bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Helicopters Solve the Transport Dilemma for Patients With Symptoms of Large-Vessel Occlusion Stroke in Intermediate Density Areas? A Simulation Model Based on Real Life Data
Authors: Behrndtz Anne , Beare Richard , Iievlieva Svitlana , Andersen Grethe , Mainz Jeppe , Gude Martin , Ma Henry , Srikanth Velandai , Simonsen Claus Z. , Phan Thanh
Published: April 2022

Background

This modeling study aimed to determine if helicopters may optimize the transportation of patients with symptoms of large vessel stroke in “intermediate density” areas, such as Denmark, by bringing them directly to the comprehensive stroke center.

Methods

We estimated the time for the treatment of patients requiring endovascular therapy or intravenous thrombolysis under four configurations: “drip and ship” with and without helicopter and “bypass” with and without helicopter. Time delays, stroke numbers per municipality, and helicopter dispatches for four helicopter bases from 2019 were obtained from the Danish Stroke and Helicopter Registries. Discrete event simulation (DES) was used to estimate the capacity of the helicopter fleet to meet patient transport requests, given the number of stroke codes per municipality.

Results

The median onset-to-needle time at the comprehensive stroke center (CSC) for the bypass model with the helicopter was 115 min [interquartile range (IQR): 108, 124]; the median onset-to-groin time was 157 min (IQR: 150, 166). The median onset-to-needle time at the primary stroke center (PSC) by ground transport was 112 min (IQR: 101, 125) and the median onset-to-groin time when primary transport to the PSC was prioritized was 234 min (IQR: 209, 261).

A linear correlation between travel time by ground and the number of patients transported by helicopter (rho = 0.69, p < 0.001) indicated that helicopters are being used to transport more remote patients. DES demonstrated that an increase in helicopter capture zone by 20 min increased the number of rejected patients by only 5%.

Conclusions

Our model calculations suggest that using helicopters to transport patients with stroke directly to the CSC in intermediate density areas markedly reduce onset-to-groin time without affecting time to thrombolysis. In this setting, helicopter capacity is not challenged by increasing the capture zone.
Plasma Inflammatory Markers and Ventriculostomy-Related Infection in Patients With Hemorrhagic Stroke: A Retrospective and Descriptive Study
Authors: Bögli Stefan Yu , Wang Sophie S. , Pietrzko Elisabeth , Müller Achim , Eisele Amanda , Keller Emanuela , Brandi Giovanna
Published: April 2022

Background

Diagnosis of ventriculostomy-related infection (VRI) remains difficult due to the various existing definitions. In patients with hemorrhagic stroke, its diagnosis might be further complicated by the presence of intraventricular blood. Furthermore, hemorrhagic stroke per se may cause symptoms compatible with VRI. This study aimed to evaluate the benefit of plasma inflammatory markers for the diagnosis of VRI and its differentiation from patients with non-cerebral infection and patients without infection in a cohort of patients with hemorrhagic stroke.

Methods

A total of 329 patients with hemorrhagic stroke and an external ventricular drain (EVD) in situ were admitted to the Neurocritical Care Unit, University Hospital Zurich over a period of 6 years. Of those patients, 187 with subarachnoid hemorrhage and 76 with spontaneous intracerebral hemorrhage were included. Patients with VRI were compared to patients without any infection and to patients with non-cerebral infection, with regards to their clinical characteristics, as well as their inflammatory plasma and cerebrospinal fluid (CSF) markers. For the analysis, peak values were considered.

Results

The VRI was diagnosed in 36% of patients with subarachnoid and in 17% of patients with intracerebral hemorrhage. The VRI was diagnosed on an average day 9±6.2 after EVD insertion, one day after the white blood cell count (WBC) peaked in CSF (8 ± 6.3). Plasma inflammatory markers (WBC, C-reactive protein “CRP” and procalcitonin “PCT”) did not differ among patients with VRI compared to patients without infection. The CRP and PCT, however, were higher in patients with non-cerebral infection than in patients with VRI. The WBC in CSF was generally higher in patients with VRI compared to both patients without any infection and patients with non-cerebral infection.

Conclusions

No differences in plasma inflammatory markers could be found between patients with VRI and patients without any infection. Conversely, CRP/PCT were higher in patients with non-cerebral infection than in patients with VRI. Altogether, CRP, PCT, and WBC are not suitable parameters for VRI diagnosis in neurocritical care unit patients.
Different Hemodynamic Characteristics and Resulting in Different Risks of Rupture Between Wide-Neck and Narrow-Neck Aneurysms
Authors: Wei Heng , Tian Qi , Yao Kun , Wang Jianfeng , He Peibang , Guo Yujia , Han Wenrui , Gao Wenhong , Li Mingchang
Published: April 2022

Objective

This study aimed to determine the ruptured rate and hemodynamic difference between wide-neck aneurysms (WNAs) and narrow-neck aneurysms (NNAs), as well as the hemodynamic parameters of risk factors for aneurysm rupture.

Methods

A total of 121 cases of intracranial aneurysms (IAs) were studied retrospectively between January 2019 and April 2021 at Renmin Hospital of Wuhan University. Intracranial aneurysms were classified into four types: ruptured wide-neck aneurysms (RWNAs), unruptured wide-neck aneurysms (UWNAs), ruptured narrow-neck aneurysms (RNNAs), and unruptured narrow-neck aneurysms (UNNAs). The Chi-square test was used to compare differences in rupture ratios. The clinical characteristics and hemodynamics were analyzed statistically to reveal the rupture risk factors. Moreover, significant parameters were subjected to binary logistic regression analysis to identify the independent predictive factors. The receiver operating characteristic (ROC) curve was performed to obtain cutoff values.

