Navigating Nutritional Strategies: Permissive Underfeeding in Critically Ill Patients.

Nutritional support is a critical component of care for critically ill patients, impacting their recovery and overall prognosis. Traditional approaches to feeding in the intensive care unit (ICU) have focused on meeting estimated energy requirements, often resulting in unintended consequences such as overfeeding and associated complications. Permissive underfeeding, a concept gaining attention recently, offers a more controlled approach by intentionally providing fewer calories than traditionally recommended. This comprehensive review explores the rationale, evidence, and practical considerations surrounding permissive underfeeding in critically ill patients. We discuss the physiological basis of permissive underfeeding, its potential benefits in mitigating the risks of overfeeding, and the challenges associated with implementation in clinical practice. Through an analysis of critical studies and clinical trials, we evaluate the comparative effectiveness of permissive underfeeding versus traditional feeding methods and examine its impact on patient outcomes. Recommendations for patient selection, monitoring, and future research directions are provided to guide clinicians in optimizing nutritional support strategies for critically ill individuals. By considering the role of permissive underfeeding alongside traditional feeding approaches, healthcare professionals can tailor nutritional interventions to individual patient needs, ultimately improving outcomes in the ICU.

Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells.

Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.

Advances in Anesthesia for Shoulder Surgery: A Comprehensive Review of Dexmedetomidine-Enhanced Interscalene Brachial Plexus Block.

Surgical procedures on the shoulder pose distinctive challenges in managing pain during the perioperative period, underscoring the importance of exploring innovative anesthesia techniques. This comprehensive review article delves into integrating dexmedetomidine, an alpha-2 adrenergic agonist, within interscalene brachial plexus blocks for shoulder surgery. The review initiates by underscoring the pivotal role of effective anesthesia in shoulder surgery and elucidates the rationale behind investigating dexmedetomidine as an adjunct. It meticulously examines the anatomy and physiology of the brachial plexus, emphasizing its critical significance in shoulder surgery. Furthermore, the article expounds on dexmedetomidine's mechanisms of action and pharmacokinetics, encompassing its safety profile and potential side effects. The conventional interscalene brachial plexus block techniques, along with their limitations and challenges, are discussed, laying the foundation for the integration of dexmedetomidine. The review subsequently delves into exploring the role of dexmedetomidine in regional anesthesia, covering previous studies, mechanisms of action, and the potential advantages of incorporating it into nerve blocks. The review's core concentrates on the practical application of dexmedetomidine-enhanced interscalene brachial plexus blocks. This includes discussions on administration techniques, dosage guidelines, and compelling evidence supporting its utilization. Clinical scenarios where this approach proves most advantageous are thoroughly explored, comparing its effectiveness with traditional techniques in terms of pain control and patient outcomes. A comprehensive examination of relevant clinical trials and case studies highlights the evidence supporting its efficacy. The review also underscores safety considerations associated with dexmedetomidine. It proposes strategies for mitigating risks to ensure patient safety. Insights into future directions and research are provided, encompassing ongoing studies, areas necessitating further investigation, and potential refinements in technique. Finally, the article summarizes key findings, emphasizing the practicality of dexmedetomidine-enhanced interscalene brachial plexus blocks in shoulder surgery and its far-reaching implications for clinical practice and patient care.

A Multidisciplinary Approach to Tracheoesophageal Fistula Repair in a Newborn: A Case Report.

This case report details the emergency management and successful surgical repair of a tracheoesophageal fistula (TEF) in a newborn delivered by lower segment cesarean section. Despite immediate crying after birth, the neonate's distress was evident, with an Apgar score of 4, prompting an urgent referral to the Neonatal ICU (NICU). Diagnostic investigations, including ultrasonography and two-dimensional echocardiography (2D Echo), revealed associated anomalies, such as a patent ductus arteriosus, arterial septal defect, and a TEF. An anaesthetist was urgently involved due to postnatal desaturation, leading to challenging intubation and surgical repair performed under general anaesthesia, which involved separating the trachea from the oesophagus. Postoperative imaging confirmed the successful closure of the fistulous connection. This case highlights the significance of prompt diagnosis, collaborative management, and surgical intervention in optimising outcomes for neonates with complex congenital anomalies like TEF.

