bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes
Authors: Wander Pandora L. , Hinkle Stefanie N. , Enquobahrie Daniel A. , Wu Jing , Ley Sylvia H. , Grunnet Louise G. , Chavarro Jorge E. , Li Mengying , Bjerregaard Anne A. , Liu Aiyi , Damm Peter , Sherman Seth , Rawal Shristi , Zhu Yeyi , Chen Liwei , Mills James L. , Hu Frank B. , Vaag Allan , Olsen Sjurdur F. , Zhang Cuilin
Published: February 2022

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women’s Health Study (2012–2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996–2002), we assessed associations of cumulative lactation duration (none, <6 months, 6–12 months, ≥12–24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9–16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0–6, 6–12, 12–24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9–16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.
Potential of Polyphenols to Restore SIRT1 and NAD+ Metabolism in Renal Disease
Authors: Tovar-Palacio Claudia , Noriega Lilia G. , Mercado Adriana
Published: February 2022

SIRT1 is an NAD+-dependent class III histone deacetylase that is abundantly expressed in the kidney, where it modulates gene expression, apoptosis, energy homeostasis, autophagy, acute stress responses, and mitochondrial biogenesis. Alterations in SIRT1 activity and NAD+ metabolism are frequently observed in acute and chronic kidney diseases of diverse origins, including obesity and diabetes. Nevertheless, in vitro and in vivo studies and clinical trials with humans show that the SIRT1-activating compounds derived from natural sources, such as polyphenols found in fruits, vegetables, and plants, including resveratrol, quercetin, and isoflavones, can prevent disease and be part of treatments for a wide variety of diseases. Here, we summarize the roles of SIRT1 and NAD+ metabolism in renal pathophysiology and provide an overview of polyphenols that have the potential to restore SIRT1 and NAD+ metabolism in renal diseases.
Improving Lipophagy by Restoring Rab7 Cycle: Protective Effects of Quercetin on Ethanol-Induced Liver Steatosis
Authors: Lin Hongkun , Guo Xiaoping , Liu Jingjing , Liu Peiyi , Mei Guibin , Li Hongxia , Li Dan , Chen Huimin , Chen Li , Zhao Ying , Jiang Chunjie , Yu Yaqin , Liu Wen , Yao Ping
Published: February 2022

Chronic alcohol consumption retards lipophagy, which contributes to the pathogenesis of liver steatosis. Lipophagy-related Rab7 has been presumed as a crucial regulator in the progression of alcohol liver disease despite elusive mechanisms. More importantly, whether or not hepatoprotective quercetin targets Rab7-associated lipophagy disorder is unknown. Herein, alcoholic fatty liver induced by chronic-plus-single-binge ethanol feeding to male C57BL/6J mice was manifested by hampering autophagosomes formation with lipid droplets and fusion with lysosomes compared with the normal control, which was normalized partially by quercetin. The GST-RILP pulldown assay of Rab7 indicated an improved GTP-Rab7 as the quercetin treatment for ethanol-feeding mice. HepG2 cells transfected with CYP2E1 showed similar lipophagy dysfunction when exposed to ethanol, which was blocked when cells were transfected with siRNA-Rab7 in advance. Ethanol-induced steatosis and autophagic flux disruption were aggravated by the Rab7-specific inhibitor CID1067700 while alleviated by transfecting with the Rab7Wt plasmid, which was visualized by immunofluorescence co-localization analysis and mCherry-GFP-LC3 transfection. Furthermore, TBC1D5, a Rab GTPase-activating protein for the subsequent normal circulation of Rab7, was downregulated after alcohol administration but regained by quercetin. Rab7 circulation retarded by ethanol and corrected by quercetin was further revealed by fluorescence recovery after photobleaching (FRAP). Altogether, quercetin attenuates hepatic steatosis by normalizing ethanol-imposed Rab7 turnover disorders and subsequent lipophagy disturbances, highlighting a novel mechanism and the promising prospect of quercetin-like phytochemicals against the crucial first hit from alcohol.
Embryonic Exposure to Tryptophan Yields Bullying Victimization via Reprogramming the Microbiota-Gut-Brain Axis in a Chicken Model
Authors: Huang Xiaohong , Hu Jiaying , Peng Haining , Cheng Heng-wei
Published: February 2022

Maternal metabolic disorder during early pregnancy may give rise to emotional and behavioral disorders in the child, vulnerable to bullying. Placental tryptophan fluctuation consequently disrupts offspring gut microbiome and brain neurogenesis with long-lasting physiological and social behavioral impacts. The aim of this study was to examine the hypothesis that the excess gestational tryptophan may affect children’s mental and physical development via modifying the microbiota-gut-brain axis, which lays the foundation of their mental status. Chicken embryo was employed due to its robust microbiota and independence of maternal influences during embryogenesis. The results indicated that embryonic tryptophan exposure reduced body weight and aggressiveness in the male offspring before and during adolescence. Additionally, the relative gut length and crypt depth were increased, while the villus/crypt ratio was decreased in tryptophan treated roosters, which was corresponding to the changes in the cecal microbiota composition. Furthermore, the catecholamine concentrations were increased in tryptophan group, which may be associated with the alterations in the gut microbiome and the gut-brain axis’s function. These changes may underlie the sociometric status of bullying; clarify how gestational tryptophan fluctuation compromises bullying and provide a strategy to prevent bullying by controlling dietary tryptophan and medication therapy during pregnancy.
Continuous versus Intermittent Enteral Tube Feeding for Critically Ill Patients: A Prospective, Randomized Controlled Trial
Authors: Lee Hong-Yeul , Lee Jung-Kyu , Kim Hye-Jin , Ju Dal-Lae , Lee Sang-Min , Lee Jinwoo
Published: February 2022

