Four hour voiding observation study in infants with posterior urethral valves.

INTRODUCTION AND AIM: Posterior urethral valves (PUV) are often associated with bladder dysfunction. Our primary aim was to investigate bladder status following primary valves resection to gather evidence of function and to guide early clinical management. PATIENTS AND METHODS: Between July 2015-2020, we prospectively evaluated bladder function of PUV infants. Primary outcomes measured were number of voids, voided volume (VV), post-void residual (PVR) and bladder capacity (BC). Statistical comparisons and descriptive analysis were carried out between groups using 2-tails T test and Chi square test using an IBM SPSS Statistics program version 25. RESULTS: Sixty-one infants were included. Median age at resection was 28 days (5 days-11 months). In thirty-eight patients (62%) diagnosis was suspected antenatally. Vesico-ureteric reflux (VUR) was present in 16 (26%). The 4-h observational study was performed at median 4 days following primary cold-knife valve resection and 1 day (range from 1 to 12 days) after catheter removal. Infants voided an average 6 times (2-13 voids). Bladder capacity was large in 20 (33%) and small in 4 (6.5%) patients with a median ratio BC/eBC = 1.2 (0.49-22.6). Median residual urine was 9 mls but with great variability among the cohort (0-121 mls). A big variability in bladder emptying was noted between patients and between voids performed in one patient. In 13 infants (21%) average PVR was larger than the average voided volume. In 26 (42.6%) PVR was larger than VV at least once. Thirty-eight infants (62.3%) emptied their bladders almost completely at least once (with PVR <5 mls). No difference was found in PVR, Median BC/EBC and PVR/BC between infants with and without VUR (p = 0.654, P: 0.594 and p = 00.481, respectively). DISCUSSION: We presented our experience of non-invasive bladder function assessment in infants affected by PUV following primary valve resection. An interesting data is the great variability identified both between patients and between voids performed in a single patient. Average number of voids was similar to the voiding pattern in healthy newborns what reported by Gladh but variability was greater. We observed up to 13 voids in some infants and we can speculate this could reflect the presence of an overactive bladder. We observed at least 1 complete emptying in only 62% of infants and 21% of the cohort had PVR bigger than VV. In almost half of the infants (42.6%) PVR was larger than VV at least once. CONCLUSIONS: Around 40% of infants affected by PUV have abnormal bladder capacity and almost half of them have significant post void residuals following primary resection. Although controversies and limitations are present, we believe that this non-invasive study can provide valuable information to understand the dynamic of the bladder, particularly in children affected by PUV and allow early intervention in children considered "at risk". Having a non invasive way of assessing can help tailor intervention and be useful for future research into early bladder intervention and improving outcomes.

Laparoscopic strategies in complex upper urinary tract obstruction.