Oligotyping and metagenomics reveal distinct Candidatus Accumulibacter communities in side-stream versus conventional full-scale enhanced biological phosphorus removal (EBPR) systems.

Candidatus Accumulibacter phosphatis (CAP) and its clade-level micro-diversity has been associated with and implicated in functional differences in phosphorus removal performance in enhanced biological phosphorus removal (EBPR) systems. Side-stream EBPR (S2EBPR) is an emerging process that has been shown to present a suite of advantages over the conventional EBPR design, however, large knowledge gaps remain in terms of its underlying ecological mechanisms. Here, we compared and revealed the higher-resolution differences in microbial ecology of CAP between a full-scale side-stream EBPR configuration and a conventional A2O EBPR process that were operated in parallel and with the same influent feed. Even though the relative abundance of CAP, revealed by 16S rRNA gene amplicon sequencing, was similar in both treatment trains, a clade-level analysis, using combined 16S rRNA-gene based amplicon sequencing and oligotyping analysis and metagenomics analysis, revealed the distinct CAP microdiversity between the S2EBPR and A2O configurations that likely attributed to the improved performance in S2EBPR in comparison to conventional EBPR. Furthermore, genome-resolved metagenomics enabled extraction of three metagenome-assembled genomes (MAGs) belonging to CAP clades IIB (RCAB4-2), IIC (RC14) and II (RC18), from full-scale EBPR sludge for the first time, including a distinct Ca. Accumulibacter clade that is dominant and associated only with the S2EBPR configuration. The results also revealed the temporally increasing predominance of RC14, which belonged to Clade IIC, during the implementation of the S2EBPR configuration. Finally, we also show the existence of previously uncharacterized diversity of clades of CAP, namely the clades IIB and as yet unidentified clade of type II, in full-scale EBPR communities, highlighting the unknown diversity of CAP communities in full-scale EBPR systems.

IL-1R1-dependent signaling coordinates epithelial regeneration in response to intestinal damage.

Repair of the intestinal epithelium is tightly regulated to maintain homeostasis. The response after epithelial damage needs to be local and proportional to the insult. How different types of damage are coupled to repair remains incompletely understood. We report that after distinct types of intestinal epithelial damage, IL-1R1 signaling in GREM1+ mesenchymal cells increases production of R-spondin 3 (RSPO3), a Wnt agonist required for intestinal stem cell self-renewal. In parallel, IL-1R1 signaling regulates IL-22 production by innate lymphoid cells and promotes epithelial hyperplasia and regeneration. Although the regulation of both RSPO3 and IL-22 is critical for epithelial recovery from Citrobacter rodentium infection, IL-1R1-dependent RSPO3 production by GREM1+ mesenchymal cells alone is sufficient and required for recovery after dextran sulfate sodium-induced colitis. These data demonstrate how IL-1R1-dependent signaling orchestrates distinct repair programs tailored to the type of injury sustained that are required to restore intestinal epithelial barrier function.

Gremlin 1+ fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues.

Fibroblastic reticular cells (FRCs) are specialized stromal cells that define tissue architecture and regulate lymphocyte compartmentalization, homeostasis, and innate and adaptive immunity in secondary lymphoid organs (SLOs). In the present study, we used single-cell RNA sequencing (scRNA-seq) of human and mouse lymph nodes (LNs) to identify a subset of T cell-zone FRCs defined by the expression of Gremlin1 (Grem1) in both species. Grem1-CreERT2 knock-in mice enabled localization, multi-omics characterization and genetic depletion of Grem1+ FRCs. Grem1+ FRCs primarily localize at T-B cell junctions of SLOs, neighboring pre-dendritic cells and conventional dendritic cells (cDCs). As such, their depletion resulted in preferential loss and decreased homeostatic proliferation and survival of resident cDCs and compromised T cell immunity. Trajectory analysis of human LN scRNA-seq data revealed expression similarities to murine FRCs, with GREM1+ cells marking the endpoint of both trajectories. These findings illuminate a new Grem1+ fibroblastic niche in LNs that functions to maintain the homeostasis of lymphoid tissue-resident cDCs.

