Use of Suprapubic Panniculus for Split-Thickness Skin Graft in Buried Penis Repair.

Background: In the United States, acquired buried penis deformity is an increasingly more common condition. Management of the buried penis deformity is accomplished with removal of macerated skin and subcutaneous tissue from the panniculus and prepubic region, and replacement of denuded penile skin. If local tissue advancement is insufficient to cover the defect, a skin graft may be required. Though the anterior thigh is commonly used, this creates a second defect. Here we describe 2 cases of split-thickness skin grafts harvested from the panniculus to cover buried penis deformities. Methods: Two patients with a buried penis deformity were identified. The denuded suprapubic tissue was elevated. Using inferior traction, split-thickness skin grafts were harvested and placed onto the shaft of the penis. The remaining excess tissue was resected. Results: One patient had a fungal rash that resolved with topical treatment. The other patient had a hematoma requiring surgical evacuation. Neither patient had any other complications, and both had over 95% take of the split-thickness skin grafts. Conclusions: These cases demonstrate the successful use of pannicular skin grafts for buried penis deformity correction. This donor site avoids creation of a second defect. As demonstrated here, the grafts are a durable option, even in the setting of local infection and hematoma.

A Randomised Phase II Trial to Evaluate the Feasibility of Radiotherapy Dose Escalation, Facilitated by Intensity-Modulated Arc Radiotherapy Techniques, in High-Risk Neuroblastoma.

BACKGROUND AND PURPOSE: For high-risk neuroblastoma, planning target volume coverage is often compromised to respect adjacent kidney tolerance. This trial investigated whether intensity-modulated arc radiotherapy techniques (IMAT) could facilitate dose escalation better than conventional techniques. MATERIALS AND METHODS: Children with high-risk abdominal neuroblastoma referred for radiotherapy to the primary tumour site and involved regional lymph nodes were randomised to receive either standard dose (21 Gy in 14 fractions) or escalated dose (36 Gy in 24 fractions) radiotherapy. Dual planning with both a conventional anterior-posterior parallel opposed pair radiotherapy technique and an IMAT technique was performed. The quality of target volume and organ-at-risk delineation, and dosimetric plans, were externally reviewed. Dosimetric parameters were used to judge the superior technique for treatment. This feasibility trial was not powered to detect improvement in outcome with dose escalation. RESULTS: Between 2017 and 2020, 50 patients were randomised and dual-planned. The IMAT technique was judged more favourable in 48 patients. In all patients randomised to receive 36 Gy, IMAT would have permitted delivery of the full dose (median D50% 36.0 Gy, inter-quartile range 36.0-36.1 Gy) to the target volume, whereas dose compromise would have been required with conventional planning (median D50% 35.6 Gy, inter-quartile range 28.7-35.9 Gy). CONCLUSION: IMAT facilitates safe dose escalation to 36 Gy in patients receiving radiotherapy for neuroblastoma. The value of dose escalation is now being evaluated in a current prospective phase III randomised trial.

Fully Automated Measurement of the Insall-Salvati Ratio with Artificial Intelligence.

Patella alta (PA) and patella baja (PB) affect 1-2% of the world population, but are often underreported, leading to potential complications like osteoarthritis. The Insall-Salvati ratio (ISR) is commonly used to diagnose patellar height abnormalities. Artificial intelligence (AI) keypoint models show promising accuracy in measuring and detecting these abnormalities.An AI keypoint model is developed and validated to study the Insall-Salvati ratio on a random population sample of lateral knee radiographs. A keypoint model was trained and internally validated with 689 lateral knee radiographs from five sites in a multi-hospital urban healthcare system after IRB approval. A total of 116 lateral knee radiographs from a sixth site were used for external validation. Distance error (mm), Pearson correlation, and Bland-Altman plots were used to evaluate model performance. On a random sample of 2647 different lateral knee radiographs, mean and standard deviation were used to calculate the normal distribution of ISR. A keypoint detection model had mean distance error of 2.57 ± 2.44 mm on internal validation data and 2.73 ± 2.86 mm on external validation data. Pearson correlation between labeled and predicted Insall-Salvati ratios was 0.82 [95% CI 0.76-0.86] on internal validation and 0.75 [0.66-0.82] on external validation. For the population sample of 2647 patients, there was mean ISR of 1.11 ± 0.21. Patellar height abnormalities were underreported in radiology reports from the population sample. AI keypoint models consistently measure ISR on knee radiographs. Future models can enable radiologists to study musculoskeletal measurements on larger population samples and enhance our understanding of normal and abnormal ranges.

