A Smooth Transition: Assessing Transition Readiness in Adolescents with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory Bowel Disease (IBD) is an early onset condition that affects individuals of all ages. Approximately 15%-25% of patients present before the age of 20 years, with peak onset occurring during adolescence. AIMS: To evaluate transition readiness among adolescents diagnosed with IBD and identify barriers to transition. METHODS: We conducted a cross-sectional study of patients with IBD aged 12-21 years. Patients were stratified by age into three groups: A (12-14 years), B (14-17 years), and C (17 + years). Patients were asked to complete a questionnaire which assessed patient knowledge in three areas of transition: 'Taking Charge,' 'My Health,' and 'Using Health Care.' Fisher's Exact and Chi-Square tests were used to evaluate the associations between age and transition readiness. RESULTS: A total of 127 participants (68 males and 59 females) with a mean age of 16.14 years were included. Transition readiness increased with age from 60.7% in Group A to 63.2% and 77.9% in Groups B and C, respectively (p < 0.001). Patient confidence and the importance of transition increased with age, with means of 5.51, 6.17, and 6.94 in Groups A, B, and C (p = 0.02). Patient-reported knowledge of their health condition was > 70%, with no statistical differences between the groups (p = 0.65). Patient knowledge regarding 'Using Health Care' increased from 52% in Group A to 79% in Group C (p < 0.001). The greatest barriers to transitioning were carrying health information for Group A (100%) and obtaining provider referrals for Groups B (75%) and C (51%). CONCLUSION: This study demonstrated that transition readiness increases with age in adolescents with IBD.

LONGITUDINAL ELLIPSOID ZONE AND OUTER RETINAL INTEGRITY DYNAMICS AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To quantify ellipsoid zone (EZ) changes in integrity after epiretinal membrane (ERM) surgery, correlate findings to visual acuity, and determine predictors for prognosis. METHODS: A post hoc analysis of eyes undergoing ERM surgery pooled from the prospective DISCOVER intraoperative optical coherence tomography study and eyes undergoing conventional ERM surgery without intraoperative optical coherence tomography. Quantitative EZ features were extracted using a multilayer machine learning enabled automated segmentation platform after image analyst review/correction for segmentation accuracy. Visual acuity and EZ integrity were quantitatively assessed and correlated before and after ERM surgery. Multiple linear regression was performed to assess preoperative visual acuity and EZ features as predictors for improvement in visual acuity or EZ integrity. RESULTS: There were 177 eyes from 177 subjects that underwent ERM surgery from the DISCOVER and conventional arms. Improvement in visual acuity and multiple EZ integrity features was noted after ERM surgery, including EZ partial attenuation and EZ-retinal pigment epithelium (RPE) volume (P < 0.05). A reduction in EZ partial attenuation and increase in EZ-RPE central subfield thickness (EZ-RPE CST) was significantly correlated with improved visual acuity after ERM surgery (P < 0.05). More robust EZ-RPE CST at baseline predicted visual acuity improvement after ERM peel in regression modeling (ß = 0.005, P < 0.05). CONCLUSIONS: Longitudinal assessment of EZ features demonstrates significant postoperative improvement in multiple EZ integrity metrics after ERM surgery. Improving EZ integrity was correlated to improving the visual acuity. Ellipsoid zone integrity and visual acuity were significant predictors in regression modeling and may have value in clinical prognostication.

LONGITUDINAL ELLIPSOID ZONE DYNAMICS AFTER MACULAR HOLE REPAIR IN THE DISCOVER STUDY: Structure-Function Assessment.

