Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.

Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses. In addition, in both studies antibiotics treatment resulted in (1) enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (2) divergent metabolic trajectories, with a 1,000-fold reduction in serum secondary bile acids, which was highly correlated with AP-1/NR4A signaling and inflammasome activation. Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.

Metabolic Phenotypes of Response to Vaccination in Humans.

Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).

Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study.

BACKGROUND: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. METHODS: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety. RESULTS: After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × log10 copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More local injection-site pain was noted in the vaccine group than in the placebo group. No serious adverse events were observed in either group. CONCLUSIONS: RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).

Green waste immobilized Ag/Cu feather like Bi-matrix on garment dye decomposes and their bio-efficacy.

This paper describes a simple phyto-remediation of feather-like silver/copper bi-matrix (BMs) was constructed by employing pommagrant waste peel (PWP) extract as crucial role of reducing agent and chelating agents. Numerous strategies, including UV-Visible, XRD, SEM-EDX, and TEM and BET isotherm were used to analysis the optical, structural, surface area and functional properties. Ag/Cu BPNMs of TEM characterization shows feather-like architectural features with constrained size and shape. The Ag/Cu co-catalytic nanoparticles have a particle size of 34-64 nm. The photocatalytic efficiency of Ag/Cu BMs was investigated using a garment dye, Congo red (CR), at successive time intervals under halogen lamp exposure. For Ag/Cu bimetallic nanoparticles, the photocatalytic degradation rate was recorded to be 100% after 40 min which is caused by adsorption of Congo red dye molecules on Ag/Cu and their degradation by reactive oxygen species (ROS). ROS are free hydroxyl radicals such as •OH and O2• ions that have high oxidizing capacity. The developed Ag/Cu BMs shown effective bacteriostatic action against many infections.

Pyto-Architechture of Ag, Au and Ag-Au bi-metallic nanoparticles using waste orange peel extract for enable carcinogenic Congo red dye degradation.

Ecologically inspired to develop silver, gold and silver/gold bimetallic nanoparticles from discarded orange peel extract. The plant-derived compounds included in discarded orange peel extract have been accountable for the development of Ag, Au and Ag-Au bimetallic nanoparticles, that might be used in the biosynthetic process. The qualitative assessment of developed silver, gold and silver/gold bimetallic nanoparticles has been performed by UV-visible, XRD pattern, FT IR analysis, TEM/HRTEM, EDX and BET isotherm analysis. In this investigation, the photocatalytic effect of developed silver, gold and silver/gold bimetallic nanoparticles on Congo red dye breakdown efficiency was achieved at 96%, 94%, and 99.2%, respectively. Due to prolonged electron-hole recombination process was investigated using UV irradiation and reused for up to 5 consecutive runs without significant loss of photocatalytic activity. Moreover, silver, gold, and silver/gold bimetallic nanoparticles manufactured in an environmentally benign manner could potentially contribute to the ecological cleanup.

Rationally construction of 2D & 3D material on h-BN @ SnO2/TiO2 micro-sphere enables for photocatalytic debasement of textile cloth dyes in waste water treatment.

Affordable and swiftly available h-BN@SnO2/TiO2 photocatalysts are being developed through an easy hydrothermally approach was used urea as boric acid precursors. With their constructed photo catalysts, the effect of h-BN@SnO2/TiO2 has been investigated under the assessment of Adsorption agents utilizing X-ray diffraction pattern (XRD), Scanning electron microscopy, Energy dispersive spectroscopic analysis (SEM/EDS), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HR-TEM), and Burner Emit Teller (BET) isotherm testing methods, which also indicated that SnO2/TiO2 and h-BN have been tightly bound together. Because turquoise blue (TB) and Methyl orange (MO) fabric dyes can be found in the industrial wastewater being processed, the photo catalytic degradation process happens to be applied. According to the advantageous linkages of h-BN@SnO2/TiO2 photocatalysts, fantastic efficacy in breakdown towards hazardous compounds has been found. For the decomposition of Turquoise blue (TB) and Methyl orange (MO), the h-BN@SnO2/TiO2 catalysts proved the best performance stability (0.0386 min-1 and 1.524min-1) but were significantly 22 times quicker. Optical catalysis has additionally demonstrated extraordinary resilience and durability throughout five reprocessed efforts. On top of that, an approach enabling photocatalytic breakdown of harmful substances upon h-BN@SnO2/TiO2 has been presented.

