Axonal mitochondria regulate gentle touch response through control of axonal actin dynamics.

Actin in neuronal processes is both stable and dynamic. The origin & functional roles of the different pools of actin is not well understood. We find that mutants that lack mitochondria, ric-7 and mtx-2; miro-1, in neuronal processes also lack dynamic actin. Mitochondria can regulate actin dynamics upto a distance ~80 µm along the neuronal process. Absence of axonal mitochondria and dynamic actin does not markedly alter the Spectrin Membrane Periodic Skeleton (MPS) in touch receptor neurons (TRNs). Restoring mitochondria inTRNs cell autonomously restores dynamic actin in a sod-2 dependent manner. We find that dynamic actin is necessary and sufficient for the localization of gap junction proteins in the TRNs and for the C. elegans gentle touch response. We identify an in vivo mechanism by which axonal mitochondria locally facilitate actin dynamics through reactive oxygen species that we show is necessary for electrical synapses & behaviour.

The burden of antibiotic resistance of the main microorganisms causing infections in humans - review of the literature.

One of the biggest threats to human well-being and public health is antibiotic resistance. If allowed to spread unchecked, it might become a major health risk and trigger another pandemic. This proves the need to develop antibiotic resistance-related global health solutions that take into consideration microdata from various global locations. Establishing positive social norms, guiding individual and group behavioral habits that support global human health, and ultimately raising public awareness of the need for such action could all have a positive impact. Antibiotic resistance is not just a growing clinical concern but also complicates therapy, making adherence to current guidelines for managing antibiotic resistance extremely difficult. Numerous genetic components have been connected to the development of resistance; some of these components have intricate paths of transfer between microorganisms. Beyond this, the subject of antibiotic resistance is becoming increasingly significant in medical microbiology as new mechanisms underpinning its development are identified. In addition to genetic factors, behaviors such as misdiagnosis, exposure to broad-spectrum antibiotics, and delayed diagnosis contribute to the development of resistance. However, advancements in bioinformatics and DNA sequencing technology have completely transformed the diagnostic sector, enabling real-time identification of the components and causes of antibiotic resistance. This information is crucial for developing effective control and prevention strategies to counter the threat.

C. elegans touch receptor neurons direct mechanosensory complex organization via repurposing conserved basal lamina proteins.

The sense of touch is conferred by the conjoint function of somatosensory neurons and skin cells. These cells meet across a gap filled by a basal lamina, an ancient structure found in metazoans. Using Caenorhabditis elegans, we investigate the composition and ultrastructure of the extracellular matrix at the epidermis and touch receptor neuron (TRN) interface. We show that membrane-matrix complexes containing laminin, nidogen, and the MEC-4 mechano-electrical transduction channel reside at this interface and are central to proper touch sensation. Interestingly, the dimensions and spacing of these complexes correspond with the discontinuous beam-like extracellular matrix structures observed in serial-section transmission electron micrographs. These complexes fail to coalesce in touch-insensitive extracellular matrix mutants and in dissociated neurons. Loss of nidogen reduces the density of mechanoreceptor complexes and the amplitude of the touch-evoked currents they carry. Thus, neuron-epithelium cell interfaces are instrumental in mechanosensory complex assembly and function. Unlike the basal lamina ensheathing the pharynx and body wall muscle, nidogen recruitment to the puncta along TRNs is not dependent upon laminin binding. MEC-4, but not laminin or nidogen, is destabilized by point mutations in the C-terminal Kunitz domain of the extracellular matrix component, MEC-1. These findings imply that somatosensory neurons secrete proteins that actively repurpose the basal lamina to generate special-purpose mechanosensory complexes responsible for vibrotactile sensing.

A MRSA mystery: how PBP4 and cyclic-di-AMP join forces against ß-lactam antibiotics.