A multi-lesional analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a single-centre analysis.

AIM: To conduct a multi-lesional computed tomography (CT) analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) patients to determine volumetric changes in lesions over 5 years. MATERIALS AND METHODS: A retrospective case-note review was undertaken to identify 16 patients with histological and radiological features of DIPNECH between 2012-2021. Area and volume were calculated for 17 sets of lesions identified on high-resolution CT. Clinical data were extracted from electronic patient records, which included demographic data, outpatient clinic letters, histology reports, and imaging reports. RESULTS: One hundred and twenty-eight lesions were identified in 16 patients (one male, 15 female) and followed-up annually over a median 1,985 days (range 1,450-2,290). At year 1 follow-up, lesion area ranged from 1-48 mm2, and lesion volume ranged from 8-18,380 mm3; lesion area ranged from 1-45mm2 and lesion volume ranged from 11-17,800 mm3 and year 5. Half (8/16) of the patients had concomitant typical carcinoid tumours and one patient had an atypical carcinoid tumour. No statistically significant correlation (p<0.05) was found between lesion cross-sectional area or volume and duration of follow-up (years and days). No metastatic spread was observed at the time of analysis. CONCLUSIONS: No significant increase was observed in the size of over 100 lesions in patients with DIPNECH over a 5-year period and no metastasis occurred during the study period affirming the relatively indolent course of the disease.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Suspected tick-borne flavivirus meningoencephalomyelitis in dogs from the UK: six cases (2021).

OBJECTIVES: Tick-borne encephalitis virus and louping ill virus are neurotropic flaviviruses transmitted by ticks. Epidemiologically, tick-borne encephalitis is endemic in Europe whereas louping ill's predominant geographical distribution is the UK. Rarely, these flaviviruses affect dogs causing neurological signs. This case series aimed to describe the clinical, clinicopathological, and imaging findings, as well as the outcomes in six dogs with meningoencephalitis and/or meningomyelitis caused by a flavivirus in the UK in 2021. MATERIALS AND METHODS: Observational retrospective case-series study. Clinical data were retrieved from medical records of dogs with positive serological or immunohistochemical results from three different institutions from spring to winter 2021. RESULTS: Six dogs were included in the study. All dogs presented an initial phase of pyrexia and/or lethargy followed by progressive signs of spinal cord and/or intracranial disease. Magnetic resonance imaging showed bilateral and symmetrical lesions affecting the grey matter of the thalamus, pons, medulla oblongata, and thoracic or lumbar intumescences with none or mild parenchymal and meningeal contrast enhancement. Serology for tick-borne encephalitis virus was positive in five dogs with the presence of seroconversion in two dogs. The viral distinction between flaviviruses was not achieved. One dog with negative serology presented positive immunohistochemistry at post-mortem examination. Three dogs survived but presented neurological sequelae. Three dogs were euthanased due to the rapid progression of the clinical signs or static neurological signs. CLINICAL SIGNIFICANCE: These cases raise awareness of the presence of tick-borne encephalitis as an emergent disease or the increased prevalence of louping ill virus affecting dogs in the UK.

Dual carbon isotope-based brown carbon aerosol characteristics at a high-altitude site in the northeastern Himalayas: Role of biomass burning.

