bluuebunny/crossref_metadata_2025 huggingface dataset:
Kratom Use in the US: Both a Regional Phenomenon and a White Middle-Class Phenomenon? Evidence From NSDUH 2019 and an Online Convenience Sample
Authors: Rogers Jeffrey M. , Smith Kirsten E. , Strickland Justin C. , Epstein David H.
Published: December 2021

Kratom products available in the United States are becoming increasingly diverse both in terms of content and in terms of how they are marketed. Prior survey research indicates that kratom has been primarily used in the US to self-treat anxiety, depression, pain, fatigue, and substance use disorder (SUD) symptoms. Kratom is also well-known for its use as a short- or long-term full opioid agonist substitute. Therefore, use may be greater in regions particularly impacted by addiction to prescription opioids. Use may also be greater in demographic groups targeted by media outlets (such as specific podcasts) in which kratom is touted. Here, we aimed to determine whether lifetime and past-year kratom use were associated with region of residence and with being young, White, post-secondary educated, and employed. To strengthen confidence in our findings, we analyzed data from two sources: our own crowdsourced online convenience sample and the 2019 National Survey on Drug Use and Health (NSDUH). In our sample (N = 2,615), 11.1% reported lifetime and 6.7% reported past-year kratom use, and the odds of kratom use were higher among people who were White, younger, at least high school educated, employed, and above the poverty line, as well as those reporting nonmedical opioid use, past-year SUD, or lifetime SUD treatment; residence was not a significant predictor. In NSDUH data, suburban residence and other demographic factors, concordant with those from the crowdsourced sample, were associated with kratom use. Taken together, the findings support a general “White middle-class suburban” profile of the modal kratom user, but more research is needed to understand it. In the interim, focus should be on our finding that lifetime nonmedical opioid use was associated with an up to five times greater likelihood of past-year kratom use, suggesting that drug-use history may presently be the strongest predictor of kratom use.
Cerebral Erythropoietin Prevents Sex-Dependent Disruption of Respiratory Control Induced by Early Life Stress
Authors: Elliot-Portal Elizabeth , Arias-Reyes Christian , Laouafa Sofien , Tam Rose , Kinkead Richard , Soliz Jorge
Published: December 2021

Injuries that occur early in life are often at the root of adult illness. Neonatal maternal separation (NMS) is a form of early life stress that has persistent and sex-specific effects on the development of neural networks, including those that regulate breathing. The release of stress hormones during a critical period of development contributes to the deleterious consequences of NMS, but the role of increased corticosterone (CORT) in NMS-induced respiratory disturbance is unknown. Because erythropoietin (EPO) is a potent neuroprotectant that prevents conditions associated with hyperactivation of the stress neuroaxis in a sex-specific manner, we hypothesized that EPO reduces the sex-specific alteration of respiratory regulation induced by NMS in adult mice. Animals were either raised under standard conditions (controls) or exposed to NMS 3 h/day from postnatal days 3–12. We tested the efficacy of EPO in preventing the effects of NMS by comparing wild-type mice with transgenic mice that overexpress EPO only in the brain (Tg21). In 7-days-old pups, NMS augmented CORT levels ~2.5-fold by comparison with controls but only in males; this response was reduced in Tg21 mice. Respiratory function was assessed using whole-body plethysmography. Apneas were detected during sleep; the responsiveness to stimuli was measured by exposing mice to hypoxia (10% O2; 15 min) and hypercapnia (5% CO2; 10 min). In wild-type, NMS increased the number of apneas and the hypercapnic ventilatory response (HcVR) only in males; with no effect on Tg21. In wild-type males, the incidence of apneas was positively correlated with HcVR and inversely related to the tachypneic response to hypoxia. We conclude that neural EPO reduces early life stress-induced respiratory disturbances observed in males.
Dual-Hemisphere Transcranial Direct Current Stimulation on Parietal Operculum Does Not Affect the Programming of Intra-limb Anticipatory Postural Adjustments
Authors: Esposti Roberto , Marchese Silvia M. , Farinelli Veronica , Bolzoni Francesco , Cavallari Paolo
Published: December 2021

Evidence shows that the postural and focal components within the voluntary motor command are functionally unique. In 2015, we reported that the supplementary motor area (SMA) processes Anticipatory Postural Adjustments (APAs) separately from the command to focal muscles, so we are still searching for a hierarchically higher area able to process both components. Among these, the parietal operculum (PO) seemed to be a good candidate, as it is a hub integrating both sensory and motor streams. However, in 2019, we reported that transcranial Direct Current Stimulation (tDCS), applied with an active electrode on the PO contralateral to the moving segment vs. a larger reference electrode on the opposite forehead, did not affect intra-limb APAs associated to brisk flexions of the index-finger. Nevertheless, literature reports that two active electrodes of opposite polarities, one on each PO (dual-hemisphere, dh-tDCS), elicit stronger effects than the “active vs. reference” arrangement. Thus, in the present study, the same intra-limb APAs were recorded before, during and after dh-tDCS on PO. Twenty right-handed subjects were tested, 10 for each polarity: anode on the left vs. cathode on the right, and vice versa. Again, dh-tDCS was ineffective on APA amplitude and timing, as well as on prime mover recruitment and index-finger kinematics. These results confirm the conclusion that PO does not take part in intra-limb APA control. Therefore, our search for an area in which the motor command to prime mover and postural muscles are still processed together will have to address other structures.
Alcohol, Aggression, and Violence: From Public Health to Neuroscience
Authors: Sontate Kajol V. , Rahim Kamaluddin Mohammad , Naina Mohamed Isa , Mohamed Rashidi Mohamed Pakri , Shaikh Mohd. Farooq , Kamal Haziq , Kumar Jaya
Published: December 2021

