Therapy resistance in prostate cancer: mechanism, signaling and reversal strategies.

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.

Best Medical Therapy for Asymptomatic Carotid Stenosis: Imminent or Ineffective?

Carotid artery disease accounts for approximately 20% of all ischemic strokes, a major cause of morbidity, and the fifth leading cause of death in United States. Landmark trials in the 1990s such as Asymptomatic Carotid Atherosclerosis Study (ACAS) and Asymptomatic Carotid Surgery Trial (ACST) establish carotid endarterectomy (CEA) plus best medical therapy (BMT) as the standard of care for patients with asymptomatic carotid stenosis over 60%. However, advances in medical therapy and the emergence of carotid artery stenting (CAS) have prompted a reevaluation of treatment efficacy. Recent studies have questioned the superiority of CEA over BMT alone in reducing stroke risk, suggesting no significant difference in outcomes with contemporary medical management. Additionally, analysis from the US Department of Veterans Affairs indicated minimal net benefit of CEA over BMT when accounting for all-cause mortality. Comparative studies have found no significant difference in long-term stroke free survival between CEA and CAS. However, procedural risks vary, with higher myocardial infarction rates associated with CEA and higher stroke rates with CAS. Identifying high-risk plaques and patient-specific risk factors remains crucial. Meta-analyses have highlighted features such as neovascularization and lipid rich cores as predictors of stenosis progression and ischemic events. Ongoing research, particularly the CREST-2 trial, aims to provide clear guidance on the optimal treatment of asymptomatic carotid stenosis. This trial emphasizes stringent adherence to modern BMT protocols and includes comprehensive lifestyle modification programs. The evolving landscape of medical and surgical interventions necessitates continuous evaluation to optimize treatment strategies for asymptomatic carotid stenosis, which is the impetus for this review. Future findings from ongoing trials are expected to refine current guidelines and improve patient outcomes.

Household preparedness for emergencies during COVID-19 pandemic among the general population of Nepal.

The COVID-19 pandemic has negatively impacted the global economy affecting numerous people's livelihoods. Despite preventive behaviors and advancements of vaccination, the risk of infection still exists due to the emergence of new variants of concern and the changing behavior of the SARS CoV-2 virus. Therefore, preparedness measures are crucial for any emergency. In such situations, it is important to understand preparedness behavior at the household level, as it aids in reducing the risk of transmission and the severity of the disease before accessing any external support. Our study aimed to evaluate household preparedness level for emergencies during the COVID-19 pandemic and its relationship with socio-demographic characteristics among the general population of Nepal. Data was collected through a questionnaire survey. Descriptive statistics, a Chi-square test, and logistic regression model were used for analysis. The study demonstrated that 59.2% had a good preparedness level. Good preparedness was observed among the respondents living in urban areas, those who were married, had white-collar occupations, high-education with graduate and above and high-income levels with monthly income >NPR 20,000, and were young-aged. The study findings underscore the need to develop tailored programs on preparedness prioritizing vulnerable population. It further highlights the importance of proper and consistent information flow, resources distribution, capacitating human resources and better health surveillance.

Breastfeeding Success With Use of Electric Breast Pump Versus Inverted Syringe Technique in Lactating Women With Inverted Nipple: Open Labelled Randomized Control Trial.

