Conectar
by Allison P. Pack, Mary Clare Masters, Rachel O’Conor, Kenya Alcantara, Sophia Svoboda, Reneaki Smith, Fangyu Yeh, Guisselle Wismer, Amisha Wallia, Stacy C. Bailey
BackgroundOlder adults with HIV are at increased risk of developing certain chronic health conditions including type 2 diabetes mellitus (T2DM). As the number and complexity of conditions increases, so do treatment and health care needs. We explored patient and clinician preferences for HIV+T2DM care and perceived solutions to improving care.
MethodsWe conducted an exploratory qualitative study comprised of individual in-depth interviews. Participants included English-speaking patients aged 50 and older living with HIV and T2DM and infectious disease (ID) and primary care (PC) clinicians from a large academic health center in Chicago. Thematic analysis drew from the Framework Method.
ResultsA total of 19 patient and 10 clinician participants were interviewed. Many patients reported seeking HIV and T2DM care from the same clinician; they valued rapport and a ‘one-stop-shop’. Others reported having separate clinicians; they valued perceived expertise and specialty care. Nearly all clinicians reported comfort screening for T2DM and initiating first line oral therapy; ID clinicians reported placing referrals for newer, complex therapies. Patients would like educational support for T2DM management; clinicians would like to learn more about newer therapies and easier referral processes.
ConclusionsPatient-centered care includes managing T2DM from a variety of clinical settings for individuals with HIV, yet strategies are needed to better support clinicians. Future research should examine how best to implement these strategies.
by Paige K. Marty, Balaji Pathakumari, Thomas M. Cox, Virginia P. Van Keulen, Courtney L. Erskine, Maleeha Shah, Mounika Vadiyala, Pedro Arias-Sanchez, Snigdha Karnakoti, Kelly M. Pennington, Elitza S. Theel, Cecilia S. Lindestam Arlehamn, Tobias Peikert, Patricio Escalante
Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (pby Juan P. Wisnivesky, Nikita Agrawal, Jyoti Ankam, Adam Gonzalez, Alex Federman, Steven B. Markowitz, Janette M. Birmingham, Paula J. Busse
BackgroundPost-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site.
Research questionDo WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity?
Study design and methodsWe collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants.
ResultsOf the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses.
InterpretationOur results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.
by Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek
Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2–22% in symptomatic individuals and 2–14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (pby Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz
ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.
ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.
MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.
ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.
by Ting-Li Chen, Elizabeth P. Chou, Min-Yi Chen, Fushing Hsieh
We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nation’s population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.by Chee Meng Yong, Prathepamalar A. P. Yehgambaram, Shaun Wen Huey Lee
IntroductionOvarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost–effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia.
MethodsWe developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties.
ResultsIn Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold.
ConclusionThe use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.
by Rebecca H. Correia, Darly Dash, Aaron Jones, Meredith Vanstone, Komal Aryal, Henry Yu-Hin Siu, Aquila Gopaul, Andrew P. Costa
We established consensus on practice-based metrics that characterize quality of care for older primary care patients and can be examined using secondary health administrative data. We conducted a two-round RAND/UCLA Appropriateness Method (RAM) study and recruited 10 Canadian clinicians and researchers with expertise relevant to the primary care of elderly patients. Informed by a literature review, the first RAM round evaluated the appropriateness and importance of candidate quality measures in an online questionnaire. Technical definitions were developed for each endorsed indicator to specify how the indicator could be operationalized using health administrative data. In a virtual synchronous meeting, the expert panel offered feedback on the technical specifications for the endorsed indicators. Panelists then completed a second (final) questionnaire to rate each indicator and corresponding technical definition on the same criteria (appropriateness and importance). We used statistical integration to combine technical expert panelists’ judgements and content analysis of open-ended survey responses. Our literature search and internal screening resulted in 61 practice-based quality indicators for rating. We developed technical definitions for indicators endorsed in the first questionnaire (n = 55). Following the virtual synchronous meeting and second questionnaire, we achieved consensus on 12 practice-based quality measures across four Priority Topics in Care of the Elderly. The endorsed indicators provide a framework to characterize practice- and population-level encounters of family physicians delivering care to older patients and will offer insights into the outcomes of their care provision. This study presented a case of soliciting expert feedback to develop measurable practice-based quality indicators that can be examined using administrative data to understand quality of care within population-based data holdings. Future work will refine and operationalize the technical definitions established through this process to examine primary care provision for older adults in a particular context (Ontario, Canada).by Daniel W. Flowers, Brian T. Swanson, Stephen M. Shaffer, Derek J. Clewley, Sean P. Riley