Modulating cultivation regimes of Messastrum gracile SVMIICT7 for biomass productivity integrated with resource recovery via hydrothermal liquefaction.

The present study was designed to assess Messastrum gracile SVMIICT7 potential in treating dairy wastewater (autoclaved (ADWW) and raw (DWW)) with relation to nutrient removal, in-vivo Chl-a-based biomass, and bio-oil synthesis. Chlorophyll a fluorescence kinetics revealed improved photochemical efficiency (0.639, Fv/Fm) in M. gracile when grown with DWW. This may be owing to enhanced electron transport being mediated by an effective water-splitting complex at photosystem (PSII) of thylakoids. The increase in ABS/RC observed in DWW can be attributed to the elevated chlorophyll content and reduced light dissipation, as evident by higher values of ETo/RC and a decrease in non-photochemical quenching (NPQ). M. gracile inoculated in DWW had the highest Chl-a-biomass yield (1.8 g L-1) and biomolecules while maximum nutrient removal efficiency was observed in ADWW (83.7% TN and 60.07% TP). M. gracile exhibited substantial bio-oil yield of 29.6% and high calorific value of 37.19 MJ kg-1, predominantly composed of hydrocarbons along with nitrogen and oxygen cyclic compounds. This research offers a thorough investigation into wastewater treatment, illustrating the conversion of algal biomass into valuable energy sources and chemical intermediates within the framework of a biorefinery.

Review of MR spectroscopy analysis and artificial intelligence applications for the detection of cerebral inflammation and neurotoxicity in Alzheimer's disease.

INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders. MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD. RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing. CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.

Pathological and molecular studies on elephant endotheliotropic herpesvirus haemorrhagic disease among captive and free-range Asian elephants in India.

In the present research pathology and molecular diagnosis of elephant endotheliotropic herpes virus-haemorrhagic disease (EEHV-HD) among Asian elephants was studied. Out of 76 cases, 20 were positive for EEHV infection in PANPOL and POL1 based semi-nested PCR. Out of 20 samples, 10 samples were fatal cases of EEHV-HD while 10 were of either subclinical or latent infection. Acute onset haemorrhagic disease with EEHV-HD had anorexia, facial and neck swelling, cyanotic buccal mucosa and tongue, nasal and ocular discharge, and colic. The hallmark of gross finding in all cases were severe haemorrhagic lesions in the internal organs viz. cyanosis of tongue with multifocal petechial haemorrhages, diffuse epicardial and endocardial haemorrhages, swollen liver (rounded edges) with parenchymal haemorrhages, serosal and mucosal haemorrhages in gastrointestinal tract, congested kidneys with corticomedullary haemorrhages, highly congested meninges, and brain capillaries with haemorrhages. Microscopic findings in all the cases had severe vascular changes in the visceral organs. Microthrombi was present in the vasculature of tongue, heart, lung, liver, kidney, and brain. The endothelial lining of most of the blood vessels were swollen with apoptotic changes. Amphophilic to basophilic intranuclear inclusion bodies were observed in the endothelial cells. Immunostaining using anti-EEHV DNAPOL hyperimmune sera revealed intense positive signals in the endothelium of blood vessels and their walls. Quantification of viral load in necropsy tissue samples revealed highest in the heart (7.4 × 106/µg of sample) and least in the brain (9 × 103/µg of sample). The PCR amplicons from EEHV1 specific genes (POL1(U38) and TER were subjected to partial genome sequencing which had 99.9% similarity with the EEHV1A subtype. It was concluded that Asian elephants in India are latently infected for EEHV1 and in all the fatal EEHV-HD cases, EEHV1A subtype was the causative agent with characteristic pathomorphological changes in visceral organs.

TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.