PM2.5 samples (n = 34) were collected from January to April 2017 over Shillong (25.7°N, 91.9°E; 1064 m amsl), a high-altitude site situated in the northeastern Himalaya. The main aim was to understand the sources, characteristics, and optical properties of local vs long-range transported carbonaceous aerosols (CA) using chemical species and dual carbon isotopes (13C and 14C). Percentage biomass burning (BB)/biogenic fraction (fbio, calculated from 14C) varied from 67 to 92 % (78 ± 7) and correlated well with primary BB tracers like f60, and K+, suggesting BB as a considerable source. Rain events are shown to reduce the fbio fraction, indicating majority of BB-derived CA are transported. Further, δ13C (-26.6 ± 0.4) variability was very low over Shillong, suggesting it's limitations in source apportionment over the study region, if used alone. Average ratio of absorption coefficient of methanol-soluble BrC (BrCMS) to water-soluble BrC (BrCWS) at 365 nm was 1.8, indicating a significant part of BrC was water-insoluble. A good positive correlation between fbio and mass absorption efficiency of BrCWS and BrCMS at 365 nm with the higher slope for BrCMS suggests BB derived water-insoluble BrC was more absorbing. Relative radiative forcing (RRF, 300 to 2500 nm) of BrCWS and BrCMS with respect to EC were 11 ± 5 % and 23 ± 16 %, respectively. Further, the RRF of BrCMS was up to 60 %, and that of BrCWS was up to 22 % with respect to EC for the samples with fbio ≥ 0.85 (i.e., dominated by BB), reflecting the importance of BB in BrC RRF estimation.

mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency.

Transaldolase deficiency predisposes to chronic liver disease progressing from cirrhosis to hepatocellular carcinoma (HCC). Transition from cirrhosis to hepatocarcinogenesis depends on mitochondrial oxidative stress, as controlled by cytosolic aldose metabolism through the pentose phosphate pathway (PPP). Progression to HCC is critically dependent on NADPH depletion and polyol buildup by aldose reductase (AR), while this enzyme protects from carbon trapping in the PPP and growth restriction in TAL deficiency. Although AR inactivation blocked susceptibility to hepatocarcinogenesis, it enhanced growth restriction, carbon trapping in the non-oxidative branch of the PPP and failed to reverse the depletion of glucose 6-phosphate (G6P) and liver cirrhosis. Here, we show that inactivation of the TAL-AR axis results in metabolic stress characterized by reduced mitophagy, enhanced overall autophagy, activation of the mechanistic target of rapamycin (mTOR), diminished glycosylation and secretion of paraoxonase 1 (PON1), production of antiphospholipid autoantibodies (aPL), loss of CD161+ NK cells, and expansion of CD38+ Ito cells, which are responsive to treatment with rapamycin in vivo. The present study thus identifies glycosylation and secretion of PON1 and aPL production as mTOR-dependent regulatory checkpoints of autoimmunity underlying liver cirrhosis in TAL deficiency.

Glutaredoxin proteins from E. coli isoforms were compared in terms of energy frustration.

Glutaredoxin (GRXs) protein plays a vital role inside the cell, including redox control of transcription to the cell's antioxidant defense, apoptosis, and cellular differentiation regulation. In this study, we have investigated the energy landscape and characterized the pattern of local frustration in different forms and states of the GRX protein ofE. coli.Analysis was done on the conformational alterations, significant changes in the frustration pattern, and different GRXs such as GRX-II, GRX-III, GRX-II-GSH, and GRX-III-GSH complex. We have found the practice of frustration, and structure was quite similar in the same isoform having different states of protein; however, a significant difference was observed between different isoforms. Moreover, oxidation of GRX-I introduced an extra α-helix increasing the destabilizing interactions within the protein. The study of frustrated contacts on oxidized and reduced GRX and with bound and unbound Glutathione indicates its potential application in activating and regulating the behavior of GRXs.

Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030.

BACKGROUND: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence. RESULTS: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10-4 (range 7.9 × 10-7-4.9 × 10-1). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12. CONCLUSIONS: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.

