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  • Telling Baltimore Stories Through Data

    Yarnell, Amy M.; Knott, Cheryl; Little, Ryan; Sadler, James (2024-02-15)
  • Taste

    Pinho, Thom; Wink, Tara (2023-11)
    The 2024 Health Sciences and Human Services Calendar, Taste, features a selection of botanicals from the Historical Collections department. The calendar includes twelve edible botanicals as well as information on their medicinal and historical uses.
  • HS/HSL Connective Issues 2023-2024

    University of Maryland, Baltimore. Health Sciences and Human Services Library, 2024
  • Health Sciences and Human Services Library Annual Report (2022-2023)

    University of Maryland, Baltimore. Health Sciences and Human Services Library (2023)
  • Opioid use disorder in pregnancy: leveraging provider perceptions to inform comprehensive treatment

    Titus-Glover, Doris; Shaya, Fadia T.; Welsh, Christopher, M.D.; Qato, Danya; Shah, Savyasachi; Gresssler, Laura E.; Vivrette, Rebecca (2021-03-10)
    Background: Medications for opioid use disorder (MOUD) are recommended with adjuvant behavioral therapies, counseling, and other services for comprehensive treatment of maternal opioid use disorder. Inadequate access to treatment, lack of prescribing providers and complex delivery models are among known barriers to care. Multidisciplinary provider input can be leveraged to comprehend factors that facilitate or inhibit treatment. The objective of this study is to explore provider perceptions of MOUD and factors critical to comprehensive treatment delivery to improve the care of pregnant women with opioid use disorder. Methods: A qualitative research approach was used to gather data from individual provider and group semistructured interviews. Providers (n = 12) responded to questions in several domains related to perceptions of MOUD, treatment delivery, access to resources, and challenges/barriers. Data were collected, transcribed, coded (by consensus) and emerging themes were analyzed using grounded theory methodology. Results: Emerging themes revealed persistent gaps in treatment and challenges in provider, health systems and patient factors. Providers perceived MOUD to be a “lifeline” to women. Conclusions: Inconsistencies in treatment provision, access and uptake can be improved by leveraging provider perceptions, direct experiences and recommendations for an integrated team-based, patient-centered approach to guide the care of pregnant women with opioid use disorder.
  • Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon Cancer

    Schledwitz, Alyssa; Sundel, Margaret H.; Alizadeh, Madeline; Hu, Shien; Xie, Guofeng; Raufman, Jean-Pierre (2021-12-05)
    Cancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.
  • Successful Profiling of Plasmodium falciparum var Gene Expression in Clinical Samples via a Custom Capture Array

    Stucke, Emily M.; Dara, Antoine; Dwivedi, Ankit; Hodges, Theresa K.; Ott, Sandra; Coulibaly, Drissa; Koné, Abdoulaye K.; Traoré, Karim; Guindo, Bouréima; Tangara, Bourama M.; et al. (2021-11-30)
    var genes encode Plasmodium falciparum erythrocyte membrane protein- 1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of var expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved var segments. Our goal was to enrich for parasite RNA, allowing de novo assembly of var genes and detection of expressed novel variants. We used two overall approaches: (i) enriching for total mRNA in the sequencing library preparations and (ii) enriching for parasite RNA with a custom capture array based on Roche’s SeqCap EZ enrichment system. The capture array was designed with probes based on the whole 3D7 reference genome and an additional .4,000 full-length var gene sequences from other P. falciparum strains. We tested each method on RNA samples from Malian children with severe or uncomplicated malaria infections. All reads mapping to the human genome were removed, the remaining reads were assembled de novo into transcripts, and from these, var-like transcripts were identified and annotated. The capture array produced the longest maximum length and largest numbers of var gene transcripts in each sample, particularly in samples with low parasitemia. Identifying the most-expressed var gene sequences in whole-blood clinical samples without the need for extensive processing or generating sample-specific reference genome data is critical for understanding the role of PfEMP1s in malaria pathogenesis.
  • Malian adults maintain serologic responses to virulent PfEMP1s amid seasonal patterns of fluctuation