Systems biological analysis of immunity to the trivalent inactivated influenza vaccine (TIV) in humans revealed a correlation between early expression of TLR5 and the magnitude of the antibody response. Vaccination of Trl5(-/-) mice resulted in reduced antibody titers and lower frequencies of plasma cells, demonstrating a role for TLR5 in immunity to TIV. This was due to a failure to sense host microbiota. Thus, antibody responses in germ-free or antibiotic-treated mice were impaired, but restored by oral reconstitution with a flagellated, but not aflagellated, strain of E. coli. TLR5-mediated sensing of flagellin promoted plasma cell differentiation directly and by stimulating lymph node macrophages to produce plasma cell growth factors. Finally, TLR5-mediated sensing of the microbiota also impacted antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine. These results reveal an unappreciated role for gut microbiota in promoting immunity to vaccination.

In vitro fertilisation for unexplained subfertility.

BACKGROUND: In vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks. OBJECTIVES: To evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes. SEARCH METHODS: We searched following databases from inception to November 2021, with no language restriction: Cochrane Gynaecology and Fertility Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL. We searched reference lists of articles and conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing effectiveness of IVF for unexplained subfertility with expectant management, unstimulated IUI, and stimulated IUI. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. MAIN RESULTS: IVF versus expectant management (two RCTs) We are uncertain whether IVF improves live birth rate (LBR) and clinical pregnancy rate (CPR) compared to expectant management (odds ratio (OR) 22.0, 95% confidence interval (CI) 2.56 to 189.37; 1 RCT; 51 women; very low-quality evidence; OR 3.24, 95% CI 1.07 to 9.8; 2 RCTs; 86 women; I2 = 80%; very low-quality evidence). Adverse effects were not reported. Assuming 4% LBR and 12% CPR with expectant management, these would be 8.8% to 9% and 13% to 58% with IVF. IVF versus unstimulated IUI (two RCTs) IVF may improve LBR compared to unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12; 2 RCTs; 156 women; I2 = 60%; low-quality evidence). We are uncertain whether there is a difference between IVF and IUI for multiple pregnancy rate (MPR) (OR 1.03, 95% CI 0.04 to 27.29; 1 RCT; 43 women; very low-quality evidence) and miscarriage rate (OR 1.72, 95% CI 0.14 to 21.25; 1 RCT; 43 women; very low-quality evidence). No study reported ovarian hyperstimulation syndrome (OHSS). Assuming 16% LBR, 3% MPR, and 6% miscarriage rate with unstimulated IUI, these outcomes would be 18.5% to 49%, 0.1% to 46%, and 0.9% to 58% with IVF. IVF versus IUI + ovarian stimulation with gonadotropins (6 RCTs), CC (1 RCT), or letrozole (no RCTs) Stratified analysis was based on pretreatment status. Treatment-naive women There may be little or no difference in LBR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.19, 95% CI 0.87 to 1.61; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I2 = 54%; low-quality evidence); or between IVF and IUI + CC (OR 2.51, 95% CI 0.96 to 6.55; 1 RCT; 103 women; low-quality evidence). Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. Assuming 15% LBR with IUI + CC, LBR would be 15% to 54% with IVF. There may be little or no difference in CPR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.17, 95% CI 0.85 to 1.59; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 4.59, 95% CI 1.86 to 11.35; 1 RCT; 103 women; low-quality evidence); or between IVF and IUI + CC (OR 3.58, 95% CI 1.51 to 8.49; 1 RCT; 103 women; low-quality evidence). Assuming 48% CPR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 17% with IUI + gonadotropins (1 IVF to 1 IUI cycle), CPR would be 44% to 60% and 28% to 70% with IVF. Assuming 21% CPR with IUI + CC, CPR would be 29% to 69% with IVF. There may be little or no difference in multiple pregnancy rate (MPR) between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 0.82, 95% CI 0.38 to 1.77; 3 RCTs; 731 women; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I2 = 0%; low-quality evidence); or between IVF and IUI + CC (OR 0.64, 95% CI 0.17 to 2.41; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in OHSS between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 6.86, 95% CI 0.35 to 134.59; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference in OHSS with 1 IVF to 1 IUI cycle (OR 1.22, 95% CI 0.36 to 4.16; 2 RCTs; 221 women; I2 = 0%; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.53, 95% CI 0.24 to 9.57; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in miscarriage rate between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 0.31, 95% CI 0.03 to 3.04; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference with 1 IVF to 1 IUI cycle (OR 1.16, 95% CI 0.44 to 3.02; 1 RCT; 103 women; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.48, 95% CI 0.54 to 4.05; 1 RCT; 102 women; low-quality evidence). In women pretreated with IUI + CC IVF may improve LBR compared with IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57; 1 RCT; 280 women; low-quality evidence). Assuming 22% LBR with IUI + gonadotropins, LBR would be 39% to 65% with IVF. IVF may improve CPR compared with IUI + gonadotropins (OR 14.13, 95% CI 7.57 to 26.38; 1 RCT; 280 women; low-quality evidence). Assuming 30% CPR with IUI + gonadotropins, CPR would be 76% to 92% with IVF. AUTHORS' CONCLUSIONS: IVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low.