OBJECTIVES: We enumerate the various laparoscopic strategies to resolve upper urinary tract (UUT) obstruction in the context of variations in anatomy and report their outcomes. PATIENTS AND METHODS: Retrospective review of primary laparoscopic UUT reconstructions performed between May 2012 and May 2021. Anomalies included: malrotated kidney (MRK), horseshoe kidney (HSK), duplex kidney (DK), pure intrarenal pelvis (IRP) and mid-ureteric stenosis (MUS). Success was defined by postoperative resolution of symptoms, improvement of anterior-posterior renal pelvic diameter (APD) on US and drainage on Mag3. Complications were categorised by Clavien-Dindo grading. Outcomes compared using the student's t-test with P < 0.05 considered statistically significant. RESULTS: Of the 214 laparoscopic primary UUT reconstructions, 37 (17.2 %) were: 13-MRK, 12-HSK, 4-DK, 4-IRP and 4-MUS. Median age at surgery was 5-years (range 0.3-15). Dismembered pyeloplasty: 8; pyeloplasty with renal sinus dissection: 8; neo-PUJ anastomosis: 8; primary ureterocalycostomy: 7; pyeloureterostomy: 2; and uretero-ureterostomy: 4. Median follow-up was 43-months (range 8-108) with a success rate of 94.5 % (35/37). Complete resolution of symptoms in 20/21 patients; improvement of hydronephrosis on US in 35/37 patients (median pre-operative APD 27 mm vs. median postoperative APD 8 mm) [P < 0.001]; improvement of drainage on diuretic renogram in 32/34 kidneys and stable/improved DRF in 34/35 kidneys (median preoperative DRF - 45 % vs. median postoperative DRF - 47 %) [P > 0.05]. Postoperative complications managed medically (II Clavien) included urinary tract infections - 2 patients (5 %), stent-related symptoms in 2 (5 %) and umbilical port site collection in 1 patient (3 %). Recurrent pelvi-ureteric junction obstruction PUJO occurred in one patient (3 %) requiring redo surgery (IIIb Clavien), renal stones in 1 (3 %) which resolved with ESWL (IIIb Clavien); in 1 (3 %) patient with a HSK there was complete loss of ipsilateral kidney function but this was managed conservatively up to date (I Clavien). CONCLUSION: Laparoscopic transperitoneal approach allows the prompt recognition of in-situ anatomical variants. UUT obstruction in such settings calls for a variety of strategies with excellent outcomes.

Effect of Coronavirus Disease 2019 Pandemic on Spinal Surgery Patients: Our Experience at a Tertiary Care Center.

Introduction: In December 2019, a cluster of atypical cases of pneumonia was reported in Wuhan, China, which was later designated as Coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on Feb 11, 2020. We all are facing a global pandemic, and it is very important to be clear that there is no correct roadmap to navigate this difficult situation. It is imperative to state that this global pandemic impacted the spine care services of our institute. In the present study, we have assessed the spine surgeries performed by orthopedic surgeons in terms of volume and etiologies during the COVID-19 pandemic and compared the data with a pre-COVID period. Materials and Methods: We retrospectively collected data from all patients who underwent spinal surgeries at our institute under the department of orthopedics from August 20, 2019 to August 20, 2020 (a total of 12 months duration). The data was then divided into two groups-pre-COVID period (August 20, 2019-February 19, 2020-6 months) and during the COVID pandemic (February 20, 2020-August 20, 2021-6 months). Results: A total of 140 patients underwent surgery at our institute from August 20, 2019 to August 20, 2020. Of these, 91 patients underwent surgery during the pre-COVID period, and 49 patients underwent surgery during the COVID pandemic. In this devastating phase of the pandemic, our department's total number of surgeries significantly declined to 46.15%. The routine surgeries performed during the pandemic phase show a steep fall from 59.34% in the pre-COVID period to 10.20%. Conclusion: This paper is meant to focus attention on the exorbitant reduction in the operative workflow of the spine patients during the COVID-19 pandemic at a tertiary healthcare institute. It is the need of the hour that orthopedic surgeons maintain equilibrium while providing the best possible treatment to their patients and limiting the spread of the COVID-19 pandemic.

Are there anatomical limiting factors to foreskin reconstruction at the time of single-stage hypospadias repair?