The primary objective of this review was to create a ‘trustworthy,’ living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published ‘trustworthy’ systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no ‘trustworthy’ randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a ‘trustworthy,’ living systematic review on this clinically relevant topic is not yet possible due to a lack of ‘trustworthy’ randomized controlled trials.by Harikrishnan Vijayakumar Sreelatha, Hamza Palekkodan, Ansar Fasaludeen, Lissy K. Krishnan, Klas S. P. Abelson
Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.by Vi Nguyen, Arman Walia, Joshua J. Horns, Niraj Paudel, Aditya Bagrodia, Darshan P. Patel, Tung-Chin Hsieh, James M. Hotaling
PurposeAmerican Urological Association guidelines recommend testicular prosthesis discussion prior to orchiectomy. Utilization may be low. We compared outcomes and care utilization between concurrent implant (CI) and staged implant (SI) insertion after radical orchiectomy.
Materials & methodsThe MarketScan Commercial claims database (2008–2017) was queried for men ages >18 years who underwent radical orchiectomy for testicular mass, stratified as orchiectomy with no implant, CI, or SI. 90-day outcomes included rate of reoperation, readmission, emergency department (ED) presentation, and outpatient visits. Regression models provided rate ratio comparison.
Results8803 patients (8564 no implant, 190 CI, 49 SI; 2.7% implant rate) were identified with no difference in age, Charlson Comorbidity Index, insurance plan, additional cancer treatment, or metastasis. Median perioperative cost at orchiectomy (+/- implant) for no implant, CI, and SI were $5682 (3648–8554), $7823 (5403–10973), and $5380 (4130–10521), respectively (p Conclusions
CI placement has less total perioperative cost, lower explant rate, and similar postoperative utilization to SI.
by Lakmini Kosgahakumbura, Jayani Gamage, Luke P. Robertson, Taj Muhammad, Björn Hellman, Ulf Göransson, Prabath Jayasinghe, Chamari Hettiarachchi, Paco Cárdenas, Sunithi Gunasekera
Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.by Manisri Porukala, P. K. Vinod
The molecular pathogenesis of Hepatocellular Carcinoma (HCC) is a complex process progressing from premalignant stages to cancer in a stepwise manner. Mostly, HCC is detected at advanced stages, leading to high mortality rates. Hence, characterising the molecular underpinnings of HCC from normal to cancer state through precancerous state may help in early detection and improve its prognosis and treatment. In this work, we analysed the transcriptomic profile of tumour and premalignant samples from HCC or chronic liver disease patients, who had undergone either total or partial hepatectomy. The normal samples from patients with metastatic cancer/polycystic liver disease/ cholangiocarcinoma were also included. A gene co-expression network approach was applied to identify hierarchical changes: modules, pathways, and genes related to different trajectories of HCC and patient survival. Our analysis shows that the progression from premalignant conditions to tumour is accompanied by differences in the downregulation of genes associated with HNF4A activity and the immune system and upregulation of cell cycle genes, bringing about variability in patient outcomes. However, an increase in immune and cell cycle activity is observed in premalignant samples. Interestingly, co-expression modules and genes from premalignant stages are associated with survival. THBD, a classical marker for dendritic cells, is a predictor of survival at the premalignant stage. Further, genes linked to microtubules, kinetochores, and centromere are altered in both premalignant and tumour conditions and are associated with survival. Our analysis revealed a three-way molecular axis of liver function, immune pathways, and cell cycle driving HCC pathogenesis.by Luke Bracegirdle, Matthew Stubbs, Rezaur Rahman, Alexander I. R. Jackson, Helmi C. Burton-Papp, Robert Chambers, Sanjay Gupta, Michael P. W. Grocott, Ahilanandan Dushianthan
BackgroundCOVID-19 placed immense strain on healthcare systems, necessitating innovative responses to the surge of critically ill patients, particularly those requiring mechanical ventilation. In this report, we detail the establishment of a dedicated critical care prone positioning team at University Hospital Southampton in response to escalating demand for prone positioning during the initial wave of the pandemic.