The high-level resistance to next-generation ß-lactams frequently found in Staphylococcus aureus isolates lacking mec, which encodes the transpeptidase PBP2a traditionally associated with methicillin-resistant Staphylococcus aureus (MRSA), has remained incompletely understood for decades. A new study by Lai et al. found that the co-occurrence of mutations in pbp4 and gdpP, which respectively cause increased PBP4-mediated cell wall crosslinking and elevated cyclic-di-AMP levels, produces synergistic ß-lactam resistance rivaling that of PBP2a-producing MRSA (L.-Y. Lai, N. Satishkumar, S. Cardozo, V. Hemmadi, et al., mBio 15:e02889-23. 2024, https://doi.org/10.1128/mbio.02889-23). The combined mutations are sufficient to explain the high-level ß-lactam resistance of some mec-lacking strains, but the mechanism of synergy remains elusive and an avenue for further research. Importantly, the authors establish that co-occurrence of these mutations leads to antibiotic therapy failure in a Caenorhabditis elegans infection model. These results underscore the need to consider this unique and novel ß-lactam resistance mechanism during the clinical diagnosis of MRSA, rather than relying on mec as a diagnostic.

Cyclical heat stress during lactation influences the microstructure of the bovine mammary gland.

This study aimed to evaluate the impact of heat stress on mammary epithelial cell (MEC) losses into milk, secretory mammary tissue structure, and mammary epithelial cell activity. Sixteen multiparous Holstein cows (632 ± 12 kg BW) approximately 100 d in milk housed in climate-controlled rooms were paired by body weight and randomly allocated to one of 2 treatments, heat stress (HS) or pair feeding thermoneutral (PFTN) using 2 cohorts. Each cohort was subjected to 2 periods of 4 d each. In period 1, both treatments had ad libitum access to a common total mixed ration and were exposed to a controlled daily temperature-humidity index (THI) of 64. In period 2, HS cows were exposed to controlled cyclical heat stress (THI: 74 to 80), while PFTN cows remained at 64 THI and daily dry matter intake was matched to HS. Cows were milked twice daily, and milk yield was recorded at each milking. Individual milk samples on the last day of each period were used to quantify MEC losses by flow cytometry using butyrophilin as a cell surface marker. On the final day of period 2, individual bovine mammary tissue samples were obtained for histomorphology analysis, assessment of protein abundance, and evaluation of gene expression of targets associated with cellular capacity for milk and milk component synthesis, heat response, cellular proliferation, and autophagy. Statistical analysis was performed using the GLIMMIX procedure of SAS. Milk yield was reduced by 4.3 kg by HS (n = 7) compared with PFTN (n = 8). Independent of treatment, MEC in milk averaged 174 cells/mL (2.9% of total cells). There was no difference between HS vs. PFTN cows for MEC shed or concentration in milk. Alveolar area was reduced 25% by HS, and HS had 4.1 more alveoli than PFTN. Total number of nucleated MEC per area were greater in HS (389 ± 1.05) compared with PFTN (321 ± 1.05); however, cell number per alveolus was similar between groups (25 ± 1.5 vs. 26 ± 1.4). There were no differences in relative fold expression for GLUT1, GLUT8, CSN2, CSN3, LALBA, FASN, HSPA5, and HSPA8 in HS compared with PFTN. Immunoblotting analyses showed a decrease abundance for phosphorylated STAT5 and S6K1, and an increase in LC3 II in HS compared with PFTN. These results suggest that even if milk yield differences and histological changes occur in the bovine mammary gland after 4 d of heat exposure, MEC loss into milk, nucleated MEC number per alveolus, and gene expression of nutrient transport, milk component synthesis, and heat stress related targets are unaffected. In contrast, the abundance of proteins related to protein synthesis and cell survival decreased significantly, while an upregulation of proteins associated with autophagy in HS compared with PFTN.

UAV-Assisted Mobile Edge Computing: Dynamic Trajectory Design and Resource Allocation.

The recent advancements of mobile edge computing (MEC) technologies and unmanned aerial vehicles (UAVs) have provided resilient and flexible computation services for ground users beyond the coverage of terrestrial service. In this paper, we focus on a UAV-assisted MEC system in which the UAV equipped with MEC servers is used to assist user devices in computing their tasks. To minimize the weighted average energy consumption and delay in the UAV-assisted MEC system, a LQR-Lagrange-based DDPG (LLDDPG) algorithm, which jointly optimizes the user task offloading and the UAV trajectory design, is proposed. To be specific, the LLDDPG algorithm consists of three subproblems. The DDPG algorithm is used to address the issue of UAV desired trajectory planning, and subsequently, the LQR-based algorithm is employed to achieve the real-time tracking control of UAV desired trajectory. Finally, the Lagrange duality method is proposed to solve the optimization problem of computational resource allocation. Simulation results indicate that the proposed LLDDPG algorithm can effectively improve the system resource management and realize the real-time UAV trajectory design.

