The anatomy and pathology of the space of Retzius.

The space of Retzius is an important anatomic location for pathology. Pathology in the space of Retzius is more common than previously believed, especially as more cases are discovered with increased use of cross-sectional imaging. Knowledge of the anatomy of the Space of Retzius is crucial for identifying and distinguishing between benign and pathological findings. This paper uses several case examples to discuss benign etiologies, including normal tissue or a foreign body. The paper also demonstrates a case series with pathologic findings in the Space of Retzius under the broad categories of infection, neoplasm, hemorrhage, or urine extravasation. Understanding of the anatomy and these example cases can improve the diagnostic accuracy of radiologists.

Evaluation of Antifungal Activity of Endophytic Bacillus spp. and Identification of Secondary Metabolites Produced Against the Phytopathogenic Fungi.

Endophytic bacteria serve as a rich source of diverse antimicrobial compounds. Recently, there has been a growing interest in utilizing endophytic Bacillus spp. as biological agents against phytogenic fungi, owing to their potential to produce a wide range of antimicrobial substances. The objective of this research was to investigate the protective abilities of 15 endophytic Bacillus spp. isolated from previous study from wheat plant, against the phytopathogenic fungi, Fusarium graminearum and Macrophomina phaseolina. A dual culture plate assay was conducted as a preliminary analysis, revealing that 7 out of 15 endophytic Bacillus spp. demonstrated inhibition against one or both of the phytopathogenic fungi used in this study. All seven endophytes were further assessed for the presence of diffusible antifungal metabolites. The cultures were grown in potato dextrose broth for 120 h, and the cell-free supernatant was extracted and analyzed using the cup plate method. The methanolic extract yielded similar results to the dual culture plate analysis, except for WL2-15. Additionally, deformities in the mycelial structure were examined under the light microscope upon exposure to methanolic extract. Furthermore, the analysis and identification of metabolites were carried out via gas chromatography-mass spectrometry of methanolic extract from selected seven endophytic Bacillus spp. The chromatogram revealed the presence of some major peaks such as tridecanoic acid, methyl ester, hydroperoxide, 1-methylbutyl, 9-octadecenamide, (z)-, hexane-1,3,4-triol, 3,5-dimethyl- tetradecanoic acid. To the best of our knowledge, this is the first report of these biocontrol agents in endophytic Bacillus spp. Interestingly, volatile organic compound production was also seen in all the isolates against the phytopathogenic fungi.

Perioperative pain optimization in the age of the opioid epidemic.

PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.

Comparative negation of amphiphile production using nutrition factors: Amyloids versus biosurfactants.

Microbial amphiphiles play an important role in environmental activities such as microbial signaling, bioremediation, and biofilm formation. Microorganisms rely on their unique characteristics of interfaces to carry out critical biological functions, which are helped by amphipathic biomolecules known as amphiphiles. Bacillus amyloids aid in cell adhesion and biofilm formation. Pseudomonas sp. are essential in biofilm development and are a vital survival strategy for many bacteria. Furthermore, Pseudomonas and Bacillus are well-known for their ability to produce biosurfactants with a range of applications, including bioremediation and removing biological pollutants from different environments. The study employed 31 different media types and a range of analytical techniques to assess the presence of amyloid proteins and the absence of biosurfactants in Bacillus licheniformis K125 (GQ850525.1) and Pseudomonas fluorescens CHA0. The presence of amyloid proteins was confirmed through Congo red and thioflavin T staining. The carefully constructed medium also efficiently inhibited the synthesis of biosurfactants by these bacteria. Additionally, surface tension measurements, emulsification index, thin-layer chromatography, and high-performance thin-layer chromatography analyses indicated the absence of biosurfactants in the tested media.

An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.

Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.

The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. Unexpectedly, given prior emphasis on descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We also report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings significantly revise current models of the DPMS and establish a novel supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.

Case series of perianal and pelvic MRI imaging findings in monkeypox.