MethodsThe formation of a prone positioning team involved meticulous planning and collaboration across disciplines to ensure safe and efficient manoeuvrers. A comprehensive training strategy, aligned with national guidelines, was implemented for approximately 550 staff members from a diverse background. We surveyed team members to gain insight to the lived experience.
ResultsA total of 78 full-time team members were recruited and successfully executed over 1200 manoeuvres over an eight-week period. Our survey suggests the majority felt valued and expressed pride and willingness to participate again should the need arise.
ConclusionThe rapid establishment and deployment of a dedicated prone positioning team may have contributed to both patient care and staff well-being. We provide insight and lessons that may be of value for future respiratory pandemics. Future work should explore objective clinical outcomes and long-term sustainability of such services.
by Susan P. Phillips, Fiona Costello, Naomi Gazendam, Afshin Vafaei
BackgroundDespite reporting poorer self-rated mental health (SRMH) than boys, girls exhibit greater resilience and academic achievement, and less risk taking or death by suicide. Might this apparent paradox be an artefact arising from girls’ and boys’ different interpretations of the meaning of SRMH? We examined whether the indicator, SRMH, had a different meaning for girls and boys.
MethodsIn 2021–2, we circulated social media invitations for youth age 13–18 to complete an online survey about their mental health, and which of 26 individual and social circumstances shaped that rating. All data were submitted anonymously with no link to IP addresses. After comparing weightings for each characteristic, factor analyses identified domains for the whole group and for girls and boys.
ResultsPoor SRMH was reported by 47% of 506 girls and 27.8% of 216 boys. In general, circumstances considered important to this rating were similar for all, although boys focussed more on sense of identity, self-confidence, physical well-being, exercise, foods eaten and screen time, while girls paid more attention to having a boyfriend or girlfriend, comparisons with peers, and school performance. With factor analysis and common to boys and girls, domains of resilience, behavior/community, family, relationships with peers and future vision emerged. Girls’ poorer SRMH did not arise from a more expansive interpretation of mental health. Instead, it may reflect perceived or real disadvantages in individual or social circumstances. Alternatively, girls’ known greater resilience may propel lower SRMH which they use intuitively to motivate future achievement and avoid the complacency of thinking that ‘all is well’.
ConclusionsThe relative similarity of attributes considered before rating one’s mental health suggests validity of this subjective measure among girls and boys.
by Sowmya C. Karantha, Ravi P. Upadhyay, Abhinav Jain, Nita Bhandari, Neeta Dhabhai, Savita Sapra, Sitanshi Sharma, Ranadip Chowdhury, Sunita Taneja
BackgroundThere is a paucity of studies which have examined associations between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants. We examined the association between ultrasound based fetal anthropometric parameters and neurodevelopment in all infants through a secondary analysis of data collected in a large community based randomized controlled trial.
MethodsA total of 1465 mother-child dyads were included. Ultrasound based fetal anthropometric parameters which included the head circumference (HC), abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and transcerebellar diameter (TCD) were collected at 26–28 weeks of gestation and their association with neurodevelopment at 24 months of age was examined.
ResultsOnly the transcerebellar diameter z score was positively associated +0.54 units (95% CI: 0.15, 0.93) with motor composite score. When the neurodevelopment outcomes were analyzed as categorical, none of the fetal variables were associated with risk of moderate to severe neurodevelopment impairment.
ConclusionThe findings suggest that transcerebellar diameter could be useful for early prediction of neurodevelopmental outcomes in childhood.