Multi-step control of homologous recombination via Mec1/ATR suppresses chromosomal rearrangements.

The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection. Upon loss of Rad53 signaling and resection control, Mec1 becomes hyperactivated and triggers a salvage pathway in which the Sgs1 helicase is recruited to sites of DNA lesions via the 911-Dpb11 scaffolds and phosphorylated by Mec1 to favor heteroduplex rejection and limit HR-driven GCR accumulation. Fusing an ssDNA recognition domain to Sgs1 bypasses the requirement of Mec1 signaling for GCR suppression and nearly eliminates D-loop formation, thus preventing non-allelic recombination events. We propose that Mec1 regulates multiple steps of HR to prevent GCRs while ensuring balanced HR usage when needed for promoting tolerance to replication stress.

Sch9S6K controls DNA repair and DNA damage response efficiency in aging cells.

Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1ATR DNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1ATR. We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1AMPK rescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9S6K axis restores NER and enhances DDR by tuning PP2A activity, specifically in aging cells. Age-related repair deficiency depends on Snf1AMPK-mediated phosphorylation of Sch9S6K on Ser160 and Ser163. PP2A activity in old cells is detrimental for DDR and influences NER by modulating Snf1AMPK and Sch9S6K. Hence, the DDR and repair pathways in aging cells are influenced by the metabolic tuning of opposing AMPK and TORC1 networks and by PP2A activity. Specific Sch9S6K phospho-isoforms control DDR and NER efficiency, specifically during aging.

From mec cassette to rdhA: a key Dehalobacter genomic neighborhood in a chloroform and dichloromethane-transforming microbial consortium.

Chloroform (CF) and dichloromethane (DCM) are groundwater contaminants of concern due to their high toxicity and inhibition of important biogeochemical processes such as methanogenesis. Anaerobic biotransformation of CF and DCM has been well documented but typically independently of one another. CF is the electron acceptor for certain organohalide-respiring bacteria that use reductive dehalogenases (RDases) to dechlorinate CF to DCM. In contrast, known DCM degraders use DCM as their electron donor, which is oxidized using a series of methyltransferases and associated proteins encoded by the mec cassette to facilitate the entry of DCM to the Wood-Ljungdahl pathway. The SC05 culture is an enrichment culture sold commercially for bioaugmentation, which transforms CF via DCM to CO2. This culture has the unique ability to dechlorinate CF to DCM using electron equivalents provided by the oxidation of DCM to CO2. Here, we use metagenomic and metaproteomic analyses to identify the functional genes involved in each of these transformations. Though 91 metagenome-assembled genomes were assembled, the genes for an RDase-named acdA-and a complete mec cassette were found to be encoded on a single contig belonging to Dehalobacter. AcdA and critical Mec proteins were also highly expressed by the culture. Heterologously expressed AcdA dechlorinated CF and other chloroalkanes but had 100-fold lower activity on DCM. Overall, the high expression of Mec proteins and the activity of AcdA suggest a Dehalobacter capable of dechlorination of CF to DCM and subsequent mineralization of DCM using the mec cassette. IMPORTANCE: Chloroform (CF) and dichloromethane (DCM) are regulated groundwater contaminants. A cost-effective approach to remove these pollutants from contaminated groundwater is to employ microbes that transform CF and DCM as part of their metabolism, thus depleting the contamination as the microbes continue to grow. In this work, we investigate bioaugmentation culture SC05, a mixed microbial consortium that effectively and simultaneously degrades both CF and DCM coupled to the growth of Dehalobacter. We identified the functional genes responsible for the transformation of CF and DCM in SC05. These genetic biomarkers provide a means to monitor the remediation process in the field.

A Multi-Agent RL Algorithm for Dynamic Task Offloading in D2D-MEC Network with Energy Harvesting.