Monkeypox is a viral infection historically rarely seen in humans, but currently the focus of international attention due to a multi-country outbreak outside endemic countries of Central and West Africa, where cases are typically confined. Perianal pain and lesions have recently been recognised as a feature of monkeypox. We present a case series of the imaging findings of patients with monkeypox, including active proctitis, anal canal inflammation, and perianal inflammation. The aim is to increase awareness of perianal and rectal monkeypox MRI imaging features during this current outbreak.

Mutational analysis of mechanosensitive ion channels in the carnivorous Venus flytrap plant.

How the Venus flytrap (Dionaea muscipula) evolved the remarkable ability to sense, capture, and digest animal prey for nutrients has long puzzled the scientific community.1 Recent genome and transcriptome sequencing studies have provided clues to the genes thought to play a role in these tasks.2,3,4,5 However, proving a causal link between these and any aspect of the plant's hunting behavior has been challenging due to the genetic intractability of this non-model organism. Here, we use CRISPR-Cas9 methods to generate targeted modifications in the Venus flytrap genome. The plant detects prey using touch-sensitive trigger hairs located on its bilobed leaves.6 Upon bending, these hairs convert mechanical touch signals into changes in the membrane potential of sensory cells, leading to rapid closure of the leaf lobes to ensnare the animal.7 Here, we generate mutations in trigger-hair-expressed MscS-like (MSL)-family mechanosensitive ion channel genes FLYCATCHER1 (FLYC1) and FLYCATCHER2 (FLYC2)5 and find that double-mutant plants have a reduced leaf-closing response to mechanical ultrasound stimulation. While we cannot exclude off-target effects of the CRISPR-Cas9 system, our genetic analysis is consistent with these and other functionally redundant mechanosensitive ion channels acting together to generate the sensory system necessary for prey detection.

An innovative hematopoietic stem cell gene therapy approach benefits CLN1 disease in the mouse model.

Hematopoietic stem and progenitor cells (HSPCs) can establish a long-lasting microglia-like progeny in the central nervous system of properly myeloablated hosts. We exploited this approach to treat the severe CLN1 neurodegenerative disorder, which is the most aggressive form of neuronal ceroid lipofuscinoses due to palmitoyl-protein thioesterase-1 (PPT1) deficiency. We here provide the first evidence that (i) transplantation of wild-type HSPCs exerts partial but long-lasting mitigation of CLN1 symptoms; (ii) transplantation of HSPCs over-expressing hPPT1 by lentiviral gene transfer enhances the therapeutic benefit of HSPCs transplant, with first demonstration of such a dose-effect benefit for a purely neurodegenerative condition like CLN1 disease; (iii) transplantation of hPPT1 over-expressing HSPCs by a novel intracerebroventricular (ICV) approach is sufficient to transiently ameliorate CLN1-symptoms in the absence of hematopoietic tissue engraftment of the transduced cells; and (iv) combinatorial transplantation of transduced HSPCs intravenously and ICV results in a robust therapeutic benefit, particularly on symptomatic animals. Overall, these findings provide first evidence of efficacy and feasibility of this novel approach to treat CLN1 disease and possibly other neurodegenerative conditions, paving the way for its future clinical application.

Effectiveness of Induction Training on Newly Joined Employee Knowledge and Hospital Performance.

Introduction: Every organization needs well-trained employees to perform job activities effectively and efficiently. Training and development is a continuous process that helps to develop skills, knowledge, and abilities in its workers, which leads to better performance of employees. This study aims to assess the effectiveness of an induction training program for hospital employees as well as the impact on employee knowledge and performance in the clinical field according quality indicator benchmarks. Methods: A sample of individuals (N = 775) who were newly hired, promoted, or re-categorized at our institution in 2021 were included in the program. The effectiveness of the induction training program was assessed with a pre- and post-test and feedback form. Topics covered in the training program will help employees know about the institute and increase knowledge and skills. Results: The average pre-test score was 60%, which increased to 84% after the training (p = 0.0001). There was a significantly positive relationship between the quality indicators and the clinical audit results (p = 0.006). Conclusion: The induction training program effectively improved the employees' knowledge regarding their rights and responsibilities as well as clinical knowledge (i.e., Infection control and prevention, quality, disaster management, biomedical waste management, and facility safety).

