Clinicopathologic Characteristics of Crystalglobulin-Induced Nephropathy: A Case Series.

RATIONALE & OBJECTIVE: Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN). STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Nineteen CIN cases were identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light (LM) and electron microscopy (EM). FINDINGS: Among the cases, 68% were male and 65% were Caucasian (median age 56 years). Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017). LIMITATIONS: Retrospective design, small sample size. CONCLUSIONS: CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires IF performed on paraffin embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.

Shattering and yield expression of sesame (Sesamum indicum L) genotypes influenced by paclobutrazol concentration under rainfed conditions of Pothwar.

Seed shattering is a critical challenge that significantly reduces sesame production by 50%. These shattering losses can be reduced by selecting shattering resistant genotypes or by incorporating modern agronomic management such as paclobutrazol, which can boost productivity and prevent seed shattering in sesame. Two-years of field trials were conducted to examine the effect of sesame genotypes, environment, and paclobutrazol (PBZ) concentrations. Twelve sesame genotypes were used in a four-way factorial RCBD with three replications and five PBZ concentrations (T0 = Control; T1 = 150; T2 = 300; T3 = 450; and T4 = 600 mg L- 1) under rainfed conditions of Pothwar. The findings revealed significant variations in the major effects of all examined variables (genotypes, locations, years, and PBZ levels). Sesame genotypes PI-154304 and PI-175907 had the highest plant height, number of capsule plant- 1, seed capsule- 1, 1000 seed weight, biological yield, and seed yield, while also having the lowest seed losses and shattering percentage. Regarding environments, NARC-Islamabad generated the highest plant height, number of capsule plant- 1, shattering percentage, and biological yield; however, the URF-Koont produced the highest seed yield with the lowest shattering percentage. Additionally, plant height, capsules plant- 1, and biological yield were higher in 2021, while seed capsule- 1, 1000 seed weight, seed losses, shattering percentage, and seed yield were higher in 2020. PBZ concentration affected all measured parameters; plant height and number of seed capsule- 1 decreased with increasing PBZ concentrations. 450 mg L- 1 PBZ concentration generated the highest biomass, number of capsules plant- 1, and seed yield. At the same time, PBZ concentration 600 mg L- 1 generated the smallest plant, the lowest seed capsules- 1, the greatest thousand seed weight, and the lowest shattering percentage. The study concluded that paclobutrazol could dramatically reduce shattering percentage and shattering losses while increasing economic returns through better productivity. Based on the findings, the genotypes PI-154304 and PI-175907 with paclobutrazol level 450 mgL- 1 may be suggested for cultivation in Pothwar farming community under rainfed conditions, as they showed promising shattering resistance as well as enhanced growth and yield.

Efficiently editing the vaccinia virus genome by using the CRISPR-Cas9 system.

Vaccinia virus (VACV) continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer since its use for the eradication of smallpox. However, the current method of editing the VACV genome is not efficient. Here, we demonstrate that the CRISPR-Cas9 system can be used to edit the VACV genome rapidly and efficiently. Additionally, a set of 8,964 computationally designed unique guide RNAs (gRNAs) targeting all VACV genes will be valuable for the study of VACV gene functions.

Unusual case of Reinke's oedema.

This case report describes a man in his mid 40s, with a history of chronic smoking, who presented with dysphonia. He underwent microlaryngoscopy and biopsy for a suspicious lesion on the anterior right vocal cord. Mask ventilation proved difficult on induction of general anaesthesia due to a solid lesion acting as a ball valve into the glottis. This mass was LASER debulked and sent for histopathology. This demonstrated a haematoma, likely traumatic in origin, with some polypoidal features, consistent with advanced Reinke's oedema. Reinke's oedema is a benign condition where chronic inflammation causes fluid accumulation within the vocal cords. Long-standing inflammation leads to disarrangement of the vocal cord lamina propria, causing fluid accumulation and thereby resulting oedema of the vocal cords. This process can subsequently lead to polyp formation and can cause gravelly voice. This case report describes the potential airway sequelae of this benign condition.