INTRODUCTION: Foreskin reconstruction (FR) at the time of primary hypospadias repair is a truly anatomically complete reconstruction of the hypospadic penis. We prospectively collected penile and preputial measurement of children undergoing single-stage hypospadias repair and FR with the aim to identify possible relations between penile and preputial anatomy and the likelihood to develop complications. MATERIALS AND METHODS: We prospectively studied children who underwent single stage hypospadias repair associated with FR from 2016 to 2019. We recorded intra-operative foreskin and penile measurements and post-operative outcomes. Logistic Regression analysis was performed to explore independent factors affecting urethroplasty and skin complications. Chi square test was used to compare outcomes in different groups based on ventral foreskin defect (VFD) width, Glans size, age at surgery and meatal location. RESULTS: From a total of 181 consecutive patients, 86 boys who underwent a single stage hypospadias repair combined with FR were included in the study. Patients were excluded because they were either lost at follow up (n = 10), required a 2-stage repair (n = 2), were circumcised at birth (n = 3) or parents requested a circumcision (n = 78); in 2 patients, a decision to perform circumcision was made intraoperatively due to aesthetic reasons (monk-hood deformity of the prepuce). Median age at surgery was 17 months. Mean glans width was 14.4 mm. Mean unstretched and stretched foreskin circumference were 29.5 mm and 40.9 mm, respectively. Mean VFD (the distance between the proximal insertion of the foreskin hood on either side of the midline at the level of the coronal sulcus) was 7.2 mm (Fig. 1). At median follow-up of 8 months (6-23), 9 complications were recorded (10.4%): foreskin dehiscence occurred in 1% (1/86), a foreskin fistula was noted in 4.6% (4/86), tight, non-retractile, foreskin in 1% (1/86); urethrocutaneous fistula in 2.3% (2/86) and complete dehiscence of the glans and foreskin in 1 (1.2%). Multiple logistic regression analysis demonstrated that none of the measurements obtained was an independent risk factor for developing urethroplasty or skin complications. There was no significant difference in complications between wide VFD (>7 mm) vs. narrow VFD (≤7 mm), large glans (>14 mm) vs. small glans (≤14 mm), age at surgery ≤24 months vs. > 24 month and meatal location distal (glanular, coronal, subcoronal and distal penile) vs. proximal (midpenile, proximal penile and penoscrotal). CONCLUSION: To the best of our knowledge, this is the first study reporting a prospective and objective assessment of the foreskin in the context of single stage hypospadias repair. Individual anatomical differences in preputial and penile anatomy do not seem to affect the likelihood of skin and urethroplasty complications. FR can, therefore, be offered to all boys undergoing primary single stage hypospadias repair . Further studies on larger numbers and external validation of these measurements is necessary.

Molecular dissection studies of TAC1, a transcription activator of Candida drug resistance genes of the human pathogenic fungus Candida albicans.

The up-regulation of ABC transporters Cdr1p and Cdr2p that efflux antifungal azole drugs are a leading cause of Multi-Drug Resistance (MDR) in the white fungus Candida albicans. C. albicans was reported to infect patients following the recent Covid-19 pandemic after they were given steroids for recovery. Previously, the TAC1 gene was identified as the transcriptional activator of Candida drug resistance genes (CDR1 and CDR2) and has no known human homologs. This makes it a good target for the development of novel antifungals. We, therefore, carried out the molecular dissection study of TAC1 to understand the functional regulation of the ABC transporter genes (CDR1 and CDR2) under its control. The N-terminal DNA Binding Domain (DBD) of Tac1p interacts with the Drug Responsive Element (DRE) present in the upstream promoter region of CDR1 and CDR2 genes of C. albicans. The interaction between DBD and DRE recruits Tac1p to the promoter of CDR genes. The C-terminal Acidic Activation Domain (AAD) of Tac1p interacts with the TATA box Binding Protein (TBP) and thus recruits TBP to the TATA box of CDR1 and CDR2 genes. Taking a cue from a previous study involving a TAC1 deletion strain that suggested that Tac1p acts as a xenobiotic receptor, in this study, we identified that the Middle Homology Region (MHR) of Tac1p acts as a probable xenobiotic binding domain (XBD) which plays an important role in Candida drug resistance. In addition, we studied the role of Tac1p in the regulation of some lipid profiling genes and stress response genes since they also contain the DRE consensus sequence and found that some of them can respond to xenobiotic stimuli.

Three-Year Experience and Outcomes of Near-Early Internal Fixation for Femoral Neck Fractures in Pediatric Trauma Patients: A Retrospective Study.