The appropriate strategy for enteral feeding remains a matter of debate. We hypothesized that continuous enteral feeding would result in higher rates of achieving target nutrition during the first 7 days compared with intermittent enteral feeding. We conducted an unblinded, single-center, parallel-group, randomized controlled trial involving adult patients admitted to the medical intensive care unit who required mechanical ventilation to determine the efficacy and safety of continuous enteral feeding for critically ill patients compared with intermittent enteral feeding. The primary endpoint was the achievement of ≥80% of the target nutrition requirement during the first 7 days after starting enteral feeding. A total of 99 patients were included in the modified intention-to-treat analysis (intermittent enteral feeding group, n = 49; continuous enteral feeding group, n = 50). The intermittent enteral feeding group and continuous enteral feeding group received 227 days and 226 days of enteral feeding, respectively. The achievement of ≥80% of the target nutrition requirement occurred significantly more frequently in the continuous enteral feeding group than in the intermittent enteral feeding group (65.0% versus 52.4%, respectively; relative risk, 1.24; 95% confidence interval, 1.06–1.45; p = 0.008). For patients undergoing mechanical ventilation, continuous enteral feeding significantly improved the achievement of target nutrition requirements.
Gestational Diabetes Mellitus Is Associated with Differences in Human Milk Hormone and Cytokine Concentrations in a Fully Breastfeeding United States Cohort
Authors: Choi Yuni , Nagel Emily M. , Kharoud Harmeet , Johnson Kelsey E. , Gallagher Tipper , Duncan Katy , Kharbanda Elyse O. , Fields David A. , Gale Cheryl A. , Jacobs Katherine , Jacobs David R. , Demerath Ellen W.
Published: February 2022

It is unclear whether gestational diabetes mellitus (GDM) alters breast milk composition. We prospectively examined associations of GDM status with concentrations of six potentially bioactive elements (glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), leptin, and adiponectin) in human milk. These were measured at both 1 and 3 months postpartum in 189 fully breastfeeding women. Mixed-effects linear regression assessed GDM status-related differences in these milk bioactives, adjusting for demographics, maternal factors, and diet. At 1 and 3 months postpartum, milk CRP was higher (1.46 ± 0.31 ng/mL; p < 0.001 and 1.69 ± 0.31 ng/mL; p < 0.001) in women with GDM than in women without GDM, whereas milk glucose (−5.23 ± 2.22 mg/dL; p = 0.02 and −5.70 ± 2.22; p = 0.01) and milk insulin (−0.38 ± 0.17 μIU/mL; p = 0.03 and −0.53 ± 0.17; p = 0.003) were lower in women with GDM. These significant associations remained similar after additional adjustment for maternal weight status and its changes. No difference was found for milk IL-6, leptin, and adiponectin. There was no evidence of association between these milk bioactive compounds and 1 h non-fasting oral glucose challenge serum glucose in the women without GDM. This prospective study provides evidence that potentially bioactive elements of human milk composition are altered in women with GDM.
Lower Intake of Saturated Fatty Acids Is Associated with Improved Lipid Profile in a 6-Year-Old Nationally Representative Population
Authors: Helgadottir Hafdis , Thorisdottir Birna , Gunnarsdottir Ingibjorg , Halldorsson Thorhallur I. , Palsson Gestur , Thorsdottir Inga
Published: February 2022

To strengthen the organization of new national dietary surveys and interventions in childhood, our aim was to study macronutrient intake and blood lipid profile at 6 years of age by comparing results from two earlier population-based cohorts. Subjects were n = 131 and n = 162 in the years 2001–2002 and 2011–2012, respectively. Three-day weighed food records were used to estimate diet and calculate nutrient intake. Total cholesterol, HDL-cholesterol and triacylglycerol were measured in serum and LDL-cholesterol was calculated. The average intake of saturated fatty acids (SFA) and trans FA was lower in 2011–2012 than 2001–2002 (13.3E% vs. 14.7E%, p < 0.001, and 0.8E% vs. 1.4E%, p < 0.001, respectively), replaced by a higher intake of unsaturated fatty acids. Total cholesterol and LDL-cholesterol were significantly lower in 2011–2012 than 2001–2002 (4.6 vs. 4.4 mmol/L, p = 0.003 and 2.8 vs. 2.5 mmol/L, p < 0.001, respectively). In a multiple linear regression model, one E% increase in SFA intake was related to a 0.03 mmol/L increase in LDL cholesterol (p = 0.04). A lower intake of saturated and trans fatty acids, replaced by unsaturated fatty acids, may have contributed to an improved lipid profile in a healthy 6-year-old population. Biological data for analysis of blood lipids are important in national dietary surveys in healthy children to monitor important health outcomes of interventions.
Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre
Authors: Lobbes Hervé , Durupt Stéphane , Mainbourg Sabine , Pereira Bruno , Nove-Josserand Raphaele , Durieu Isabelle , Reynaud Quitterie
Published: February 2022