Nanoencapsulated Aquafeeds and Current Uses in Fisheries/Shrimps: A Review.

Feeds for aquaculture animals are designed to provide them with the greatest amount of nourishment they need to carry out their regular physiological activities, such as maintaining a potent natural immune system and boosting growth and reproduction. However, the problems that severely hamper this sector's ability to contribute to achieving global food security include disease prevalence, chemical pollution, environmental deterioration, and inadequate feed usage. The regulated release of active aquafeed components; limited water solubility, bioaccessibility, and bioavailability, as well as their potent odour and flavour, limit their utilisation. They are unstable under high temperatures, acidic pH, oxygen, or light. Recent advancements in nano-feed for aquaculture (fish/shrimp) have attract enormous attention due to its excellent nutritional value, defeating susceptibility and perishability. Encapsulation is a multifunctional smart system that could bring benefits of personalized medicine; minimize costs and resources in the preclinical and clinical study in pharmacology. It guarantees the coating of the active ingredient as well as its controlled release and targeted distribution to a particular area of the digestive tract. For instance, using nanotechnology to provide more effective fish/shrimps feed for aquaculture species. The review enables a perspective points on safety and awareness in aquafeeds that have been made by the advancements of nanosystem. Therefore, potential of nano-delivery system in aquafeed industry for aquaculture act as concluding remark on future directions.

In Silico and In Vitro Investigation of Phytochemicals Against Shrimp AHPND Syndrome Causing PirA/B Toxins of Vibrio parahaemolyticus.

In Southeast Asia, the penaeid shrimp aquaculture production faces a new pandemic bacterial disease called acute hepatopancreatic necrosis disease (AHPND). The highly profitable pacific white shrimp, Litopenaeus vannamei, has become a challenging species due to severe lethal infections. Recent research has identified a critical pathogen, Vibrio parahaemolyticus, which caused significant loss in the shrimp industry. The disease pathway involves a virulence plasmid encoding binary protein toxins (PirA/B) that cause cell death. The protein toxins were inherited and conjugatively transferred to other Vibrio species through a post-segregational killing system. In this study, "in silico" (Glide, 2021) analysis identified four phytocompounds as myricetin (Myr), ( +)-taxifolin (TF), (-)-epigallocatechin gallate (EGCG), and strychnine (STN) which could be most effective against both the toxins concerning its docking score and affinity. The interactions of complexes and the critical amino acids involved in docking were analyzed using the Discovery Studio (version 2016). Molecular dynamic studies showed lower root mean square deviations (RMSD) and improved stabilization of ( +)-taxifolin (TF) and (-)-epigallocatechin-3-gallate (EGCG) against both the protein toxins. The antibacterial potential of all four selected compounds had tested against pathogenic strains of V. parahaemolyticus through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The best MBC results were observed at concentrations of 1 mg/mL for EGCG and 1.25 mg/mL for TF. Moreover, the complete reduction of viable cell counts in the in vitro bactericidal activity had recorded after 24 h of incubation.

Preoperative and postoperative optimisation of patients undergoing thyroid surgery: a multicentre quality improvement project at Barts Health NHS Trust.