Alcohol has been associated with violent crimes and domestic violence across many nations. Various etiological factors were linked to chronic alcohol use and violence including psychiatric comorbidities of perpetrators such as personality disorders, mood disorders, and intermittent explosive disorders. Aggression is the precursor of violence and individuals prone to aggressive behaviors are more likely to commit impulsive violent crimes, especially under the influence of alcohol. Findings from brain studies indicate long-term alcohol consumption induced morphological changes in brain regions involved in self-control, decision-making, and emotional processing. In line with this, the inherent dopaminergic and serotonergic anomalies seen in aggressive individuals increase their susceptibility to commit violent crimes when alcohol present in their system. In relation to this, this article intends to investigate the influence of alcohol on aggression with sociopsychological and neuroscientific perspectives by looking into comorbidity of personality or mood disorders, state of the mind during alcohol consumption, types of beverages, environmental trigger, neurochemical changes, and gender differences that influence individual responses to alcohol intake and susceptibility to intoxicated aggression.
Bridging Classical and Revised Reinforcement Sensitivity Theory Research: A Longitudinal Analysis of a Large Population Study
Authors: Espinoza Oyarce Daniela A. , Burns Richard , Butterworth Peter , Cherbuin Nicolas
Published: December 2021

The reinforcement sensitivity theory (RST) proposes that neurobiological systems mediate protective and appetitive behaviours and the functioning of these systems is associated to personality traits. In this manner, the RST is a link between neuroscience, behaviour, and personality. The theory evolved to the present revised version describing three systems: fight-flight-freezing, behavioural approach/activation (BAS), and behavioural inhibition (BIS). However, the most widely available measure of the theory, the BIS/BAS scales, only investigates two systems. Using a large longitudinal community survey, we found that the BIS/BAS scales can be re-structured to investigate the three systems of the theory with a BIS scale, three BAS scales, and a separate fight-flight-freezing system (FFFS) scale. The re-structured scales were age, sex, and longitudinally invariant, and associations with personality and mental health measures followed theoretical expectations and previously published associations. The proposed framework can be used to investigate behavioural choices influencing physical and mental health and bridge historical with contemporary research.
Top Management Team Knowledge Hiding and Enterprise Innovation Performance: A Moderated Mediation Model
Authors: Rong Pengfei , Liu Shuang
Published: December 2021

Top management team (TMT) knowledge hiding, which is not only related to the normal operation of the team but also closely related to enterprise innovation performance, has been paid little attention to in the previous studies. Based on the theories of upper echelons, knowledge management, and innovation, this study proposed a moderated mediation model to research how TMT knowledge hiding affected enterprise innovation performance. In this model, TMT knowledge hiding was the independent variable, TMT creativity was the mediating variable, enterprise innovation performance was the dependent variable, and team competitive climate was the moderating variable. MPLUS7.0 was used for the CFAs to evaluate the discriminate validities of the key variables, and SPSS 22.0 was used to calculate the descriptive statistics, analyze the correlations between variables, make the multiple regression analysis, and process the data obtained from 612 executives in 53 TMTs. The results showed that TMT knowledge hiding had a significant negative impact on enterprise innovation performance; TMT creativity had a partial mediating effect between TMT knowledge hiding and enterprise innovation performance, and team competitive climate had a moderating effect on the relationship between TMT knowledge hiding and TMT creativity. These research results fill up the gap of the theoretical research in TMT knowledge hiding and provide scientific guidance to reasonably reduce or eliminate the phenomenon of TMT knowledge hiding and improve enterprise innovation performance.
Suicidal Ideation Among Adolescents—The Role of Sexual Abuse, Depression, and Impulsive Behavior
Authors: Kumar Pradeep , Srivastava Shobhit , Mishra Prem Shankar , Sinha Debashree
Published: December 2021

Suicide is the second leading cause of death among adolescents. With every fifth Indian to be an adolescent, the cost of an adolescent dying by suicide is enormous. This necessitates an understanding of the potential risk factors of suicidal ideation among adolescents. Secondary data analysis is performed on cross-sectional survey data obtained from Understanding the Lives of Adolescents and Young Adults. The survey was conducted in two Indian states of Bihar and Uttar Pradesh. Descriptive statistics, bivariate analysis and logistic regression are done to examine the results. Adolescent girls reported more suicidal ideation than boys. The odds of suicidal ideation are significantly higher among adolescents whose mother faced physical abuse and adolescents who themselves experienced sexual abuse. Adolescent boys and girls who have moderate depressive symptoms and impulsive behavior are significantly more likely to report suicidal ideation. The results help in identifying the adolescents who are at a particular risk for suicidal ideation while planning for intervention program for prevention of suicide.
Individual, Prenatal, Perinatal, and Family Factors for Anxiety Symptoms Among Preschool Children
Authors: Ding Xiuxiu , Wang Jun , Li Ning , Su Wanying , Wang Hao , Song Qiuxia , Guo Xianwei , Liang Mingming , Qin Qirong , Sun Liang , Chen Mingchun , Sun Yehuan
Published: December 2021