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) μg/L, or ≤100 μg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age—31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31–5.31), age < 30 years (OR 2.30, CI95% 1.16–4.56), and P. aeruginosa (OR 2.09, CI95% 1.04–4.19).
Systematic Review of the Effects of Exercise and Physical Activity on the Gut Microbiome of Older Adults
Authors: Ramos Catarina , Gibson Glenn R. , Walton Gemma E. , Magistro Daniele , Kinnear Will , Hunter Kirsty
Published: February 2022

Recent evidence suggests that exercise/physical activity (PA) can beneficially alter the gut microbiome composition of young people, but little is known about its effects in older adults. The aim of this systematic review was to summarize results of human studies that have assessed the effects/associations of PA/exercise on the gut microbiome of older adults and to better understand whether this can help promote healthy ageing. Seven studies were included in the review and overall, exercise and increased amounts of PA were associated with decreases in the abundance of several well-known harmful taxa and increases in the abundance of health-promoting taxa. Altogether, the findings from the included studies suggest that exercise/PA have a beneficial impact on the gut health of older adults by improving the gut microbiome composition. However, due to methodological and sampling disparities, it was not possible to reach a consensus on which taxa were most affected by exercise or PA.
Bowel Health in U.S. Vegetarians: A 4-Year Data Report from the National Health and Nutrition Examination Survey (NHANES)
Authors: Storz Maximilian Andreas , Rizzo Gianluca , Müller Alexander , Lombardo Mauro
Published: February 2022

Dietary fiber is of paramount importance in the prevention of large-bowel diseases, yet fiber intake in many high income countries is well below daily recommendations. Vegetarian diets high in fiber-rich plant-foods have been associated with a higher frequency of bowel movements and softer stools. Thus, vegetarians appear to suffer less frequently from constipation and other bowel disorders. The number of studies investigating these associations, however, is limited. The present study sought to investigate bowel health and constipation prevalence in a self-identified vegetarian population from the U.S. National Health and Nutrition Examination Survey (2007–2010). Bowel health assessment included Bristol Stool Scale (BSS), Bowel Movement (BM) frequency and Fecal Incontinence Severity Index (FISI). The present study included 9531 non-vegetarians and 212 vegetarians. We found no associations between vegetarian status and all examined bowel health items (BM frequency, BSS and FISI). Vegetarians consumed significantly more fiber than omnivores (21.33 vs. 16.43 g/d, p < 0.001) but had a lower moisture intake (2811.15 vs. 3042.78 g/d, p = 0.045). The lack of an association of vegetarian status and bowel health is surprising, and may be a result of the relatively low fiber intake in this particular vegetarian cohort, which did not meet the daily fiber recommendations.
Distribution and Determinants of Serum Zinc, Copper, and Selenium Levels among Children under Five Years from Popokabaka, Democratic Republic of Congo: A Cross-Sectional Study
Authors: Mbunga Branly Kilola , Engebretsen Ingunn M. S. , Strand Tor A. , Gjengdal Elin L. F. , Akilimali Pierre Z. , Langfjord Mina M. , Tugirimana Pierrot L. , Mapatano Mala Ali
Published: February 2022

Information about essential trace elements among children in many African countries, including the Democratic Republic of Congo (DRC), is limited. We aimed to measure the distribution and determinants of serum zinc (Zn), copper (Cu), and selenium (Se) concentrations in a representative sample of children under five years old. We conducted a community-based cross-sectional study in Popokabaka, DRC. Blood samples were drawn from 412 children. The serum concentrations of minerals were measured using inductively coupled plasma–mass spectrometry. The median concentrations (P25–P75) of Zn, Cu, and Se were 61.9 µg/dL (52.8–70.2), 145.5 (120.0–167.0) µg/dL and 5.3 (4.3–6.3) µg/dL. The CRP-adjusted prevalence of serum Se deficiency was 84.1% (95% confidence interval [CI] 81.4–87.0) and of Zn deficiency was 64.6% (95% CI 59.8–69.1%). Only a few children were Cu deficient [1.5% (0.6–3.2)]. Evidence of inflammation (C-reactive protein, >5 mg/L) was associated with a lower Se concentration and higher Cu concentration. Furthermore, serum Se concentration was positively associated with linear growth. The average Cu/Zn molar ratio (2:1) was twice that recommended. Children in western Popokabaka had higher Zn and Se levels than their eastern neighbors. Zinc and selenium deficiencies are common among children in Popokabaka and require attention and prioritization.
Investigation of the Effect of Nutritional Supplementation with Whey Protein and Vitamin D on Muscle Mass and Muscle Quality in Subacute Post-Stroke Rehabilitation Patients: A Randomized, Single-Blinded, Placebo-Controlled Trial
Authors: Honaga Kaoru , Mori Naoki , Akimoto Tomonori , Tsujikawa Masahiro , Kawakami Michiyuki , Okamoto Tomoyuki , Sakata Yasuyuki , Hamano Hirokazu , Takeda Yasuhiro , Kondo Kunitsugu
Published: February 2022