Hypocalcaemia following thyroid surgery can occur in up to 38% of patients. With over 7100 thyroid surgeries performed in 2018 in the UK, this is a common postoperative complication. Undertreated hypocalcaemia can result in cardiac arrhythmias and death. Preventing adverse events from hypocalcaemia requires preoperative identification and treatment of at-risk patients with vitamin D deficiency, timely recognition of postoperative hypocalcaemia and prompt appropriate treatment with calcium supplementation. This project aimed to design and implement a perioperative protocol for prevention, detection and management of post-thyroidectomy hypocalcaemia. A retrospective audit of thyroid surgeries (n=67; October 2017 to June 2018) was undertaken to establish baseline practice of (1) preoperative vitamin D levels assessment, (2) postoperative calcium checks and incidence of postoperative hypocalcaemia and (3) management of postoperative hypocalcaemia. A multidisciplinary team approach following quality improvement principles was then used to design a perioperative management protocol with all relevant stakeholders involved. After dissemination and implementation, the above measures were reassessed prospectively (n=23; April-July 2019). The percentage of patients having their preoperative vitamin D measured increased from 40.3% to 65.2%. Postoperative day-of-surgery calcium checks increased from 76.1% to 87.0%. Hypocalcaemia was detected in 26.8% of patients before and 30.43% of patients after protocol implementation. The postoperative component of the protocol was followed in 78.3% of patients. Limitations include low number of patients which precluded from analysis of the impact of the protocol on length of stay. Our protocol provides a foundation for preoperative risk stratification and prevention, early detection and subsequent management of hypocalcaemia in thyroidectomy patients. This aligns with enhanced recovery protocols. Moreover, we offer suggestions for others to build on this quality improvement project with the aim to further advance the perioperative care of thyroidectomy patients.

Functional endoscopic balloon dilation of sinus ostia for chronic rhinosinusitis.

BACKGROUND: Dilation of sinus ostia using a high-pressure balloon has been introduced as a treatment for chronic rhinosinusitis (CRS) refractory to medical treatment. The efficacy of this technology, however, has not been systematically reviewed. OBJECTIVES: To assess the effectiveness of balloon sinus ostial dilation as a treatment for patients suffering with CRS refractory to medical treatment. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL; PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 20 December 2010. SELECTION CRITERIA: Randomised controlled trials in patients of any age with rhinosinusitis lasting longer than 12 weeks who have failed a prolonged course of medical treatment. Studies compared either balloon sinus ostial dilation or a hybrid procedure (balloon dilation in conjunction with functional endoscopic sinus surgery (FESS)) versus conventional surgery (e.g. FESS) or a waiting list control. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and assessed risk of bias. MAIN RESULTS: One study (34 patients) met our inclusion criteria although it was not yet a peer reviewed publication. The study randomised patients with chronic frontal sinusitis who had failed a prolonged course of medical treatment into two groups: balloon dilatation of the frontal recess (plus conventional FESS of other involved sinuses) versus conventional FESS (Draf type 1/2a procedures on the frontal sinuses). At 12 months follow up there was no statistically significant difference in radiological resolution of frontal sinuses between the two groups. The percentages of directly observed patent frontal recesses at 12 months were 75% in the balloon dilation group versus 63% in the FESS-only group. The authors state that this was statistically significant but details of the analysis were not presented. Indeed the study as a whole suffers from a bias in the way its outcome measures were reported.No major complications were reported. Three patients in the FESS-only group required further revision frontal sinus surgery compared to one in the balloon dilation group, although synechiae were more common in the latter. AUTHORS' CONCLUSIONS: At present there is no convincing evidence supporting the use of endoscopic balloon sinus ostial dilation compared to conventional surgical modalities in the management of CRS refractory to medical treatment. With the escalating use of balloon sinuplasty, there is an urgent need for more randomised controlled trials to determine its efficacy over conventional surgical treatment modalities.

Impact of long-term nasopharyngeal airway on health-related quality of life of children with obstructive sleep apnea caused by syndromic craniosynostosis.