Background The fractured neck of the femur in children is commonly caused by high-energy trauma, and despite its low incidence, complications are more frequent. Delayed presentation is not unusual in developing countries. The interval between injury and surgery is thought to be a critical factor in determining outcomes. This study aims to evaluate the effectiveness of "near early" internal fixation (24-72 hours) for fractured neck of the femur in children. Methods This is a retrospective observational study that analyzed complete case records from a period of seven years. Cases were classified according to the Delbet classification and outcomes were assessed using the Ratliff criteria with a minimum follow-up of three years. Results The study included 24 male and 11 female patients, with an average age of 11.28 years. The most common cause of injury was road traffic accidents. The fracture distribution in the study population was as follows: Delbet type II in 18 patients, Delbet type III in 10 patients, and Delbet type IV in seven patients. In our study, all patients underwent near-early fixation, meaning their fractures were fixed within 24-72 hours of injury. The average time for the clinical-radiological union was 8 weeks, and the most common complication was premature physeal fusion, followed by osteonecrosis. Conclusion In developing countries, where patients often experience delayed referrals and lack of awareness, near-early fixation (24-72 hours) of a fractured neck of the femur in children is a crucial option that holds significant value.

Posterior Urethral Valves, Unilateral Vesicoureteral Reflux, and Renal Dysplasia (VURD) Syndrome: Long-Term Longitudinal Evaluation of the Kidney Function.

The presence of unilateral vesicoureteral reflux (VUR), and renal dysplasia associated with posterior urethral valves (PUV) (VURD syndrome) was believed to represent a pressure-released pop-off mechanism protecting kidney function. We aimed to investigate its role with respect to long-term kidney function in a cross-sectional and longitudinal analysis. We compared the iohexol glomerular filtration rate (GFR) measured at 5 (GFR5) and 10 (GFR10) years of age in children with (Group A) and without (Group B) VURD syndrome, who underwent PUV resection under 2 years of age. VURD syndrome was diagnosed in cases of unilateral loss of kidney function (<15% on nuclear medicine test) associated with ipsilateral grade IV-V VUR. VURD syndrome was diagnosed in 16 (12.8%) out of 125 patients who met the inclusion criteria. While the median GFR5 was similar in the 2 groups [Group A: 87.3 (74.7-101.2) mL/min/1.73 m2 vs. Group B: 99.6 (77-113) mL/min/1.73 m2, p-value: 0.181], the median GFR10 values were significantly lower in children with VURD syndrome [Group A: 75.7 (71.2-85.9) mL/min/1.73 m2 vs. Group B: 95.1 (81.2-114.2) mL/min/1.73 m2, p-value: 0.009]. Similar results were obtained in a longitudinal analysis of the children with GFR measurement available both at 5 and 10 years of age [GFR5 in Group A: 93.1 (76.9-103.5) mL/min/1.73 m2 vs. Group B: 97.5 (80-113) mL/min/1.73 m2, p-value: 0.460; GFR10: Group A: 71.9 (71.9-85.9) mL/min/1.73 m2 vs. Group B: 94.8 (81.5-110.6) mL/min/1.73 m2, p-value: 0.024]. In conclusion, VURD syndrome does not show a protective role in kidney function preservation. On the contrary, it seems to be associated with a deterioration of the kidney function on a long-term follow-up.

Morbidity following suprapubic line insertion for videourodynamics in children.