In post-stroke hemiparesis patients, the skeletal muscle mass decrease rapidly with the histological degradation. We investigated the effect of nutritional supplementation with whey protein and vitamin D on the muscle mass and muscle quality, in post-stroke convalescent rehabilitation patients in a randomized, single-blinded, placebo-controlled trial. Fifty patients were randomly assigned to two groups; HP group received supplemental jelly (100 kcal; whey protein 10 g; vitamin D 20 μg) twice a day throughout up to 16-week period, the control group received placebo jelly. Cross-sectional area (CSA) of thigh muscle, skeletal muscle index (SMI), muscle strength, activity of daily living (ADL), and some nutritional indicators in blood were measured. Although no significant difference was observed in CSA and SMI between the groups, fat infiltration into the thighs muscle was singnificantly lower in the HP group. There were no significant difference in muscle strength and ADL between the groups. Blood urea nitrogen and serum 25(OH)D at endpoint were significantly higher in the HP group but physiological normal ranges. Supplementation with whey protein and vitamin D in post-stroke patients led to suppression of fat infiltration into the muscle. Long-term follow-up studies are needed to verify whether this nutritional intervention provides substantial benefits for the prognosis of stroke survivors.
Casein Oligochitosan-Glycation by Transglutaminase Enhances the Anti-Inflammatory Potential of Casein Hydrolysates to the Lipopolysaccharide-Stimulated IEC-6 Cells
Authors: Chen Na , Wang Li , Zhang Qiang , Zhao Xin-Huai , Shi Jia
Published: February 2022

In this study, milk protein casein was glycated by oligochitosan through the catalysis of transglutaminase (TGase) and then hydrolyzed by trypsin. The obtained glycated casein hydrolysates (GCNH) were assessed for their anti-inflammatory activities, using the lipopolysaccharide (LPS)-stimulated rat intestinal epithelial cells (IEC-6) as cell models and the casein hydrolysates (CNH) without TGase catalysis as controls. The results showed that GCNH had oligochitosan incorporation and thus possessed a glucosamine content of 5.74 g/kg protein. In general, GCNH at dose levels of 25–100 μg/mL could elevate IEC-6 cell growth, and at dose levels of 25–50 μg/mL, they were also able to alleviate the LPS-induced cytotoxicity by increasing cell viability efficiently. Although LPS caused clear inflammation in the LPS-stimulated cells, GCNH were capable of reducing the secretion of three pro-inflammatory mediators including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, or promoting the secretion of two anti-inflammatory mediators like IL-10 and transforming growth factor-β, demonstrating their anti-inflammatory activities to the stimulated cells. Moreover, GCNH also could down-regulate the expression of three inflammation-related proteins including TLR4, p-p38, and p-p65 in the stimulated cells, and thus possessed a capacity to suppress the phosphorylation of p38 and p65 proteins as well as to inactivate the NF-κB and MAPK signaling pathways. Additionally, a higher GCNH dose level consistently led to higher anti-inflammatory effect in the cells, while GCNH were always more potent than CNH at performing anti-inflammatory function targets. It is thus suggested that the TGase-catalyzed casein oligochitosan-glycation could enhance the anti-inflammatory activities of casein hydrolysates efficiently. TGase-catalyzed protein glycation thus might enhance the healthcare function of protein ingredients in the body.
Hydrolyzed Proteins and Vegetable Peptides: Anti-Inflammatory Mechanisms in Obesity and Potential Therapeutic Targets
Authors: de Medeiros Amanda Fernandes , de Queiroz Jaluza Luana Carvalho , Maciel Bruna Leal Lima , de Araújo Morais Ana Heloneida
Published: February 2022

Chronic low-grade inflammation is present in overweight and obesity, causing changes in several metabolic pathways. It impairs systemic functioning and positively feeds back the accumulation of more adipose tissue. Studies with hydrolyzed proteins and plant peptides have demonstrated a potential anti-inflammatory and immunomodulatory effect of these peptides. However, it is challenging and necessary to explore the mechanism of action of such molecules because understanding their effects depends on their structural characterizations. Furthermore, the structure might also give insights into safety, efficacy and efficiency, with a view of a possible health application. Thus, the present narrative review aimed to discuss the mechanisms of action of hydrolyzed proteins and plant peptides as anti-inflammatory agents in obesity. Keywords and related terms were inserted into databases for the search. Based on the studies evaluated, these biomolecules act by different pathways, favoring the reduction of inflammatory cytokines and adipokines and the polarization of macrophages to the M2 phenotype. Finally, as a future perspective, bioinformatics is suggested as a tool to help understand and better use these molecules considering their applicability in pre-clinical and clinical studies.
Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice
Authors: Cabello-Olmo Miriam , Oneca María , Pajares María José , Jiménez Maddalen , Ayo Josune , Encío Ignacio J. , Barajas Miguel , Araña Miriam
Published: February 2022

Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.
Post-Mortem Microbiology: Retrospective Analysis of Infections Caused by Enterococcus Strains
Authors: Jermakow Katarzyna , Rorat Marta
Published: February 2022

Post-mortem microbiological tests are one of the basic methods for diagnosing the etiology of infections in forensic pathology. One of the major groups of microorganisms abundant in various parts of the human body during life and after death is Enterococcus spp. Depending on the area of the body involved and the patient’s condition, enterococci can be considered to be a microbiome, transient flora or a pathogen responsible for infection. The data used for the analysis were 12 medico-legal autopsy and microbiological reports. Enterococcus spp. was isolated in 10 out of 12 cultures of blood samples collected post-mortem. The abdominal origin of enterococci in the blood was detected in 8 cases. The non-abdominal origin of enterococci in the blood was associated with a skin and soft tissue infection, purulent pneumonia and infective endocarditis. These results suggest that enterococci may be considered a cause of severe infections and with high likelihood. Microbiological cultures are a valuable source of information for helping to confirm the cause of infection. Interpretation of the results of post-mortem examinations must be carried out on the basis of data collected before and after death with the participation of specialists from various fields.
Engineered Cell Line Imaging Assay Differentiates Pathogenic from Non-Pathogenic Bacteria
Authors: Phillips Shelby M. B. , Bergstrom Carson , Walker Brian , Wang George , Alfaro Trinidad , Stromberg Zachary R. , Hess Becky M.
Published: February 2022

Cell culture systems have greatly expanded our understanding of how bacterial pathogens target signaling pathways to manipulate the host and cause infection. Advances in genetic engineering have allowed for the creation of fluorescent protein readouts within signaling pathways, but these techniques have been underutilized in pathogen biology. Here, we genetically engineered a lung cell line with fluorescent reporters for extracellular signal-related kinase (ERK) and the downstream transcription factor FOS-related antigen 1 (Fra1) and evaluated signaling after inoculation with pathogenic and non-pathogenic bacteria. Cells were inoculated with 100 colony-forming units of Acinetobacter baylyi, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus agalactiae, or Staphylococcus epidermidis and imaged in a multi-mode reader. The alamarBlue cell viability assay was used as a reference test and showed that pathogenic P. aeruginosa induced significant (p < 0.05) cell death after 8 h in both wild-type and engineered cell lines compared to non-pathogenic S. epidermidis. In engineered cells, we found that Fra1 signaling was disrupted in as little as 4 h after inoculation with bacterial pathogens compared to delayed disruption in signaling by non-pathogenic S. epidermidis. Overall, we demonstrate that low levels of pathogenic versus non-pathogenic bacteria can be rapidly and sensitively screened based on ERK-Fra1 signaling.
BoLA-DRB3 Polymorphism Controls Proviral Load and Infectivity of Bovine Leukemia Virus (BLV) in Milk
Authors: Nakatsuchi Ayumi , Watanuki Sonoko , Borjigin Liushiqi , Sato Hirotaka , Bai Lanlan , Matsuura Ryosuke , Kuroda Maho , Murakami Hironobu , Sato Reiichiro , Asaji Sakurako , Ando Asako , Matsumoto Yasunobu , Takeshima Shin-Nosuke , Aida Yoko
Published: February 2022

Bovine leukemia virus (BLV), which causes enzootic bovine leukosis, is transmitted to calves through the milk of BLV-infected dams. Bovine leukocyte antigen (BoLA)-DRB3 is a polymorphic gene associated with BLV infectivity and proviral load (PVL). However, the effect of BoLA-DRB3 polymorphism on the infectivity and PVL of milk from BLV-infected dams remains unknown. This study examined milk from 259 BLV-infected dams, including susceptible dams carrying at least one BoLA-DRB3*012:01 or *015:01 allele with high PVL, resistant dams carrying at least one BoLA-DRB3*002:01, *009:02, or *014:01:01 allele with low PVL, and neutral dams carrying other alleles. The detection rate of BLV provirus and PVL were significantly higher in milk from susceptible dams than in that from resistant dams. This result was confirmed in a three-year follow-up study in which milk from susceptible dams showed a higher BLV provirus detection rate over a longer period than that from resistant dams. The visualization of infectivity of milk cells using a luminescence syncytium induction assay showed that the infectious risk of milk from BLV-infected dams was markedly high for susceptible dams compared to resistant ones. This is the first report confirming that BoLA-DRB3 polymorphism affects the PVL and infectivity of milk from BLV-infected dams.
Zoonotic Episodes of Scabies: A Global Overview
Authors: Moroni Barbara , Rossi Luca , Bernigaud Charlotte , Guillot Jacques
Published: February 2022