High broadband photoconductivity of few-layered MoS2 field-effect transistors measured using multi-terminal methods: effects of contact resistance.

Among the layered two dimensional semiconductors, molybdenum disulfide (MoS2) is considered to be an excellent candidate for applications in optoelectronics and integrated circuits due to its layer-dependent tunable bandgap in the visible region, high ON/OFF current ratio in field-effect transistors (FET) and strong light-matter interaction properties. In this study, using multi-terminal measurements, we report high broadband photocurrent response (R) and external quantum efficiency (EQE) of few-atomic layered MoS2 phototransistors fabricated on a SiO2 dielectric substrate and encapsulated with a thin transparent polymer film of Cytop. The photocurrent response was measured using a white light source as well as a monochromatic light of wavelength λ = 400 nm-900 nm. We measured responsivity using a 2-terminal configuration as high as R = 1 × 103 A W-1 under white light illumination with an optical power Popt = 0.02 nW. The R value increased to 3.5 × 103 A W-1 when measured using a 4-terminal configuration. Using monochromatic light on the same device, the measured values of R were 103 and 6 × 103 A W-1 under illumination of λ = 400 nm when measured using 2- and 4-terminal methods, respectively. The highest EQE values obtained using λ = 400 nm were 105% and 106% measured using 2- and 4-terminal configurations, respectively. The wavelength dependent responsivity decreased from 400 nm to the near-IR region at 900 nm. The observed photoresponse, photocurrent-dark current ratio (PDCR), detectivity as a function of applied gate voltage, optical power, contact resistances and wavelength were measured and are discussed in detail. The observed responsivity is also thoroughly studied as a function of contact resistance of the device.

Distinct Mesenchymal Cell Populations Generate the Essential Intestinal BMP Signaling Gradient.

Intestinal stem cells (ISCs) are confined to crypt bottoms and their progeny differentiate near crypt-villus junctions. Wnt and bone morphogenic protein (BMP) gradients drive this polarity, and colorectal cancer fundamentally reflects disruption of this homeostatic signaling. However, sub-epithelial sources of crucial agonists and antagonists that organize this BMP gradient remain obscure. Here, we couple whole-mount high-resolution microscopy with ensemble and single-cell RNA sequencing (RNA-seq) to identify three distinct PDGFRA+ mesenchymal cell types. PDGFRA(hi) telocytes are especially abundant at the villus base and provide a BMP reservoir, and we identified a CD81+ PDGFRA(lo) population present just below crypts that secretes the BMP antagonist Gremlin1. These cells, referred to as trophocytes, are sufficient to expand ISCs in vitro without additional trophic support and contribute to ISC maintenance in vivo. This study reveals intestinal mesenchymal structure at fine anatomic, molecular, and functional detail and the cellular basis for a signaling gradient necessary for tissue self-renewal.

Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling.

Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8+ T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8+ T cells via interleukin-6. These epigenetic changes facilitated metabolic reprogramming and amplified the activity of pro-survival pathways through differential transcription factor activity. Accordingly, FRC conditioning significantly enhanced the persistence of virus-specific CD8+ T cells in vivo and augmented their differentiation into tissue-resident memory T cells. Our study demonstrates that FRCs play a role beyond restricting T cell expansion-they can also shape the fate and function of CD8+ T cells.

Comparative analysis of 2-week glycaemic profile of healthy versus mild gestational diabetic pregnant women using flash glucose monitoring system: an observational study.