Anxiety is one of the most common psychological disorders among children. Few studies have investigated the prevalence and comprehensive factors for anxiety among preschool children in China. This study aimed to assess the prevalence of anxiety and explore influential factors at multiple levels including individual, prenatal and perinatal, and family factors, associated with anxiety symptoms among preschool children. The multisite cross-sectional study was conducted in Anhui Province and included 3,636 preschool children aged 3–6 years. Anxiety symptoms of children were assessed using the Chinese version of the Spence Preschool Anxiety Scale. Logistic regression analyses were performed to explore associations between factors at multiple levels and significant anxiety symptoms, and the model was validated internally using 10-fold cross-validation. Among the participants, 9.1% of children had significant anxiety symptoms. Girls reported more significant anxiety symptoms. Children's poor dietary habits, sleep disturbances, autistic tendencies, and left-behind experience; maternal poor prenatal emotional symptoms; and more caregivers' anxiety symptoms were significantly associated with anxiety symptoms among children. The result of 10-fold cross-validation indicated that the mean area under the curve, sensitivity, specificity, and accuracy were 0.78, 70.45%, 78.18%, and 71.15%, respectively. These factors were slightly different among different subtypes of anxiety symptoms. The results of this study suggested that anxiety symptoms in preschool children were prevalent, particularly in girls. Understanding early-life risk factors for anxiety is crucial, and efficient prevention and intervention strategies should be implemented in early childhood even pregnancy.
Differences in Clinical Outcomes of Adults Referred to a Homeless Transitional Care Program Based on Multimorbid Health Profiles: A Latent Class Analysis
Authors: Smith Colin M. , Feigal Jacob , Sloane Richard , Biederman Donna J.
Published: December 2021

Background: People experiencing homelessness face significant medical and psychiatric illness, yet few studies have characterized the effects of multimorbidity within this population. This study aimed to (a) delineate unique groups of individuals based on medical, psychiatric, and substance use disorder profiles, and (b) compare clinical outcomes across groups.

Methods: We extracted administrative data from a health system electronic health record for adults referred to the Durham Homeless Care Transitions program from July 2016 to June 2020. We used latent class analysis to estimate classes in this cohort based on clinically important medical, psychiatric and substance use disorder diagnoses and compared health care utilization, overdose, and mortality at 12 months after referral.

Results: We included 497 patients in the study and found 5 distinct groups: “low morbidity” (referent), “high comorbidity,” “high tri-morbidity,” “high alcohol use,” and “high medical illness.” All groups had greater number of admissions, longer mean duration of admissions, and more ED visits in the 12 months after referral compared to the “low morbidity” group. The “high medical illness” group had greater mortality 12 months after referral compared to the “low morbidity” group (OR, 2.53, 1.03–6.16; 95% CI, 1.03–6.16; p = 0.04). The “high comorbidity” group (OR, 5.23; 95% CI, 1.57–17.39; p < 0.007) and “high tri-morbidity” group (OR, 4.20; 95% CI, 1.26–14.01; p < 0.02) had greater 12-month drug overdose risk after referral compared to the referent group.

Conclusions: These data suggest that distinct groups of people experiencing homelessness are affected differently by comorbidities, thus health care programs for this population should address their risk factors accordingly.
Listen With Your Wrists
Authors: Fletcher Mark D.
Published: December 2021

Most of us have five senses that our brains use to create a model of the world around us. We see, hear, smell, taste, and touch our way around. If one of your senses is not working properly, your brain fills in the gaps by paying more attention to the other senses. However, your other senses cannot always fill in the gaps. If your ears are not working, your eyes alone may not be able to tell your brain that an out-of-control car is screeching toward you! But what if we could help the brain fill in the gaps by purposefully sending the missing information through another sense? What if you could “hear” where a sound is through your sense of touch? This article will explain how people were able to do just that, using wristbands that converted sound into vibration.
A Multiplex Real-Time Reverse Transcription Polymerase Chain Reaction Assay With Enhanced Capacity to Detect Vesicular Stomatitis Viral Lineages of Central American Origin
Authors: Hole Kate , Nfon Charles , Rodriguez Luis L. , Velazquez-Salinas Lauro
Published: December 2021