PURPOSE: To evaluate association of the baseline macular hole (MH) geometric features and longitudinal ellipsoid zone integrity with the visual acuity outcome after surgical repair. METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing vitrectomy repair for MH. Anatomical and functional data were collected through one year postoperatively. An automated retinal layer segmentation platform was used for the assessment of outer retinal metrics and volumetric reconstruction of MH. Association of longitudinal ellipsoid zone features and baseline MH height, width, and volume with VA outcomes were investigated. RESULTS: Eighty-four eyes with MH were included. The mean baseline VA was 20 of 114 and increased to 20 of 45 (P < 0.001) at postoperative Month 12 (N = 45). Successful MH closure was achieved in 98.8% of cases. Ellipsoid zone integrity metrics significantly improved from baseline (P = 0.002) and postoperative Month 1 (P < 0.001) to post-operative Month 12. Ellipsoid zone metrics independently correlated with VA at all follow-up visits (P < 0.05). Increased baseline MH width and volume negatively correlated with the VA at postoperative Month 12 (P < 0.001). Preoperative VA and EZ integrity on optical coherence tomography were predictors for postoperative VA. CONCLUSION: Baseline MH volumetric parameters and EZ parameters were associated with VA outcomes after repair.

Evaluating the potential of using urine and saliva specimens for malaria diagnosis in suspected patients in Ghana.

BACKGROUND: This study aimed at detecting PfHRP2 and pLDH malaria antigens in urine and salivary specimens of suspected malaria patients using RDT kits, and identifying factors influencing the detection of these antigens. METHODS: Malaria rapid test kit (SD Bioline RDT kit) was used to detect malaria antigens, PfHRP2 and pLDH, in blood, urine and saliva samples received from patients suspected of malaria. Subsequently, malaria parasitaemia was determined. From the same patients, body temperature readings and haemoglobin concentrations were recorded. Also, micro-haematuria and saliva occult blood were determined. Relative to blood, the sensitivities and the performance of urine and saliva as alternative samples were evaluated. RESULTS: A total of 706 suspected malaria patients provided all three specimens. Prevalence of malaria by microscopy and RDT was 44.2% and 53.9%, respectively. Compared to blood, the sensitivities of urine and saliva were 35.2% and 57.0% respectively. Haemoglobin concentration < 9.9 g/dL, body temperature > 38.7 °C and occult blood influenced the detection of malaria antigens in both urine and saliva. Furthermore, the antigens were not detected in urine and saliva when parasitaemia was < 60,000 parasites/µL and < 40,000 parasites/µL, respectively. CONCLUSION: Saliva, with or without blood contamination, was found to be more efficient that urine samples. Therefore these non-blood specimens have the potential to be used as non-invasive samples for malaria diagnosis. However, this approach is useful in severe to moderate anaemia, hyperthermia, parasitaemia > 60,000 parasites/µL and samples contaminated with blood.

Reduction in lead exposures with lead-free ammunition in an advanced urban assault course.

The training of soldiers for urban conflict involves marksmanship instruction on outdoor flat ranges and the teaching of close-quarter battle techniques in indoor facilities, referred to as shoot houses, where intense firing exercises can generate high air lead levels from small arms ammunition, flash bang grenades, and explosive devices. Levels of lead and copper in air were evaluated during five training activities of a 45-day training course using both stationary general area and breathing zone sampling over a 2-year period. Individual blood lead values were determined prior to and at course completion. Mean breathing zone lead concentrations for the five training activities ranged from 0.014 on the outdoor flat range to 0.064 mg/m3 inside shoot houses; with a change to lead-free ammunition the values were reduced to a range of 0.006-0.022 mg/m3. Isolated flash bang grenades generated very high general area lead concentrations (2.0 mg/m3), which in training were associated with the highest measured breathing zone concentration (0.16 mg/m3). For copper, mean breathing zone concentrations increased from 0.010 to 0.037 mg/m3 with the change to lead-free frangible ammunition on the outdoor range, but remained below the permissible exposure limit for copper fume. Inside shoot houses, mean breathing zone copper concentrations exceeded the permissible exposure limit with ball and lead-free frangible ammunition, ranging from 0.077-0.13 mg/m3. With the introduction of lead-free ammunition, when comparing the blood lead differences between start and finish of the course, there was a significant reduction in the mean blood lead difference from 13.3 µg/dL to 5.4 µg/dL. Options for mitigation of potentially high exposure areas using improved ventilation designs are discussed. These results advocate for improved designs for shoot house training facilities, stress the importance of removing lead from ammunition and explosive devices for training, and promote the continued need for implementation of controls to mitigate and manage metal exposures during training.