OBJECTIVE: To compare glycaemic profiles in women with mild gestational diabetes (GDM) and those with a healthy pregnancy. DESIGN: Observational study. SETTING: Hospital-based. POPULATION: Healthy nonpregnant, healthy pregnant, and women with GDM, diagnosed by oral glucose tolerance test. METHODS: Nine nonpregnant women, 33 healthy pregnant women, 29 pregnant women with GDM between 24 and 36 weeks' gestation, received ambulatory glucose profile (AGP) monitoring for a 2-week period. AGP values were compared in the three groups: 100 days (9600 data points) for nonpregnant women, 396 days (33 792 data points) for healthy pregnant women, and 348 days (34 408 data points) for women with GDM. RESULTS: Mean glucose values for fasting and postmeals were highest in nonpregnant healthy women and lowest in healthy pregnant women (P < 0.001). Women with mild GDM had significantly higher blood glucose values than did healthy pregnant women, though still within the target range. Blood glucose values >160 mg/dl were observed in 41.4% (12/29) in the GDM group compared with 18.2% in women with a healthy pregnancy. The maximum peak of day and night time glucose was respectively 234 and 215 mg/dl in women with GDM compared with 183 and 171 mg/dL in the control group. Glycaemic variability as measured by interquartile range was higher in GDM pregnancies. CONCLUSIONS: Although the blood glucose level remained within the target levels in women with mild GDM, glycaemic variability and mean blood glucose levels were significantly higher among women with GDM than among women with a healthy pregnancy. TWEETABLE ABSTRACT: Average blood glucose levels and glycaemic variability are significantly higher in women with GDM than in women with a healthy pregnancy.

Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.

Apoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Loss of Fas and Bim function in Bcl2l11-/-Faslpr/lpr mice inhibited apoptosis of T cells and prevented the early T cell attrition resulting from lymphocytic choriomeningitis virus infection. Bcl2l11-/-Faslpr/lpr mice were also resistant to prolonged allograft survival induced by CoB targeting the CD40-CD154 pathway. These results demonstrate that both extrinsic and intrinsic apoptosis pathways function concurrently to regulate T cell homeostasis during the early stages of immune responses and allograft survival during CoB.

Glutathione as a photo-stabilizer of avobenzone: an evaluation under glass-filtered sunlight using UV-spectroscopy.

Avobenzone is the most widely used UVA filter in sunscreen lotion and it is prone to degradation in the presence of sunlight/UV radiation. To overcome the photo-instability of avobenzone, various photostabilizers have been used as additives, including antioxidants such as vitamin C, vitamin E, and ubiquinone. In the present study, the well known antioxidant, glutathione, was evaluated for protecting avobenzone from photodegradation in the presence of glass-filtered sunlight. The features of glutathione as a skin whitener and a radical scavenger in cells have prompted the assessment of the photostabilzing activity of glutathione on avobenzone. Glutathione significantly attenuated the glass-filtered sunlight-induced degradation of avobenzone at equimolar or higher ratios of glutathione and avobenzone. Mutational studies have been undertaken to investigate the role of the thiol group and the isopeptide bond of glutathione on its photoprotection activity towards avobenzone. The thiol group of glutathione plays a vital role in exhibiting the photoprotection activity, which was further supported by the studies on photodegradation of avobonzone in the presence of ß-mercaptoethanol. The dual role of glutathione as a skin whitening agent and a photostabilizer of avobenzone may be useful for the development of multipurpose cosmetic lotions.

Testosterone is an endogenous regulator of BAFF and splenic B cell number.

Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.

Transient expression of ZBTB32 in anti-viral CD8+ T cells limits the magnitude of the effector response and the generation of memory.

Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8+ T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32-/- mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8+ T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8+ effector T cells that is required for the balanced regulation of effector versus memory responses to infection.