Results

WNAs ruptured more frequently than NNAs (P = 0.033). Ruptured intracranial aneurysms (RIAs) were characterized by significantly higher intra-aneurysmal pressure (IAP), wall shear stress (WSS), wall shear stress gradient (WSSG), and lower normalized wall shear stress (NWSS) than unruptured intracranial aneurysms (UIAs). RWNAs had higher IAP, WSS, and lower NWSS than UWNAs (P < 0.05). RNNAs had higher IAP, Streamwise WSSG and lower NWSS compared to UNNAs (P < 0.05). Binary logistic regression revealed that IAP and WSS were independent predictive risk factors for WNAs rupture, with cut-off values of 405.5 and 6.66 Pa, respectively. Also, IAP was an independent predictive risk factor for NNA rupture, with a cut-off value of 255.3 Pa.

Conclusions

Wide-neck aneurysms and narrow-neck aneurysms have diverse hemodynamics, which prompts a higher rupture ratio for WNAs. IAP could characterize the rupture risk in both WNAs and NNAs independently, but WSS could only predict the rupture risk in WNAs. This research might assist neurosurgeons with fostering a more sensible strategy for the treatment of IAs.
Scoliosis Orthopedic Surgery Combined With Nusinersen Intrathecal Injection Significantly Improved the Outcome of Spinal Muscular Atrophy Patient: A Case Report
Authors: Xu Beiyu , Wei Cuijie , Hu Xiao , Li Wenzhu , Huang Zhen , Que Chengli , Qiu Jianxing , Li Chunde , Xiong Hui
Published: April 2022

Background

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by pathogenic variation of the survival motor neuron (SMN) 1 gene. Symptoms of SMA include progressive limb muscle weakness, atrophy, and severe scoliosis. Nusinersen is an antisense oligonucleotide that can enhance the production of the SMN protein. Here, we report a case with scoliosis who received orthopedic surgery combined with Nusinersen intrathecal injections.

Case Presentation

Scoliosis orthopedic surgery followed by Nusinersen intrathecal injections was given to a 16-year-old girl who had thoracic and lumbar scoliosis and type 3 SMA. Surgery was performed for T3-S2 posterolateral fusion (PLF), with a channel left on the vertebral laminae of L3-L4. The balance of the spine and pelvis was significantly improved and the height increased by 9 cm. Lumbar puncture was conducted with local anesthesia under ultrasound and CT guidance through the laminae channel and Nusinersen was successfully injected. Comparing the two approaches, real-time ultrasound guidance for intrathecal Nusinersen injections after spinal surgery is preferred, however, CT guidance is an alternative if the initial puncture procedure is difficult. After the aforementioned multidisciplinary treatment, a good outcome was achieved, as demonstrated by a 2-point increase in RULM and MFM32 scores 2 months later.

Conclusion

Scoliosis orthopedic surgery combined with Nusinersen intrathecal injection is an effective treatment for SMA patients with scoliosis.
Corticosteroid Treatment-Resistance in Myasthenia Gravis
Authors: Kaminski Henry J. , Denk Jordan
Published: April 2022

Chronic, high-dose, oral prednisone has been the mainstay of myasthenia gravis treatment for decades and has proven to be highly beneficial in many, toxic in some way to all, and not effective in a significant minority. No patient characteristics or biomarkers are predictive of treatment response leading to many patients suffering adverse effects with no benefit. Presently, measurements of treatment response, whether taken from clinician or patient perspective, are appreciated to be limited by lack of good correlation, which then complicates correlation to biological measures. Treatment response may be limited because disease mechanisms are not influenced by corticosteroids, limits on dosage because of adverse effects, or individual differences in corticosteroids. This review evaluates potential mechanisms that underlie lack of response to glucocorticoids in patients with myasthenia gravis.
Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation
Authors: Dell'Italia John , Sanguinetti Joseph L. , Monti Martin M. , Bystritsky Alexander , Reggente Nicco
Published: April 2022

Low intensity focused ultrasound (LIFU) has been gaining traction as a non-invasive neuromodulation technology due to its superior spatial specificity relative to transcranial electrical/magnetic stimulation. Despite a growing literature of LIFU-induced behavioral modifications, the mechanisms of action supporting LIFU's parameter-dependent excitatory and suppressive effects are not fully understood. This review provides a comprehensive introduction to the underlying mechanics of both acoustic energy and neuronal membranes, defining the primary variables for a subsequent review of the field's proposed mechanisms supporting LIFU's neuromodulatory effects. An exhaustive review of the empirical literature was also conducted and studies were grouped based on the sonication parameters used and behavioral effects observed, with the goal of linking empirical findings to the proposed theoretical mechanisms and evaluating which model best fits the existing data. A neuronal intramembrane cavitation excitation model, which accounts for differential effects as a function of cell-type, emerged as a possible explanation for the range of excitatory effects found in the literature. The suppressive and other findings need additional theoretical mechanisms and these theoretical mechanisms need to have established relationships to sonication parameters.
Target-Related Alpha Attenuation in a Brain-Computer Interface Rapid Serial Visual Presentation Calibration
Authors: Klee Daniel , Memmott Tab , Smedemark-Margulies Niklas , Celik Basak , Erdogmus Deniz , Oken Barry S.
Published: April 2022

