Nonparametric Research Articles

Abstract B031: Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid

Abstract Purpose For up to 90% of cancer patients, pain is a substantial symptom, contributing to morbidity and, possibly, mortality. In this study we sought to test the hypothesis that a flavonoid, derived from Cannabis, and previously shown to suppress cancer cell growth in vitro and tumor progression in mice in vivo, could also reduce the pain caused by pancreatic tumors in vivo. Methods A subcutaneous tumor in the dorsum of C57BL/6 mouse was generated by sub- dermal injection of KPC mouse pancreatic cancer cell line (ATCC). All the mice were video recorded to observe and analyze their spontaneous pain-related behaviors, including facial washing, dorsal hunching, dorsal skin twitch, licking of dorsal skin and overall locomotion around the cage. Two five minute recording sessions were analyzed by a blinded observer during times before the cancer cell injection (Baseline), after tumor growth, to about 8mm diameter (30d and 37d post-injection) and just before and then 24h after intra-tumor injection of the flavonoid ( Group A: FBL-03G, 1 nmole in 100µL) or Vehicle(100µL; Group B). Pain-related behavioral changes were averaged from the two recording sessions and analyzed from Baseline, just before FBL-03G and 24h after and compared between test compound-and vehicle injected groups (n=7 in each), using non-parametric statistics. Results Facial washing (events/5min) was: reduced to 87% of Baseline in tumor-bearing mice, then increased by 150% at 24h post-injection in Group A (FBL-03G); reduced to 65% of Baseline in tumor-bearing mice of Group B, then reduced a further 9% by Vehicle. Dorsal hunching, which events occur only after tumor growth (Baseline =0), was reduced at 24h by 62% in Group A but increased by 75% in Group B. Dorsal twitch, also absent before tumor growth, was reduced by 64% in Group A, but increased by 19% in Group B. Dorsal skin licking was reduced from Baseline by 33% in tumor-bearing mice of Group A, then increased by 76% after FBL-03g injection whereas licking, reduced by 22% by tumors in Group B and then by an additional 4% by vehicle (Group B). Tumors reduced locomotion by 58% in Group A, which was reversed by 32% after FBL-03g (Group A); vehicle injection resulted in a 38% reduction in locomotion (Group B). Thus, in 4 of the 5 pain-related behaviors from tumors quantitated symptoms were reversed by FBL-03G and oppositely affected, or not at all, by Vehicle. Conclusions These results indicate a substantial relief of spontaneous pain-related pain in this mouse model of pancreatic cancer. Such an acute effect occurs much more rapidly than the previously published in vitro suppression of KPC cell growth (assayed after 9-12d of treatment) or the reduction of tumor size (1-7 weeks) in vivo and suggest that the anti-hyperalgesic affect is due to mechanisms that do not involve reduction in tumor mass. The findings, using a single dose and a small number of mice, appear promising for further studies that examine a range of doses or FBL-03G and its actions in intra-pancreatic tumors. Citation Format: Sayeda Yasmin-Karim, Suheera Haq, Mike Makrigiorgos, Gary Strichartz, Geraud Richards, Natasha Rayman. Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B031.

MRI quantitative T1 and T2 mapping of the renal cortex: Assessment of normal values and potential usefulness for renal masses at 3 T