Background Inverted nipple is a commonly encountered impediment to proper attachment and latch establishment. Correction of inversion using a disposable syringe represents the conventional method of management. However, it is understudied, cumbersome, and inconvenient. Using electric breast pump represents a more physiological method to achieve correction of inversion. This open-label, randomized control trial investigated syringing versus electric breast pump both in terms of effectiveness in achieving correction of inversion of nipple and patient satisfaction with the use of the assigned intervention. Objectives The primary objective of this study was to compare breastfeeding success by Day 3 postnatal age (achieving correction of inversion of nipple and establishment of direct breastfeeding) in syringing versus electric breast pump in mothers with inverted or flat nipples. The secondary objective was to compare the two methods for the pain experienced by the mother while using syringing versus an electric breast pump. Methodology/Design This was a single-center, open-label randomized control trial performed at a tertiary care neonatal unit in Eastern India, from December 2022 to September 2023. 60 healthy mothers with inverted nipples were randomly allocated to one of two interventions: Group A (n=30, syringing); or Group B (n=30, electric breast pump). Both groups were compared for the establishment of breastfeeding by Day 3 postnatal age and daily maximum pain scores till Day 3 (visual analogue scale). Multivariable logistic regression was used to look for factors independently associated with establishment of breast feeding by Day 3 postnatal period. Chi square test was used to compare the proportions of different outcomes between the groups. Results The primary outcome of establishment of breastfeeding by Day 3 postnatal period was achieved in 18 (60%) mothers in syringe group vs. 17 (56.67%) in the breast pump group, with no statistically significant difference (p=0.793). In the first two days the pain score differences were not statistically significant, but on Day 3, 28 (93.99%) mothers in the electric breast pump group had no/mild pain compared to 22 (73.33%) mothers in the syringe usage group. This difference was statistically significant (p= 0.038). Conclusion In hospital settings where electric breast pump is easily available, the same may be preferred over inverted syringe technique for achieving establishment of breastfeeding by Day 3 postnatal period with minimal nipple pain in mothers. However, further large scale studies will be required to confirm these findings.

A Fluorescence-Based Assay for Measuring Polyamine Biosynthesis Aminopropyl Transferase-Mediated Catalysis.

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), which are promising targets for antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation in studying APT enzymes, however, is the lack of high-throughput assays to measure their activity. We have developed the first fluorescence-based assay, DAB-APT, for the measurement of APT activity using 1,2-diacetyl benzene (DAB), which forms fluorescent conjugates with putrescine, spermidine, and spermine, with fluorescence intensity increasing with the carbon chain length. The assay has been validated using APT enzymes from Saccharomyces cerevisiae and Plasmodium falciparum, and the data further validated by mass spectrometry and thin-layer chromatography. Using mass spectrometry analysis, the structures of the fluorescent putrescine, spermidine and spermine 1,2-DAB adducts were determined to be substituted 1,3-dimethyl isoindoles. The DAB-APT assay is optimized for high-throughput screening, facilitating the evaluation of large chemical libraries. Given the critical roles of APTs in infectious diseases, oncology, and neurobiology, the DAB-APT assay offers a powerful tool with broad applicability, poised to drive advancements in research and drug discovery.

Transcarotid Artery Revascularization Learning Curves Differ between Surgeon Experience Level.

BACKGROUND: There has been ensuing interest in adopting transcarotid artery revascularization (TCAR), because of its low perioperative stroke and complication rates. In our study, we aimed to identify the case number at which there is improvement in TCAR technical proficiency. We also assessed how surgeon experience influenced outcomes. METHODS: The primary outcome was technical proficiency, measured by skin-to-skin, fluoroscopy, and flow reversal times. Secondary outcomes included hospital length of stay and perioperative complication rate. Data was collected from a deidentified database, which included all patients that had a TCAR between 2017 and 2023 at one of four hospitals. Cases were grouped by the experience of the surgeon who performed the case (<10 and >10 years). Linear mixed models were used to analyze primary outcomes after being log-transformed, due to their skewed distributions. The estimated level of the outcome was compared at the 1st, 5th, 10th and 15th surgery between surgeon groups, and the significance level was adjusted using the Bonferroni correction. RESULTS: There were 160 cases performed by 13 surgeons included in the study. Patients with hostile necks (23.9% vs. 9.7%, P=0.015) and contralateral occlusions (7.5% vs. 0%, P=0.007) were operated on more frequently by surgeons with <10 years of experience. There was no difference in secondary outcomes between groups. While primary outcomes between groups were not significant when comparing median values, linear mixed models demonstrated a significant improvement among the group of surgeons with less experience after the 15th case relative to their senior partners. At this point, they were operating with 30% less skin-to-skin time (P=0.002, 95% CI 13% to 44%) and 51% less fluoroscopy time (P=0.005, 95% CI 20% to 70%) compared to surgeons with >10 years of experience. There was no significant difference between groups with respect to flow reversal times. CONCLUSIONS: There was significant improvement experienced by the junior attendings relative to their senior partners after the fifteenth case. This was not influenced by patient characteristics nor the type of anesthesia used.