This study evaluated the feasibility of using occipitoparietal alpha activity to drive target/non-target classification in a brain-computer interface (BCI) for communication. EEG data were collected from 12 participants who completed BCI Rapid Serial Visual Presentation (RSVP) calibrations at two different presentation rates: 1 and 4 Hz. Attention-related changes in posterior alpha activity were compared to two event-related potentials (ERPs): N200 and P300. Machine learning approaches evaluated target/non-target classification accuracy using alpha activity. Results indicated significant alpha attenuation following target letters at both 1 and 4 Hz presentation rates, though this effect was significantly reduced in the 4 Hz condition. Target-related alpha attenuation was not correlated with coincident N200 or P300 target effects. Classification using posterior alpha activity was above chance and benefitted from individualized tuning procedures. These findings suggest that target-related posterior alpha attenuation is detectable in a BCI RSVP calibration and that this signal could be leveraged in machine learning algorithms used for RSVP or comparable attention-based BCI paradigms.
Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes
Authors: Leung Ryan F. , George Ankita M. , Roussel Enola M. , Faux Maree C. , Wigle Jeffrey T. , Eisenstat David D.
Published: April 2022

Forebrain development in vertebrates is regulated by transcription factors encoded by homeobox, bHLH and forkhead gene families throughout the progressive and overlapping stages of neural induction and patterning, regional specification and generation of neurons and glia from central nervous system (CNS) progenitor cells. Moreover, cell fate decisions, differentiation and migration of these committed CNS progenitors are controlled by the gene regulatory networks that are regulated by various homeodomain-containing transcription factors, including but not limited to those of thePax(paired),Nkx,Otx(orthodenticle),Gsx/Gsh(genetic screened), andDlx(distal-less) homeobox gene families. This comprehensive review outlines the integral role of key homeobox transcription factors and their target genes on forebrain development, focused primarily on the telencephalon. Furthermore, links of these transcription factors to human diseases, such as neurodevelopmental disorders and brain tumors are provided.
Effects of Acute Hypoxia on Early Visual and Auditory Evoked Potentials
Authors: Blacker Kara J. , McHail Daniel G.
Published: April 2022

Reduced levels of environmental oxygen lead to hypoxic hypoxia and are a primary threat in tactical aviation. The visual system is particularly vulnerable to hypoxia, and its impairment can severely impact performance. The auditory system is relatively spared by hypoxia, although which stages of auditory processing are most impacted by hypoxia remains unclear. Previous work has used electroencephalography (EEG) to assess neural markers of cognitive processing for visual and auditory stimuli and found that these markers were sensitive to a normobaric hypoxic exposure. In the current study, we assessed whether early sensory evoked potentials, that precede cognitive activity, are also impaired by normobaric hypoxia. In a within-subjects design, we compared visual (P100) and auditory evoked potentials (sensory gating for the P50, N100, and P200) in 34 healthy adults during normoxic (21% O2) and two separate hypoxic (9.7% O2) exposures. Self-reported symptoms of hypoxia were also assessed using the Hypoxia Symptom Questionnaire (HSQ). We found that P100 mean amplitude was not reduced under hypoxic compared to normoxic conditions, suggesting no statistically significant impairment of early visual processing. The sensory gating ratio for auditory stimuli was intact for paired responses of the P50 and N100. However, the P200 sensory gating ratio was attenuated under hypoxic compared to normoxic conditions, suggesting disruption of the auditory system specific to the level of allocating attention that follows basic auditory processing. Exploratory analyses of HSQ scores identified a robust effect of hypoxia. However, consistency of symptoms reported between the two hypoxia exposures exhibited high intra-individual variability, which may have implications for the theory that individuals have a consistent hypoxia signature or reliable constellation of responses to hypoxia. These findings suggest that early sensory processing is not impaired during hypoxia, but for the auditory system there is impairment at the level of attentional processing. Given the previous findings of impaired visual performance under hypoxia, these results suggest that this impairment does not stem from early visual processing deficits in visual cortex. Together these findings help focus the search on when and where hypoxia-induced deficits occur and may guide the development of countermeasures for hypoxia in tactical aviation.
Adherence to a priori-Defined Diet Quality Indices Throughout the Early Disease Course Is Associated With Survival in Head and Neck Cancer Survivors: An Application Involving Marginal Structural Models
Authors: Maino Vieytes Christian A. , Rodriguez-Zas Sandra L. , Madak-Erdogan Zeynep , Smith Rebecca L. , Zarins Katie R. , Wolf Gregory T. , Rozek Laura S. , Mondul Alison M. , Arthur Anna E.
Published: April 2022

No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HRQ5–Q1:0.07, 95% CI:0.01–0.43, ptrend:0.04), and cancer-specific mortality (HRQ5–Q1:0.15, 95% CI:0.02–1.07, ptrend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.
Genetically Predicted Circulating Concentrations of Micronutrients and COVID-19 Susceptibility and Severity: A Mendelian Randomization Study
Authors: Daniel Neil , Bouras Emmanouil , Tsilidis Konstantinos K. , Hughes David J.
Published: April 2022

Background

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which since 2019 has caused over 5 million deaths to date. The pathogenicity of the virus is highly variable ranging from asymptomatic to fatal. Evidence from experimental and observational studies suggests that circulating micronutrients may affect COVID-19 outcomes.