Vesicular stomatitis virus (VSV) causes a disease in susceptible livestock that is clinically indistinguishable from foot-and-mouth disease. Rapid testing is therefore critical to identify VSV and rule out FMD. We previously developed and validated a multiplex real-time reverse transcription polymerase chain reaction assay (mRRT-PCR) for detection of both VS New Jersey virus (VSNJV) and VS Indiana virus (VSIV). However, it was subsequently apparent that this assay failed to detect some VSNJV isolates in Mexico, especially in genetic group II, lineage 2.1. In order to enhance the sensitivity of the mRRT-PCR for VSNJV, parts of the assay were redesigned and revalidated using new and improved PCR chemistries. The redesign markedly improved the assay by increasing the VSNJV detection sensitivity of lineage 2.1 and thereby allowing detection of all VSNJV clades. The new assay showed an increased capability to detect VSNJV. Specifically, the new mRRT-PCR detected VSNJV in 100% (87/87) of samples from Mexico in 2006-2007 compared to 74% for the previous mRRT-PCR. Furthermore, the analytical sensitivity of the new mRRT-PCR was enhanced for VSNJV. Importantly, the modified assay had the same sensitivity and specificity for VSIV as the previously published assay. Our results highlight the challenges the large genetic variability of VSV pose for virus detection by mRRT-PCR and show the importance of frequent re-evaluation and validation of diagnostic assays for VSV to ensure high sensitivity and specificity.
Lactate Upregulates the Expression of DNA Repair Genes, Causing Intrinsic Resistance of Cancer Cells to Cisplatin
Authors: Govoni Marzia , Rossi Valentina , Di Stefano Giuseppina , Manerba Marcella
Published: December 2021

Intrinsic or acquired drug resistance is one of the major problems compromising the success of antineoplastic treatments. Several evidences correlated some therapeutic failures with changes in cell metabolic asset and in line with these findings, hindering the glycolytic metabolism of cancer cells via lactate dehydrogenase (LDH) inhibition was found to overcome the resistance to chemotherapeutic agents. Lactate, the product of LDH reaction, was shown to be involved in epigenetic regulation of gene expression. The experiments described in this paper were aimed at highlighting a possible direct effect of lactate in modifying the response of cancer cells to a chemotherapeutic treatment. To discriminate between the effects potentially caused by glycolytic metabolism from those directly referable to lactate, we selected cancer cell lines able to grow in glucose deprived conditions and evaluated the impact of lactate on the cellular response to cisplatin-induced DNA damage. In lactate-exposed cells we observed a reduced efficacy of cisplatin, which was associated with reduced signatures of DNA damage, enhanced DNA recombination competence and increased expression of a panel of genes involved in DNA repair. The identified genes take part in mismatch and nucleotide excision repair pathways, which were found to contribute in restoring the cisplatin-induced DNA damage. The obtained results suggest that this metabolite could play a role in reducing the efficacy of antineoplastic treatments.
Molecular Cloning of Dynein Heavy Chain and the Effect of Dynein Inhibition on the Testicular Function of Portunus trituberculatus
Authors: Xiang Qiumeng , Wei Chaoguang , Gao Xinming , Chen Yiner , Tang Daojun , Zhu Junquan , Hou Congcong
Published: December 2021

Dynein is a motor protein with multiple transport functions. However, dynein’s role in crustacean testis is still unknown. We cloned the full-length cDNA of cytoplasmic dynein heavy chain (Pt-dhc) gene and its structure was analyzed. Its expression level was highest in testis. We injected the dynein inhibitor sodium orthovanadate (SOV) into the crab. The distribution of Portunus trituberculatus dynein heavy chain (Pt-DHC) in mature sperm was detected by immunofluorescence. The apoptosis of spermatids was detected using a TUNEL kit; gene expression in testis was detected by fluorescence quantitative PCR (qPCR). The expression of immune-related factors in the testis were detected by an enzyme activity kit. The results showed that the distribution of Pt-DHC was abnormal after SOV injection, indicating that the function of dynein was successfully inhibited. Apoptosis-related genes p53 and caspase-3, and antioxidant stress genes HSP70 and NOS were significantly decreased, and anti-apoptosis gene bcl-2 was significantly increased. The activities of superoxide dismutase (SOD) and alkaline phosphatase (AKP) were significantly decreased. The results showed that there was no apoptosis in testicular cells after dynein function was inhibited, but the cell function was disordered. This study laid a theoretical foundation for the further study of apoptosis in testis and the function of dynein in testis and breeding of P. trituberculatus.
Three Studies Evaluating the Potential for Lidocaine, Bupivacaine or Procaine to Reduce Pain-Related Behaviors following Ring Castration and/or Tail Docking in Lambs
Authors: Small Alison , Fetiveau Manon , Smith Robin , Colditz Ian
Published: December 2021

The use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L), and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post-treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post-procedure (p < 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10–20 min (0.05 < p < 0.01), 20–30 min (p < 0.05) and 40–50 min (0.05 < p < 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 < p < 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10–20 min (0.05 < p < 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0–10 min (0.05 < p < 0.01), and 10–40 min (p < 0.05). Benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer-lasting pain relief. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post-procedure to establish efficacy.
Assessing the Feasibility of Using Kinect 3D Images to Predict Light Lamb Carcasses Composition from Leg Volume
Authors: Silva Severiano R. , Almeida Mariana , Condotta Isabella , Arantes André , Guedes Cristina , Santos Virgínia
Published: December 2021