PurposeThe purpose of this monocentric retrospective study consisted in exploring the potential improvement of the assessment of renal masses on MRI by using the T1 (T1m) and T2 (T2m) mapping relaxation times. Materials and MethodsWe recorded the renal cortex values of 125 patients with normal kidneys (reference group) and 75 patients with renal masses on a clinical 3 T MR unit using T1m and T2m sequences.For the quantitative evaluation, measurements were performed by delineating ROIs on T1m and T2m sequences in renal cortex of the reference group and in renal masses.Interobserver agreement for the qualitative analysis of image quality was assessed using quadratic Cohen’s weighted kappa statistics (k).Student’s paired t-test and non-parametric Kruskal-Wallis test were used to compare our datasets in terms of T1m and T2m values. ResultsFor the cohort of reference group, mean renal cortex T1m and T2m values were 1,529 ± 83 ms and 98 ± 7 ms, respectively. No statistically significant differences were found for T1m and T2m in the reference group regardless of age, gender or eGRF categories.For the group with renal masses, mean T1m and T2m values were 1,667 ± 87 ms and 105 ± 8 ms; 1,621 ± 96 ms and 117 ± 6 ms, and 1,530 ± 62 ms and 85 ± 4 ms for renal cell carcinomas, angiomyolipomas, and oncocytomas, respectively. For T1m values, there was no significant difference (p = 0.37) among the three types of renal masses. Among histological subtypes we have found: RCC versus angiomyolipoma (p = 0.25), RCC versus oncocytoma (p = 0.15), and oncocytoma versus angiomyolipoma (p = 0.47).However, we have found a statistically significant difference for the T2m value (p = 0.0005). Among histological subtypes, only T2m values were statistically significant for each combination: RCC versus angiomyolipoma (p = 0.012), RCC versus oncocytoma (p = 0.0002), and oncocytoma versus angiomyolipoma (p = 0.003). ConclusionAs this is the largest normal patient cohort, the T1m and T2m values recorded could be proposed as reference values and can play a role in the differential diagnosis between benign and malignant renal tumoral masses.

PSIX-8 A multistrain probiotic modifies fecal microbial populations of healthy adult cats

Abstract Probiotics can modulate the intestinal microbiota and benefit the host’s health, whereas environmental stressors can negatively impact the composition of the intestinal microbiota. Lactic acid bacteria (LAB), most commonly Lactobacillus and Bifidobacterium species, are well-known organisms with probiotic potential. The objective of this study was to determine the impact on the fecal microbial population of healthy Cats, after ingestion of a probiotic blend of Lactobacillus acidophilus-286, Bifidobacterium animalis subs. Lactis-689, and Enterococcus faecium-202. Thirty adult cats (15 male, 15 female; mean BW=3.39 kg; mean age=3.3 y) were enrolled in this placebo-controlled and blinded study. After a 7-d washout period, cats were allocated into two groups similar in terms of body weight, age, and sex. Cats were fed a complete dry extruded diet and at time 0 h on d-0 received orally 4 g of a placebo paste or probiotic paste corresponding to the target dose of 4x107 total CFU. Administration of the placebo or probiotic was repeated 12 h and 24 h after the first dose. Afterward, fecal scores were evaluated daily for 7 days. Fresh fecal samples were collected on days 0, 3, and 7 for microbial enumerations and fecal metabolite measurements. Fecal microbial count data did not conform to the assumptions of normality and homogeneity of variances, consequently, non-parametric tests were performed for comparisons. Fecal scores, dry matter, and metabolites were not different between groups. Fecal counts of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. were greater on both d-3 and d-7 (P < 0.01) in cats that consumed probiotics. Fecal counts of both Escherichia coli and Clostridium perfringens were fewer (P < 0.05) in cats that consumed probiotics. In conclusion, the consumption by cats on d-0 of a probiotic blend of Lactobacillus acidophilus-286, Bifidobacterium animalis subs. Lactis-689, and Enterococcus faecium-202 modified the intestinal microbiota up to 7 days after consumption, as evidenced by the increase of lactic acid bacteria and the decrease of Escherichia coli and Clostridium perfringens in feces.

PSIX-7 A multi-strain probiotic modifies fecal microbial populations of healthy adult dogs