Objectives

To complement and inform observational studies, we investigated the associations of genetically predicted concentrations of 12 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, vitamin D, and zinc) with SARS-CoV-2 infection risk and COVID-19 severity using Mendelian randomization (MR).

Methods

Two-sample MR was conducted using 87,870 individuals of European descent with a COVID-19 diagnosis and 2,210,804 controls from the COVID-19 host genetics initiative. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results

Compared to the general population, nominally significant associations were noted for higher genetically predicted vitamin B-6 (Odds ratio per standard deviation [ORSD]: 1.06; 95% confidence interval [CI]: 1.00, 1.13; p-value = 0.036) and lower magnesium concentrations (ORSD: 0.33; 95%CI: 0.11, 0.96; P = 0.042) with COVID-19 infection risk. However, the association for magnesium was not consistent in some sensitivity analyses, and sensitivity analyses could not be performed for vitamin B-6 as only two genetic instruments were available. Genetically predicted levels of calcium, folate, β-carotene, copper, iron, vitamin B-12, vitamin D, selenium, phosphorus, or zinc were not associated with the outcomes from COVID-19 disease.

Conclusion

These results, though based only on genetically predicated circulating micronutrient concentrations, provide scant evidence for possible associations of micronutrients with COVID-19 outcomes.
A Body Shape Index and Body Roundness Index in Relation to Anxiety, Depression, and Psychological Distress in Adults
Authors: Lotfi Keyhan , Hassanzadeh Keshteli Ammar , Saneei Parvane , Afshar Hamid , Esmaillzadeh Ahmad , Adibi Peyman
Published: April 2022

Background

Despite the large evidence on the association between obesity and psychological disorders, studies investigating new anthropometric indices in relation to mental health are limited. We aimed to explore the association between A Body Shape Index (ABSI) and Body Roundness Index (BRI) and common psychological disorders (anxiety, depression, and psychological distress) among Iranian adults.

Methods

In this cross-sectional investigation, anthropometric measures of 3213 Iranian adults were gathered using a validated self-reported questionnaire. ABSI and BRI values of participants were calculated through pre-defined formulas. General Health Questionnaire (GHQ) and Hospital Anxiety and Depression Scale (HADS) validated for Iranians were used to assess psychological distress, anxiety, and depression.

Results

Mean age of participants was 36.6 ± 7.73, and 62.8% of them were women. ABSI and BRI were higher in subjects with anxiety and psychological distress. Also, depressed participants had higher BRI. After considering potential confounders, individuals in the last tertile of ABSI, compared to the first tertile, had higher odds of anxiety (OR: 1.41, 95%CI: 1.04, 1.93) and psychological distress (OR: 1.39, 95%CI: 1.09, 1.79). Also, a marginal association was found between the highest category of ABSI and depression (OR: 1.27; 95%CI: 1.00, 1.61). In the sex-stratified analysis, ABSI was positively related to odds of anxiety (OR: 1.58; 95%CI; 1.12, 2.22), depression (OR: 1.40; 95%CI; 1.07, 1.84), and psychological distress (OR: 1.51; 95%CI; 1.13, 2.01) among women, but not men. We failed to find any significant association between BRI and depression, anxiety and psychological distress.

Conclusion

We found that ABSI was associated with anxiety, depression and psychological distress among females, but not males. However, we did not find a significant relation between BRI and the outcomes. Further prospective studies are required to confirm our findings.
Predictors of Major Dietary Patterns Among Pregnant Women Attending Public Health Facilities in Eastern Ethiopia: A New Epidemiological Approach
Authors: Oumer Abdu , Abraham Mihret , Nuri Aliya
Published: April 2022

Background

Dietary pattern analysis is a robust statistical procedure that efficiently characterize the dietary intakes of individuals. However, there is a lack of robust dietary intake evidence beyond nutrient intake in Ethiopia. This study was to answer, what are the major dietary consumption patterns and its predictors among pregnant women in Ethiopia.

Methods

A facility-based survey among 380 randomly selected pregnant women using a contextualized food frequency questionnaire (FFQ) over 1 month recall was used. The frequency of food consumption was standardized to daily frequency equivalents, and a sequential exploratory factor analysis was used to derive major dietary patterns. A multivariable ordinary logistic regression model was fitted with all its assumptions.

Results

Three major dietary patterns (“fruits and animal-source foods,” “cereals, tubers, and sweet foods,” “legumes and vegetables”), explaining 65% of the total variation were identified. Women snacks (AOR = 1.93; 1.23–2.75), without food aversion (AOR = 1.59; 1.08–2.35), non-fasting (AOR = 0.75; 1.12–2.12), and receiving nutritional counseling (AOR = 1.96; 1.25–3.07) were significantly positively associated with a higher tercile of fruits and animal-source food consumption. Non-working mothers (AOR = 1.8;1.23–2.76), chronic disease (AOR = 1.88; 1.14–3.09), or received nutritional counseling (AOR = 1.33; 0.88–2.01), were fasting (AOR = 1.33;0.88–2.01), and no food cravings (AOR = 4.27;2.67–6.84), and aversion (AOR = 1.60;1.04–2.44) had significantly higher odds of consuming cereals, tubers, and sweet foods. Literacy (AOR = 1.87; 1.14–3.09), urban residence (AOR = 2.10; 1.10–3.93), low socioeconomic class (AOR = 2.68; 1.30–5.23), and skipping meals (AOR = 1.73; 1.15–2.62) were associated with higher odds of legume and vegetable consumption.