Obstructive sleep apnea in children with syndromic craniosynostosis is a well-documented entity, and airway management in these group of children is difficult, with well-documented cardiorespiratory and neurodevelopment consequences. Numerous well-documented techniques are available for airway management in this group of children. In our center, the nasopharyngeal airway (NPA) is the first-line treatment. This study aimed to evaluate the improvement in health-related quality of life in this group of children using the Glasgow Children's Benefit Inventory. We conducted a retrospective postal study of 24 patients with craniofacial disorders who had an NPA inserted as part of their airway management. A 79.2% (n = 19) response rate was obtained. Mean (SD) age was 5.8 (4.1) years. Patients were classified into 3 main groups: Crouzon (n = 11), Apert (n = 6), and Pfeiffer (n = 2) syndromes. There was improvement in 3 of the 4 domains, namely, learning (P = 0.006), vitality (P = 0.003), physical (range, -3 to 8; mean, 2; P = 0.005). There was significant improvement in the sleep study parameters; however, no correlation was found between this and the Glasgow Children's Benefit Inventory findings. Parents also preferred an NPA as opposed to a tracheostomy when given a choice. Our study shows that NPA confers significant improvement not only in health-related quality of life but also in severity of obstructive sleep apnea as judged by sleep study parameters. The NPA is also well tolerated by patients and is much preferred by parents for airway management for their children as opposed to having a tracheostomy. We think that this should be considered in other centers as first-line management in children with syndromic craniosynostosis.

The molecular march of primary and recurrent nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) results from the aberrant and uncontrolled growth of the nasopharyngeal epithelium. It is highly associated with the Epstein-Barr virus, especially in regions where it is endemic. In the last decade, significant advances in genetic sequencing techniques have allowed the discovery of many new abnormal molecular processes that undoubtedly contribute to the establishment, growth and spread of this deadly disease. In this review, we consider NPC as EBV induced. We summarise the recent discoveries and how they add to our understanding of the pathophysiology of NPC in the context of genomics first in primary and then in recurrent disease. Overall, we find key early events lead to p16 inactivation and cyclin D1 expression, allowing latent viral infection. Host and viral factors work together to affect a variety of molecular pathways, the most fundamental being activation of NF-κB. Nonetheless, much still yearns to be discovered, especially in recurrent NPC.

Toxicity of NiO nanoparticles to soil nutrient availability and herbage N uptake from poultry manure.

Recently, there is an increasing trend of using metallic nanoparticles (NPs) in agriculture due to their potential role in remediating soil pollution and improving nutrient utilization from fertilizers. However, evidence suggested that these NPs were toxic to the soil life and their associated functions, and this toxicity depended on their dose, type, and size. Here, a dose-dependent (5, 50, and 100 mg kg-1 soil) toxicity of NiO NPs on poultry manure (PM: 136 kg N ha-1) decomposition, nutrient mineralization, and herbage N uptake were studied in a standard pot experiment. The NPs doses were mixed with PM and applied in soil-filled pots where then ryegrass was sown. Results revealed that the lowest dose significantly increased microbial biomass (C and N) and respiration from PM, whereas a high dose reduced these parameters. This decrease in such parameters by the highest NPs dose resulted in 13 and 41% lower soil mineral N and plant available K from PM, respectively. Moreover, such effects resulted in 32 and 35% lower herbage shoot and root N uptakes from PM in this treatment. Both intermediate and high doses decreased herbage shoot Ni uptake from PM by 33 and 34%, respectively. However, all NPs doses did not influence soil Ni content from PM. Hence, our results indicated that high NPs dose (100 mg kg-1) was toxic to decomposition, nutrient mineralization, and herbage N uptake from PM. Therefore, such NiONPs toxicity should be considered before recommending their use in agriculture for soil remediation or optimizing nutrient use efficiency of fertilizers.

A systemically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer.

BACKGROUND: Pancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved. METHODS: VVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer. RESULTS: VVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. CONCLUSIONS: Intravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.

Does dictating the letter to the GP in front of a follow-up patient improve satisfaction with the consult? A randomised controlled trial.