Abstract Probiotics can modulate the intestinal microbiota and benefit the health of the host, whereas environmental stressors can negatively impact the composition of the intestinal microbiota. Lactic acid bacteria (LAB), most commonly Lactobacillus and Bifidobacterium species, are well-known organisms with probiotic potential. The objective of this study was to determine the impact on the fecal microbial population of healthy dogs, after ingestion of a probiotic blend of Lactobacillus acidophilus-286, Bifidobacterium animalis subs. Lactis-689, and Enterococcus faecium-202. Adult dogs [n = 30; 15 male, 15 female; mean body weight (BW) = 14.7 kg; mean age = 3.3 yr) were enrolled in this placebo-controlled and blinded study. After a 7-d washout period, dogs were allocated into two groups similar in terms of breed, BW, age, and sex. Dogs were fed a complete dry extruded diet and at time 0 h on d 0 received orally 4 g of a placebo paste or probiotic paste corresponding to the target dose of 4x107 total CFU. Administration of the placebo or probiotic was repeated 12 h and 24 h after the first dose. Afterward, fecal scores were evaluated daily for 7 d. Fresh fecal samples were collected on d 0, 3, and 7 for microbial enumerations and fecal metabolite measurements. Fecal microbial count data did not conform to the assumptions of normality and homogeneity of variances, consequently, non-parametric tests were performed for comparisons. Fecal scores, dry matter, and metabolites were not different between groups. Fecal counts of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. were greater on both d 3 and d 7 (P < 0.01) in dogs that consumed probiotics. Fecal counts of both Escherichia coli and Clostridium perfringens were fewer (P < 0.01) in dogs that consumed probiotics. In conclusion, the consumption by dogs on d 0 of a probiotic blend of Lactobacillus acidophilus-286, Bifidobacterium animalis subs. Lactis-689, and Enterococcus faecium-202 modified the intestinal microbiota up to 7 d after consumption, as evidenced by the increase of lactic acid bacteria and the decrease of Escherichia coli and Clostridium perfringens in feces.

PSI-30 Effects of high canola meal diet with acidifiers supplementation on cecal microbiota of nursery pigs

Abstract Inclusion of canola meal (CM) in swine diets is typically limited stemming from the presence of glucosinolates (Gls), which can reduce growth performance and cause thyroid dysfunction in nursery pigs. While certain members of hindgut bacterial communities are capable of degrading dietary Gls, which would mitigate their detrimental effects, they have yet to be identified. Moreover, lowering the pH in the hindgut of the pig can break down Gls into less toxic compounds, potentially reducing harm. Thus, this study aimed to characterize major bacterial species populating the hindgut of nursery pigs fed a high CM diet supplemented with acidifier and encapsulated butyrate. A total of 315 nursery pigs weaned at 21 d old, average body weight (BW) 6.0 ± 1.2 kg, were assigned to one of five dietary treatments with 9 replicate pens (7 pigs/pen) in a randomized complete block design. The dietary treatments included PC: a corn-soybean meal-based diet with 20% CM, NC: a corn-soybean meal-based diet with 40% CM, NC+A: NC diet supplemented with an acidifier at 1,500 ppm, NC+B: NC diet supplemented with encapsulated butyrate at 500 ppm, and NC+A+B: NC diet supplemented with both an acidifier and encapsulated butyrate. All diets were formulated to meet or exceed the nutrient requirements of NRC (2012). At the end of the feeding trial (6 wk), one pig from each pen was euthanized to collect fresh cecal digesta. Samples were analyzed using the 16S rRNA gene through PCR-amplification of the V1-V3 regions from microbial genomic DNA, followed by Illumina MiSeq 2X300 sequencing. A comparative analysis of the highly represented taxonomic groups and operational taxonomic units (OTU) using non-parametric Kruskal-Wallis sum-rank test and Wilcoxon pairwise test identified candidate bacterial groups or species enriched across different diets. Bacillota was the predominant phylum across all diets, ranging from 83.2% to 86.3%. At the genus level, Lachnospiracea incertae sedis was less abundant in the NC diets with acidifier (Acidifier effect, P < 0.05), whereas Dialister was less in the NC diets with encapsulated butyrate (Butyrate effect, P < 0.05). The OTU Ssd-00001 (Lactobacillus amylovorus, 99.6%) tended to be greater in the cecal microbiota of pigs fed the NC diets with acidifier (Acidifier effect, P = 0.09). Interestingly, OTU Ssd-00188 (Agathobacter rectalis, 99.2%) tended to be higher in PC diet than in NC diet (P = 0.06), while its abundance was less in the cecal microbiota of pigs fed the NC diets with acidifier (Acidifier effect, P = 0.09). In conclusion, these results provide valuable insights into the microbiome of pigs fed high CM diets. Understanding the interplay between microbial communities and high CM diet with acidifier supplementation is crucial for optimizing swine diets and mitigating challenges associated with the antinutritional effects of dietary Gls from CM.