Conclusion

Socioeconomic class, literacy, occupation, getting nutritional counseling, habits of food craving, food aversion, and fasting can predict a woman’s dietary pattern.
Crude Polysaccharide Extracted From Moringa oleifera Leaves Prevents Obesity in Association With Modulating Gut Microbiota in High-Fat Diet-Fed Mice
Authors: Li Lingfei , Ma Li , Wen Yanlong , Xie Jing , Yan Liang , Ji Aibing , Zeng Yin , Tian Yang , Sheng Jun
Published: April 2022

Moringa oleifera is a commonly used plant with high nutritional and medicinal values. M. oleifera leaves are considered a new food resource in China. However, the biological activities of M. oleifera polysaccharides (MOP) in regulating gut microbiota and alleviating obesity remain obscure. In the present study, we prepared the MOP and evaluated its effects on obesity and gut microbiota in high-fat diet (HFD)-induced C57BL/6J mice. The experimental mice were supplemented with a normal chow diet (NCD group), a high-fat diet (HFD group), and HFD along with MOP at a different dose of 100, 200, and 400 mg/kg/d, respectively. Physiological, histological, biochemical parameters, genes related to lipid metabolism, and gut microbiota composition were compared among five experimental groups. The results showed that MOP supplementation effectively prevented weight gain and lipid accumulation induced by HFD, ameliorated blood lipid levels and insulin resistance, alleviated the secretion of pro-inflammatory cytokines, and regulated the expression of genes related to lipid metabolism and bile acid metabolism. In addition, MOP positively reshaped the gut microbiota composition, significantly increasing the abundance of Bacteroides, norank_f_Ruminococcaceae, and Oscillibacter, while decreasing the relative abundance of Blautia, Alistipes, and Tyzzerella, which are closely associated with obesity. These results demonstrated that MOP supplementation has a protective effect against HFD-induced obesity in mice, which was associated with reshaping the gut microbiota. To the best of our knowledge, this is the first report on the potential of MOP to prevent obesity and modulating gut microbiota, which suggests that MOP can be used as a potential prebiotic.
DIet and Health From reGIstered Trials on ClinicalTrials.gov: The DIGIT Study
Authors: Dinu Monica , Pagliai Giuditta , Del Bo' Cristian , Porrini Marisa , Riso Patrizia , Serafini Mauro , Sofi Francesco , Martini Daniela , Angelino Donato
Published: April 2022

Background

Clinical trial registration has become a valuable tool that can be used to track the status and nature of trials conducted on a specific topic. This approach has been applied to many areas of research, but less is known about the characteristics and trends over time of clinical trials focused on diet and health. The aim of this study was to analyze diet-related clinical trials registered on the National Institute of Health “ClinicalTrials.gov” web platform in the last 10 years, to list and describe their characteristics, and to identify possible gaps to be filled in the future research.

Methods

A search was performed on the ClinicalTrials.gov database. Intervention studies registered from January 2010 to December 2020, conducted on adults, with a follow-up of ≥2 weeks, evaluating the impact of different diets on all outcomes except those assessed with scales or questionnaires were considered.

Results

At the end of the selection process, a total of 1,016 registered clinical trials were identified and included in the analysis. The most investigated dietary approaches were balanced diets (n = 381 trials), followed by those based on a modification of macronutrients (n = 288) and time-restricted feeding and intermittent fasting diets (n = 140). The main measured outcomes included anthropometric parameters and body composition (57.8%), glycemic control parameters (49.7%), lipid parameters (40.1%), inflammatory markers (29.1%), and blood pressure and/or heart rate (24.5%). A growing body of studies also focused on microbiota and host metabolism (17.8%). Most studies had a duration of less than 12 weeks (~60%), and more than 90% of studies enrolled volunteers with overweight/obesity or other diseases. Regarding aging, only 21 studies focused only on older adults.

Conclusion

The number of studies investigating the relationship between diet and health has increased over the years. Despite the growing interest in the topic, there are some gaps, such as the limited duration of most trials, the underrepresentation of some population groups, and the limited number of studies for some diets that, although popular in the population, lack robust scientific evidence.
Dietary Fats, Human Nutrition and the Environment: Balance and Sustainability
Authors: Meijaard Erik , Abrams Jesse F. , Slavin Joanne L. , Sheil Douglas
Published: April 2022

Dietary fats are essential ingredients of a healthy diet. Their production, however, impacts the environment and its capacity to sustain us. Growing knowledge across multiple disciplines improves our understanding of links between food, health and sustainability, but increases apparent complexity. Whereas past dietary guidelines placed limits on total fat intake especially saturated fats, recent studies indicate more complex links with health. Guidelines differ between regions of general poverty and malnutrition and those where obesity is a growing problem. Optimization of production to benefit health and environmental outcomes is hindered by limited data and shared societal goals. We lack a detailed overview of where fats are being produced, and their environmental impacts. Furthermore, the yields of different crops, for producing oils or feeding animals, and the associated land needs for meeting oil demands, differ greatly. To illuminate these matters, we review current discourse about the nutritional aspects of edible fats, summarize the inferred environmental implications of their production and identify knowledge gaps.
Fitness Levels and Gender Are Related With the Response of Plasma Adipokines and Inflammatory Cytokines in Prepubertal Children
Authors: Llorente-Cantarero Francisco Jesus , Aguilera Concepción M. , Perez-Navero Juan Luis , Gil Angel , Benitez-Sillero Juan de Dios , Gil-Campos Mercedes
Published: April 2022

Background and Aim

Changes in adipokines have been related with the development of metabolic syndrome, frequently associated with obesity, and other risk factors. Fitness seems to promote a healthy cardiovascular status and could be a protector factor, just from childhood. Therefore, the present study aimed to evaluate the relationship between fitness levels with plasma adipokines and inflammatory biomarkers in prepubertal children.