"Blockchain technology in food safety and traceability concern to livestock products".

Livestock products share more than fifteen percent of total agri-foods traded worldwide. A global increase in food demand has increased the risk to food safety. Improvements in food quality, cold chain transit, and preservation are required for safe livestock products. Though, the food safety and regulation authorities demand complete food traceability from farm to fork, but in traditional supply chain it is ignored by fiddling with the transit paperwork and bill invoices. The process of supply chain reformation and activities linked to food recalls during food safety issues are insanely expensive and challenging. Traceability-driven food supply chain management is likely to implement novel technologies like the Internet of Things (IoT). The capability of the Blockchain era within the food sector is emerging with use cases across different regions, as shown via the growing number of studies. Credibility, efficiency, and safety are all improved when food products can be instantly traced from their point of origin through all points of contact on their way to the consumer. Blockchain assures a tamper-proof and transparent system that allows an innovative business solution, together with smart contracts. However, there are significant difficulties with the implementation of blockchain technology for food traceability. It necessitates more and more training platforms as well as trainers, who can make understanding and operability of this technology easy among ground-level participants and food entities. For the tactical application of this technology, it is essential to comprehend the legal and regulatory framework.

Evaluation of the impact of continuous Kangaroo Mother Care (KMC) initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to < 1.8 kg on neurodevelopmental outcomes: Protocol for a follow-up study.

BACKGROUND: Preterm birth or low birth weight is the single largest cause of death in newborns, however this mortality can be reduced through newborn care interventions, including Kangaroo Mother Care (KMC). Previously, a multi-country randomized controlled trial, coordinated by the World Health Organization (WHO), reported a significant survival advantage with initiation of continuous KMC immediately after birth compared with initiation of continuous KMC a few days after birth when the baby is considered clinically stable. Whether the survival advantage would lead to higher rates of neurodevelopmental morbidities, or the immediate KMC will also have a beneficial effect on cognitive development also, has not been investigated. We therefore propose to test the hypothesis that low-birth-weight infants exposed to immediate KMC will have lower rates of neurodevelopmental impairment in comparison to traditional KMC-treated infants, by prospectively following up infants already enrolled in the immediate KMC trial for the first 2 years of life, and assessing their growth and neurodevelopment. METHODS: This prospective cohort study will enroll surviving neonates from the main WHO immediate KMC trial. The main trial as well as this follow-up study are being conducted in five low- and middle-income countries in South Asia and sub-Saharan Africa. The estimated sample size for comparison of the risk of neurodevelopmental impairment is a total of 2200 children. The primary outcome will include rates of cerebral palsy, hearing impairment, vision impairment, mental and motor development, and epilepsy and will be assessed by the age of 3 years. The analysis will be by intention to treat. DISCUSSION: Immediate KMC can potentially reduce low-birth-weight-associated complications such as respiratory disease, hypothermia, hypoglycemia, and infection that can result in impaired neurocognitive development. Neuroprotection may also be mediated by improved physiological stabilization that may lead to better maturation of neural pathways, reduced risk of hypoxia, positive parental impact, improved sleep cycles, and improved stress responses. The present study will help in evaluating the overall impact of KMC by investigating the long-term effect on neurodevelopmental impairment in the survivors. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2019/11/021899. Registered on 06 November 2019. Trials registration of parent trial: ACTRN12618001880235; Clinical Trials Registry-India: CTRI/2018/08/015369.

Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model.

Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice.

The impact of electronic pathways and digital systems on neck of femur fracture outcomes globally: a systematic review.