    Ventimiglia, Noah T.; Stucke, Emily M.; Coulibaly, Drissa; Berry, Andrea A.; Lyke, Kirsten E.; Laurens, Matthew B.; Bailey, Jason A.; Adams, Matthew; Niangaly, Amadou; Koné, Abdoulaye K.; et al. (2021-07-13)
    Plasmodium falciparum erythrocyte membrane protein-1s (PfEMP1s), diverse malaria proteins expressed on the infected erythrocyte surface, play an important role in pathogenesis, mediating adhesion to host vascular endothelium. Antibodies to particular non-CD36-binding PfEMP1s are associated with protection against severe disease. We hypothesized that given lifelong P. falciparum exposure, Malian adults would have broad PfEMP1 serorecognition and high seroreactivity levels during follow-up, particularly to non-CD36-binding PfEMP1s such as those that attach to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1). Using a protein microarray, we determined serologic responses to 166 reference PfEMP1 fragments during a dry and subsequent malaria transmission season in Malian adults. Malian adult sera had PfEMP1 serologic responses throughout the year, with decreased reactivity to a small subset of PfEMP1 fragments during the dry season and increases in reactivity to a different subset of PfEMP1 fragments during the subsequent peak malaria transmission season, especially for intracellular PfEMP1 domains. For some individuals, PfEMP1 serologic responses increased after the dry season, suggesting antigenic switching during asymptomatic infection. Adults were more likely to experience variable serorecognition of CD36- binding PfEMP1s than non-CD36-binding PfEMP1s that bind EPCR or ICAM-1, which remained serorecognized throughout the year. Sustained seroreactivity to non-CD36-binding PfEMP1s throughout adulthood amid seasonal fluctuation patterns may reflect underlying protective severe malaria immunity and merits further investigation.
  • Outcomes in Hepatitis C Positive Liver Transplantation: Timing of Direct-Acting Antiviral Treatment and Impact on Graft Fibrosis

    Wellington, Jennifer; Ma, Andrew; Kottilil, Shyamasundaran; Ravichandran, Bharath; Husson, Jennifer; Bruno, David; Wilson, Eleanor, M.D. (2021-09-14)
    Liver transplantation for hepatitis C virus (HCV)-related disease has the lowest five-year graft survival among all liver transplant recipients. Graft failure due to accelerated fibrosis from unrestrained HCV replication is common. Optimal timing of HCV treatment with direct-acting antiviral agents remains unknown. We compared HCV liver transplant recipients successfully treated for HCV before transplant to those treated within 1 year of transplant to determine if graft fibrosis, measured by Fib-4 scores, differs with timing of treatment. Fib-4 scores less than or equal to 1.45 defined minimal fibrosis and greater than 1.45 defined greater than minimal fibrosis. We identified 117 liver transplant recipients: 52 treated before transplantation and 65 treated within 1 year of transplantation. Overall, 34% of recipients had minimal fibrosis, and the likelihood of having minimal fibrosis following treatment and liver transplantation did not differ by timing of treatment. The odds ratio of having greater than minimal fibrosis was 0.65 (95% CI 0.30, 1.42) among those treated within 1 year after transplantation compared to those treated before transplantation (p-value 0.28). Importantly, nearly 2/3 of these patients had evidence of fibrosis progression one year after sustained virologic response, supporting recommendations for early antiviral-based treatment to prevent accumulation of HCV-related disease.
  • Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

    Singh, Prerna; Eley, John; Mahmood, Nayab; Bhandary, Binny; Dukic, Tijana; Tu, Kevin J.; Polf, Jerimy C.; Lamichhane, Narottam; Mahmood, Javed; Vujaskovic, Zelijko; et al. (2021-12-04)
    Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP.We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3-1.7) at the E-SOBP compared with the M-SOBP.
  • The subunits of IL-12, originating from two distinct cells, can functionally synergize to protect against pathogen dissemination in vivo