PSXI-22 Effects of a palatability enhancer and olive bioactives on performance and physiological status of veal calves after farm reception

Abstract Veal calves have to deal with several stressors early in life, such as transport and commingling with animals of unknown health histories from multiple different origins; making the reception a possible critical period where animals should adapt to all these challenges. Previous studies in unweaned rosée calves have shown that the use of feed additives (FA) to enhance intake and immunity at farm arrival could be a strategy to minimize the negative effects of stress and feed restriction during transportation. The aim of this study was to evaluate the effects of a palatability enhancer (PE) and olive bioactives (OB) on performance and serum biomarkers in veal calves. Dairy beef calves [n = 252; BVD-free; body weight (BW) = 44.6 ± 3.63 kg] coming from auction market were distributed in 3 treatments (84 animals/tr) during 8 wk: i) calves fed concentrate and MR without FA (negative control, NC); ii) calves fed concentrate and MR with a PE based on sweeteners (PE); and iii) calves fed concentrate with PE and MR with PE and OB (PEOB). On farm arrival animals were housed individually until 5 wk of age, when animals were grouped in pens of 4 calves. Performance was monitored during the trial and serum samples were collected 48 h after the mixing (25 animals/tr) to analyze several biomarkers related to immune system (MILLIPLEX MAP Kit) and energy status (BHBA). Performance data were analyzed with a mixed-effects model and serum biomarkers by One-Way Anova with Fisher’s LSD correction for multiple comparisons (normally distributed data) or by non-parametric Kruskal-Wallis test with Dunn’s correction (data not normally distributed). Final BW was greater (P = 0.01) in PE and PEOB groups compared with NC (+2.2 kg and +2.6 kg, respectively). Concentrate feed intake (FI) during first 4 wk tended (P = 0.06) to be greater in PEOB compared with NC (+15%); however, after grouping (wk 5 to wk 8), PE showed a ldecreased FI compared with NC (-9.5%, P = 0.01). Forty-eight hours after animal grouping, PEOB showed reduced concentration of tumor necrosis factor (TNF) α than NC and PE (P = 0.03). Moreover, PEOB and PE had a greater concentration of interleukin (IL) 36Rα (P < 0.05) and IP10 (P < 0.01) compared with NC. Besides PEOB tended (P < 0.15) to have decreased concentrations of MIP1α, IL1α, and BHBA compared with PE. In conclusion, the addition of a PE and OB improved the adaptation of veal calves after reception, resulting in greater final BW. The improvement in early FI and the immunomodulatory effect in challenging situations displayed by the treatments may partially explain the observed benefits.

The clinical significance of pyogenic liver abscess after transarterial chemoembolization or microwave ablation on malignant liver tumors: A retrospective study.

Pyogenic liver abscess (PLA) is a rare but severe complication of interventional therapy that has been little studied. We aimed to find the risk factors for PLA after transarterial chemoembolization (TACE) or microwave ablation (MWA), further explore its clinical significance and summarize our experience with its treatment. Twenty-two patients with PLA and 118 randomly selected patients without PLA after TACE/MWA were enrolled. Logistic regression was used to analyze risk factors, a nonparametric test was used to compare recovery duration, the log-rank test was used to compare progression-free survival, and Spearman correlation coefficient was calculated between the time from fever to drainage and the total duration of fever. The disease process and treatment were summarized. Sphincter of Oddi manipulation increased the risk of PLA by 70.781-fold. The PLA group took longer to recover (36.56 ± 16.42 days) than the control group (5.54 ± 4.33 days), and had a shorter progression-free survival. Escherichia coli was the major pathogenic bacterium, and multidrug resistance was found in 8 patients with E coli or Enterococcus faecium. The time from fever to drainage was 15.89 ± 13.78 days, which was positively correlated with the total duration of fever (24.29 ± 18.24 days). Overall, 18 patients recovered, and 4 patients died of PLA, for a mortality rate of 18.18%. The fever of 10 patients (45.45%) was controlled by cefoperazone sodium and sulbactam sodium or piperacillin sodium and tazobactam sodium; the fever of 7 patients (31.81%) was controlled by imipenem and cilastatin sodium; and the fever of 3 patients (13.63%) was controlled by tigecycline. Sphincter of Oddi manipulation is a high-risk factor for PLA after TACE or MWA. PLA can accelerate cancer progression and even lead to death. E coli was the major pathogenic bacterium, and multidrug resistance was most common in E coli and E faecium. Timely drainage and appropriate antibiotics are the key primary measures for treating PLA. Cefoperazone sodium and sulbactam sodium or piperacillin sodium and tazobactam sodium is a good choice for the first treatment of PLA, especially before pathogenic bacteria are identified. With the emergence of drug resistance, imipenem and cilastatin sodium, and tigecycline can be used for posterior treatment.

