for their prolonged or sustained systemic availability. Further, the need to improve patient tolerance to medication, limit invasive drug use and overall treatment outcome are pertinent considerations for embracing sustained release designs for medications used in managing SUDs. This review aims to provide an overview on up-to-date advances made with regards to sustained delivery systems for the drugs for treatment of different types of SUDs such as opioid, alcohol, tobacco, cocaine, and cannabis use disorders. The clinical relevance, promises and the limitations of deployed sustained release approaches along with future opportunities are discussed.

A Case of Transvaginal Small Bowel Evisceration following Hysterectomy with Discussion of Emergency Department Diagnosis and Management.

Transvaginal small bowel evisceration is a rare surgical emergency that requires urgent surgery to prevent bowel necrosis, sepsis, and death. It was first reported in 1864 by Hyernaux with less than 100 cases reported since the original publication. The overall mortality rate is reported as 5.6 percent. We present the case of a 49-year-old woman who presented to the emergency department with a chief complaint of moderate abdominal pain and vaginal bleeding for 1 hour. The patient reported that she underwent a robotic-assisted laparoscopic hysterectomy 11 weeks prior for uterine fibroids. Visual examination revealed a loop of the small bowel coming from the superior aspect of her vagina. Literature reviews have noted a higher incidence of dehiscence following robotic-assisted total laparoscopic hysterectomy. It is important for the emergency physician to make the diagnosis, initiate prompt consultation with departments of obstetrics and gynecology and general surgery, and treat for potential infection.

A Prospective, Nonrandomized, Open-label Study, Comparing the Efficacy, Safety, and Tolerability of Fractional CO2 Laser versus Fractional Microneedling Radio Frequency in Acne Scars.

BACKGROUND: Acne scar is a distressing psychosocial problem, and it has a negative effect on the quality of life. Although variety of approaches are available, demand of less invasive and more effective ways for their treatment is needed. OBJECTIVE: This study aimed to assess and compare the clinical safety, efficacy, and tolerability of fractional carbon dioxide (FCO2) laser versus fractional microneedling radio frequency (MNRF) in the management of acne scars. MATERIALS AND METHODS: This study was a prospective, observational, nonrandomized, open-labeled study of total 50 patients selected according to Goodman and Baron global qualitative acne scar grading, and they were divided into two groups of 25 each, having Fitzpatrick skin type III-V. A total of four sessions were given for both the groups at an interval of 2 months. The assessment was done by the treating physician as well as by the blinded physician. Both the subjective and the objective assessment was done at the last follow up given at second month of the fourth session. RESULTS: The mean score of 25 patients in each group of FCO2 and fractional MNRF, decreased from 29.24 to 10.7 (i.e., 63.41%) and from 33.24 to 13.04 (i.e., 60.72%), respectively, as calculated by Goodman and Baron quantitative grading assessed by the treating physician (P = 0.0001). Grade 4 (>75%) improvement was shown by four patients and Grade 3 improvement (51%-75%) was shown by 14 patients among FCO2 group, and similarly Grade 4 (>75%) improvement was shown by three patients and Grade 3 improvement (51%-75%) was shown by 12 patients among MNRF group, as observed by a blinded physician (P = 0.689). CONCLUSION: Both modalities are equally effective in the treatment of acne scars; however, fractional MNRF having lesser down time and Post inflammatory hyperpigmentation (PIH) among darker skin shades, with good patient satisfaction score, makes it an efficient and safer treatment option as compared to FCO2.

NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation.