Zoonotic scabies (ZS), also referred to as “pseudoscabies”, is considered a self-limiting disease with a short incubation period and transient clinical skin signs. It is commonly thought that Sarcoptes scabiei mites from animals are unable to successfully reproduce and persist on human skin; however, several ZS case reports have mentioned the persistence of symptoms and occasionally mites for weeks. The aim of this review was to collect and organize the sparse literature explicitly referring to S. scabiei zoonotic transmission, focusing on the source of the outbreak, the circumstances leading to the transmission of the parasite, the diagnosis including the identification of the Sarcoptes “strain” involved, and the applied treatments. A total of 46 articles, one conference abstract and a book were collected describing ZS cases associated with twenty animal hosts in five continents. Dogs were by far the most common source among pet owners, while diverse livestock and wildlife contributed to the caseload as an occupational disease. Genetic epidemiological studies of ZS outbreaks are still limited in number, but tools are available to fill this knowledge gap in the near future. Further research is also needed to understand the apparent heterogeneity in the morbidity, disease severity and timing of the response to treatment among people infected with different animal-derived strains.
Seasonal Patterns of Enteric Pathogens in Colombian Indigenous People—A More Pronounced Effect on Bacteria Than on Parasites
Authors: Kann Simone , Hartmann Maria , Alker Juliane , Hansen Jessica , Dib Juan Carlos , Aristizabal Andrés , Concha Gustavo , Schotte Ulrich , Kreienbrock Lothar , Frickmann Hagen
Published: February 2022

Enteric pathogens, which are frequently food- and waterborne transmitted, are highly abundant in Indigenous people living in remote rural areas of Colombia. As the frequency of gastroenteritis in the tropics shows seasonal differences, we analyzed variations of pathogen patterns in the stool samples of a Colombian Indigenous tribe called Wiwa during the dry (n = 105) and the rainy (n = 227) season, applying real-time PCR from stool samples and statistical analysis based on a multi-variable model. Focusing on bacterial pathogens, increased detection rates could be confirmed for enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli with a tendency for an increase in Campylobacter jejuni detections during the rainy season, while there was no seasonal effect on the carriage of Tropheryma whipplei. Salmonellae were recorded during the rainy season only. A differentiated pattern was seen for the assessed parasites. Entamoeba histolytica, Necator americanus and Trichuris trichiura were increasingly detected during the rainy season, but not Ascaris lumbricoides, Giardia duodenalis, Hymenolepis nana, Strongyloides stercoralis, and Taenia solium, respectively. Increased detection rates during the dry season were not recorded. Negative associations were found for Campylobacter jejuni and Giardia duodenalis with age and for Tropheryma whipplei with the body mass index, respectively. Positive associations of enteropathogenic Escherichia coli and Taenia solium detections were observed with age. In conclusion, facilitating effects of the tropical rainy season were more pronounced on bacterial enteric pathogens compared to enteropathogenic parasites.
The Epidemiology and Control of Bovine Viral Diarrhoea Virus in Tropical Indonesian Cattle
Authors: Nugroho Widi , Silitonga Risma Juniarti Paulina , Reichel Michael Philipp , Irianingsih Sri Handayani , Wicaksono Muhammad Satryo
Published: February 2022

This review aims to update the knowledge of the epidemiology of Bovine viral diarrhoea virus (BVDV) in Indonesia and Southeast Asia and provide a perspective on the control options for BVDV in the Indonesian cattle population in the future. Studies on BVDV in Indonesia, since its first report in that country, and the updated beef and dairy cattle industries are reviewed. In ten of 34 provinces, BVDV is endemic. The subgenotypes of BVDV-1a and BVDV-1c are predominant in Indonesian cattle. However, BVDV is currently not a priority disease to control in Indonesia. Cattle imports from Australia appear to be potentially the most significant source of transmission of BVDV into native cattle, but the control of BVDV conducted in the local quarantine facilities is currently not achieving the aim of controlling BVDV; thus, complementary measures are needed. With the small-scale nature of the vast majority of cattle breeding in the country, the control of BVDV in provinces in which cattle breeding is economically essential may need to be organised by regional and provincial governments. Gaps in our knowledge of BVDV are identified in this review, and strategies for the control of BVDV in Indonesia are discussed.
Pharmacokinetics and Bioequivalence of Two Empagliflozin, with Evaluation in Healthy Jordanian Subjects under Fasting and Fed Conditions
Authors: Hailat Mohammad , Zakaraya Zainab , Al-Ani Israa , Meanazel Osaid Al , Al-Shdefat Ramadan , Anwer Md. Khalid , Saadh Mohamed J. , Abu Dayyih Wael
Published: February 2022

The current study is a randomized, open-label, two-period, two-sequence, two-way crossover pharmacokinetic study in healthy Jordanian subjects to evaluate the pharmacokinetics and bioequivalence profile of two cases of empagliflozin 10 mg under fasting and fed conditions. The plasma concentrations of empagliflozin were determined using an HPLC-MS/MS method. Tolerability and safety were assessed throughout the study. This study included 26 subjects, 26 in both fasting and fed groups.The pharmacokinetic parameters, which included the area under the concentration–time curve from time zero to infinity (AUC0–inf) and the final quantifiable concentration (AUC0–last), maximum serum concentration (Cmax), and time to reach the maximum drug concentration (Tmax) were found to be within an equivalence margin of 80.00–125.00%. The pharmacokinetic profiles show that the empagliflozin test and parent reference cases were bioequivalent in healthy subjects. The two treatments’ safety evaluations were also comparable.
Understanding the Anti-Diarrhoeal Properties of Incomptines A and B: Antibacterial Activity against Vibrio cholerae and Its Enterotoxin Inhibition
Authors: Calzada Fernando , Bautista Elihu , Hidalgo-Figueroa Sergio , García-Hernández Normand , Velázquez Claudia , Barbosa Elizabeth , Valdes Miguel , Solares-Pascasio Jesús Iván
Published: February 2022