    Gerber, Allison N.; Abdi, Kaveh; Singh, Nevil J. (2021-10-12)
    Cytokines are typically single gene products, except for the heterodimeric interleukin (IL)-12 family. The two subunits (IL-12p40 and IL-12p35) of the prototype IL-12 are known to be simultaneously co-expressed in activated myeloid cells, which secrete the fully active heterodimer to promote interferon (IFN)g production in innate and adaptive cells. We find that chimeric mice containing mixtures of cells that can only express either IL-12p40 or IL-12p35, but not both together, generate functional IL-12. This alternate two-cell pathway requires IL-12p40 from hematopoietic cells to extracellularly associate with IL-12p35 from radiation-resistant cells. The two-cell mechanism is sufficient to propel local T cell differentiation in sites distal to the initial infection and helps control systemic dissemination of a pathogen, although not parasite burden, at the site of infection. Broadly, this suggests that early secretion of IL-12p40 monomers by sentinel cells at the infection site may help prepare distal host tissues for potential pathogen arrival.
  • Acute Limb Ischemia Caused by Inadvertent Arterial Drug Self-Injection: A Case Report

    Maldarelli, Mary Elizabeth; Traver, Edward C.; Norcross, Gregory; Gann, Donald; Kattakuzhy, Sarah; Welsh, Christopher, M.D.; Schmalzle, Sarah Ann (2021-08-15)
    Objective: Unusual clinical course Background: A predictable consequence of long-term injection drug use is the destruction of the native venous system; as a consequence, people who inject drugs may eventually move to injection into skin and subcutaneous tissue, wounds, muscles, and arteries. These practices put people who inject drugs at risk for injection-related softtissue infection, vascular damage, ischemia, and compartment syndrome, all of which have overlapping presenting symptoms. Case Report: A 35-year-old man who injects drugs presented with foot swelling and discoloration initially concerning for necrotizing fasciitis or compartment syndrome. After progression despite appropriate antimicrobial and surgical treatment for soft-tissue infection, he was diagnosed with arterial insufficiency and resultant distal ischemia. This diagnosis was discovered only after obtaining additional history of the patient’s drug use practices. Just prior to his symptoms, he had unintentionally injected a formed thrombus into his dorsalis pedis artery. Conclusions: Intra-arterial injection of drugs can cause ischemia through a variety of mechanisms, including direct vessel trauma, arterial spasm, toxicity from the drug of abuse or an adulterant, embolism of particulate matter, and as proposed here, direct injection of preformed thrombus. Medical providers should be aware of the steps of injection drug use and their associated risks so that they can ask appropriate questions to focus their differential diagnosis, increase their understanding of common or current local injection practices, and develop rapport with the patient. Patient education on safe injection techniques may also reduce the risk of serious complications.
  • Effect of Stretching of Spastic Elbow Under Intelligent Control in Chronic Stroke Survivors—A Pilot Study

    Rao, Sanjana; Huang, Mei Zhen; Chung, Sun Gun; Zhang, Li-Qun (2021-12-14)
    Objective: To assess the short-termeffects of strenuous dynamic stretching of the elbow joint using an intelligent stretching device in chronic spastic stroke survivors. Methods: The intelligent stretching device was utilized to provide a single session of intensive stretching to the spastic elbow joint in the sagittal plane (i.e., elbow flexion and extension). The stretching was provided to the extreme range, safely, with control of the stretching velocity and torque to increase the joint range of motion (ROM) and reduce spasticity and joint stiffness. Eight chronic stroke survivors (age: 52.6 ± 8.2 years, post-stroke duration: 9.5 ± 3.6 years) completed a single 40-min stretching intervention session. Elbow passive and active ROM, strength, passive stiffness (quantifying the non-reflex component of spasticity), and instrumented tendon reflex test of the biceps tendon (quantifying the reflex component of the spasticity) were measured before and after stretching. Results: After stretching, there was a significant increase in passive ROM of elbow flexion (p = 0.021, r = 0.59) and extension (p = 0.026, r = 0.59). Also, elbow active ROM and the spastic elbow flexors showed a trend of increase in their strength. Conclusion: The intelligent stretching had a short-term positive influence on the passive movement ROM. Hence, intelligent stretching can potentially be used to repeatedly and regularly stretch spastic elbow joints, which subsequently helps to reduce upper limb impairments post-stroke.
  • Comparative Ca2D channel contributions to intracellular Ca2D levels in the circadian clock