The role of inorganic nitrogen in successful formation of granular biofilms for wastewater treatment that support cyanobacteria and bacteria.

Recently, the use of phototrophs for wastewater treatment has been revisited because of new approaches to separate them from effluent streams. One manifestation uses oxygenic photogranules (OPGs) which are dense, easily-settleable granular biofilms of cyanobacteria, which surrounding populations of heterotrophs, autotrophs, and microalgae. OPGs can remove COD and nitrogenous compounds without external aeration. To better grow and maintain biomass in the proposed wastewater process, this study seeks to understand the factors that contribute to successful granulation. Availability of initial inorganic nitrogen, particularly ammonium, was associated with successful cultivation of OPGs. In the first days of granulation, a decrease in ammonium coupled with an increase in a cyanobacterial-specific 16S rRNA gene, may suggest that ammonium was assimilated in cyanobacteria offering a competitive environment for growth. Though both successful and unsuccessful OPG formation demonstrated a shift from non-phototrophic bacterial dominated communities on day 0 to cyanobacterial dominated communities on day 42, the successful community had a greater relative abundance (46%) of OTUs associated with genera Oscillatoria and Geitlernema than the unsuccessful community (27%), supporting that filamentous cyanobacteria are essential for successful OPG formation. A greater concentration of chlorophyll b in the unsuccessful OPG formation suggested a greater abundance of algal species. This study offers indicators of granulation success, notably availability of inorganic nitrogen and chlorophyll a and b concentrations for monitoring the health and growth of biomass for a potential OPG process.

Ecological and Transcriptional Responses of Anode-Respiring Communities to Nitrate in a Microbial Fuel Cell.

A poorly understood phenomenon with a potentially significant impact on electron recovery is competition in microbial fuel cells (MFC) between anode-respiring bacteria and microorganisms that use other electron acceptors. Nitrate is a constituent of different wastewaters and can act as a competing electron acceptor in the anode. Studies investigating the impact of competition on population dynamics in mixed communities in the anode are lacking. Here, we investigated the impact of nitrate at different C/N ratios of 1.8, 3.7, and 7.4 mg C/mg N on the electrochemical performance and the biofilm community in mixed-culture chemostat MFCs. The electrochemical performance of the MFC was not affected under electron donor non-limiting conditions, 7.4 mg C/mg N. At lower C/N, electron donor limiting and ratio electron recovery were significantly affected. The electrochemical performance recovered upon removal of nitrate at 3.7 mg C/mg N but did not at 1.8 mg C/mg N. Microbial community analysis showed a decrease in Deltaproteobacteria accompanied by an increase in Betaproteobacteria in response to nitrate at low C/N ratios and no significant changes at 7.4 mg C/mg N. Transcriptional analysis showed increased transcription of nirK and nirS genes during nitrate flux, suggesting that denitrification to N2 and not facultative nitrate reduction by Geobacter spp. might be the primary response to perturbation with nitrate.

Utilizing Smartphone-Based Machine Learning in Medical Monitor Data Collection: Seven Segment Digit Recognition.

Biometric measurements captured from medical devices, such as blood pressure gauges, glucose monitors, and weighing scales, are essential to tracking a patient's health. Trends in these measurements can accurately track diabetes, cardiovascular issues, and assist medication management for patients. Currently, patients record their results and date of measurement in a physical notebook. It may be weeks before a doctor sees a patient's records and can assess the health of the patient. With a predicted 6.8 billion smartphones in the world by 20221, health monitoring platforms, such as Apple's HealthKit2, can be leveraged to provide the right care at the right time. This research presents a mobile application that enables users to capture medical monitor data and send it to their doctor swiftly. A key contribution of this paper is a robust engine that can recognize digits from medical monitors with an accuracy of 98.2%.

Regulation of tissue-dependent differences in CD8+ T cell apoptosis during viral infection.