Incomptines A (IA) and B (IB) are two sesquiterpene lactones with antiprotozoal, antibacterial, cytotoxic, antitumor, spermicidal, and phytotoxic properties. The antibacterial activity of IA and IB against bacteria causing diarrhoea have been reported; however, no information is available regarding their antibacterial activity on Vibrio cholerae. In this work, both compounds were evaluated for their anti-diarrhoeal potential using the bacterium V. cholerae, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) analysis on cholera toxin, and a cholera toxin-induced diarrhoea model in male Balb/c mice. In addition, a molecular docking study was carried out to understand the interaction of IA and IB with cholera toxin. In terms of antibacterial activity, IB was three times more active than IA on V. cholerae. In the case of SDS-PAGE analysis and the in silico study, IA was most effective, revealing its potential binding mode at a molecular level. In terms of anti-diarrhoeal activity, IA was 10 times more active than IB and racecadotril, an antisecretory drug used as positive control; the anti-diarrheal activity of IB was also closer than racecadotril. The results obtained from in vitro, in vivo, and computational studies on V. cholerae and cholera toxin support the potential of IA and IB as new anti-diarrhoeal compounds.
Pyrazole and Triazole Derivatives as Mycobacterium tuberculosis UDP-Galactopyranose Inhibitors
Authors: Ahmed Dalia M. , Chen Jeffrey M. , Sanders David A. R.
Published: February 2022

UDP-galactopyranose mutase (UGM) is an essential enzyme involved in the bacterial cell wall synthesis, and is not present in mammalian cells. Thus, UGM from Mycobacterium tuberculosis (Mtb) represents a novel and attractive drug target for developing antituberculosis agents. A pyrazole-based compound, MS208, was previously identified as a mixed inhibitor of MtbUGM which targets an allosteric site. To understand more about the structure activity relationship around the MS208 scaffold as a MtbUGM inhibitor, thirteen pyrazoles and triazole analogues were synthesized and tested against both MtbUGM and Mycobacterium tuberculosis in vitro. While the introduced structural modifications to MS208 did not improve the antituberculosis activity, most of the compounds showed MtbUGM inhibitory activity. Interestingly, the pyrazole derivative DA10 showed a competitive model for MtbUGM inhibition with improved Ki value of 51 ± 4 µM. However, the same compound did not inhibit the growth of Mycobacterium tuberculosis.
Dementia and COVID-19: A Case Report and Literature Review on Pain Management
Authors: Scuteri Damiana , Contrada Marianna , Tonin Paolo , Corasaniti Maria Tiziana , Nicotera Pierluigi , Bagetta Giacinto
Published: February 2022

The coronavirus disease 2019 (COVID-19) pandemic imposes an unprecedented lifestyle, dominated by social isolation. In this frame, the population to pay the highest price is represented by demented patients. This group faces the highest risk of mortality, in case of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, and they experience rapid cognitive deterioration, due to lockdown measures that prevent their disease monitoring. This complex landscape mirrors an enhancement of neuropsychiatric symptoms (NPSs), with agitation, delirium and reduced motor performances, particularly in non-communicative patients. Due to the consistent link between agitation and pain in these patients, the use of antipsychotics, increasing the risk of death during COVID-19, can be avoided or reduced through an adequate pain treatment. The most suitable pain assessment scale, also feasible for e-health implementation, is the Mobilization-Observation-Behaviour-Intensity-Dementia (MOBID-2) pain scale, currently under validation in the Italian real-world context. Here, we report the case of an 85-year-old woman suffering from mild cognitive impairment, subjected to off-label treatment with atypical antipsychotics, in the context of undertreated pain, who died during the pandemic from an extensive brain hemorrhage. This underscores the need for appropriate assessment and treatment of pain in demented patients.
Efficacy, Safety and Patient-Reported Outcomes with Preservative-Free (PF) Tafluprost or PF-Dorzolamide/Timolol Compared with Preserved Latanoprost: A Prospective Multicenter Study in Korean Glaucoma Patients with Ocular Surface Disease
Authors: Park Sang-Woo , Lee Jiwoong , Kook Michael
Published: February 2022