Delay-sensitive task offloading in a device-to-device assisted mobile edge computing (D2D-MEC) system with energy harvesting devices is a critical challenge due to the dynamic load level at edge nodes and the variability in harvested energy. In this paper, we propose a joint dynamic task offloading and CPU frequency control scheme for delay-sensitive tasks in a D2D-MEC system, taking into account the intricacies of multi-slot tasks, characterized by diverse processing speeds and data transmission rates. Our methodology involves meticulous modeling of task arrival and service processes using queuing systems, coupled with the strategic utilization of D2D communication to alleviate edge server load and prevent network congestion effectively. Central to our solution is the formulation of average task delay optimization as a challenging nonlinear integer programming problem, requiring intelligent decision making regarding task offloading for each generated task at active mobile devices and CPU frequency adjustments at discrete time slots. To navigate the intricate landscape of the extensive discrete action space, we design an efficient multi-agent DRL learning algorithm named MAOC, which is based on MAPPO, to minimize the average task delay by dynamically determining task-offloading decisions and CPU frequencies. MAOC operates within a centralized training with decentralized execution (CTDE) framework, empowering individual mobile devices to make decisions autonomously based on their unique system states. Experimental results demonstrate its swift convergence and operational efficiency, and it outperforms other baseline algorithms.

Mucoepidermoid carcinoma-a rare salivary gland-type tumor of the breast: are we dealing with primary or secondary?-a case report and literature review.

Background: Salivary gland-like tumors are extremely unusual in the breast, and their histology is very similar to primary salivary gland neoplasms. Mucoepidermoid carcinoma (MEC), a common salivary gland tumor, displays an infrequent occurrence in the breast, accounting for a mere 0.2-0.3% incidence. Given its rarity, it is critical to accurately distinguish it from metastatic cases before diagnosing it as a primary breast MEC for appropriate treatment. Currently, there is no consensus on the treatment of MEC, and there is a paucity of literature highlighting the ideal treatment modality, especially for estrogen receptor (ER)-positive cancers. Therefore, the aim of our case report was to underscore the diagnostic process, surgical and adjunctive treatments for our patient with ER-positive, progesterone receptor (PR)-negative and human epidermal growth factor receptor 2 (HER2)-negative MEC while also conducting a literature review to contribute to the limited existing data. Case Description: A 67-year-old African American woman presented with a lobulated 3.1-cm left breast mass on mammography, for which she underwent ultrasound-guided core needle biopsy that revealed invasive carcinoma with squamous differentiation. The carcinoma was ER-positive, PR-negative and HER2-negative. Subsequently, she underwent a lumpectomy with sentinel lymph node biopsy. Her final pathology revealed an intermediate-grade MEC with negative lymph nodes. She had a past medical history of benign salivary gland tumor, as well as a family history of BReast CAncer gene 1 (BRCA1)-associated breast cancer in her daughter. Conclusions: MEC of the breast is a rare tumor with a relatively favorable overall prognosis. The early and precise diagnosis of this condition plays a pivotal role in formulating effective treatment strategies and ensuring positive survival rates. Nonetheless, future studies are recommended to further explore the role of surgical approaches and adjuvant therapy to improve treatment outcomes.

Potential mechanisms of propionate degradation and methanogenesis in anaerobic digestion coupled with microbial electrolysis cell system: Importance of biocathode.

Microbial electrolysis cells (MEC) have the potential for enhancing the efficiency of anaerobic digestion (AD). In this study, microbiological and metabolic pathways in the biocathode of anaerobic digestion coupled with microbial electrolysis cells system (AD-MEC) were revealed to separate bioanode. The biocathode efficiently degraded 90 % propionate within 48 h, leading to a methane production rate of 3222 mL·m-2·d-1. The protein and heme-rich cathodic biofilm enhanced redox capacity and facilitated interspecies electron transfer. Key acid-degrading bacteria, including Dechloromonas agitata, Ignavibacteriales bacterium UTCHB2, and Syntrophobacter fumaroxidans, along with functional proteins such as cytochrome c and e-pili, established mutualistic relationships with Methanothrix soehngenii. This synergy facilitated a multi-pathway metabolic process that converted acetate and CO2 into methane. The study sheds light on the intricate microbial dynamics within the biocathode, suggesting promising prospects for the scalable integration of AD-MEC and its potential in sustainable energy production.

An Open-Label, Single-Arm, Multicenter, Observational Study Evaluating the Safety and Effectiveness of Akynzeo® in the Management of Chemotherapy-Induced Nausea and Vomiting in India.