This study aimed to evaluate the accuracy of the leg volume obtained by the Microsoft Kinect sensor to predict the composition of light lamb carcasses. The trial was performed on carcasses of twenty-two male lambs (17.6 ± 1.8 kg, body weight). The carcasses were split into eight cuts, divided into three groups according to their commercial value: high-value, medium value, and low-value group. Linear, area, and volume of leg measurements were obtained to predict carcass and cuts composition. The leg volume was acquired by two different methodologies: 3D image reconstruction using a Microsoft Kinect sensor and Archimedes principle. The correlation between these two leg measurements was significant (r = 0.815, p < 0.01). The models to predict cuts and carcass traits that include leg Kinect 3D sensor volume are very good in predicting the weight of the medium value and leg cuts (R2 of 0.763 and 0.829, respectively). Furthermore, the model, which includes the Kinect leg volume, explained 85% of its variation for the carcass muscle. The results of this study confirm the good ability to estimate cuts and carcass traits of light lamb carcasses with leg volume obtained with the Kinect 3D sensor.
Effects of Season on Donor and Recipient Cows and Calf Performance from Birth to Weaning in Embryo Transfer Programs in the Tropics
Authors: Martínez José Francisco , Galina Carlos Salvador , Ortiz Pablo , Maquivar Martín Guillermo , Romero-Zúñiga Juan José
Published: December 2021

The aim of this study was to assess the seasonal effect of an embryo transfer program in the tropics on the donor response, recipient reproductive performance and calf growth from birth to weaning. This study included five-year records from 145 donors, 1149 embryo transfers (ET) and 609 in calves. The effect of the season (dry or wet) was evaluated at the time of embryo flushing, embryo transfer and birth of the calves. There was a seasonal effect on the yield and quality of the embryos. The number of nonfertilized and transferable good quality embryos increased in the wet season. For the recipients, the probability of pregnancy after an ET decreased by 6% for each year of the dam’s age. However, no seasonal effect was found when comparing ET calves with their control group (natural mating—NM), nevertheless, weaning weight was associated with birth body weight, treatment, sex of the calf, season at birth, year of treatment, and dam’s age. Calves born by NM had lower average daily gain (ADG), and male calves registered higher gains than females. Likewise, calves born during the rainy season had lower ADG compared with calves born during the dry season. In conclusion, this study shows that seasonal effect is more apparent in donor and calf performance than in the recipients.
Chicken Immune Cell Assay to Model Adaptive Immune Responses In Vitro
Authors: Larsberg Filip , Sprechert Maximilian , Hesse Deike , Brockmann Gudrun A. , Kreuzer-Redmer Susanne
Published: December 2021

Knowledge about the modes of action of immunomodulating compounds such as pathogens, drugs, or feed additives, e.g., probiotics, gained through controlled but animal-related in vitro systems using primary cultured peripheral blood mononuclear cells (PBMCs) will allow the development of targeted nutrition strategies. Moreover, it could contribute to the prevention of infectious diseases and the usage of antimicrobials, and further promote the health of the animals. However, to our knowledge, a protocol for the isolation of PBMCs with reduced thrombocyte count from chicken blood and subsequent cell culture over several days to assess the effects of immunomodulating compounds is not available. Therefore, we established an optimized protocol for blood sampling and immune cell isolation, culture, and phenotyping for chicken PBMCs. For blood sampling commercial Na–citrate tubes revealed the highest count of vital cells compared to commercial Li–heparin (p < 0.01) and K3EDTA (p < 0.05) tubes. Using combined dextran and ficoll density gradient separation, the thrombocyte count was significantly reduced (p < 0.01) compared to slow-speed centrifugation with subsequent ficoll. For cell culture, the supplementation of RPMI-1640 medium with 10% chicken serum resulted in the lowest relative cell count of thrombocytes compared to fetal calf serum (FCS) (p < 0.05). To validate the ability of the cell culture system to respond to stimuli, concanavalin A (conA) was used as a positive control. The optimized protocol allows the isolation and cultivation of vital PBMCs with reduced thrombocyte count from chicken blood for subsequent investigation of the modes of action of immunomodulating compounds.
Effect of Suckling Management and Ewe Concentrate Level on Methane-Related Carbon Footprint of Lamb Meat in Sardinian Dairy Sheep Farming
Authors: Battacone Gianni , Lunesu Mondina Francesca , Rassu Salvatore Pier Giacomo , Nudda Anna , Pulina Giuseppe
Published: December 2021

The aim of this study was to estimate the methane-linked carbon footprint (CF) of the suckling lamb meat of Mediterranean dairy sheep. Ninety-six Sarda dairy ewes, divided into four groups of 24 animals each, were assigned to 2 × 2 factorial design. The experiment included the suckling lamb feeding system: traditional (TS), in which lambs followed their mothers on pasture during grazing time, vs. separated (SS), in which lambs remained indoors, separated from their mothers during the grazing time. Each group was divided into high (HS) and low (LS) supplemented ewes (600 g/d vs. 200 g/d of concentrate). The estimated CH4 emission of the ewes, calculated per kg of body weight (BW) gain of the lamb during the suckling period, was then converted to CO2eq with multiplying factor of 25. The TS lambs showed lower methane-linked emissions than SS ones (p < 0.05). The sex of lambs affected their methane-linked CF, with males having lower (p < 0.05) values than females. Twins displayed much lower methane-linked CF than singles (4.56 vs. 7.30 kg of CO2eq per kg of BW gained), whereas the level of supplementation did not affect greenhouse gases (GHG) emission. Interaction displayed lower and not-different GHG emissions for both indoor- and outdoor-reared twins. In conclusion, the methane-linked CF of the suckling lamb meat can be reduced by maintaining the traditional lamb rearing system and by improving flock prolificacy.
Pan-Resistome Characterization of Uropathogenic Escherichia coli and Klebsiella pneumoniae Strains Circulating in Uganda and Kenya, Isolated from 2017–2018
Authors: Decano Arun Gonzales , Pettigrew Kerry , Sabiiti Wilber , Sloan Derek J. , Neema Stella , Bazira Joel , Kiiru John , Onyango Hellen , Asiimwe Benon , Holden Matthew T. G.
Published: December 2021