To compare the efficacy, patient-reported satisfaction, and safety of preservative-free (PF)-tafluprost, PF-dorzolamide/timolol and preservative-containing (P)-latanoprost in Korean glaucoma patients with ocular surface disease (OSD). In a multicenter, prospective, interventional, non-randomized, controlled 12-week trial, 107 eligible patients received PF-tafluprost (n = 37), PF-dorzolamide/timolol (n = 34), or P-latanoprost eye drops (n = 36). Outcomes included changes from baseline in OSD Index (OSDI) scores (primary endpoint), intraocular pressure (IOP), and patient-reported treatment satisfaction, and safety at 12 weeks. At 12 weeks, the mean total OSDI and subdomain (dry eye symptoms, visual-related function, environmental triggers) scores significantly improved from baseline with PF-tafluprost and PF-dorzolamide/timolol, but not with P-latanoprost. Significantly more PF-tafluprost than P-latanoprost recipients reported ‘highly improved/improved’ satisfaction (no significant difference between PF-dorzolamide/timolol and P-latanoprost). IOP changes were comparable among all three treatment groups. No new safety concerns were observed. PF-tafluprost and PF-dorzolamide/timolol showed statistically and clinically significant reductions in OSDI compared with P-latanoprost in Korean glaucoma patients with OSD.
Development and Use of a Residence Time Distribution (RTD) Model Control Strategy for a Continuous Manufacturing Drug Product Pharmaceutical Process
Authors: Hurley Samantha , Tantuccio Anthony , Escotet-Espinoza Manuel Sebastian , Flamm Matthew , Metzger Matthew
Published: February 2022

Residence-time-distribution (RTD)-based models are key to understanding the mixing dynamics of continuous manufacturing systems. Such models can allow for material traceability throughout the process and can provide the ability for removal of non-conforming material from the finished product. These models have been implemented in continuous pharmaceutical manufacturing mainly for monitoring purposes, not as an integral part of the control strategy and in-process specifications. This paper discusses the steps taken to develop an RTD model design space and how the model was statistically incorporated into the product’s control strategy. To develop the model, experiments were conducted at a range of blender impeller speeds and total system mass flow rates. RTD parameters were optimized for each condition tested using a tank-in-series-type model with a delay. Using the experimental RTD parameters, an equation was derived relating the mean residence time to the operating conditions (i.e., blender impeller speed and mass flow rate). The RTD parameters were used in combination with real-time upstream process data to predict downstream API concentration, where these predictions allowed validation across the entire operating range of the process by comparison to measured tablet assay. The standard in-process control limits for the product were statistically tightened using the validation acceptance criteria. Ultimately, this model and strategy were accepted by regulatory authorities.
Parietin Cyclodextrin-Inclusion Complex as an Effective Formulation for Bacterial Photoinactivation
Authors: Ayoub Abdallah Mohamed , Gutberlet Bernd , Preis Eduard , Abdelsalam Ahmed Mohamed , Abu Dayyih Alice , Abdelkader Ayat , Balash Amir , Schäfer Jens , Bakowsky Udo
Published: February 2022

Multidrug resistance in pathogenic bacteria has become a significant public health concern. As an alternative therapeutic option, antimicrobial photodynamic therapy (aPDT) can successfully eradicate antibiotic-resistant bacteria with a lower probability of developing resistance or systemic toxicity commonly associated with the standard antibiotic treatment. Parietin (PTN), also termed physcion, a natural anthraquinone, is a promising photosensitizer somewhat underrepresented in aPDT because of its poor water solubility and potential to aggregate in the biological environment. This study investigated whether the complexation of PTN with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) could increase its solubility, enhance its photophysical properties, and improve its phototoxicity against bacteria. At first, the solubilization behavior and complexation constant of the PTN/HP-β-CD inclusion complexes were evaluated by the phase solubility method. Then, the formation and physicochemical properties of PTN/HP-β-CD complexes were analyzed and confirmed in various ways. At the same time, the photodynamic activity was assessed by the uric acid method. The blue light-mediated photodegradation of PTN in its free and complexed forms were compared. Complexation of PTN increased the aqueous solubility 28-fold and the photostability compared to free PTN. PTN/HP-β-CD complexes reduce the bacterial viability of Staphylococcus saprophyticus and Escherichia coli by > 4.8 log and > 1.0 log after irradiation, respectively. Overall, the low solubility, aggregation potential, and photoinstability of PTN were overcome by its complexation in HP-β-CD, potentially opening up new opportunities for treating infections caused by multidrug-resistant bacteria.
Design Principles Governing the Development of Theranostic Anticancer Agents and Their Nanoformulations with Photoacoustic Properties
Authors: Kyrkou Stavroula G. , Vrettos Eirinaios I. , Gorpas Dimitris , Crook Timothy , Syed Nelofer , Tzakos Andreas G.
Published: February 2022

The unmet need to develop novel approaches for cancer diagnosis and treatment has led to the evolution of theranostic agents, which usually include, in addition to the anticancer drug, an imaging agent based mostly on fluorescent agents. Over the past few years, a non-invasive photoacoustic imaging modality has been effectively integrated into theranostic agents. Herein, we shed light on the design principles governing the development of theranostic agents with photoacoustic properties, which can be formulated into nanocarriers to enhance their potency. Specifically, we provide an extensive analysis of their individual constituents including the imaging dyes, drugs, linkers, targeting moieties, and their formulation into nanocarriers. Along these lines, we present numerous relevant paradigms. Finally, we discuss the clinical relevance of the specific strategy, as also the limitations and future perspectives, and through this review, we envisage paving the way for the development of theranostic agents endowed with photoacoustic properties as effective anticancer medicines.