INTRODUCTION: Electronic pathways (e-pathways) and digital systems are novel interventions with several uses in healthcare, ranging from clinical decision support systems to checklists for care delivery. Their application in the management of neck of femur (NOF) fractures is evolving and they may play a key role in facilitating improvements in care delivery. The primary aim of this review was to outline the impact of e-pathways/digital systems on NOF fracture outcomes. METHODS: A systematic literature search was performed using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. A total of 698 citations were evaluated, of which 38 passed the inclusion/exclusion criteria. Six studies were then finalised following full-text review. Heterogenous data meant a narrative synthesis was undertaken. Risk of bias for each paper was assessed using the Downs and Black scale. RESULTS: A statistically significant improvement was demonstrated for time to theatre (3/6 studies), length of hospital stay (2/6 studies) and secondary fracture prevention (2/6 studies). Although postoperative delirium and mortality improved with the introduction of e-pathways/digital systems, statistical significance was not achieved. No outcome measures were adversely affected. CONCLUSIONS: This systematic review of the literature demonstrates that e-pathways and digital systems are promising novel interventions, displaying a significant positive impact on several NOF fracture outcomes. Owing to the novel nature of e-pathways and digital systems in orthopaedics, a limited number of studies were identified for review, each with variable study design. More high quality homogenous prospective cohort studies with a standardised primary outcome measure are required for more definitive conclusions of efficacy to be drawn.

Metal nanoparticles produced by plants with antibacterial properties against Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a pathogenic bacteria that causes a variety of potentially fatal infections. The emergence of antibiotic-resistant strains of S. aureus has made treatment even more difficult. In recent years, nanoparticles have been used as an alternative therapeutic agent for S. aureus infections. Among various methods for the synthesis of nanoparticles, the method utilizing plant extracts from different parts of a plant, such as root, stem, leaf, flower, seeds, etc. is gaining widespread usage. Phytochemicals present in plant extract are an inexpensive, eco-friendly, natural material that act as reducing and stabilization agent for the nanoparticle synthesis. The utilization of plant-fabricated nanoparticles against S. aureus is currently in trend. The current review discusses recent findings in the therapeutic application of phytofabricated metal-based nanoparticles against Staphylococcus aureus.

Embolic Agent Choice in Middle Meningeal Artery Embolization as Primary or Adjunct Treatment for Chronic Subdural Hematoma: A Systematic Review and Meta-analysis.

BACKGROUND: Middle meningeal artery embolization is an emerging treatment option for chronic subdural hematomas. PURPOSE: Our aim was to assess outcomes following middle meningeal artery embolization by different techniques, including in comparison with traditional surgical methods. DATA SOURCES: We searched the literature databases from inception to March 2022. DATA SELECTION: We selected studies reporting outcomes after middle meningeal artery embolization as a primary or adjunctive treatment for chronic subdural hematoma. DATA ANALYSIS: We analyzed the risk of recurrence of chronic subdural hematoma, reoperation for recurrence or residual hematoma, complications, and radiologic and clinical outcomes using random effects modeling. Additional analyses were performed on the basis of whether middle meningeal artery embolization was used as the primary or adjunct treatment and by embolic agent type. DATA SYNTHESIS: Twenty-two studies were included with 382 patients with middle meningeal artery embolization and 1373 surgical patients. The rate of subdural hematoma recurrence was 4.1%. Fifty (4.2%) patients underwent a reoperation for a recurrent or residual subdural hematoma. Thirty-six (2.6%) experienced postoperative complications. The rates of good radiologic and clinical outcomes were 83.1% and 73.3%, respectively. Middle meningeal artery embolization was significantly associated with decreased odds of subdural hematoma reoperation (OR = 0.48; 95% CI, 23.4-99.1; P = .047) compared with surgery. The lowest rates of subdural hematoma radiologic recurrence, reoperation, and complications were observed among patients receiving embolization with Onyx, whereas good overall clinical outcome occurred most commonly with combined polyvinyl alcohol and coils. LIMITATIONS: A limitation was the retrospective design of studies included. CONCLUSIONS: Middle meningeal artery embolization is safe and effective, either as a primary or adjunctive treatment. Treatment using Onyx seems to yield lower rates of recurrence, rescue operation, and complications whereas particles and coils produce good overall clinical outcomes.