Social needs and healthcare utilization in NICU graduates.

Unplanned healthcare utilization after neonatal intensive care unit (NICU) discharge challenges families and healthcare systems. The impact of social needs on post-NICU healthcare utilization is underexplored. Our objective was to identify social needs among NICU graduates and examine associations between social needs and post-NICU healthcare utilization. A prospective cohort design was used to screen for social needs and track healthcare utilization among 112 NICU graduates attending a NICU follow-up clinic (2021-2022). Associations between social needs and healthcare utilization were analyzed using non-parametric statistical tests. Of 112 patients screened, 20 (18%) had some social need. Infants with social needs experienced statistically significant higher rates of hospitalizations, overall encounters, and missed appointments. Social needs are associated with increased unplanned healthcare utilization and missed appointments. Addressing these needs during NICU follow-up may improve preventative care attendance and reduce unplanned healthcare use, leading to better outcomes for vulnerable infants and cost-savings for healthcare systems.

Temporal Statistical Analysis and Retrospective Assessment of Mortality Rate in the United States from 1999 to 2018

Objectives: To retrospectively examine the mortality trend in the USA from 1999 to 2018 using a basic statistical model while examining multiple variables. The inferential and descriptive statistical tools will be prioritized to elucidate the mortality of both years in simple terms. Methods: We conducted a retrospective observational descriptive analysis of data on the 10 leading causes of death in the United States by age, race, and sex over 2 decades (1999 to 2018). The data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia. The causes of death are classified by the International Classification of Diseases, 10th Revision (ICD–10), which is ranked according to the number of deaths (Cause-of-death statistics are based on the underlying cause of death). This report supplements “Deaths: Final Data for 2020,” the National Center for Health Statistics’ annual report of final mortality statistics. SPSS (statistical package for social sciences) version 29 Software in Excel sheet was used to analyze the generated datasets. Descriptive and inferential (parametric and non-parametric) analyses were used. The statistically significant relationships and assumptions were made using the chi-square/t-test, Kruskal-Wallis, and Fischer's exact tests with the significance level set at p ≤ 0.05. The analysis and determination of the level of agreement between the initial diagnosis and findings from the new analysis done. Results: The proportion of age-adjusted death rates of the heart (such as coronary artery disease) account for the highest proportion of 24%, while Malignant neoplasms (cancers) represent 23%, Chronic lower respiratory diseases contribute 6%, Unintentional injuries (accidents) also play a significant role, accounting for 5% of deaths. The regression analysis reveals a strong and statistically significant relationship between the number of causes in females and males. There was a high death rate of around 60 years in 1999 and a consistent decline over the years, reaching below 40 by 2018, with a 15/100,000 death fluctuation mark. Asian or Pacific Islander has the lowest age adjustment value of 8762.4, American Indian or Alaska Native, Hispanic, or Latino(11673.2), Black or African American, Hispanic, or Latino (12992.1), White, not Hispanic or Latino(15457.1), Black or African American (15708.2), Hispanic or Latino(19624.1), American Indian or Alaska Native, not Hispanic or Latino (16287.9).Asian or Pacific Islander, not Hispanic or Latino( 8791.3), and 99.2% of the variability in the dependent variable and standard error of 6.7240. Conclusions: Cardiovascular death remains the most common cause of death, with a significant decrease in the death rate from 1999 to 2018 due to improved health care and the provision of measures to improve health care. The regression analysis reveals a strong and statistically significant relationship between the number of causes in females and males. Therefore, based on the results, the number of causes in females strongly predicts the number of causes in males.