Methods

One hundred and thirty-seven healthy normal-weight prepubertal children were recruited from local schools and divided after performing the fitness tests, into two groups according to fitness level—low cardiovascular fitness group (LF) and equal or higher cardiovascular fitness group (HF). Anthropometric variables, blood pressure (BP) and plasma insulin, and leptin, resistin, adiponectin, tumor necrosis factor-alpha, hepatic growth factor, interleukin (IL)-8, monocyte chemoattractant protein-1, nerve growth factor (NGF), and plasminogen activator inhibitor-1 (PAI-1) were measured fasting in both groups to be compared. Univariate analysis of variance, comparative analysis, binary logistic regression, stepwise linear regression, and principal component analysis were conducted to evaluate the association between fitness, BMI, gender, and the biochemical parameters.

Results

Girls and boys with HF presented lower waist circumference Z-score, BMI Z-score, systolic BP (only boys) as well as lower levels of leptin and NGF compared with their respective LF group. Regarding the association between variables, fitness showed an inverse relationship with BMI Z-score, leptin, PAI-1, HOMA-IR, resistin, IL-8, and NGF.

Conclusion

An adequate level of fitness seems to protect against risk factors related to low-grade inflammation and altered adipokines that are related to the onset of obesity just from the prepubertal stage.
NR4A Family Genes: A Review of Comprehensive Prognostic and Gene Expression Profile Analysis in Breast Cancer
Authors: Yousefi Hassan , Fong Jordyn , Alahari Suresh K.
Published: April 2022

This report analyzes nuclear receptor (NR) subfamily 4A’s potential role in treating those diagnosed with breast cancer. Here we reviewed the current literature on NR4 family members. We also examined the relative gene expression of the NR4A receptor subfamily in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). These data showed a positive link between NR4A1-NR4A3 expression and increased overall survival and relapse-free survival in breast cancer patients. In addition, we observed that high expression of NR4A1, NR4A2, and NR4A3 led to better survival. Furthermore, NR4A family genes seem to play an essential regulatory role in glycolysis and oxidative phosphorylation in breast cancer. The novel prognostic role of the NR4A1–NR4A3 receptors implicates these receptors as important mediators controlling breast cancer metabolic reprograming and its progression. The review establishes a strong clinical basis for the investigation of the cellular, molecular, and physiological roles of NR4A genes in breast cancer.
Intra-Tumoral CD8+ T-Cell Infiltration and PD-L1 Positivity in Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma
Authors: Golesworthy Bryn , Wang Yifan , Tanti Amanda , Pacis Alain , Romero Joan Miguel , Cuggia Adeline , Domecq Celine , Bourdel Guillaume , Denroche Robert E. , Jang Gun Ho , Grant Robert C. , Borgida Ayelet , Grünwald Barbara T. , Dodd Anna , Wilson Julie M. , Bourque Guillaume , O’Kane Grainne M. , Fischer Sandra E. , Kron Chelsea Maedler , Fiset Pierre-Olivier , Omeroglu Atilla , Foulkes William D. , Gallinger Steven , Guiot Marie-Christine , Gao Zu-Hua , Zogopoulos George
Published: April 2022

The immune contexture of pancreatic ductal adenocarcinoma (PDAC) is generally immunosuppressive. A role for immune checkpoint inhibitors (ICIs) in PDAC has only been demonstrated for the rare and hypermutated mismatch repair (MMR) deficient (MMR-d) subtype. Homologous recombination repair (HR) deficient (HR-d) PDAC is more prevalent and may encompass up to 20% of PDAC. Its genomic instability may promote a T-cell mediated anti-tumor response with therapeutic sensitivity to ICIs. To investigate the immunogenicity of HR-d PDAC, we used multiplex immunohistochemistry (IHC) to compare the density and spatial distribution of CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and CD68+ tumor-associated macrophages (TAMs) in HR-d versus HR/MMR-intact PDAC. We also evaluated the IHC positivity of programmed death-ligand 1 (PD-L1) across the subgroups. 192 tumors were evaluated and classified as HR/MMR-intact (n=166), HR-d (n=25) or MMR-d (n=1) based on germline testing and tumor molecular hallmarks. Intra-tumoral CD8+ T-cell infiltration was higher in HR-d versus HR/MMR-intact PDAC (p<0.0001), while CD8+ T-cell densities in the peri-tumoral and stromal regions were similar in both groups. HR-d PDAC also displayed increased intra-tumoral FOXP3+ Tregs (p=0.049) and had a higher CD8+:FOXP3+ ratio (p=0.023). CD68+ TAM expression was similar in HR-d and HR/MMR-intact PDAC. Finally, 6 of the 25 HR-d cases showed a PD-L1 Combined Positive Score of >=1, whereas none of the HR/MMR-intact cases met this threshold (p<0.00001). These results provide immunohistochemical evidence for intra-tumoral CD8+ T-cell enrichment and PD-L1 positivity in HR-d PDAC, suggesting that HR-d PDAC may be amenable to ICI treatment strategies.
Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects
Authors: Li Shanshan , Zhao Suhong , Guo Yi , Yang Yuanzhen , Huang Jin , Wang Jiaqi , Lu Shanshan , Wang Bin , Chai Chao , Xu Zhifang , Chin Yenlie
Published: April 2022