Sinai Abbreviated Geriatric Evaluation: Development and Validation of a Practical Test.

OBJECTIVE: To develop and validate a simple geriatric screening tool that performs as well as more complex assessments BACKGROUND:: Many tools that predict treatment risk in older adults are impractical for routine clinical use. METHODS: We prospectively conducted comprehensive preoperative evaluations on 1025 patients age ≥75 years who presented to Sinai Hospital of Baltimore for major elective surgery, then retrospectively reviewed patients' medical records for occurrence of postoperative outcomes. Using logistic regression modeling and receiver operating characteristic curve analysis we selected the best combination of simple tests, labeling this the Sinai Abbreviated Geriatric Evaluation (SAGE). The performance of the SAGE was then compared with 3 standard tools in its power to predict postoperative outcomes. RESULTS: The SAGE is a statistically significant predictor of postoperative outcomes. Each unit decrease in SAGE score was significantly associated with a 51% (95% CI 1.30-1.77) increase in odds of a complication, a 2-fold increase in odds of postoperative delirium (95% CI 1.65-2.66), a 27% increase in odds of length of hospital stay >2 days (95% CI 1.10-1.47), a 54% increase in odds of a hospital readmission within 30 days (95% CI 1.25-2.88), and a 38% increase in odds of an unanticipated discharge to higher-level care (95% CI 1.18-1.61). We estimated the receiver operating characteristic curve area under the curve (AUC) for the SAGE of 0.69, 0.77, 0.73, 0.66, and 0.78 for the above outcomes, respectively. The SAGE performed as well in predicting postoperative outcomes as Fried's frailty phenotype, Charlson Comorbidity Index, and American Society of Anesthesiologists Physical Status Class (ASA). CONCLUSION: The SAGE performs as well as other geriatric evaluations that require equipment or memorization.

Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder.

HERC2 is a giant protein with E3 ubiquitin ligase activity and other known and suspected functions. Mutations of HERC2 are implicated in the pathogenesis of various cancers and result in severe neurological conditions in Herc2-mutant mice. Recently, a pleotropic autosomal recessive HERC2-associated syndrome of intellectual disability, autism and variable neurological deficits was described; its pathogenetic basis is largely unknown. Using peripheral blood-derived lymphoblasts from 3 persons with homozygous HERC2 variants and 14 age- and gender-matched controls, we performed label-free unbiased HPLC-tandem mass spectrometry-based proteomic analyses to provide insights into HERC2-mediated pathobiology. We found that out of 3427 detected proteins, there were 812 differentially expressed proteins between HERC2-cases vs. controls. 184 canonical pathways were enriched after FDR adjustment, including mitochondrial function, energy metabolism, EIF2 signaling, immune functions, ubiquitination and DNA repair. Ingenuity Pathway Analysis® identified 209 upstream regulators that could drive the differential expression, prominent amongst which were neurodegeneration-associated proteins. Differentially expressed protein interaction networks highlighted themes of immune function/dysfunction, regulation of cell cycle/cell death, and energy metabolism. Overall, the analysis of the HERC2-associated proteome revealed striking differential protein expression between cases and controls. The large number of differentially expressed proteins likely reflects HERC2's multiple domains and numerous interacting proteins. Our canonical pathway and protein interaction network findings suggest derangements of multiple pathways in HERC2-associated disease.

Proteomic Investigations of Autism Spectrum Disorder: Past Findings, Current Challenges, and Future Prospects.