Clinical trial registrationClinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry–India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).
by Pedro A. R. Vanzele, Luiz Gustavo Sparvoli, Patricia P. de Camargo, Carla R. Tragante, Glenda P. N. S. Beozzo, Vera L. J. Krebs, Ramon V. Cortez, Carla R. Taddei
Very low birth weight (VLBW) infants, mostly preterm, have many barriers to feeding directly from the mother’s breast, and need to be fed alternatively. Feeding is a major influencer in oral microbial colonization, and this colonization in early life is crucial for the promotion of human health. Therefore, this research aimed to observe the establishment of oral microbiome in VLBW infants during their first month of life through hospitalization, and to verify the impact caused by the implementation of oral diet on the colonization of these newborns. We included 23 newborns followed during hospitalization and analyzed saliva samples collected weekly, using 16S rRNA gene sequencing. We observed a significant decrease in richness and diversity and an increase in dominance over time (q-value Streptococcus. Our results indicate that although time is related to significant changes in the oral microbial profile, oral feeding benefits genera that will remain colonizers throughout the host’s life.by M. E. Coleman, T. P. Oscar, T. L. Negley, M. M. Stephenson
Conflicting claims exist regarding pathogen growth in raw milk. A small pilot study was designed to provide definitive data on trends for pathogen growth and decline in raw bovine milk hygienically produced for direct human consumption. An independent laboratory conducted the study, monitoring growth and decline of pathogens inoculated into raw milk. Raw milk samples were inoculated with foodborne pathogens (Campylobacter, E. coli O157:H7, Listeria monocytogenes, or Salmonella) at lower (L. monocytogenes in 8 of 12 replicates (P = 0.001 to P = 0.028). Analysis of variance confirmed significant increases for L. monocytogenes at both initial levels in week 2. No evidence of growth was documented over 14 days for the three pathogens predominantly associated with raw milk outbreaks in the US (Campylobacter, E. coli O157:H7, and Salmonella). Further research is needed to characterize parameters for pathogen growth and decline to support re-assessment of risks that were based on incorrect assumptions about interactions of pathogens with the raw milk microbiota.by Linda J. Paul, Aaron C. Ericsson, Frank M. Andrews, Zachary McAdams, Michael L. Keowen, Michael P. St Blanc, Heidi E. Banse
Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD.by Peng Wang, Onno J. Arntz, Johanna F. A. Husch, Van der Kraan P. M., Jeroen J. J. P. van den Beucken, Fons A. J. van de Loo
Mesenchymal stromal/stem cell derived-extracellular vesicles (MSC-EVs) have gained interest as drug delivery nanoparticles, having immunoregulatory and potentiating tissue repair property. To maintain growth of MSCs and obtain pure MSC-derived EVs, the culture media should contain fetal bovine serum (FBS) devoid of EVs, as the presence of FBS EVs confounds the properties of MSC-EVs. Therefore, we tested three methods: 18h ultracentrifugation (UC) and ultrafiltration (UF), which are common FBS EV depletion methods in current MSC-EV research, and polyethylene glycol (PEG) precipitation to obtain three EV depleted FBS (EVdFBS) batches, and compared them to FBS and commercial (Com) EVdFBS on human adipose stem cell (hADSC) growth, differentiation, enrichment of EVs in hADSC supernatant and their biological function on collagen metabolism. Our comparative study showed UC and UF vary in terms of depletion efficiency and do not completely deplete EVs and affects the growth-promoting quality of FBS. Specifically, FBS EV depletion was comparable between PEG (95.6%) and UF (96.6%) but less by UC (82%), as compared to FBS. FBS protein loss was markedly different among PEG (47%), UF (87%), and UC (51%), implying the ratio of EV depletion over protein loss was PEG (2.03), UF (1.11), and UC (1.61). A significant decrease of TGFβ/Smad signaling, involving in MSC growth and physiology, was observed by UF. After 96 hours of exposure to 5% FBS or 5% four different EVdFBS cell growth media, the osteogenesis ability of hADSCs was not impaired but slightly lower mRNA expression level of Col2a observed in EVdFBS media during chondrogenesis. In consistent with low confluency of hADSCs observed by optical microscope, cell proliferation in response to 5% UF EVdFBS media was inhibited significantly. Importantly, more and purer ADSCs EVs were obtained from ADSCs cultured in 5% PEG EVdFBS media, and they retained bioactive as they upregulated the expression of Col1a1, TIMP1 of human knee synovial fibroblast. Taken together, this study showed that PEG precipitation is the most efficient method to obtain EV depleted FBS for growth of MSCs, and to obtain MSC EVs with minimal FBS EV contamination.
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