INTRODUCTION: Previously in our unit, urodynamics were delayed after insertion of suprapubic (SP) lines. We postulated that performing urodynamics on the same day as SP line insertion would not result in increased morbidity. We retrospectively compared complications in those having urodynamics on the same day against those who had delayed urodynamics. PATIENTS AND METHODS: Notes were reviewed for patients undergoing urodynamics via SP lines from May 2009 until December 2018. In 2014 we modified our practice to allow urodynamics on the same day as SP line insertion in some patients. Patients undergoing videourodynamics would have two 5 Fr (mini Paed) SP lines inserted under general anaesthesia. Patients were divided into two groups: those that had urodynamics on the same day as SP line insertion and those that had urodynamics after an interval of more than one day. The outcome measure was the number of problems affecting those in each group. The two groups were compared using Mann-Whitney U tests and Fisher's Exact tests. RESULTS: There were a total of 211 patients with a median age of 6.5 years (range three months to 15.9 years). Urodynamics were performed on the same day in 86. Delayed Urodynamics were performed at an interval of more than one day in 125. Adverse events included pain or difficulty with voiding, increased urinary frequency, urinary incontinence, leak from catheter site, extravasation, extension of in-patient stay, visible haematuria, urethral catheterisation, and urinary tract infection. Problems affected 43 (20.4%) children. In the same day group, 11 (13.3%) patients had problems, in the delayed group 32 (25.6%) had problems; this was statistically significant (p = 0.03). The difference in combined incidence of important problems (requiring urethral catheterisation, extended admission or abandonment of urodynamics) was not statistically significant between the two groups. CONCLUSION: When using suprapubic catheters for urodynamics there is no additional morbidity when catheters are inserted on the same day as the urodynamics study compared to when urodynamic are delayed.

Credibility assessment of cold adaptive Pseudomonas jesenni MP1 and P. palleroniana N26 on growth, rhizosphere dynamics, nutrient status, and yield of the kidney bean cultivated in Indian Central Himalaya.

Kidney bean (Phaseolus vulgaris) productivity and nutritional quality are declining due to less nutrient accessibility, poor soil health, and indigent agronomic practices in hilly regions, which collectively led to a fall in farmer's income, and to malnutrition in consumers. Addressing such issues, the present investigation was designed to assess the impact of Pseudomonas jesenii MP1 and Pseudomonas palleroniana N26 treatment on soil health, microbial shift, yield, and nutrient status of the kidney bean in the Harsil and Chakrata locations of Indian Central Himalaya. P. jesenii MP1 and P. palleroniana N26 were characterized as cold adaptive PGPR as they possessed remarkable in vitro plant growth promoting traits. Further, field trial study with PGPR treatments demonstrated remarkable and prolific influence of both strains on yield, kidney bean nutrient status, and soil health at both geographical locations, which was indicated with improved grain yield (11.61%-23.78%), protein (6.13%-24.46%), and zinc content (21.86%-61.17%) over control. The metagenomic study revealed that use of bioinoculants also concentrated the nutrient mobilizing and plant beneficial microorganisms in the rhizosphere of the kidney bean. Moreover, correlation analysis also confirmed that the plant growth-promoting traits of P. jesenii MP1 and P. palleroniana N26 are the basis for improved yield and nutrient status of the kidney bean. Further, cluster and principal component analysis revealed that both P. jesenii MP1 and P. palleroniana N26 exhibited pronounced influence on yield attributes of the kidney bean at both the locations. At the Harsil location, the P. jesenii MP1-treated seed demonstrated highest grain yield over other treatments, whereas at Chakarata, P. jesenii MP1, and P. palleroniana N26 treatment showed almost equal enhancement (~23%) in grain yield over control. The above results revealed that these bioinoculants are efficient plant growth promoters and nutrient mobilizers; they could be used as green technology to improve human health and farmer's income by enhancing soil health, yield, and nutrient status of the kidney bean at hilly regions.

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells.

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

Longitudinal Analysis of Biologic Correlates of COVID-19 Resolution: Case Report.

While the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. We report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a subset of monocytes characterized by hyperactivated Interferon responses and decreased TNF-α signaling. Monitoring specific dysfunctional myeloid cell subsets in peripheral blood may provide prognostic keys in COVID-19.

Masked Transformer for Image Anomaly Localization.

Image anomaly detection consists in detecting images or image portions that are visually different from the majority of the samples in a dataset. The task is of practical importance for various real-life applications like biomedical image analysis, visual inspection in industrial production, banking, traffic management, etc. Most of the current deep learning approaches rely on image reconstruction: the input image is projected in some latent space and then reconstructed, assuming that the network (mostly trained on normal data) will not be able to reconstruct the anomalous portions. However, this assumption does not always hold. We thus propose a new model based on the Vision Transformer architecture with patch masking: the input image is split in several patches, and each patch is reconstructed only from the surrounding data, thus ignoring the potentially anomalous information contained in the patch itself. We then show that multi-resolution patches and their collective embeddings provide a large improvement in the model's performance compared to the exclusive use of the traditional square patches. The proposed model has been tested on popular anomaly detection datasets such as MVTec and head CT and achieved good results when compared to other state-of-the-art approaches.

Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells.

Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape of highly purified human bone marrow HSCs displaying varying degrees of dormancy. We identify the orphan receptor GPRC5C, which enriches for dormant human HSCs. GPRC5C is also essential for HSC function, as demonstrated by genetic loss- and gain-of-function analyses. Through structural modelling and biochemical assays, we show that hyaluronic acid, a bone marrow extracellular matrix component, preserves dormancy through GPRC5C. We identify the hyaluronic acid-GPRC5C signalling axis controlling the state of dormancy in mouse and human HSCs.

Machine learning based COVID -19 disease recognition using CT images of SIRM database.

The COVID-19 pandemic, probably one of the most widespread pandemics humanity has encountered in the twenty first century, caused death to almost 1.75 M people worldwide, impacting almost 80 M lives with direct contact. In order to contain the spread of coronavirus, it is necessary to develop a reliant and quick method to identify those who are affected and isolate them until full recovery is made. The imagery knowledge has been shown to be useful for quick COVID-19 diagnosis. Though the scans of computational tomography (CT) demonstrate a range of viral infection signals, considering the vast number of images, certain visual characteristics are challenging to distinguish and can take a long time to be identified by radiologists. In this study for detection of the COVID-19, a dataset is formed by taking 3764 images. The feature extraction process is applied to the dataset to increase the classification performance. Techniques like Grey Level Co-occurrence Matrix (GLCM) and Discrete Wavelet Transform (DWT) are used for feature extraction. Then various machine learning algorithms applied such as Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), Multi- Level Perceptron, Naive Bayes, K-Nearest Neighbours and Random Forests are used for classification of COVID-19 disease detection. Sensitivity, Specificity, Accuracy, Precision, and F-score are the metrics used to measure the performance of different machine learning models. Among these machine learning models SVM with GLCM as feature extraction technique using 10-fold cross validation gives the best classification result with 99.70% accuracy, 99.80% sensitivity and 97.03% F-score. We also ran these tests on different data sets and found that the results are similar across those too, as discussed later in the results section.

Long-term urology outcomes of anorectal malformation.

INTRODUCTION: Urological problems are a recognised feature of anorectal malformation (ARM). Previous assumptions of favourable long-term urinary outcomes are being challenged. OBJECTIVE: We hypothesised that urinary tract problems are common in ARM and frequently persist into adulthood. We retrospectively reviewed long-term renal and bladder outcomes in ARM patients. STUDY DESIGN: Patients with ARM born between 1984-2005 were identified from electronic hospital databases. Their case notes were reviewed. Renal outcomes included serum creatinine and the need for renal replacement therapy. Bladder outcomes included symptom review, bladder medication, need for intermittent catheterisation, videourodynamics and whether the patient had undergone augmentation cystoplasty. RESULT (TABLE 1): The case notes of 50 patients were reviewed. The median age at last follow up was 18 years (range 12-34 years). The level of fistula was noted to be high in 17 patients, intermediate in eight, and low in 10. Four had cloaca. Congenital urological abnormalities were present in 25 (50%). An abnormal spinal cord was present in 22 (44%) patients. VACTERL association occurred in 27 (54%). Chronic kidney disease stage II or above was found in 14 (28%) patients, of whom four required a renal transplant. Abnormal bladder outcomes were found in 39 (78%) patients. Augmentation cystoplasty with Mitrofanoff had been performed in 12. Of those who had not undergone cystoplasty, 17 had urinary symptoms, including urinary incontinence in 12. Of the 39 patients with abnormal bladder outcome, 19 (49%) did not have a spinal cord abnormality. There was no significant statistical association between level of ARM and abnormal renal outcome or presence of bladder abnormality. DISCUSSION: Adverse renal and bladder outcomes are common in our cohort of young people with ARM with a significantly higher incidence compared with current literature. We did not demonstrate an association between level of ARM or presence of spinal cord anomaly with persistent bladder problems. Congenital urological anomalies are more common in those who later have an abnormal renal outcome. Although this difference is statistically significant, one fifth of patients born with anatomically normal upper tracts develop reduced renal function, implying an important acquired component. CONCLUSION: Bladder problems and reduced renal function affect a significant proportion of young adults with ARM. Neither adverse outcome is reliably predicted from ARM level, congenital urological anomaly or spinal cord anomaly. We advise continued long-term bladder and kidney follow-up for all patients with ARM.