Background Chemotherapy-induced nausea and vomiting is a common and unpleasant treatment-related side effect reported by cancer patients receiving chemotherapy. Akynzeo® or NEPA (NEtupitant + PAlonosetron) is the first fixed combination of netupitant and palonosetron that targets both critical pathways involved in emesis while providing a convenient, single oral dose therapy. The current study aimed to assess the effectiveness and safety of NEPA in a real-world setting in India. Methodology This was an open-label, multicenter, prospective, single-arm study conducted at six different locations across India. The study included patients of either gender, aged ≥18 years, naive to chemotherapy, scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC), and scheduled to receive oral NEPA, as determined by the investigator. Results A total of 360 people were screened and enrolled in the study. HEC was prescribed to 289 (81.64%) patients, while MEC was prescribed to 65 (18.36%) patients. Complete response was achieved in 94.92% of patients during the acute phase, 95.20% during the delayed phase, and 93.22% during the overall phase. During the overall phase, 92.73% and 95.38% of patients on the HEC and MEC regimens, respectively, achieved complete response. Adverse events were reported in 3.88% of patients. Conclusions Oral NEPA was found to be effective in the Indian real-world setting, eliciting a >90% complete response with HEC and MEC regimens across the acute, delayed, and overall phases.

Altered PBP4 and GdpP functions synergistically mediate MRSA-like high-level, broad-spectrum ß-lactam resistance in Staphylococcus aureus.

Infections caused by Staphylococcus aureus are a leading cause of mortality worldwide. S. aureus infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are particularly difficult to treat due to their resistance to next-generation ß-lactams (NGBs) such as methicillin, nafcillin, and oxacillin. Resistance to NGBs, which is alternatively known as broad-spectrum ß-lactam resistance, is classically mediated by PBP2a, a penicillin-binding protein encoded by mecA (or mecC) in MRSA. Thus, presence of mec genes among S. aureus spp. serves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated, mecA-deficient S. aureus strains can also exhibit NGB resistance. These strains, which are collectively termed as methicillin-resistant lacking mec (MRLM), are currently being identified in increasing numbers among natural resistant isolates of S. aureus. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs, can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance toward NGBs at levels comparable to those of MRSAs. Our study provides a fresh new perspective about alternative mechanisms of NGB resistance, challenging our current overall understanding of high-level, broad-spectrum ß-lactam resistance in S. aureus. It thus suggests reconsideration of the current approach toward diagnosis and treatment of ß-lactam-resistant S. aureus infections. IMPORTANCE: In Staphylococcus aureus, high-level, broad-spectrum resistance to ß-lactams such as methicillin, also referred to as methicillin resistance, is largely attributed to mecA. This study demonstrates that S. aureus strains that lack mecA but contain mutations that functionally alter PBP4 and GdpP can also mediate high-level, broad-spectrum resistance to ß-lactams. Resistance brought about by the synergistic action of functionally altered PBP4 and GdpP was phenotypically comparable to that displayed by mecA, as seen by increased bacterial survival in the presence of ß-lactams. An analysis of mutations detected in naturally isolated strains of S. aureus revealed that a significant proportion of them had similar pbp4 and GGDEF domain protein containing phosphodiesterase (gdpP) mutations, making this study clinically significant. This study not only identifies important players of non-classical mechanisms of ß-lactam resistance but also indicates reconsideration of current clinical diagnosis and treatment protocols of S. aureus infections.

Guidelines in Practice: Manual High-Level Disinfection.

There are several steps involved when performing high-level disinfection (HLD) of semicritical devices. The recently updated AORN "Guideline for manual high-level disinfection" provides perioperative nurses with evidence-based best practices for performing safe and effective HLD of reusable semicritical items. The guideline also addresses preventing injury to patients and health care workers associated with the handling of high-level disinfectants. This article provides an overview of the guideline and discusses recommendations for selection of a processing method, sterile processing areas, preparation of items for HLD, preparation of high-level disinfectants, manual HLD, drying and storage of items after HLD, and processing records. It also includes a scenario that illustrates specific concerns related to performing quality tests on high-level disinfectant solutions. Perioperative nurses should review the guideline in its entirety and apply the recommendations when performing manual HLD.

Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation.

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of ß-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% ß-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.

Two-Layer Edge Intelligence for Task Offloading and Computing Capacity Allocation with UAV Assistance in Vehicular Networks.