Ophthalmologic manifestations of organoid nevus syndrome: A series of 13 cases.

Background: The organoid nevus syndrome is a rare neurocutaneous syndrome typified by cutaneous sebaceous nevus, seizures and epibulbar choristomas. The condition is associated with multiple ocular abnormalities. Herein, the authors aim to study and report the ophthalmic features of cases diagnosed with organoid nevus syndrome. Methods: The authors retrospectively evaluated the records of patients with the organoid nevus syndrome who had presented to a tertiary care eye hospital in northern India. The ocular features were studied and entered in MS excel and the data were evaluated. Results: Data of 13 patients with the organoid nevus syndrome were found. All 13 patients had cutaneous features in the form of Sebaceous nevus of Jadasson, 8 patients had alopecia of the scalp area, 2 had history seizures and 10 had arachnoid cysts on neuroimaging of the head. All 13 patients had a complex choristoma involving the ocular surface. Conclusions: We conclude that the most common ophthalmologic features associated with organoid nevus are complex choristoma of the bulbar surface, scleral coat calcification and upper eyelid coloboma.

Analysis of salivary alpha-L-fucosidase and salic acid among oral sub-mucous fibrosis patients.

The salivary concentrations of alpha L fucosidase (AFU) and salic acid (SA) in oral submucous fibrosis patients and compare it with healthy controls is of interest to dentists. 40 patients of OSMF and 40 healthy controls were included. Estimation of AFU and SA in saliva and serum was carried out in every patient. The serum level of AFU was 37.4±26.8 in OSMF patients and saliva level of AFU was 35.4±14.5. The serum level of AFU was 19.2±4.3 in control group and saliva level of AFU was 35.4±14.5 in control group. The serum level of SA was 20.32±2.71 in OSMF patients and saliva level of SA was 18.21±2.40. The serum level of SA was 4.89 ±1.17 in control group and saliva level of SA was 3.13 ±1.04 in control group. Estimation of concentration of SA and AFU in saliva can be effective biomarker in diagnosis of OSMF.

Insights into the evolution, virulence and speciation of Babesia MO1 and Babesia divergens through multiomics analyses.

Babesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.

Recurrent subcutaneous abscesses and pneumonia in a toddler with a novel pathogenic variation in IL-17RA gene.

A toddler presented with recurrent subcutaneous abscesses, otitis media and pneumonia, requiring frequent hospitalisations and intravenous antimicrobials. He also had oral thrush and difficulty in gaining weight; hence, an underlying inborn error of immunity (IEI) was strongly suspected. The complete haemogram showed leucocytosis with neutrophilic predominance. Both erythrocyte sedimentation rate and C reactive protein were elevated. Klebsiella pneumoniae was isolated from blood culture. The dihydrorhodamine-123 assay was negative, and the immunoglobulin profile showed an increased IgG level. Whole exome sequencing revealed a novel homozygous pathogenic variation in the IL-17RA gene (c.2563G>A, p. Asp855Asn). He showed remarkable improvement following intravenous colistin and fluconazole with complete resolution of abscesses. Thus, it is prudent to consider the possibility of IL-17RA deficiency in children with a history of recurrent abscesses, skin ulcerations and pneumonia after excluding the common groups of IEI.

Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi.

Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies.

Prenatal exposure to vortioxetine and vilazodone: Impact on depressive- and anxiety-like behavioral manifestations in young rat offspring.

Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ) are newer antidepressants with improved therapeutic profile commonly used, but their safety during pregnancy and long-term effects on offspring are poorly understood due to paucity of literature in preclinical and clinical studies. This study aimed to investigate whether prenatal exposure to VOX and VLZ impacts depressive- and anxiety-like neurobehavioral alterations in offspring, focusing on neurotransmitter-mediated mechanisms. Pregnant Wistar dams received either VOX or VLZ, 1 mg/day and 2 mg/day of the drug orally from gestation day (GD) 6-21. The dams naturally delivered their offspring and reared until they reached postnatal day (PND) 21. Offspring of both sexes were tested for display of depressive-and anxiety-like behaviors from PND 56-70. After PND 70, offspring were sacrificed, and their brains were collected to estimate neurotransmitter levels. As per protocol, controls were maintained simultaneously for each experimental design. Prenatal exposure to VOX or VLZ induced an increased state of depressive- and anxiety-like behaviors in both male and female offspring. Additionally, neurotransmitter (serotonin, dopamine, and nor-epinephrine) levels in the prefrontal cortex region of the brain were substantially reduced in exposed offspring. No sex specific neurobehavioral and neurochemical implications were observed in the present study. Our findings suggest that prenatal exposure to VOX and VLZ disrupts neurochemical balance in the fetal brain, leading to long-lasting neurobehavioral impairments in offspring of both sexes.

An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate.

PURPOSE: To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy. METHODS AND MATERIALS: Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 using information from a prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analyzed with univariable and multivariable binary logistic regression. RESULTS: A total of 203 eligible patients were included (MHRT = 114, 64-68 Gy/25#; SBRT = 89, 35-37.5 Gy/5#). Median time from TURP to radiation therapy was 10 months (IQR, 7-16 months), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17 cc (IQR, 0.5-1.35 cc), whereas in MHRT and SBRT groups it was 1.03 cc (IQR, 0.4-1.15 cc) and 1.27 cc (IQR, 0.5-1.4 cc), respectively. At a median follow-up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n = 17) and 23.2% (n = 47), respectively. Grade 3 symptoms were observed at median 29 months (IQR, 19-62 months) after radiation therapy completion, lasting for a median duration of 8 months (IQR, 2-14 months). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiation therapy, fraction size, prostate volume, TURP to radiation therapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. CONCLUSIONS: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiation therapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiation therapy.

Bright Innovations: Review of Next-Generation Advances in Scintillator Engineering.

This review focuses on modern scintillators, the heart of ionizing radiation detection with applications in medical diagnostics, homeland security, research, and other areas. The conventional method to improve their characteristics, such as light output and timing properties, consists of improving in material composition and doping, etc., which are intrinsic to the material. On the contrary, we review recent advancements in cutting-edge approaches to shape scintillator characteristics via photonic and metamaterial engineering, which are extrinsic and introduce controlled inhomogeneity in the scintillator's surface or volume. The methods to be discussed include improved light out-coupling using photonic crystal (PhC) coating, dielectric architecture modification producing the Purcell effect, and meta-materials engineering based on energy sharing. These approaches help to break traditional bulk scintillators' limitations, e.g., to deal with poor light extraction efficiency from the material due to a typically large refractive index mismatch or improve timing performance compared to bulk materials. In the Outlook section, modern physical phenomena are discussed and suggested as the basis for the next generations of scintillation-based detectors and technology, followed by a brief discussion on cost-effective fabrication techniques that could be scalable.

DAB-APT: a Fluorescence-Based Assay for Determining Aminopropyl Transferase Activity and Inhibition.

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), promising targets in antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation, however, is the lack of high-throughput assays to measure their activity. We developed the first fluorescence-based assay, DAB-APT, for measurement of APT activity using 1,2-diacetyl benzene, which forms fluorescent conjugates with putrescine, spermidine and spermine with fluorescence intensity increasing with increasing carbon chain length. The assay has been validated using APT enzymes from S. cerevisiae and P. falciparum and is suitable for high-throughput screening of large chemical libraries. Given the importance of APTs in infectious diseases, cancer and neurobiology, our DAB-APT assay has broad applications, holding promise for advancing research and drug discovery efforts.

Functional Recovery Associated with Dendrite Regeneration in PVD Neuron of Caenorhabditis elegans.