Proteomics is a powerful tool to study biological systems and is potentially useful in identifying biomarkers for clinical screening and diagnosis, for monitoring treatment, and for exploring pathogenetic mechanisms in autism. Unlike numerous other experimental approaches employed in autism research, there have been few proteomic-based analyses. Herein, we discuss the findings of studies regarding autism that utilized a proteomic approach and review key considerations in sample acquisition, processing, and analysis. Most proteomic studies on autism used blood or other peripheral tissues. Few studies used brain tissue, the main site of biological difference between persons with autism and others. The findings have varied and are not yet replicated. Some showed abnormalities of synaptic proteins or proteins of mitochondrial bioenergetics. Various abnormalities of proteins relating to immune processes and lipid metabolism have also been noted. Whether any of the proteomic differences between autism and control cases are primary or secondary phenomena is currently unclear. Consequently, no definitive biomarkers for autism have been identified, and the pathophysiological insights provided by proteomic studies to date are uncertain in the absence of replication. Based on this body of work and the challenges in using proteomics to study autism, we suggest considerations for future study design. These include attention to subject and specimen inclusion/exclusion criteria, attention to the state of specimens prior to proteomic analysis, and use of a replicate set of specimens. We end by discussing especially promising applications of proteomics in the study of autism pathobiology.

Acute Kidney Injury after Partial Nephrectomy of Solitary Kidneys: Impact on Long-Term Stability of Renal Function.

PURPOSE: Acute kidney injury often leads to chronic kidney disease in the general population. The long-term functional impact of acute kidney injury observed after partial nephrectomy has not been adequately studied. MATERIALS AND METHODS: From 2004 to 2014 necessary studies for analysis were available for 90 solitary kidneys managed by partial nephrectomy. Functional data at 4 time points included preoperative serum creatinine, peak postoperative serum creatinine, new baseline serum creatinine 3 to 12 months postoperatively and long-term followup serum creatinine more than 12 months postoperatively. Adjusted acute kidney injury was defined by the ratio, observed peak postoperative serum creatinine/projected postoperative serum creatinine adjusted for parenchymal mass loss to reveal the true effect of ischemia. The long-term change in renal function (the long-term functional change ratio) was defined as the most recent glomerular filtration rate/the new baseline glomerular filtration rate. The relationship between the grade of the adjusted acute kidney injury and the long-term functional change was assessed by Spearman correlation analysis and multivariable regression. RESULTS: Median patient age was 64 years and median followup was 45 months. Median parenchymal mass preservation was 80%. Adjusted acute kidney injury occurred in 42% of patients, including grade 1 injury in 20 (22%) and grade 2/3 in 18 (20%). On univariable analysis the degree of the adjusted acute kidney injury did not correlate with the long-term glomerular filtration rate change (p = 0.55). On multivariable analysis adjusted acute kidney injury was not associated with a long-term functional change (p >0.05) while diabetes and warm ischemia were modestly associated with a long-term functional decline (each p <0.05). CONCLUSIONS: Acute kidney injury after partial nephrectomy was not a significant or independent predictor of long-term functional decline in our institutional cohort. A prospective study with larger sample sizes and longer followup is required to evaluate factors associated with long-term nephron stability.

Impact of Comorbidities on Functional Recovery from Partial Nephrectomy.

PURPOSE: Parenchymal mass preservation, and ischemia type and/or duration can influence functional recovery after partial nephrectomy. Some groups have hypothesized that relevant comorbidities may also impact nephron stability and functional recovery but this has not been adequately investigated. MATERIALS AND METHODS: At our center 405 patients treated with partial nephrectomy from 2007 to 2015 had the necessary data to determine the function and parenchymal mass preserved in the ipsilateral kidney. Comorbidities potentially associated with renal functional status were reviewed, including various degrees of hypertension, diabetes, cardiovascular disease, obesity, smoking status and related medications. Multivariable linear regression was done to assess factors associated with functional recovery, defined as the percent of preserved ipsilateral glomerular filtration rate. RESULTS: Median tumor size was 3.5 cm and the median R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touching main renal artery or vein) score was 8. Warm and cold ischemia were done in 264 (65%) and 141 patients for a median duration of 21 and 27 minutes, respectively. The median preserved ipsilateral glomerular filtration rate was 79%. Patient age, comorbidity index, hypertension and proteinuria were each associated with the preoperative glomerular filtration rate (all p <0.01). On univariable and multivariable analyses the preserved parenchymal mass, and ischemia type and duration were significantly associated with functional recovery (all p <0.001). On univariable analysis of comorbidities only hypertension was significantly associated with functional recovery. However, on multivariable analysis none of the analyzed comorbidities were associated with functional recovery. CONCLUSIONS: Recovery of function after partial nephrectomy depends primarily on parenchymal mass preservation and ischemia characteristics. Comorbidities failed to be associated with functional outcomes. Comorbidities can impact function, leading to surgery, and may influence long-term functional stability. However, our data suggest that they do not influence short-term recovery after partial nephrectomy.