With the exponential growth of wireless devices and the demand for real-time processing, traditional server architectures face challenges in meeting the ever-increasing computational requirements. This paper proposes a collaborative edge computing framework to offload and process tasks efficiently in such environments. By equipping a moving unmanned aerial vehicle (UAV) as the mobile edge computing (MEC) server, the proposed architecture aims to release the burden on roadside units (RSUs) servers. Specifically, we propose a two-layer edge intelligence scheme to allocate network computing resources. The first layer intelligently offloads and allocates tasks generated by wireless devices in the vehicular system, and the second layer utilizes the partially observable stochastic game (POSG), solved by duelling deep Q-learning, to allocate the computing resources of each processing node (PN) to different tasks. Meanwhile, we propose a weighted position optimization algorithm for the UAV movement in the system to facilitate task offloading and task processing. Simulation results demonstrate the improved performance by applying the proposed scheme.

Case report: Fibroadenomas associated with atypical ductal hyperplasia and infiltrating epitheliosis mimicking invasive carcinoma.

Infiltrating epitheliosis (IE) is an uncommon type of complex sclerosing lesion in the breast. This condition is characterized by the infiltration of ducts into a scleroelastotic stroma, along with the presence of cells that display architectural and cytological patterns similar to those observed in usual ductal hyperplasia. We herein report a case of a 24-year-old woman who presented with bilateral breast nodules, which were initially identified as multiple fibroadenomas based on ultrasound findings. The patient underwent Mammotome system and regional mastectomy procedures, and subsequent pathological analysis confirmed the presence of multiple fibroadenomas with atypical ductal hyperplasia and infiltrating epitheliosis. This case discusses the challenges faced in diagnosing malignancy in a patient with multiple fibroadenomas accompanied by atypical ductal hyperplasia and infiltrating epitheliosis.

Enhancing CH4 production in microbial electrolysis cells: Optimizing electric field via carbon cathode resistivity.

Microbial electrolysis cells (MECs) are increasingly recognized as a promising technology for converting CO2 to CH4, offering the dual benefits of energy recovery from organic wastewater and CO2 emission reduction. A critical aspect of this technology is the enhancement of the electron-accepting capacity of the methanogenic biocathode to improve CH4 production efficiency. This study demonstrates that adjusting the cathode resistivity is an effective way to control the electric field intensity, thereby enhancing the electron accepting capacity and CH4 production. By maintaining the electric field intensity within approximately 8.50-10.83 mV·cm-1, the CH4 yield was observed to increase by up to two-fold. The improvement in CH4 production under optimized electric field conditions was attributed to the enhancement of the direct accepting capacity of the biocathode. This enhancement was primarily due to an increase in the relative abundance of Methanosaeta by approximately 10 % and an up to 83.78 % rise in the electron-accepting capacity of the extracellular polymeric substance. These insights offer a new perspective on the operation of methanogenic biocathodes and propose a novel biocathode construction methodology based on these findings, thus contributing to the enhancement of MEC efficiency.

Methicillin Resistance Elements in the Canine Pathogen Staphylococcus pseudintermedius and Their Association with the Peptide Toxin PSM-mec.

Staphylococcus pseudintermedius is a frequent cause of infections in dogs. Infectious isolates of this coagulase-positive staphylococcal species are often methicillin- and multidrug-resistant, which complicates therapy. In staphylococci, methicillin resistance is encoded by determinants found on mobile genetic elements called Staphylococcal Chromosome Cassette mec (SCCmec), which, in addition to methicillin resistance factors, sometimes encode additional genes, such as further resistance factors and, rarely, virulence determinants. In this study, we analyzed SCCmec in a collection of infectious methicillin-resistant S. pseudintermedius (MRSP) isolates from predominant lineages in the United States. We found that several lineages characteristically have specific types of SCCmec elements and Agr types and harbor additional factors in their SCCmec elements that may promote virulence or affect DNA uptake. All isolates had SCCmec-encoded restriction-modification (R-M) systems of types I or II, and sequence types (STs) ST84 and ST64 had one type II and one type I R-M system, although the latter lacked a complete methylation enzyme gene. ST68 isolates also had an SCCmec-encoded CRISPR system. ST71 isolates had a psm-mec gene, which, in all but apparently Agr-dysfunctional isolates, produced a PSM-mec peptide toxin, albeit at relatively small amounts. This study gives detailed insight into the composition of SCCmec elements in infectious isolates of S. pseudintermedius and lays the genetic foundation for further efforts directed at elucidating the contribution of identified accessory SCCmec factors in impacting SCCmec-encoded and thus methicillin resistance-associated virulence and resistance to DNA uptake in this leading canine pathogen.