    Plante, Amber E.; Rao, Vishnu P.; Rizzo, Megan A.; Meredith, Andrea L. (2021-07-08)
    ABSTRACT Circadian rhythms in mammals are coordinated by the central clock in the brain, located in the suprachiasmatic nucleus (SCN). Multiple molecular and cellular signals display a circadian variation within SCN neurons, including intracellular Ca2þ, but the mechanisms are not definitively established. SCN cytosolic Ca2þ levels exhibit a peak during the day, when both action potential firing and Ca2þ channel activity are increased, and are decreased at night, correlating with a reduction in firing rate. In this study, we employ a single-color fluorescence anisotropy reporter (FLARE), Venus FLARE-Cameleon, and polarization inverted selective-plane illumination microscopy to measure rhythmic changes in cytosolic Ca2þ in SCN neurons. Using this technique, the Ca2þ channel subtypes contributing to intracellular Ca2þ at the peak and trough of the circadian cycle were assessed using a pharmacological approach with Ca2þ channel inhibitors. Peak (218 5 16 nM) and trough (172 5 13 nM) Ca2þ levels were quantified, indicating a 1.3-fold circadian variance in Ca2þ concentration. Inhibition of ryanodine-receptor-mediated Ca2þ release produced a larger relative decrease in cytosolic Ca2þ at both time points compared to voltage-gated Ca2þchannels. These results support the hypothesis that circadian Ca2þ rhythms in SCN neurons are predominantly driven by intracellular Ca2þ channels, although not exclusively so. The study provides a foundation for future experiments to probe Ca2þ signaling in a dynamic biological context using FLAREs.
  • Immunomodulatory Nanoparticles Mitigate Macrophage Inflammation via Inhibition of PAMP Interactions and Lactate-Mediated Functional Reprogramming of NF- B and p38 MAPK

    Lasola, Jackline Joy; Cottingham, Andrea; Scotland, Brianna; Truong, Nhu; Hong, Charles C., 1967-; Shapiro, Paul, Ph.D.; Pearson, Ryan (2021-11-02)
    Inflammation is a key homeostatic process involved in the body’s response to a multitude of disease states including infection, autoimmune disorders, cancer, and other chronic conditions. When the initiating event is poorly controlled, severe inflammation and globally dysregulated immune responses can occur. To address the lack of therapies that efficaciously address the multiple aspects of the dysregulated immune response, we developed cargo-less immunomodulatory nanoparticles (iNPs) comprised of poly(lactic acid) (PLA) with either poly(vinyl alcohol) (PVA) or poly(ethylene-altmaleic acid) (PEMA) as stabilizing surfactants and investigated the mechanisms by which they exert their inherent anti-inflammatory effects. We identified that iNPs leverage a multimodal mechanism of action by physically interfering with the interactions between pathogen-associated molecular patterns (PAMPs) and bone marrow-derived macrophages (BMMFs). Additionally, we showed that iNPs mitigate proinflammatory cytokine secretions induced by LPS via a time- and composition-dependent abrogation of NF- B p65 and p38 MAPK activation. Lastly, inhibition studies were performed to establish the role of a pH-sensing G-protein-coupled receptor, GPR68, on contributing to the activity of iNPs. These data provide evidence for the multimodal mechanism of action of iNPs and establish their potential use as a novel therapeutic for the treatment of severe inflammation.
  • Epitope-based sieve analysis of Plasmodium falciparum sequences from a FMP2.1/AS02A vaccine trial is consistent with differential vaccine efficacy against immunologically relevant AMA1 variants