Impact of tubal patency test selection on the live birth rate following intrauterine insemination in couples with unexplained infertility: a retrospective cohort study.

OBJECTIVE: We planned a study to evaluate the impact of selecting hysterosalpingography (HSG) over diagnostic laparoscopy during initial fertility evaluation on IUI treatment outcomes in couples diagnosed with unexplained infertility. METHODS: The study comprised a retrospective cohort and included couples evaluated for infertility at our tertiary level hospital between January 2008 and December 2019. Couples diagnosed with unexplained infertility based on tubal patency tests (either HSG or diagnostic laparoscopy) were included. We compared outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between women who underwent HSG versus laparoscopy for up to three treatment cycles. RESULTS: A total of 7413 women were screened, out of which 1002 women were diagnosed with unexplained infertility. We did not find a significant statistical difference in the clinical pregnancy (16.7% vs. 11.7%; OR (odds ratio) 1.51; 95% CI (confidence interval) 0.90-2.5) or live birth rate per IUI cycle (15.1% vs. 10.7%; OR 1.51, 95% CI 0.9-2.6) in women who underwent HSG for tubal evaluation as compared to laparoscopy. After adjustment for potential confounders through multivariate analysis, we found that outcomes were comparable between the HSG and laparoscopy. CONCLUSION: The current study did not find any significant difference in treatment outcomes following OS and IUI in women with unexplained infertility who underwent HSG compared to laparoscopy for the assessment of the tubal patency during the initial fertility workup. The finding suggests minimal or no impact of selecting HSG over diagnostic laparoscopy as a tubal patency test on the subsequent IUI outcomes.

Review of robot-assisted laparoscopic surgery in management of infant congenital urology: Advances and limitations in utilization and learning.

As robotic-assisted (RAL) surgery expanded to treat pediatric congenital disease, infant anatomy and physiology posed unique challenges that prompted adaptations to the technology and surgical technique, which are compiled and reviewed in this manuscript. From the beginning, collaboration with anesthesia is critical for a safe, efficient case including placement of an endotracheal tube rather than a laryngeal mask (LMA) and placement of a nasogastric tube and/or rectal tube to relieve distended stomach or bowel, respectively. Furthermore, end-tidal CO2 (EtCO2 ) is important for monitoring and predicting the effects of pneumoperitoneum on caridiovascular physiology, incranial pressure, and risk of acidosis and hypercarbia. Positioning can further exacerbate these effects and affect intra-abdominal working space. For infant robotic pyeloplasty and heminephrectomy, a "beanbag" is commonly used for stabilization in the lateral decubitus position. We advise against the use of a "baby bump" because it brings the bowels and vasculature more anterior than expected. Pnuemoperitoneum pressure of 8-10 mmHg during port placement maximizes safety, but thereafter, the pneumoperitoneum pressure can be minimized to 6-8 mmHg during the procedure without compromising the visual field. Port sites should be marked after insufflation, followed by the open Hasson technique for peritoneal access and port placement under direct vision with intussusception of the trocars to avoid vascular or bowel injury. Additional tips can be obtained through this manuscript, immersive fellowships, and mini-fellowships. Ulitmately, infant robotic surgery has the potential to benefit many children but is presently limited by the lack of pediatric-specific robotic technology and its associated costs.