PVD neuron of Caenorhabditis elegans is a highly polarized cell with well-defined axonal, and dendritic compartments. PVD neuron operates in multiple sensory modalities including the control of both nociceptive touch sensation and body posture. Although both the axon and dendrites of this neuron show a regeneration response following laser-assisted injury, it is rather unclear how the behavior associated with this neuron is affected by the loss of these structures. It is also unclear whether neurite regrowth would lead to functional restoration in these neurons. Upon axotomy, using a femtosecond laser, we saw that harsh touch response was specifically affected leaving the body posture unperturbed. Subsequently, recovery in the touch response is highly correlated to the axon regrowth, which was dependent on DLK-1/MLK-1 MAP Kinase. Dendrotomy of both major and minor primary dendrites affected the wavelength and amplitude of sinusoidal movement without any apparent effect on harsh touch response. We further correlated the recovery in posture behavior to the type of dendrite regeneration events. We found that dendrite regeneration through the fusion and reconnection between the proximal and distal branches of the injured dendrite corresponded to improved recovery in posture. Our data revealed that the axons and dendrites of PVD neurons regulate the nociception and proprioception in worms, respectively. It also revealed that dendrite and axon regeneration lead to the restoration of these differential sensory modalities.

Optimization of RNAi efficiency in PVD neuron of C. elegans.

PVD neuron of C. elegans has become an attractive model for the study of dendrite development and regeneration due to its elaborate and stereotype dendrite morphology. RNA interference (RNAi) by feeding E. coli expressing dsRNA has been the basis of several genome wide screens performed using C. elegans. However, the feeding method often fails when it comes to knocking down genes in nervous system. In order to optimize the RNAi conditions for PVD neuron, we fed the worm strains with E. coli HT115 bacteria expressing dsRNA against mec-3, hpo-30, and tiam-1, whose loss of function are known to show dendrite morphology defects in PVD neuron. We found that RNAi of these genes in the available sensitive backgrounds including the one expresses sid-1 under unc-119 promoter, although resulted in reduction of dendrite branching, the phenotypes were significantly modest compared to the respective loss of function mutants. In order to enhance RNAi in PVD neurons, we generated a strain that expressed sid-1 under the promoter mec-3, which exhibits strong expression in PVD. When Pmec-3::sid-1 is expressed in either nre-1(-)lin-15b(-) or lin-15b(-) backgrounds, the higher order branching phenotype after RNAi of mec-3, hpo-30, and tiam-1 was significantly enhanced as compared to the genetic background alone. Moreover, knockdown of genes playing role in dendrite regeneration in the nre-1(-)lin-15b(-), Pmec-3-sid-1[+] background resulted in significant reduction in dendrite regeneration following laser injury. The extent of dendrite regrowth due to the RNAi of aff-1 or ced-10 in our optimized strain was comparable to that of aff-1 and ced-10 mutants. Essentially, our strain expressing sid-1 in PVD neuron, provides an RNAi optimized platform for high throughput screening of genes involved in PVD development, maintenance and regeneration.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

PURPOSE: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. METHODS AND MATERIALS: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSIONS: During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Traumatic subcutaneous emphysema following blood donation: A case report.

BACKGROUND: Subcutaneous emphysema is a condition where air becomes trapped under the skin, typically resulting from surgery or skin trauma. It is mostly localized and its occurrence in blood donors is exceedingly rare. Phlebotomy poses minimal risk of subcutaneous emphysema, but procedural errors may lead to such complications. STUDY DESIGN AND METHOD: This is a case report of 29-year-old repeat blood donor who experienced subcutaneous emphysema following blood donation. The donor was vigorously squeezing sponge ball during donation resulting in displacement of the needle which required readjustment. Post-donation, the donor reported a crackling sensation and mild swelling near phlebotomy site. Non-contrast computed tomography (NCCT) scans confirmed subcutaneous emphysema, attributing its development to air trapping in subcutaneous plane due to ball valve mechanism. RESULTS: Computed tomography (CT) imaging revealed subcutaneous emphysematous changes in the right cubital region and no evidence of hematoma. The swelling spontaneously subsided in 10-12 days without any intervention. The case underscores the importance of differentiating subcutaneous emphysema from common complications like hematoma. DISCUSSION: Subcutaneous emphysema in blood donors is exceptionally rare but should be managed with clear communication. Donors should be reassured that the condition, although rare, is benign and self-resolving. Healthcare providers should be equipped to handle such rare complications, offering appropriate care and documenting incidents for future prevention.