Various studies have shown that receiving a copy of the letter to the General Practitioner (GP) improves patient satisfaction with the consult. We aimed to establish whether dictating the letter to the GP in front of a listening patient does likewise. Follow-up patients have shorter allotted consultation times. This may contribute to dissatisfaction, hence the choice of our target group. One hundred consecutive follow-up patients who met the eligibility criteria were randomised to listen to the GP letter or not. Immediately after the consult, they were asked to fill in a questionnaire which, in addition to enquiring about various aspects of the consult asked them to quantify their overall satisfaction by means of a ten-point graded visual analogue score. Forty-nine patients received dictation. The mean age and sex distribution of the two groups were matched. The median overall satisfaction in the dictation and non-dictation groups were ten and eight, respectively, this was statistically significant. There was no significant difference between patients' rating of whether the consult had addressed their ailment adequately, explanation(s) given or the length of consult. Sixty-one percent of patients in the non-dictation group would like to have listened to the dictation, whilst all patients in the dictation group found it useful. This study is the first of its kind in the ENT population. Dictating a letter to the GP in front of a listening patient led to a statistically significant improvement in satisfaction independent of possible confounding aspects of the consult.

A new oncolytic Vacciniavirus augments antitumor immune responses to prevent tumor recurrence and metastasis after surgery.

BACKGROUND: Local recurrence and remote metastasis are major challenges to overcome in order to improve the survival of patients with cancer after surgery. Oncolytic viruses are a particularly attractive option for prevention of postsurgical disease as they offer a non-toxic treatment option that can directly target residual tumor deposits and beneficially modulate the systemic immune environment that is suppressed post surgery and allows residual disease escape from control. Here, we report that a novel Vaccinia virus (VV), VVΔTKΔN1L (with deletion of both thymidine kinase (TK) and N1L genes) armed with interleukin 12 (IL-12), can prolong postoperative survival when used as a neoadjuvant treatment in different murine and hamster surgical models of cancer. METHODS: A tumor-targeted replicating VV with deletion of TK gene and N1L gene (VVΔTKΔN1L) was created. This virus was armed rationally with IL-12. The effect of VVΔTKΔN1L and VVΔTKΔN1L-IL12 on modulation of the tumor microenvironment and induction of tumor-specific immunity as well the feasibility and safety as a neoadjuvant agent for preventing recurrence and metastasis after surgery were assessed in several clinically relevant models. RESULTS: VVΔTKΔN1L can significantly prolong postoperative survival when used as a neoadjuvant treatment in three different surgery-induced metastatic models of cancer. Efficacy was critically dependent on elevation of circulating natural killer cells that was achieved by virus-induced cytokine production from cells infected with N1L-deleted, but not N1L-intact VV. This effect was further enhanced by arming VVΔTKΔN1L with IL-12, a potent antitumor cytokine. Five daily treatments with VVΔTKΔN1L-IL12 before surgery dramatically improved postsurgical survival. VVΔTKΔN1L armed with human IL-12 completely prevented tumor recurrence in surgical models of head and neck cancer in Syrian hamsters. CONCLUSIONS: These data provide a proof of concept for translation of the regime into clinical trials. VVΔTKΔN1L-IL12 is a promising agent for use as an adjuvant to surgical treatment of solid tumors.

No evidence of cholesteatoma in untreated otitis media with effusion in children with primary ciliary dyskinesia.

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited disorders that result in abnormal ciliary motion leading to mucous stasis. Clinical features include almost universally otitis media with effusion (OME), particularly in infants. PCD patients provide us with a cohort of patients with OME that is not treated with ventilatory tube (VT) insertion as these have been shown to result in frequent complications including chronic otorrhoea, early extrusion and persistent perforation without significant improvement to hearing in the long term. This cohort was used to investigate whether children with PCD and OME not treated with VT were predisposed to cholesteatoma formation in the setting of a paediatric quaternary referral centre. METHODS: A retrospective chart review was performed of all the children attending a multi-disciplinary PCD clinic at a national quaternary referral centre with a diagnosis of OME. We reviewed otoscopic findings, and audiometry and tympanometry results. We assessed the children in four groups: Watchful waiting, hearing aids, VT, and VT and hearing aids. RESULTS: One-hundred-and-one of 107 patients included in the study had a diagnosis of otitis media with effusion. No child with OME and PCD was diagnosed with a cholesteatoma during the follow up period. The only children who had insertion of a ventilatory tube were those who had the procedure prior to the formal diagnosis of PCD. We found a significant complication rate in the children with VT insertion. Hearing improved over time. The prevalence of retraction pockets in untreated OME was 1.72% (3 out of 174 ears). CONCLUSIONS: In children with PCD, OME is an almost universal finding in younger children, but not in adolescents. The study supports the current preference to avoid VT insertion in children with PCD as it confers a significantly higher rate of complications. No cases of cholesteatoma were found in this cohort of PCD children with OME managed without VTs.