UNLABELLED: Virus-specific CD8+ T cells in the lymphoid organs contract at the resolution of virus infections by apoptosis or by dissemination into peripheral tissues, and those residing in nonlymphoid organs, including the peritoneal cavity and fat pads, are more resistant to apoptosis than those in the spleen and lymph nodes. This stability of memory T cells in the nonlymphoid tissues may enhance protection to secondary challenges. Here, we show that lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells in nonlymphoid tissues were enriched for memory precursors (expressing high levels of interleukin-7 receptor and low levels of killer cell lectin-like receptor G1 [IL-7Rhi KLRG1lo]) and had higher expression of CD27, CXCR3, and T cell factor-1 (TCF-1), each a marker that is individually correlated with decreased apoptosis. CD8+ T cells in the peritoneal cavity of TCF-1-deficient mice had decreased survival, suggesting a role for TCF-1 in promoting survival in the nonlymphoid tissues. CXCR3+ CD8+ T cells resisted apoptosis and accumulated in the lymph nodes of mice treated with FTY720, which blocks the export of lymph node cells into peripheral tissue. The peritoneal exudate cells (PEC) expressed increased amounts of CXCR3 ligands, CXCL9 and CXCL10, which may normally recruit these nonapoptotic cells from the lymph nodes. In addition, adoptive transfer of splenic CD8+ T cells into PEC or spleen environments showed that the peritoneal environment promoted survival of CD8+ T cells. Thus, intrinsic stability of T cells which are present in the nonlymphoid tissues along with preferential migration of apoptosis-resistant CD8+ T cells into peripheral sites and the availability of tissue-specific factors that enhance memory cell survival may collectively account for the tissue-dependent apoptotic differences. IMPORTANCE: Most infections are initiated at nonlymphoid tissue sites, and the presence of memory T cells in nonlymphoid tissues is critical for protective immunity in various viral infection models. Virus-specific CD8+ T cells in the nonlymphoid tissues are more resistant to apoptosis than those in lymphoid organs during the resolution and memory phase of the immune response to acute LCMV infection. Here, we investigated the mechanisms promoting stability of T cells in the nonlymphoid tissues. This increased resistance to apoptosis of virus-specific CD8+ T cells in nonlymphoid tissues was due to several factors. Nonlymphoid tissues were enriched in memory phenotype CD8+ T cells, which were intrinsically resistant to apoptosis irrespective of the tissue environment. Furthermore, apoptosis-resistant CD8+ T cells preferentially migrated into the nonlymphoid tissues, where the availability of tissue-specific factors may enhance memory cell survival. Our findings are relevant for the generation of long-lasting vaccines providing protection at peripheral infection sites.

Visualizing and quantifying dose distribution in a UV reactor using three-dimensional laser-induced fluorescence.

Evaluating the performance of typical water treatment UV reactors is challenging due to the complexity in assessing spatial and temporal variation of UV fluence, resulting from highly unsteady, turbulent nature of flow and variation in UV intensity. In this study, three-dimensional laser-induced fluorescence (3DLIF) was applied to visualize and quantitatively analyze a lab-scale UV reactor consisting of one lamp sleeve placed perpendicular to flow. Mapping the spatial and temporal fluence delivery and MS2 inactivation revealed the highest local fluence in the wake zone due to longer residence time and higher UV exposure, while the lowest local fluence occurred in a region near the walls due to short-circuiting flow and lower UV fluence rate. Comparing the tracer based decomposition between hydrodynamics and IT revealed similar coherent structures showing the dependency of fluence delivery on the reactor flow. The location of tracer injection, varying the height and upstream distance from the lamp center, was found to significantly affect the UV fluence received by the tracer. A Lagrangian-based analysis was also employed to predict the fluence along specific paths of travel, which agreed with the experiments. The 3DLIF technique developed in this study provides new insight on dose delivery that fluctuates both spatially and temporally and is expected to aid design and optimization of UV reactors as well as validate computational fluid dynamics models that are widely used to simulate UV reactor performances.