Chikungunya virus (CHIKV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. Within the last 2 decades, CHIKV has expanded its presence to both hemispheres and is currently circulating in both Old and New Worlds. Despite the severity and persistence of the arthritis it causes in humans, no approved vaccines or therapeutic means have been developed for CHIKV infection. Replication of alphaviruses, including CHIKV, is determined not only by their nonstructural proteins but also by a wide range of host factors, which are indispensable components of viral replication complexes (vRCs). Alphavirus nsP3s contain hypervariable domains (HVDs), which encode multiple motifs that drive recruitment of cell- and virus-specific host proteins into vRCs. Our previous data suggested that NAP1 family members are a group of host factors that may interact with CHIKV nsP3 HVD. In this study, we performed a detailed investigation of the NAP1 function in CHIKV replication in vertebrate cells. Our data demonstrate that (i) the NAP1-HVD interactions have strong stimulatory effects on CHIKV replication, (ii) both NAP1L1 and NAP1L4 interact with the CHIKV HVD, (iii) NAP1 family members interact with two motifs, which are located upstream and downstream of the G3BP-binding motifs of CHIKV HVD, (iv) NAP1 proteins interact only with a phosphorylated form of CHIKV HVD, and HVD phosphorylation is mediated by CK2 kinase, and (v) NAP1 and other families of host factors redundantly promote CHIKV replication and their bindings have additive stimulatory effects on viral replication. IMPORTANCE Cellular proteins play critical roles in the assembly of alphavirus replication complexes (vRCs). Their recruitment is determined by the viral nonstructural protein 3 (nsP3). This protein contains a long, disordered hypervariable domain (HVD), which encodes virus-specific combinations of short linear motifs interacting with host factors during vRC assembly. Our study defined the binding mechanism of NAP1 family members to CHIKV HVD and demonstrated a stimulatory effect of this interaction on viral replication. We show that interaction with NAP1L1 is mediated by two HVD motifs and requires phosphorylation of HVD by CK2 kinase. Based on the accumulated data, we present a map of the binding motifs of the critical host factors currently known to interact with CHIKV HVD. It can be used to manipulate cell specificity of viral replication and pathogenesis, and to develop a new generation of vaccine candidates.

Areas of Non-Consensus Around One Anastomosis/Mini Gastric Bypass (OAGB/MGB): A Narrative Review.

PURPOSE: One anastomosis/mini gastric bypass (OAGB/MGB) is now an established bariatric and metabolic surgical procedure with good outcomes. Despite two recent consensus statements around OAGB/MGB, there are some issues which are not accepted as consensus and need more long-term data and research. MATERIAL AND METHODS: After identifying the topic of non-consensus from the two recent OAGB/MGB consensuses, PubMed, Scopus, and Cochrane were searched for articles published by November 2020. RESULTS: In this study, we evaluated these non-consensus topics around OAGB/MGB and all related articles on these topics were assessed by authors to have an argument on these items. CONCLUSION: There is enough evidence to include OAGB/MGB as an accepted standard bariatric and metabolic surgical procedure. However, long-term data and more research are needed to have a consensus in all aspects including these non-consensus topics.

A Global Survey by the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) on Perceptions of Bariatric Medical Tourism (BMT) by Health Professionals: Guidelines from IFSO for BMT.

BACKGROUND: Bariatric medical tourism (BMT) is a rapidly expanding industry, with over 650 million people with obesity worldwide and total number rising by over 300% between 2003 and 2014. The overall health tourism industry is worth over $400 billion/year. METHODS: International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) conducted a global survey to analyze the details of BMT and the perceptions of bariatric health care professionals (HCP) regarding BMT. RESULTS: A total of 383 bariatric HCP's with experience of 272,548 procedures responded from 65 countries. Seventy-three percent of respondents had managed BMT patients, whilst low cost of surgery was felt to be the driving factor in 77% of cases. The USA contributed the most patients travelling for BMT with 11.6%. Twenty-four percent of respondents stated that they had no access to adequate notes regarding the patient's operation, whilst 12% felt BMT is associated with a higher mortality. Only 49% of respondents felt that IFSO guidelines were followed by the operating surgeon. Sleeve gastrectomy was the commonly offered surgery and an overall mean operation cost was $8716. Nearly 64% of respondents felt BMT needed better coordination between practitioners, whilst almost 85% of respondents supported the idea of a forum to facilitate safe BMT worldwide. CONCLUSION: This IFSO survey has outlined the current BMT trends worldwide and highlighted areas of concern in the care of such patients. It has expanded our knowledge and should be used as a starting point to establish international forums to aid collaboration.

One Anastomosis/Mini Gastric Bypass (OAGB-MGB) as revisional bariatric surgery after failed primary adjustable gastric band (LAGB) and sleeve gastrectomy (SG): A systematic review of 1075 patients.

BACKGROUND: One Anastomosis/Mini Gastric Bypass (OAGB-MGB) is rapidly gaining popularity and is now the third common bariatric procedure performed in the world. The aim of this review is to look at the role of this operation as a revisional bariatric surgery (RBS). METHODS: Literature review was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and the AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. Total 17 studies were eligible. RESULTS: This review reports cumulative results of 1075 revisional OAGB-MGB procedures. Primary procedures included gastric banding (LAGB), Sleeve gastrectomy (SG), vertical banded gastroplasty (VBG) and gastric plication. The mean age was 43.1 years and female to male ratio was 3.04: 1. The body mass index (BMI) at primary procedure was 47.05 kg/m2. The mean BMI at revisional surgery was 41.6 kg/m2 (range 28-70.8). The mean time between the primary and the secondary operation was 46.5 months (3-264). The mean follow-up was 2.44 years (6-60 months). The mean operative time was 119.3 min. The mean length of hospital stay was 4.01 days (2-28). The median limb length was 200 cm (range 150-250 cm). Leak rate was 1.54%. Marginal ulcer rate was 2.44%. Anemia rate was 1.9%. Mortality was 0.3%. The excess weight loss (%EWL) at 1 year and 2 years was 65.2% and 68.5% respectively. CONCLUSION: We conclude that there is evidence to consider OAGB-MGB as a safe and effective choice for RBS. Randomised studies with long term follow-up are suggested for the future.