Objective assessment of facial asymmetry in rhinoplasty patients.

OBJECTIVES: To determine the incidence and nature of facial asymmetry in patients referred for consideration of aesthetic rhinoplasty and to assess whether objective anthropometric facial measurements correlate with subjective perceptions of asymmetry. DESIGN: Two independent observers measured facial features, including midline to medial and lateral canthi, tragus, ala, and oral commissure distances, in 234 prerhinoplasty surgical photographs. The photographs were rated by 10 independent observers for a global "first impression" of facial symmetry, and the relationship between anthropometric measurement and subjective perception of facial symmetry was explored with logistic regression. RESULTS: Objectively, 97% of patients had significant degrees of facial asymmetry, with the midline to ala distances showing the most variations and the midline to oral commissures showing the least variations. Subjectively, 38% of results were perceived as asymmetrical, with the degree of midline to lateral alar margin asymmetry being an independent predictor of the perception of facial asymmetry on binary logistic regression (P<.003). CONCLUSIONS: A significant correlation was found between the degree of objective facial asymmetry, particularly in anthropometric nasal measurements, and the subjective perception of a face as asymmetrical in patients requesting aesthetic rhinoplasty. This relationship may be a factor in patients who request rhinoplasty and should be explored in this patient group.

Degradation of anthropogenic pollutant and organic dyes by biosynthesized silver nano-catalyst from Cicer arietinum leaves.

The work represents the potent catalytic activity of silver nanoparticles synthesized from Cicer arietinum (chickpea) leaf extract (CAL-AgNPs). Here, silver nano-catalysts were used against the anthropogenic pollutants mainly involving nitro-amines and azo dyes. These pollutants are extremely harmful to our environment and causes severe health issues. The CAL-AgNPs have the potential to degrade harmful toxins and their by-products, thereby decreasing the pollutants from the environment. The green synthesis of nano-catalyst includes a simple, cost effective and eco-friendly method using the leaf extract from the plant. A systematic study was conducted, including synthesis, optimization and characterization of the silver particles. The AgNPs were further assessed through DLS and TEM for size and morphological evaluation. The obtained particles have shown spherical morphology with the size range of 88.8nm. Further, FTIR were performed for compositional and functional group analysis of the particles. The antibacterial efficiency was also evaluated against E. coli and P. aeruginosa. For their catalytic evaluation, CAL-AgNPs were assessed for 4-nitrophenol, methylene blue and congo red. The results obtained through catalytic evaluation suggested that the CAL-AgNPs could be helpful to surmount the environmental pollution in a very effective manner.

Aberrant facial flushing following monobloc fronto-facial distraction.