Automatic Segmentation of Psoriasis Skin Images Using Adaptive Chimp Optimization Algorithm-Based CNN.

Psoriasis is a severe skin disease that is surveyed outwardly by dermatologists. In recent years, computer vision is the major solution for diagnosing the psoriasis skin disease by segmenting the infected skin images. Besides, many researchers had presented efficient machine learning techniques for segmenting the psoriasis skin images. Nevertheless, accuracy and time consumption of the model are further to be improved. Thus, in this work, we present adaptive chimp optimization algorithm (AChOA)-based convolutional neural network (CNN) which is introduced for automatic segmentation of psoriasis skin images. After pre-processing, the input images are segmented using AChOA-CNN model where weight and bias values of CNN are optimized with the AChOA. The search ability of ChOA is enhanced by adapting the chaotic sequence based on tent map. At final, from the segmented output images, artifacts are removed by applying the threshold module. From the simulation, we attain 97% of accuracy.

A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years. METHODS: Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2. RESULTS: All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo. CONCLUSIONS: RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.

Pediatric robotic urologic procedures: Indications and outcomes.

Introduction: Robotic-assisted laparoscopic surgery (RALS) has revolutionized minimally invasive surgery in pediatric urology. The robotic platform allows surgeons to maintain the benefits of laparoscopic surgery while having enhanced three-dimensional view, dexterity, range of motion, and control of high-resolution cameras. In this review, we summarize the indications and recent outcomes for various pediatric urologic RALS procedures to illustrate the current state of robotics in pediatric urology. Methods: We systematically searched the PubMed and EMBASE databases. We extrapolated and summarized recent evidence on RALS in pediatric urology patients, with an emphasis on indications and outcomes, with regard to the following procedures and search terms: pyeloplasty, kidney stone surgery, partial nephrectomy, nephroureterectomy, ureteral reimplantation, appendico-vesicostomy, augmentation cystoplasty, bladder neck reconstruction, and Malone antegrade continence enema. Additional Medical Subject Headings terms used to augment the search included "Treatment Outcome" and "Robotic Surgical Procedures." Results: Increasing usage of RALS has shown many benefits in perioperative and postoperative outcomes. In addition, there is growing evidence that robotic procedures in pediatric urology result in similar or better surgical outcomes when compared to the standard of care. Conclusions: RALS has shown considerable effectiveness in pediatric urologic procedures and may achieve surgical outcomes comparable to the standard approaches of open or laparoscopic surgery. However, larger case series and prospective randomized controlled trials are still necessary to validate the reported outcomes, in addition to cost analyses and studies on the surgical learning curve. We believe that the continuous evolution of robotic platforms will allow for enhanced care and quality of life for pediatric urology patients.

Tuberculosis in free-ranging and captive wild animals: Pathological and molecular diagnosis with histomorphological differentiation of granulomatous lesions.