Global geological occurrence and character of the carcinogenic zeolite mineral, erionite: A review.

As with the six regulated asbestos minerals (chrysotile, amosite, crocidolite, anthophyllite, tremolite, and actinolite), the zeolite mineral, erionite, can exhibit a fibrous morphology. When fibrous erionite is aerosolized and inhaled, it has been linked to cases of lung cancers, such as malignant mesothelioma. Importantly, fibrous erionite appears to be more carcinogenic than the six regulated asbestos minerals. The first health issues regarding erionite exposure were reported in Cappadocia (Turkey), and more recently, occupational exposure issues have emerged in the United States. Erionite is now classified as a Group 1 carcinogen. Thus, identifying the geological occurrence of erionite is a prudent step in determining possible exposure pathways, but a global review of the geological occurrence of erionite is currently lacking. Here, we provide a review of the >100 global locations where erionite has been reported, including: 1) geological setting of host rocks; 2) paragenetic sequence of erionite formation, including associated zeolite minerals; 3) fiber morphological properties and erionite mineral series (i.e., Ca, K, Na); and 4) a brief overview of the techniques that have been used to identify and characterize erionite. Accordingly, erionite has been found to commonly occur within two major rock types: felsic and mafic. Within felsic rocks (in particular, tuffaceous layers within lacustrine paleoenvironments), erionite is disseminated through the layer as a cementing matrix. In contrast, within mafic (i.e., basaltic) rocks, erionite is typically found within vesicles. Nevertheless, aside from detailed studies in Italy and the United States, there is a paucity of specific information on erionite geological provenance or fiber morphology. The latter issue is a significant drawback given its impact on erionite toxicity. Future erionite studies should aim to provide more detailed information, including variables such as rock type and lithological properties, quantitative geochemistry, and fiber morphology.

Gender Disparities in Academic Pain Medicine: A Retrospective, Cross-Sectional Bibliometric Analysis.

Purpose: This study was conducted to characterize the gender disparities within academic pain management departments in the United States, specifically focusing on its relation to research and academic leadership. This will allow for targeted improvements in efforts made to reduce gender gaps within academic pain medicine. Methods: This is a retrospective, cross-sectional analysis study evaluating pain management faculty of various positions at academic institutions across the United States. We utilized publicly available data on faculty positions and sex to analyze research impact, H-index, number of publications and citations through bibliometric and linear regression analysis. Results: Our analysis found that female faculty had significantly less research output to male faculty. The three research measurement indices used in this study including H-index, number of publications, and number of citations were significantly lower in females than in males among associate and full professor faculty ranking. Multivariable analysis did not display any significant disparities of research output at the division director and department chair level. Discussion: As in many areas of medicine, there continues to be a significant gender disparity in academic pain management departments, particularly with regard to leadership positions and research impact within the field. Our study found that female pain physicians had a significantly less research output based on the three variables of H indices, number of publications, and number of citations compared to their male counterparts. This has been shown to have the impact on discrepancies in female faculty ranking. Interestingly, these variables were not significantly different between male and female faculty members of the same level of leadership except for program director. There are various contributory reasons for these disparities, including implicit biases, lack of mentorship, and familial obligations. Addressing some of these factors can help narrow the schism and promote greater gender equality within academic pain management.

Efficacy of Liposomal Bupivacaine for Sternotomy Pain After Cardiac Surgery: A Retrospective Analysis.