Biologic correlates of beneficial convalescent plasma therapy in a COVID-19 patient reveal disease resolution mechanisms.

BACKGROUND: While the biomarkers of COVID-19 severity have been thoroughly investigated, the key biological dynamics associated with COVID-19 resolution are still insufficiently understood. MAIN BODY: We report a case of full resolution of severe COVID-19 due to convalescent plasma transfusion in a patient with underlying multiple autoimmune syndrome. Following transfusion, the patient showed fever remission, improved respiratory status, and rapidly decreased viral burden in respiratory fluids and SARS-CoV-2 RNAemia. Longitudinal unbiased proteomic analysis of plasma and single-cell transcriptomics of peripheral blood cells conducted prior to and at multiple times after convalescent plasma transfusion identified the key biological processes associated with the transition from severe disease to disease-free state. These included (i) temporally ordered upward and downward changes in plasma proteins reestablishing homeostasis and (ii) post-transfusion disappearance of a particular subset of dysfunctional monocytes characterized by hyperactivated Interferon responses and decreased TNF-α signaling. CONCLUSIONS: Monitoring specific subsets of innate immune cells in peripheral blood may provide prognostic keys in severe COVID-19. Moreover, understanding disease resolution at the molecular and cellular level should contribute to identify targets of therapeutic interventions against severe COVID-19.

Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2.

BACKGROUND: Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. MAIN BODY: We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class 5 months earlier on average. After controlling for the time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. CONCLUSIONS: A dichotomy exists between the humoral and cellular responses elicited by the two vaccine classes. Testing only for humoral responses to compare the durability of SARS-CoV-2 vaccine-induced responses, as typically performed for public health and research purposes, is insufficient.

Constitutive expression and discovery of antimicrobial peptides in Zygogramma bicolorata (Coleoptera: Chrysomelidae).

The expression, identification, and discovery of less toxic antimicrobial peptides (AMPs) are significant in managing infectious pathogens. AMPs triggered in response to the immune system have evolved to defend against pathogens and wounding. The protein composition of Zygogramma bicolorata hemolymph is of diagnostic importance as the open circulatory systems of the insects involve signaling through hemolymph. They have conserved many ancestral vertebrate genes that may help better understand the evolution of innate immunity. The present work describes the isolation, purification, identification, and bioinformatics analysis of AMPs from the immunized hemolymph of Z. bicolorata. Thirty-nine peptides were isolated from reverse-phase high-performance liquid chromatography and sequenced via mass spectrometry analysis. The immunization process recorded a threefold higher protein concentration in immunized hemolymph when compared with nonimmunized one. For the first time, the proteomic study on Z. bicolorata hemolymph unveils the three novel proteins in the family Chrysomelidae with no homology in the database, indicating its novelty and the expression of the rest of 36 well-known proteins, including heat-shock, immune, structural, signaling proteins, and others speak for its method validity. Combining the expression of novel AMPs, detoxifying enzymes, hemolytic, and cytotoxic assays, and this work can elucidate new pathways to immune response mechanisms. Its molecular basis also holds the potential applicability in the future drug development process against pathogenic fungi such as Aspergillus niger and Candida albicans.