Urinary tract infection (UTI) develops after a pathogen adheres to the inner lining of the urinary tract. Cases of UTIs are predominantly caused by several Gram-negative bacteria and account for high morbidity in the clinical and community settings. Of greater concern are the strains carrying antimicrobial resistance (AMR)-conferring genes. The gravity of a UTI is also determined by a spectrum of other virulence factors. This study represents a pilot project to investigate the burden of AMR among uropathogens in East Africa. We examined bacterial samples isolated in 2017–2018 from in- and out-patients in Kenya (KY) and Uganda (UG) that presented with clinical symptoms of UTI. We reconstructed the evolutionary history of the strains, investigated their population structure, and performed comparative analysis their pangenome contents. We found 55 Escherichia coli and 19 Klebsiella pneumoniae strains confirmed uropathogenic following screening for the prevalence of UTI virulence genes including fimH, iutA, feoA/B/C, mrkD, and foc. We identified 18 different sequence types in E. coli population while all K. pneumoniae strains belong to ST11. The most prevalent E. coli sequence types were ST131 (26%), ST335/1193 (10%), and ST10 (6%). Diverse plasmid types were observed in both collections such as Incompatibility (IncF/IncH/IncQ1/IncX4) and Col groups. Pangenome analysis of each set revealed a total of 2862 and 3464 genes comprised the core genome of E. coli and K. pneumoniae population, respectively. Among these are acquired AMR determinants including fluoroquinolone resistance-conferring genes aac(3)-Ib-cr and other significant genes: aad, tet, sul1, sul2, and cat, which are associated with aminoglycoside, tetracycline, sulfonamide, and chloramphenicol resistance, respectively. Accessory genomes of both species collections were detected several β-lactamase genes, blaCTX-M, blaTEM and blaOXA, or blaNDM. Overall, 93% are multi-drug resistant in the E. coli collection while 100% of the K. pneumoniae strains contained genes that are associated with resistance to three or more antibiotic classes. Our findings illustrate the abundant acquired resistome and virulome repertoire in uropathogenic E. coli and K. pneumoniae, which are mainly disseminated via clonal and horizontal transfer, circulating in the East African region. We further demonstrate here that routine genomic surveillance is necessary for high-resolution bacterial epidemiology of these important AMR pathogens.
Matcha Green Tea Exhibits Bactericidal Activity against Streptococcus pneumoniae and Inhibits Functional Pneumolysin
Authors: Sasagawa Karin , Domon Hisanori , Sakagami Rina , Hirayama Satoru , Maekawa Tomoki , Isono Toshihito , Hiyoshi Takumi , Tamura Hikaru , Takizawa Fumio , Fukushima Yoichi , Tabeta Koichi , Terao Yutaka
Published: December 2021

Streptococcus pneumoniae is a causative pathogen of several human infectious diseases including community-acquired pneumonia. Pneumolysin (PLY), a pore-forming toxin, plays an important role in the pathogenesis of pneumococcal pneumonia. In recent years, the use of traditional natural substances for prevention has drawn attention because of the increasing antibacterial drug resistance of S. pneumoniae. According to some studies, green tea exhibits antibacterial and antitoxin activities. The polyphenols, namely the catechins epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC) are largely responsible for these activities. Although matcha green tea provides more polyphenols than green tea infusions, its relationship with pneumococcal pneumonia remains unclear. In this study, we found that treatment with 20 mg/mL matcha supernatant exhibited significant antibacterial activity against S. pneumoniae regardless of antimicrobial resistance. In addition, the matcha supernatant suppressed PLY-mediated hemolysis and cytolysis by inhibiting PLY oligomerization. Moreover, the matcha supernatant and catechins inhibited PLY-mediated neutrophil death and the release of neutrophil elastase. These findings suggest that matcha green tea reduces the virulence of S. pneumoniae in vitro and may be a promising agent for the treatment of pneumococcal infections.
Factors Associated with Inadequate Intravenous Colistin Dosages: Post Hoc Analysis of a Multicenter, Cross-Sectional Study
Authors: Giacobbe Daniele Roberto , Mirabella Michele , Rinaldi Matteo , Losito Angela Raffaella , Raffaelli Francesca , Del Puente Filippo , Saffioti Carolina , Mikulska Malgorzata , Giannella Maddalena , Viale Pierluigi , Tumbarello Mario , Bassetti Matteo ,   on behalf of SITA GIOVANI (Young Investigators Group of the Società Italiana Terapia Antinfettiva) and the COLI-CROSS Study Group
Published: December 2021

Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48–10.74 for stage 1, OR 4.44 with 95% CI 1.17–16.93 for stage 2, OR 9.41 with 95% CI 1.59–55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16–0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.
A Mitochondria-Penetrating Peptide Exerts Potent Anti-Plasmodium Activity and Localizes at Parasites’ Mitochondria
Authors: Somsri Sangdao , Mungthin Mathirut , Klubthawee Natthaporn , Adisakwattana Poom , Hanpithakpong Warunee , Aunpad Ratchaneewan
Published: December 2021

Mitochondria are considered a novel drug target as they play a key role in energy production and programmed cell death of eukaryotic cells. The mitochondria of malaria parasites differ from those of their vertebrate hosts, contributing to the drug selectivity and the development of antimalarial drugs. (Fxr)3, a mitochondria-penetrating peptide or MPP, entered malaria-infected red cells without disrupting the membrane and subsequently killed the blood stage of P. falciparum parasites. The effects were more potent on the late stages than on the younger stages. Confocal microscopy showed that the (Fxr)3 intensely localized at the parasite mitochondria. (Fxr)3 highly affected both the lab-strain, chloroquine-resistant K1, and freshly isolated malaria parasites. (Fxr)3 (1 ng/mL to 10 μg/mL) was rarely toxic towards various mammalian cells, i.e., mouse fibroblasts (L929), human leukocytes and erythrocytes. At a thousand times higher concentration (100 μg/mL) than that of the antimalarial activity, cytotoxicity and hemolytic activity of (Fxr)3 were observed. Compared with the known antimalarial drug, atovaquone, (Fxr)3 exhibited more rapid killing activity. This is the first report on antimalarial activity of (Fxr)3, showing localization at parasites’ mitochondria.
Umuhengerin Neuroprotective Effects in Streptozotocin-Induced Alzheimer’s Disease Mouse Model via Targeting Nrf2 and NF-Kβ Signaling Cascades
Authors: Sirwi Alaa , El Sayed Nesrine S. , Abdallah Hossam M. , Ibrahim Sabrin R. M. , Mohamed Gamal A. , El-Halawany Ali M. , Safo Martin K. , Abdel Rasheed Nora O.
Published: December 2021

Alzheimer’s disease (AD) is the most common type of dementia and is characterized by advanced cognitive deterioration, deposition of Aβ (amyloid-beta), and the formation of neurofibrillary tangles. Administration of streptozotocin (STZ) via the intracerebroventricular (ICV) route is a reliable model resembling sporadic AD (SAD) associated neuropathological changes. The present study was undertaken to explore the neuroprotective effects of the methoxy flavonoid, umuhengerin, in an STZ-induced SAD mouse model as a potential therapy for AD. Mice were injected once with STZ (3 mg/kg, ICV), followed by daily administration of umuhengerin (orally, 30 mg/kg) or the positive control donepezil (orally, 2.5 mg/kg) for 21 days. The pharmacological activity of umuhengerin was assessed through estimation of oxidative stress and inflammatory markers via mouse ELISA kits, Western blot analysis, and brain histopathological examination. Morris water maze test was also conducted to investigate umuhengerin-induced cognitive enhancement. The results showed that umuhengerin attenuated STZ-produced neuroinflammation and oxidative stress with a notable rise in the expression of Nrf2 (nuclear factor erythroid 2-related factor 2). In contrast, it downregulated Keap-1 (Kelch-like ECH associated protein 1), as well as elevated brain contents of GSH (reduced glutathione) and HO-1 (heme oxygenase-1). STZ-injected animals receiving umuhengerin showed marked downregulation of the nuclear factor kappa beta (NF-Kβp65) and noticeable increment in the expression of its inhibitor kappa beta alpha protein (IKβα), as well as prominent reduction in malondialdehyde (MDA), H2O2 (hydrogen peroxide), and TNF-α (tumor-necrosis factor-alpha) contents. Β-secretase protein expression and acetylcholinesterase (AchE) activity were also diminished upon umuhengerin injection in the STZ group, leading to decreased Aβ formation and cognitive improvement, respectively. In conclusion, umuhengerin neuroprotective effects were comparable to the standard drug donepezil; thus, it could be an alternative approach for AD management.
Free Radicals and Neonatal Brain Injury: From Underlying Pathophysiology to Antioxidant Treatment Perspectives
Authors: Martini Silvia , Castellini Laura , Parladori Roberta , Paoletti Vittoria , Aceti Arianna , Corvaglia Luigi
Published: December 2021