Demographic and Practice Characteristics of Physicians Who Care for Medically Underserved People: A National Survey.

OBJECTIVES: Few national studies have examined the influence of role models as a potential predictor for caring for medically underserved (MUS) patients. This study tested associations between previous physician role model exposure and caring for MUS populations, as well as examines the practice environments of these physicians. METHODS: Between October and December 2011, we mailed a confidential questionnaire to a representative sample of 2000 US physicians from various specialties. The primary criterion variable was "Is your patient population considered medically underserved?" We assessed demographic and other personal characteristics (calling, spirituality, and reporting a familial role model). We also asked about their practice characteristics, including a validated measure that assessed whether their work environment was considered chaotic/hectic or calm. RESULTS: The survey response rate was 64.5% (1289/2000). Female physicians and African American physicians were more likely to report working in MUS settings (multivariate odds ratio [OR] 1.32, confidence interval [CI] 1.00-1.76 and OR 2.65, CI 1.28-5.46, respectively). Physicians with high spirituality (OR 1.69, CI 1.02-2.79) and who reported familial role model exposure (OR 1.91, CI 1.11-3.30) also were associated with working with MUS populations. Physicians who worked in academic medical centers (OR 1.93, CI 1.45-2.56) and in chaotic work environments (OR 3.25, CI 1.64-6.44) also were more likely to report working with MUS patients. CONCLUSIONS: Familial role models may be influencing physicians to work with MUS patients, but the quality of their current work environments raises concerns about the long-term retention of physicians in MUS settings.

Are T cells the only HIV-1 reservoir?

Current antiretroviral therapies have improved the duration and quality of life of people living with HIV-1. However, viral reservoirs impede complete eradication of the virus. Although there are many strategies to eliminate infectious virus, the most actively pursued are latency reversing agents in conjunction with immune modulation. This strategy, known as "shock and kill", has been tested primarily against the most widely recognized HIV-1 latent reservoir found in resting memory CD4+ T cells. This is in part because of the dearth of conclusive evidence about the existence of non-T cell reservoirs. Studies of non-T cell reservoirs have been difficult to interpret because of technical and biological issues that have hampered a better understanding. This review considers the current knowledge of non-T cell reservoirs, the challenges encountered in a better understanding of these populations, and their implications for HIV-1 cure research.

PI3KCA plays a major role in multiple myeloma and its inhibition with BYL719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance.

The phosphatidylinositide 3-kinase (PI3K) pathway is activated and correlated with drug resistance in multiple myeloma (MM). In the present study we investigated the role of PI3KCA (PI3K-α) in the progression and drug resistance in MM. We showed that the gene expression of PI3KCA isoform was higher in MM compared to normal subjects. BYL719, a novel and specific PI3KCA inhibitor inhibited the survival of primary MM cells and cell lines but not normal peripheral blood mononuclear cells. BYL719 induced the apoptosis of MM cells and inhibited their cell cycle by causing G1 arrest. BYL719 inhibited PI3K signalling, decreased proliferation and cells cycle signalling, and induced apoptosis signalling in MM cells. Finally, BYL719 synergized with bortezomib and carfilzomib, and overcame drug resistance induced by bone marrow stroma. These results were confirmed using in silico simulation of MM cell lines, BYL719 and bortezomib, and showed similar trends in survival, proliferation, apoptosis, cell signalling and synergy with drugs. In conclusion, PI3KCA plays a major role in proliferation and drug resistance of MM cells, the effects of which were inhibited with BYL719. These results provide a preclinical basis for a future clinical trial of BYL719 in MM as a single agent or in combination with other drugs.