Although chemotherapy is the first-line treatment strategy for a variety of tumors, its side effects have limited its efficacy. This review summarizes the progress on the use of acupoint stimulation to combat chemotherapy-associated side effects, including chemotherapy-induced peripheral neuropathy (CIPN), cognitive impairment (CICI), and gastrointestinal toxicity (GI), as well as myelosuppression and immunosuppression. It was found that acupoint stimulation attenuated CIPN and GI by modulating the 5-hydroxytryptamine system in dorsal root ganglia, the dorsal horn of the spinal cord, and the duodenum by reducing oxidative stress and neuroinflammation. Acupoint stimulation also alleviated GI by activating vagal activity in the nucleus tractus solitarius and promoting the secretion of gastrointestinal neuropeptide hormones. Acupoint stimulation restored both bone marrow hematopoiesis and immune function to combat cancer. In addition, the combination of acupoint stimulation and chemotherapy could inhibit tumor growth by promoting tumor cell apoptosis and the enrichment of chemotherapeutic agents in tumor tissue and by modulating the tumor immune microenvironment and normalizing the vasculature. Multiple evidence also indicates that neuroimmune regulation may be involved in the effects of acupoint stimulation. In conclusion, the evidence suggests that acupoint stimulation can alleviate the side effects of chemotherapy and can also assist chemotherapeutic agents in inhibiting tumor growth, which expands the clinical application of acupoint stimulation in cancer treatment. However, more high-quality clinical studies are needed to confirm the clinical value of acupoint stimulation.
Clinical and Histological Prognostic Factors of Recurrence and Malignant Transformation in a Large Series of Oral Potentially Malignant Disorders
Authors: Lorini Luigi , Tomasoni Michele , Gurizzan Cristina , Magri Chiara , Facchetti Mattia , Battocchio Simonetta , Romani Chiara , Ravanelli Marco , Oberti Arianna , Bozzola Anna , Bardellini Elena , Paderno Alberto , Mattavelli Davide , Lombardi Davide , Grammatica Alberto , Deganello Alberto , Facchetti Fabio , Calza Stefano , Majorana Alessandra , Piazza Cesare , Bossi Paolo
Published: April 2022

Background

Oral potentially malignant disorders (OPMDs) represent a heterogeneous set of different histological lesions, characterized by the capacity to transform in oral squamous cell carcinoma (OSCC). Despite optimal surgical treatment, approximately 20%–30% of OPMDs may evolve into OSCC. No clear clinical/histological factors are able to identify OPMDs at higher risk of malignant transformation.

Materials and Methods

We considered surgically treated patients with a diagnosis of OPMDs, enrolled from 1996 to 2019 at ASST Spedali Civili of Brescia without a diagnosis of OSCC within the previous 2 years. Clinical and histological characteristics were recorded. Outcomes of interest were recurrence-free survival (RFS), defined as the time from surgery for primary OPMD to any relapse of OPMD or malignant transformation, whichever occurred first, and carcinoma-free survival (CFS), defined as the time from surgery for OPMD to malignant transformation.

Results

We retrospectively reviewed 106 OPMDs cases. Median age at first diagnosis was 64 years old (IQR = 18.75); female patients comprise 51.9% of the cases. During a median follow-up of 30.5 months (IQR = 44), in 23.5% of patients, malignant transformation occurred. RFS at 1, 5, and 10 years was 92.4%, 60.9%, and 43.2%, respectively. Female sex and history of previous OSCC were independent risk factors for RFS. CFS at 1, 5, and 10 years of follow-up was 97.1%, 75.9%, and 64.4%, respectively. Previous OSCC was an independent risk factor for CFS.

Conclusions

In this large series of OPMDs, only previous diagnosis of OSCC was a prognostic factor for further OSCC occurrence. Given the lack of additional clinical/pathological prognostic factors, we advocate further studies into molecular characterization of OPMDs to better stratify the risk of malignant transformation.
Use of a Liquid Supplement Containing 2 Human Milk Oligosaccharides: The First Double-Blind, Randomized, Controlled Trial in Pre-term Infants
Authors: Hascoët Jean-Michel , Chevallier Marie , Gire Catherine , Brat Roselyne , Rozé Jean-Christophe , Norbert Karine , Chen Yipu , Hartweg Mickaël , Billeaud Claude
Published: April 2022