Tuberculosis (TB) is a serious zoonotic threat, impacting the human-livestock-wildlife interface globally. Here, we evaluated the status and histomorphological differentiation of TB lesions in 89 morbid cases of wild animals (bovids, cervids, carnivores, non-human primates, and pachyderms) in India. Histomorphological and molecular studies were done using Ziehl-Neelsen (ZN) staining, immunohistochemistry, and polymerase chain reaction (PCR), whereas cultural isolation was performed on selected samples. A total of 32 (35.95%) cases were confirmed as TB, comprising of 12 carnivores, 09 bovids, 06 cervids, 04 non-human primates, and a pachyderm. The TB lesions in the lungs, liver, and lymph nodes varied from the large-sized caseous nodules filled with dry cheesy material in bovids and cervids to variable-sized cavitations containing liquefied caseum in carnivores' lungs. The lungs, livers, and spleens of non-human primates exhibited small to medium-sized nodules. Histologically, lesions were divided into four categories (Types I, II, III, and IV) based on the extent of necrosis, the presence of mineralization, giant cells, and fibrous encapsulation. Extensive caseous necrosis with calcification, abundant giant cells, and thick fibroblastic encapsulation were consistent findings in the lungs, livers, and lymph nodes of bovids and cervids, whereas airway impaction with cellular exudate containing a teeming number of acid-fast bacilli and, at times, alveolar rupture leading to cavity formation was present in the lungs of carnivores. Absence of calcification and fibrous encapsulation was recorded in lungs of non-human primates. Immunohistochemical labelling with anti-early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) antibodies showed mild, moderate, and intense positive reactions in type II and III, type I, and type IV granulomatous lesions, respectively. Molecular detection by PCR revealed Mycobacterium tuberculosis (12 carnivores, 02 non-human primates and 01 pachyderm), M. bovis (02 cervids and 01 bovid) and M. orygis (02 cervids and 01 bovid). Cultural isolation confirmed M. tuberculosis in 03 carnivores and M. orygis in 02 cervids and 01 bovid. Our findings imply that TB is quite prevalent in the wildlife of India and there are considerable differences in the histomorphological lesions induced by distinct Mycobacterium species in different wild animals. The circulation of TB organisms in wild animals warrants a strict surveillance programme to identify the carrier status of these animals so that effective TB control strategies can be formulated to prevent spillover and spillback incidences at the human-livestock-wildlife interface.

A processive GH9 family endoglucanase of Bacillus licheniformis and the role of its carbohydrate-binding domain.

One of the critical steps in lignocellulosic deconstruction is the hydrolysis of crystalline cellulose by cellulases. Endoglucanases initially facilitate the breakdown of cellulose in lignocellulosic biomass and are further aided by other cellulases to produce fermentable sugars. Furthermore, if the endoglucanase is processive, it can adsorb to the smooth surface of crystalline cellulose and release soluble sugars during repeated cycles of catalysis before dissociating. Most glycoside hydrolase family 9 (GH9) endoglucanases have catalytic domains linked to a CBM (carbohydrate-binding module) (mostly CBM3) and present the second-largest cellulase family after GH5. GH9 endoglucanases are relatively less characterized. Bacillus licheniformis is a mesophilic soil bacterium containing many glycoside hydrolase (GH) enzymes. We identified an endoglucanase gene, gh9A, encoding the GH9 family enzyme H1AD14 in B. licheniformis and cloned and overexpressed H1AD14 in Escherichia coli. The purified H1AD14 exhibited very high enzymatic activity on endoglucanase substrates, such as ß-glucan, lichenan, Avicel, CMC-Na (sodium carboxymethyl cellulose) and PASC (phosphoric acid swollen cellulose), across a wide pH range. The enzyme is tolerant to 2 M sodium chloride and retains 74% specific activity on CMC after 10 days, the highest amongst the reported GH9 endoglucanases. The full-length H1AD14 is a processive endoglucanase and efficiently saccharified sugarcane bagasse. The deletion of the CBM reduces the catalytic activity and processivity. The results add to the sparse knowledge of GH9 endoglucanases and offer the possibility of characterizing and engineering additional enzymes from B. licheniformis toward developing a cellulase cocktail for improved biomass deconstruction. KEY POINTS: • H1AD14 is a highly active and processive GH9 endoglucanase from B. licheniformis. • H1AD14 is thermostable and has a very long half-life. • H1AD14 showed higher saccharification efficiency than commercial endoglucanase.

Non-invasive Prenatal Testing in Pregnancies Following Assisted Reproduction.

In the decade since non-invasive prenatal testing (NIPT) was first implemented as a prenatal screening tool, it has gained recognition for its sensitivity and specificity in the detection of common aneuploidies. This review mainly focuses on the emerging role of NIPT in pregnancies following assisted reproductive technology (ART) in the light of current evidence and recommendations. It also deals with the challenges, shortcomings and interpretational difficulties related to NIPT in ART pregnancies, with particular emphasis on twin and vanishing twin pregnancies, which are widely regarded as the Achilles' heel of most pre-natal screening platforms. Future directions for exploration towards improving the performance and extending the scope of NIPT are also addressed.