    Ouattara, Amed; Niangaly, Amadou; Adams, Matthew; Coulibaly, Drissa; Kone, Abdoulaye K.; Traore, Karim; Laurens, Matthew B.; Tolo, Youssouf; Kouriba, Bourema; Diallo, Dapa A.; et al. (2020-06-20)
    To prevent premature dismissal of promising vaccine programs, it is critical to determine if lack of efficacy in the field is due to allele specific-efficacy, rather than to the lack of immunogenicity of the candidate antigen. Here we use samples collected during a field trial of the AMA1-based FMP2.1/AS02A malaria vaccine, which incorporates the AMA1 variant encoded by the reference Plasmodium falciparum 3D7 strain, to assess the usefulness of epitope-based sieve analysis for the detection of vaccine-induced allele-specific immune responses. The samples used are from volunteers who received the malaria vaccine FMP2.1/AS02A or a control (rabies vaccine), during a vaccine efficacy field trial, and who later developed malaria. In a previous study, P. falciparum DNA was extracted from all samples, and the ama1 locus amplified and sequenced. Here, a sieve analysis was used to measure T and B-cell escape, and difference in 3D7-like epitopes in the two treatment arms. Overall, no difference was observed in mean amino acid distance to the 3D7 AMA1 variant between sequences from vaccinees and controls in B-cell epitopes. However, we found a significantly greater proportion of 3D7-like T-cell epitopes that map to the AMA1 cluster one loop (c1L) region in the control vs. the vaccinee group (p = 0.02), consistent with allele-specific vaccine efficacy. Interestingly, AMA1 epitopes in infections from vaccinees had higher mean IC50, and consequently lower binding affinity, than epitopes generated from the control group (p = 0.01), suggesting that vaccine-induced selection impacted the immunological profile of the strains that pass through the sieve imposed by the vaccine-induced protection. These findings are consistent with a vaccine-derived sieve effect on the c1L region of AMA1 and suggest that sieve analyses of malaria vaccine trial samples targeted to epitopes identified in silico can help identify protective malaria antigens that may be efficacious if combined in a multivalent vaccine.
  • Lipiodol Deposition and Washout in Primary and Metastatic Liver Tumors After Chemoembolization

    Nezami, Nariman; Mijnte van Breugel, Johanna Maria; Konstantindis, Menelaos; Chapiro, Julius; Savic, Lynn Jeanette; Miszczuk, Milena Anna; Rexha, Irvin; Lin, Mingde; Hong, Kelvin; Georgiades, Christos (2021-09-06)
    Background/Aim: Lipiodol is the key component of conventional trans-arterial chemoembolization. Our aim was to evaluate lipiodol deposition and washout rate after conventional trans-arterial chemoembolization in intrahepatic cholangiocarcinoma and hepatic metastases originating from neuroendocrine tumors and colorectal carcinoma. Patients and Methods: This was a retrospective analysis of 44 patients with intrahepatic cholangiocarcinoma and liver metastasis from neuroendocrine tumors or colorectal carcinoma who underwent conventional trans-arterial chemoembolization. Lipiodol volume (cm3) was analyzed on non-contrast computed tomography imaging obtained within 24 h post conventional trans-arterial chemoembolization, and 40-220 days after conventional trans-arterial chemoembolization using volumetric image analysis software. Tumor response was assessed on contrast-enhanced magnetic resonance imaging 1 month after conventional trans-arterial chemoembolization. Results: The washout rate was longer for neuroendocrine tumors compared to colorectal carcinoma, with half-lives of 54.61 days (p<0.00001) and 19.39 days (p<0.001), respectively, with no exponential washout among intrahepatic cholangiocarcinomas (p=0.83). The half-life for lipiodol washout was longer in tumors larger than 300 cm3 compared to smaller tumors (25.43 vs. 22.71 days). Lipiodol wash out half-life was 54.76 days (p<0.01) and 29.45 days (p<0.00001) for tumors with a contrast enhancement burden of 60% or more and less than 60%, respectively. A negative exponential relationship for lipiodol washout was observed in nonresponders (p<0.00001). Conclusion: Lipiodol washout is a time-dependent process, and occurs faster in colorectal carcinoma tumors, tumors smaller than 300 cm3, tumors with baseline contrast enhancement burden of less than 60%, and non-responding target lesions.
  • Repertoire of Naturally Acquired Maternal Antibodies Transferred to Infants for Protection Against Shigellosis