Thinner is better: Intentional weight loss and cardiovascular risk.

The relationship between overweight/obesity and cardiovascular events needs to be tackled. The SELECT trial earns praise in showing that using GLP-1 receptor agonists to reduce overweight/obesity itself, in patients without dysglycemia, has beneficial effects on cardiovascular risk factors and clinical outcomes.1.

Becoming Endemic: Anaplasmosis Imported Across State Borders.

Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis (HGA), a tick-borne illness with increasing incidence since being described in the 1990s. Importantly, the presentation can be vague, yet prompt treatment is paramount. An 81-year-old Caucasian female was hospitalized in Cincinnati, Ohio, for fever and confusion following prolonged outdoor exposure in Emlenton, Pennsylvania. She initially was treated for sepsis from presumed community-acquired pneumonia; however, the combination of leukopenia, thrombocytopenia, and elevated liver enzymes prompted empiric tick-borne illness consideration and treatment with rapid resolution in symptoms. Early recognition of HGA can reduce unnecessary treatments and improve patient outcomes.

Combination of optical coherence tomography-derived shape and texture features are associated with development of sub-foveal geographic atrophy in dry AMD.

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss. Identifying patients with greatest risk of GA progression is important for targeted utilization of emerging therapies. This study aimed to comprehensively evaluate the role of shape-based fractal dimension features ( F fd ) of sub-retinal pigment epithelium (sub-RPE) compartment and texture-based radiomics features ( F t ) of Ellipsoid Zone (EZ)-RPE and sub-RPE compartments for risk stratification for subfoveal GA (sfGA) progression. This was a retrospective study of 137 dry AMD subjects with a 5-year follow-up. Based on sfGA status at year 5, eyes were categorized as Progressors and Non-progressors. A total of 15 shape-based F fd of sub-RPE surface and 494 F t from each of sub-RPE and EZ-RPE compartments were extracted from baseline spectral domain-optical coherence tomography scans. The top nine features were identified from F fd and F t feature pool separately using minimum Redundancy maximum Relevance feature selection and used to train a Random Forest (RF) classifier independently using three-fold cross validation on the training set ( S t , N = 90) to distinguish between sfGA Progressors and Non-progressors. Combined F fd and F t was also evaluated in predicting risk of sfGA progression. The RF classifier yielded AUC of 0.85, 0.79 and 0.89 on independent test set ( S v , N = 47) using F fd , F t , and their combination, respectively. Using combined F fd and F t , the improvement in AUC was statistically significant on S v with p-values of 0.032 and 0.04 compared to using only F fd and only F t , respectively. Combined F fd and F t appears to identify high-risk patients. Our results show that FD and texture features could be potentially used for predicting risk of sfGA progression and future therapeutic response.

Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration.

In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD.

Noroviruses: Evolutionary Dynamics, Epidemiology, Pathogenesis, and Vaccine Advances-A Comprehensive Review.

Noroviruses constitute a significant aetiology of sporadic and epidemic gastroenteritis in human hosts worldwide, especially among young children, the elderly, and immunocompromised patients. The low infectious dose of the virus, protracted shedding in faeces, and the ability to persist in the environment promote viral transmission in different socioeconomic settings. Considering the substantial disease burden across healthcare and community settings and the difficulty in controlling the disease, we review aspects related to current knowledge about norovirus biology, mechanisms driving the evolutionary trends, epidemiology and molecular diversity, pathogenic mechanism, and immunity to viral infection. Additionally, we discuss the reservoir hosts, intra-inter host dynamics, and potential eco-evolutionary significance. Finally, we review norovirus vaccines in the development pipeline and further discuss the various host and pathogen factors that may complicate vaccine development.