Free radicals play a role of paramount importance in the development of neonatal brain injury. Depending on the pathophysiological mechanisms underlying free radical overproduction and upon specific neonatal characteristics, such as the GA-dependent maturation of antioxidant defenses and of cerebrovascular autoregulation, different profiles of injury have been identified. The growing evidence on the detrimental effects of free radicals on the brain tissue has led to discover not only potential biomarkers for oxidative damage, but also possible neuroprotective therapeutic approaches targeting oxidative stress. While a more extensive validation of free radical biomarkers is required before considering their use in routine neonatal practice, two important treatments endowed with antioxidant properties, such as therapeutic hypothermia and magnesium sulfate, have become part of the standard of care to reduce the risk of neonatal brain injury, and other promising therapeutic strategies are being tested in clinical trials. The implementation of currently available evidence is crucial to optimize neonatal neuroprotection and to develop individualized diagnostic and therapeutic approaches addressing oxidative brain injury, with the final aim of improving the neurological outcome of this population.
Biochar and Chitosan Regulate Antioxidant Defense and Methylglyoxal Detoxification Systems and Enhance Salt Tolerance in Jute (Corchorus olitorius L.)
Authors: Hasanuzzaman Mirza , Raihan Md. Rakib Hossain , Khojah Ebtihal , Samra Bassem N. , Fujita Masayuki , Nahar Kamrun
Published: December 2021

We investigated the role of biochar and chitosan in mitigating salt stress in jute (Corchorus olitorius L. cv. O-9897) by exposing twenty-day-old seedlings to three doses of salt (50, 100, and 150 mM NaCl). Biochar was pre-mixed with the soil at 2.0 g kg−1 soil, and chitosan-100 was applied through irrigation at 100 mg L−1. Exposure to salt stress notably increased lipid peroxidation, hydrogen peroxide content, superoxide radical levels, electrolyte leakage, lipoxygenase activity, and methylglyoxal content, indicating oxidative damage in the jute plants. Consequently, the salt-stressed plants showed reduced growth, biomass accumulation, and disrupted water balance. A profound increase in proline content was observed in response to salt stress. Biochar and chitosan supplementation significantly mitigated the deleterious effects of salt stress in jute by stimulating both non-enzymatic (e.g., ascorbate and glutathione) and enzymatic (e.g., ascorbate peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, glutathione reductase superoxide dismutase, catalase, peroxidase, glutathione S-transferase, glutathione peroxidase) antioxidant systems and enhancing glyoxalase enzyme activities (glyoxalase I and glyoxalase II) to ameliorate reactive oxygen species damage and methylglyoxal toxicity, respectively. Biochar and chitosan supplementation increased oxidative stress tolerance and improved the growth and physiology of salt-affected jute plants, while also significantly reducing Na+ accumulation and ionic toxicity and decreasing the Na+/K+ ratio. These findings support a protective role of biochar and chitosan against salt-induced damage in jute plants.
The Protective Effect of Carotenoids, Polyphenols, and Estradiol on Dermal Fibroblasts under Oxidative Stress
Authors: Darawsha Aya , Trachtenberg Aviram , Levy Joseph , Sharoni Yoav
Published: December 2021

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, which leads to collagen degradation. Several studies have shown the protective role of estrogens and a diet rich in fruits and vegetables on skin physiology. Previous studies have shown that dietary carotenoids and polyphenols activate the cell’s antioxidant defense system by increasing antioxidant response element/Nrf2 (ARE/Nrf2) transcriptional activity and reducing the inflammatory response. The aim of the current study was to examine the protective effect of such dietary-derived compounds and estradiol on dermal fibroblasts under oxidative stress induced by H2O2. Human dermal fibroblasts were used to study the effect of H2O2 on cell number and apoptosis, MMP-1, and pro-collagen secretion as markers of skin damage. Treatment of cells with H2O2 led to cell death, increased secretion of MMP-1, and decreased pro-collagen secretion. Pre-treatment with tomato and rosemary extracts, and with estradiol, reversed the effects of the oxidative stress. This was associated with a reduction in intracellular ROS levels, probably through the measured increased activity of ARE/Nrf2. Conclusions: This study indicates that carotenoids, polyphenols, and estradiol protect dermal fibroblasts from oxidative stress-induced damage through a reduction in ROS levels.
Linking the Dynamic Changes in the In Vitro Antioxidant Activity of Carob Kibbles upon Roasting to the Chemical and Structural Changes Revealed by FTIR Spectroscopy
Authors: Grigoriou Anna Marina , Pinakoulaki Eftychia
Published: December 2021

Recent studies have highlighted the potential of utilizing carob kibbles as a bioactive-rich food ingredient associated with substantial health benefits. Roasting is a key process in enhancing the sensory characteristics of carob kibbles, also affecting the bioactive polyphenols and leading to the formation of Maillard reaction products (MRPs), including the polymeric melanoidins that are associated with a high antioxidant potential but remain unexplored in carob. In this work, we employed for the first time attenuated total reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy to probe the dynamic chemical and structural changes upon the roasting of carob kibbles, along with the investigation of the in vitro antioxidant activity through the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and the determination of the total polyphenolic, proanthocyanidin, gallic acid and cinnamic acid contents. Roasting significantly enhanced the in vitro antioxidant activity of the polyphenolic carob extracts, with different rates at distinct roasting temperatures. The ATR-FTIR analysis enabled the identification of the changes in the structural features of polyphenolic compounds that were related to the improved antioxidant activity upon roasting. Furthermore, the detection of characteristic signatures for the polymeric melanoidins in the infrared (IR) fingerprint region provided the first evidence for the formation and structural properties of these complex, diverse compounds in roasted carob kibbles.