There is growing evidence supporting the benefit of human milk oligosaccharides (HMOs) on reducing risk of illnesses and improving immune function in newborn infants, but evidence in pre-term infants is lacking. This randomized, double-blind, placebo-controlled trial (NCT03607942) of pre-term infants evaluated the effects of HMO supplementation on feeding tolerance, growth, and safety in 7 neonatal units in France. Pre-term infants (27–33 weeks' gestation, birth weight <1,700 g) were randomized early after birth to receive HMO supplement (n = 43) [2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) in a 10:1 ratio (0.374 g/kg body weight/day)] or an isocaloric placebo (n = 43) consisting of only glucose (0.140 g/kg/day) until discharge from the neonatal unit. Anthropometric z-scores were calculated using Fenton growth standards. Primary outcome was feeding tolerance, measured by non-inferiority (NI) in days to reach full enteral feeding (FEF) from birth in HMO vs. placebo group (NI margin = 4+ days). Mean number of days on intervention prior to FEF was 8.9 and 10.3 days in HMO and placebo, respectively. Non-inferiority in time to reach FEF in HMO (vs. placebo) was achieved [LS mean difference (95% CI) = −2.16 (−5.33, 1.00); upper bound of 95% CI < NI margin] in full analysis set and similar for per protocol. Adjusted mean time to reach FEF from birth was 2 days shorter in HMO (12.2) vs. placebo (14.3), although not statistically significant (p = 0.177). There was no difference in weight-for-age z-scores between groups throughout the FEF period until discharge. Length-for-age z-scores were higher in HMO at FEF day 14 [0.29 (0.02, 0.56), p = 0.037] and 21 [0.31 (0.02, 0.61), p = 0.037]. Head circumference-for-age z-score was higher in HMO vs. placebo at discharge [0.42 (0.12, 0.71), p = 0.007]. Occurrence of adverse events (AEs) was similar in both groups and relatively common in this population, whereas 2.3 and 14.3%, respectively, experienced investigator-confirmed, related AEs. HMO supplementation is safe and well-tolerated in pre-term infants. After 9 days of supplementation, the HMO group reached FEF 2 days earlier vs. placebo, although the difference was not statistically significant. In addition, HMO supplementation supports early postnatal growth, which may have a positive impact on long-term growth and developmental outcomes.
Effect of Parental Myopia on Change in Refraction in Shanghai Preschoolers: A 1-Year Prospective Study
Authors: Ma Yingyan , Lin Senlin , Zhu Jianfeng , Zhao Rong , Zhang Bo , Yin Yao , Shao Yueqin , He Xiangui , Xu Xun , Zou Haidong
Published: April 2022

Background

To investigate the risk factors for change in refraction and refractive components in preschoolers.

Methods

Preschool children aged 3–5 years old, from the junior and the middle grades of seven randomly selected kindergartens in Jia Ding District, Shanghai, were followed for 1 year. Cycloplegic autorefraction (1% cyclopentolate) and axial length (AL) were measured at baseline and at 1-year follow-up. Questionnaires about parental myopia and environmental risk factors, such as time of outdoors and near work, were collected.

Results

A total of 603 right eyes of 603 children were included. Parental myopia was not associated with a change in refraction, but two myopic parents were associated with a longer change in AL (coefficient = 0.153, p = 0.006), after adjusted for baseline spherical refraction, age, gender, change in height, change in weight, and environment risk factors. In the multivariate analyses, boys showed a more myopic refraction shift than girls in 1 year (coefficient = −0.150, p = 0.008) and a quicker AL elongation (coefficient = 0.120, p = 0.008). Time of near work, such as watching television, using computer, reading and writing, and time of outdoor activities, was not associated with a change in refraction or AL.

Conclusions

In preschool age, environmental risk factors were not strongly associated with the change in refraction or refractive components. Parental myopia influences the refractive development of children continuously from infancy to preschool age, which might be the biological basis of school myopia.
Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease
Authors: Fiorucci Stefano , Rapacciuolo Pasquale , Fiorillo Bianca , Roselli Rosalinda , Marchianò Silvia , Di Giorgio Cristina , Bordoni Martina , Bellini Rachele , Cassiano Chiara , Conflitti Paolo , Catalanotti Bruno , Limongelli Vittorio , Sepe Valentina , Biagioli Michele , Zampella Angela
Published: April 2022

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two highly prevalent human diseases caused by excessive fat deposition in the liver. Although multiple approaches have been suggested, NAFLD/NASH remains an unmet clinical need. Here, we report the discovery of a novel class of hybrid molecules designed to function as cysteinyl leukotriene receptor 1 (CysLT1R) antagonists and G protein bile acid receptor 1 (GPBAR1/TGR5) agonists for the treatment of NAFLD/NASH. The most potent of these compounds generated by harnessing the scaffold of the previously described CystLT1R antagonists showed efficacy in reversing liver histopathology features in a preclinical model of NASH, reshaping the liver transcriptome and the lipid and energy metabolism in the liver and adipose tissues. In summary, the present study described a novel orally active dual CysLT1R antagonist/GPBAR1 agonist that effectively protects against the development of NAFLD/NASH, showing promise for further development.
Tissue-Protective Mechanisms of Bioactive Phytochemicals in Flap Surgery
Authors: Weinzierl Andrea , Ampofo Emmanuel , Menger Michael D. , Laschke Matthias W.
Published: April 2022

Despite careful preoperative planning, surgical flaps are prone to ischemic tissue damage and ischemia–reperfusion injury. The resulting wound breakdown and flap necrosis increase both treatment costs and patient morbidity. Hence, there is a need for strategies to promote flap survival and prevent ischemia-induced tissue damage. Phytochemicals, defined as non-essential, bioactive, and plant-derived molecules, are attractive candidates for perioperative treatment as they have little to no side effects and are well tolerated by most patients. Furthermore, they have been shown to exert beneficial combinations of pro-angiogenic, anti-inflammatory, anti-oxidant, and anti-apoptotic effects. This review provides an overview of bioactive phytochemicals that have been used to increase flap survival in preclinical animal models and discusses the underlying molecular and cellular mechanisms.