BACKGROUND: Patients with syndromic forms of craniosynostosis may experience functional problems such as raised intracranial pressure, proptosis, obstructive sleep apnoea and failure to thrive. The monobloc fronto-facial advancement with osteogenic distraction is increasingly used to correct these functional problems in one procedure as well as improve appearance. The authors report the phenomenon of post operative aberrant facial flushing - an unusual and previously unreported complication of the procedure. METHODS: The case notes of 80 consecutive patients undergoing fronto-facial advancement by distraction using the rigid external distraction device (RED) were reviewed for features of aberrant facial flushing. RESULTS: Four out of eighty individuals developed facial flushing after monobloc fronto-facial distraction using the rigid external distractor (RED) frame. All were female with Crouzon or Pfeiffer syndromes causing the severe functional problems for which they underwent the surgery. They were aged 6-8 years. Following removal of the frame, they developed intermittent but severe facial flushing. The flushing spontaneously settled in three patients after up to four years but persists in the other child seven years after her surgery. CONCLUSION: Aberrant facial flushing is a rare but significant complication of monobloc fronto-facial surgery. It occurred in 4 of our 80 (5%) patients. The skull base osteotomies essential for the procedure are made anterior to the pterygopalatine ganglion and it is our contention that damage from these was responsible for a neuropraxia of its efferent nerve branches. A review of the autonomic control of the facial vascular system suggests that the phenomenon is due to an unequal process of recovery that leaves the cutaneous vasodilating parasympathetic or beta-adrenergic innervation relatively unopposed - a situation that persists until with time a normal balance of autonomic input is achieved.

A marker-free system for highly efficient construction of vaccinia virus vectors using CRISPR Cas9.

The current method for creation of vaccinia virus (VACV) vectors involves using a selection and purification marker, however inclusion of a gene without therapeutic value in the resulting vector is not desirable for clinical use. The Cre-LoxP system has been used to make marker-free Poxviruses, but the efficiency was very low. To obtain a marker-free VACV vector, we developed marker gene excision systems to modify the thymidine kinase (TK) region and N1L regions using Cre-Loxp and Flp-FRET systems respectively. CRISPR-Cas9 system significantly resulted in a high efficiency (~90%) in generation of marker gene-positive TK-mutant VACV vector. The marker gene (RFP) could be excised from the recombinant virus using Cre recombinase. To make a marker-free VV vector with double gene deletions targeting the TK and N1L gene, we constructed a donor repair vector targeting the N1L gene, which can carry a therapeutic gene and the marker (RFP) that could be excised from the recombinant virus using Flp recombinase. The marker-free system developed here can be used to efficiently construct VACV vectors armed with any therapeutic genes in the TK region or N1L region without marker genes. Our marker-free system platform has significant potential for development of new marker-free VACV vectors for clinical application.

A vaccinia virus armed with interleukin-10 is a promising therapeutic agent for treatment of murine pancreatic cancer.

PURPOSE: Vaccinia virus has strong potential as a novel therapeutic agent for treatment of pancreatic cancer. We investigated whether arming vaccinia virus with interleukin-10 (IL10) could enhance the antitumor efficacy with the view that IL10 might dampen the host immunity to the virus, increasing viral persistence, thus maximizing the oncolytic effect and antitumor immunity associated with vaccinia virus. EXPERIMENTAL DESIGN: The antitumor efficacy of IL10-armed vaccinia virus (VVLΔTK-IL10) and control VVΔTK was assessed in pancreatic cancer cell lines, mice bearing subcutaneous pancreatic cancer tumors and a pancreatic cancer transgenic mouse model. Viral persistence within the tumors was examined and immune depletion experiments as well as immunophenotyping of splenocytes were carried out to dissect the functional mechanisms associated with the viral efficacy. RESULTS: Compared with unarmed VVLΔTK, VVLΔTK-IL10 had a similar level of cytotoxicity and replication in vitro in murine pancreatic cancer cell lines, but rendered a superior antitumor efficacy in the subcutaneous pancreatic cancer model and a K-ras-p53 mutant-transgenic pancreatic cancer model after systemic delivery, with induction of long-term antitumor immunity. The antitumor efficacy of VVLΔTK-IL10 was dependent on CD4(+) and CD8(+), but not NK cells. Clearance of VVLΔTK-IL10 was reduced at early time points compared with the control virus. Treatment with VVLΔTK-IL10 resulted in a reduction in virus-specific, but not tumor-specific CD8(+) cells compared with VVLΔTK. CONCLUSIONS: These results suggest that VVLΔTK-IL10 has strong potential as an antitumor therapeutic for pancreatic cancer.