    Ndungo, Esther; Andronescu, Liana R.; Buchwald, Andrea G.; Lemme-Dumit, Jose M.; Mawindo, Patricia; Kapoor, Neeraj; Fairman, Jeff; Laufer, Miriam K.; Pasetti, Marcela F. (2021-10-15)
    Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age annually worldwide. The incidence of Shigella-induced diarrhea is relatively low during the first year of life and increases substantially, reaching its peak between 11 to 24 months of age. This epidemiological trend hints at an early protective immunity of maternal origin and an increase in disease incidence when maternally acquired immunity wanes. The magnitude, type, antigenic diversity, and antimicrobial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap, Shigella-specific antibodies directed against the lipopolysaccharide (LPS) and virulence factors (IpaB, IpaC, IpaD, IpaH, and VirG), and antibody-mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific (very high levels) and Shigella LPS IgG were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively, and had preferential IgG subclass distribution (protein-specific IgG1 > LPSspecific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied among Shigella serotypes. LPS was identified as the primary target of SBA and OPKA activity. Maternal sera had remarkably elevated Shigella flexneri 2a LPS IgM, indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in a Shigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternally transferred immunity wanes.
  • Sulfa-induced acute eosinophilic pneumonia

    Nasim, Faria; Paul, Jose Antony; Wylam, Mark E.; Boland-Froemming, Jennifer (2021-08-13)
    Acute eosinophilic pneumonia (AEP) is an infrequently seen interstitial lung disease secondary to medications. We report a series of 3 case of severe AEP which developed as a result of sulfa medication. 2 patients had received treatment with sulfamethoxazole for acne and 1 was treated with sulfasalazine for colitis. Patients were on sulfa medication for 1–3 weeks prior to presentation. All patients presented with fever, acute onset bilateral pulmonary infiltrates as well as marked peripheral eosinophilia. Mean eosinophil count was 2.21 × 109/L. There was a lack of response to steroids. One patient required extracorporeal membrane oxygenation and prolonged mechanical ventilation via tracheostomy. 2 patients underwent successful lung transplantation (1 bilateral livingrelated lobar lung transplant and 1 orthotropic cardiopulmonary allotransplantation). In all cases lung biopsy and explants showed acute and organizing diffuse alveolar damage with increased interstitial and airspace eosinophils. To our knowledge, our series is the first to show the clinical features of sulfa induced AEP in an adolescent population.
  • Contributions of CaV1.3 Channels to Ca2+ Current and Ca2+-Activated BK Current in the Suprachiasmatic Nucleus

    McNally, Beth A.; Plante, Amber E.; Meredith, Andrea L. (2021-09-28)
    Daily regulation of Ca2+– and voltage-activated BK K+ channel activity is required for action potential rhythmicity in the suprachiasmatic nucleus (SCN) of the hypothalamus, the brain’s circadian clock. In SCN neurons, BK activation is dependent upon multiple types of Ca2+ channels in a circadianmanner. Daytime BK current predominantly requires Ca2+ influx through L-type Ca2+ channels (LTCCs), a time when BK channels are closely coupled with their Ca2+ source. Here we show that daytime BK current is resistant to the Ca2+ chelator BAPTA. However, at night when LTCCs contribute little to BK activation, BK current decreases by a third in BAPTA compared to control EGTA conditions. In phase with this time-of-day specific effect on BK current activation, LTCC current is larger during the day. The specific Ca2+ channel subtypes underlying the LTCC current in SCN, as well as the subtypes contributing the Ca2+ influx relevant for BK current activation, have not been identified. SCN neurons express two LTCC subtypes, CaV1.2 and CaV1.3. While a role for CaV1.2 channels has been identified during the night, CaV1.3 channel modulation has also been suggested to contribute to daytime SCN action potential activity, as well as subthreshold Ca2+ oscillations. Here we characterize the role of CaV1.3 channels in LTCC and BK current activation in SCN neurons using a global deletion of CACNA1D in mouse (CaV1.3 KO). CaV1.3 KO SCN neurons had a 50% reduction in the daytime LTCC current, but not total Ca2+ current, with no difference in Ca2+ current levels at night. During the day, CaV1.3 KO neurons exhibited oscillations in membrane potential, and most neurons, although not all, also had BK currents. Changes in BK current activation were only detectable at the highest voltage tested. These data show that while CaV1.3 channels contribute to the daytime Ca2+ current, this does not translate into a major effect on the daytime BK current. These data suggest that BK current activation does not absolutely require CaV1.3 channels and may therefore also depend on other LTCC subtypes, such as CaV1.2.

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