BACKGROUND: Multimodal analgesia is a cornerstone of postoperative pain management. Different formulations of local anesthetics are available. Data to support these treatment options are limited. OBJECTIVE: To determine the efficacy of liposomal bupivacaine compared with bupivacaine or ropivacaine in patients undergoing sternotomy for coronary artery bypass graft (CABG) and/or valve surgery. METHODS: Single-center, retrospective, observational study at a community teaching hospital. Patients included were 18 years of age or older undergoing CABG and/or valve surgery via median sternotomy and received either liposomal bupivacaine or an active comparator. The primary outcome was opioid utilization in morphine milligram equivalent (MME) from 0 to 72 hours. RESULTS: A total of 376 patients were included, 223 in the liposomal bupivacaine arm and 153 in the active comparator arm. There was no difference in the MME use from 0 to 72 hours among patients in the liposomal bupivacaine group compared with the comparator group (114.2 mg [75.55] vs 107.6 mg [68.4], P = 0.38). After Bonferroni correction, there was no difference in pain scores at individual time points. At 24- and 48-hour post-op, pain scores were higher with liposomal bupivacaine at 4.4 (2.7) vs 3.5 (2.8) (P = 0.01) and 3.1 (2.9) vs 2.4 (2.6) (P = 0.02). CONCLUSION AND RELEVANCE: Based on these findings and previous studies, liposomal bupivacaine should not be routinely used for CABG and/or valve surgery through a median sternotomy given lack of superiority. This helps inform surgical practice to the role of anesthetics as part of the multimodal analgesia regimen.

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels.

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals. However, this approach is limited as it has been challenging to target specific cells within the brain or body. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show that hsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to c-fos expression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate that hsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.

Facilitators and Barriers of COVID-19 Vaccine Promotion on Social Media in the United States: A Systematic Review.

Background and Objectives: Information regarding the COVID-19 pandemic has spread internationally through a variety of platforms, including social media. While efforts have been made to help reduce the spread of misinformation on social media, many platforms are still largely unregulated. The influence of social media use on vaccination promotion is not fully understood. This systematic review aims to identify facilitators and barriers associated with vaccine promotion through social media use. Materials and Methods: Reviewers analyzed 25 articles and identified common themes. Facilitators of vaccine promotion included an increase in the efforts of social media companies to reduce misinformation, the use of social media to spread information on public health and vaccine promotion, and the positive influence towards vaccinations of family and friends. Results and Conclusions: Identified barriers to vaccine promotion included the spread of misinformation, decreased vaccine acceptance among users of social media for COVID-19 related information due to polarization, and a lack of regulation on social media platforms. The results of this review provide insight for improving public health campaign promotion on social media and can help inform policy on social media regulation and misinformation prevention.

Enterococcus durans Cardiac Implantable Electronic Device Lead Infection and Review of Enterococcus durans Endocarditis Cases.

Introduction: Cardiac implantable electronic device (CIED) infections present a growing problem in medicine due to a significant increase in the number of implanted devices and the age of the recipient population. Enterococcus spp. are Gram-positive, facultative anaerobic, lactic acid bacteria; they are relatively common pathogens in humans, but uncommon as the cause of CIED lead infections. Only eight cases of Enterococcus durans endocarditis have been reported in the literature thus far; however, there are no reported cases of Enterococcus durans CIED lead infection. Case presentation: A 58-year-old gentleman with a previously implanted St. Jude Medical single-chamber implantable cardioverter-defibrillator (ICD) due to tachy/brady arrhythmias presented with nonspecific constitutional symptoms (i.e., low-grade fevers, chills, fatigue), and was found to have innumerable bilateral pulmonary nodules via computed tomography angiography of the chest. Many of these pulmonary nodules were cavitated and highly concerning for septic pulmonary emboli and infarcts. Within 24 h from presentation, blood cultures in all four culture bottles grew ampicillin- and vancomycin-susceptible Enterococcus durans. Transthoracic echocardiogram confirmed vegetations on the ICD lead in the right ventricle. The patient underwent laser extraction of the ICD lead with generator removal and recovered completely after a 6-week intravenous antibiotic course. Conclusion: To our knowledge, this is the first report of CIED lead infection caused by Enterococcus durans. In this case, management with antibiotics along with ICD lead extraction led to complete recovery. Clinicians should be aware of this rare but potentially devastating infection in patients with native and artificial valves, but also in those with CIEDs.

Complete Genome Sequence of Stenotrophomonas maltophilia Myophage Marzo.

Stenotrophomonas maltophilia is a Gram-negative opportunistic bacterium that is increasingly being associated with infections. Here, we report the complete genome of the S. maltophilia myophage Marzo, with a 159,384-bp genome encoding 268 proteins, 23 tRNAs, and 1 transfer-messenger RNA. Marzo is closely related to S. maltophilia phages IME-SM1 and Mendera.