Necrosis of the Nissen-Sleeve Gastrectomy (N-SG) Wrap.

BACKGROUND: Sleeve gastrectomy (SG) is the highest performed bariatric procedure in the world. Gastro-oesophageal reflux disease (GERD) is widely debated topics after SG. Nissen-Sleeve gastrectomy (N-SG) technique was reported in 2016 as an alternative solution to this problem. They reported concern about valve ischaemia but did not report any such complication in the beginning of their experience. We would like to share video showing this complication and technique to manage it. METHOD: Data was retrospectively analysed. RESULTS: A 45-year-old female with BMI of 35.5 kg/m had an uneventful Nissen-SG. She had GERD treated with proton pump inhibitor (PPI). The preoperative gastroscopy showed peptic oesophagitis with hiatal hernia. On post-operative day (POD) 1, the patient complained of severe abdominal pain, tachycardia and fever. Inflammatory markers were raised. Diagnostic laparoscopy showed necrosis of the wrap. The wrap was carefully undone and resected with a stapler (with seamguard). Thorough wash with saline was performed. Drain was left near the new staple line. A CT scan with oral contrast 4 days later confirmed absence of a gastric leak. The patient was discharged 8 days after the revision on PPI and antibiotics. Two-years post-operatively, the patient is doing well and her GERD symptoms are controlled with PPI. CONCLUSION: Wrap necrosis is a life-threatening complication after N-SG. This case is shared to raise awareness of this complication. This was successfully managed by prompt laparoscopy and wrap resection. Ideally such complications should be referred to experts or centers with high volume of bariatric surgery.

Hypervariable Domain of nsP3 of Eastern Equine Encephalitis Virus Is a Critical Determinant of Viral Virulence.

Eastern equine encephalitis virus (EEEV) is the most pathogenic member of the Alphavirus genus in the Togaviridae family. This virus continues to circulate in the New World and has a potential for deliberate use as a bioweapon. Despite the public health threat, to date no attenuated EEEV variants have been applied as live EEEV vaccines. Our previous studies demonstrated the critical function of the hypervariable domain (HVD) in EEEV nsP3 for the assembly of viral replication complexes (vRCs). EEEV HVD contains short linear motifs that recruit host proteins required for vRC formation and function. In this study, we developed a set of EEEV mutants that contained combinations of deletions in nsP3 HVD and clustered mutations in capsid protein, and tested the effects of these modifications on EEEV infection in vivo These mutations had cumulative negative effects on viral ability to induce meningoencephalitis. The deletions of two critical motifs, which interact with the members of cellular FXR and G3BP protein families, made EEEV cease to be neurovirulent. The additional clustered mutations in capsid protein, which affect its ability to induce transcriptional shutoff, diminished EEEV's ability to develop viremia. Most notably, despite the inability to induce detectable disease, the designed EEEV mutants remained highly immunogenic and, after a single dose, protected mice against subsequent infection with wild-type (wt) EEEV. Thus, alterations of interactions of EEEV HVD and likely HVDs of other alphaviruses with host factors represent an important direction for development of highly attenuated viruses that can be applied as live vaccines.IMPORTANCE Hypervariable domains (HVDs) of alphavirus nsP3 proteins recruit host proteins into viral replication complexes. The sets of HVD-binding host factors are specific for each alphavirus, and we have previously identified those specific for EEEV. The results of this study demonstrate that the deletions of the binding sites of the G3BP and FXR protein families in the nsP3 HVD of EEEV make the virus avirulent for mice. Mutations in the nuclear localization signal in EEEV capsid protein have an additional negative effect on viral replication in vivo Despite the inability to cause a detectable disease, the double HVD and triple HVD/capsid mutants induce high levels of neutralizing antibodies. Single immunization protects mice against infection with the highly pathogenic North American strain of EEEV. High safety, the inability to revert to wild-type phenotype, and high immunogenicity make the designed mutants attractive vaccine candidates for EEEV infection.