348 Repeat breeding syndrome: Dexamethasone decreases the prevalence of anti-sperm antibodies in dairy cows

Abstract Cows that require greater than two inseminations to conceive are diagnosed with repeat breeding syndrome (RBS). Anti-sperm antibodies (ASA) in serum are in greater abundance among individuals exhibiting fertility challenges. In humans, treatment with glucocorticoids has been shown to decrease the prevalence of ASA and improve fertility. Therefore, the purpose of this study was to determine the impact of dexamethasone on ASA and pregnancy outcomes in RBS cattle. Holstein multiparous cows (n = 18) diagnosed as having RBS were randomly allotted to one of three treatment groups: Control (C; n = 6), low dexamethasone (LD; n = 6) and high dexamethasone (HD; n = 6). Intramuscular injections of saline (C), 0.05 mg/kg of BW of dexamethasone (LD), or 0.10 mg/kg of BW of dexamethasone (HD) were administered daily starting 4 d prior to insemination (d 0) through insemination (d 4). All treatment volumes were standardized with saline to achieve the same treatment level. Blood was collected on d 0, 4, 8 and 18, with serum extracted on d 0 through 8. Additionally, milk weights were recorded until d 34. For breeding, cows were synchronized using the Double Ovsynch protocol and only one insemination was conducted at the time of breeding. The MIXED procedure in SAS was used to determine the relationship of treatment with the repeated measures of ASA abundance and milk yield. Additionally, a non-parametric chi-square analysis was conducted in SAS using PROC GENMOD to determine the relationship of treatment with immune cell count and pregnancy outcomes. Day, Treatment and Treatment × Day were designated as fixed effects, and a protected post hoc analysis was conducted to account for multiple comparisons. Anti-sperm antibodies tended to decrease (P ≤ 0.082) as dexamethasone increased compared with C, however, there was no Treatment × Day interaction. Daily milk yields for both LD and HD decreased (P < 0.002) compared with C cows, but there was no interaction with day. Though there was an effect for Treatment × Day (P ≤ 0.002) for white blood cell count, percentage lymphocytes, eosinophils, and neutrophils, there was no effect of treatment (P ≥ 0.181). Therefore, interaction differences were largely driven by day (P < 0.001). Surprisingly, there was a trend (P = 0.069) for an increase in pregnancy rates for C cows compared with LD and HD cows. In fact, one-half of the C cows achieved pregnancy compared with just one cow for LD and HD treatments. Overall, dosage of dexamethasone did not differ for ASA or pregnancy outcomes. However, dexamethasone did decrease ASA but did not increase pregnancy rates. Based on these results, we suggest that alternative treatment measures should be explored to improve pregnancy rates in RBS cows.

TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer’s Disease (TRANSFORM-AD): a randomized controlled clinical trial

BackgroundThe mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer’s Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity.MethodsThis is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography–functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization.ResultsA total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus.ConclusionEffects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS.Trial registrationClinicalTrials.gov, NCT 03920826; Registration Date: 2019-04-19.

The effects of health beliefs and acculturation on the acceptance of human papillomavirus vaccination among Asian Indian parents in the United States.

The available limited literature and Centers for Disease Control data suggest that human papillomavirus (HPV) vaccination acceptance is lower among Asian Indians than the general population in the United States. The purpose of the study was to determine the effects of health beliefs, subjective norms, acculturation, and demographics on HPV vaccination acceptance among Asian Indian parents. Using a comparative descriptive cross-sectional study design, immigrant and first-generation Asian Indian parents of 9- to 16-year-old children were recruited (N = 171). The survey comprised the Health Belief and Subjective Norms instrument and the Suinn-Lew Asian Self-Identity Acculturation Scale. The analysis included parametric and nonparametric tests. Participants who expressed higher levels of perceived barriers were less likely to accept HPV vaccination (odds ratio [OR] = 0.47, p = .016). Spousal opinion negatively correlated with HPV vaccination acceptance (OR = 0.57, p = .006). However, subjective norms positively predicted HPV vaccination acceptance (OR = 1.69, p = .039). Participants who perceived that friends and family approved of the vaccination also had significantly higher rates of vaccination acceptance (OR = 11.99, p = .001). The results revealed unique factors in the acceptance of HPV vaccination in Asian Indians that were not examined or understood before. The applied Health Beliefs and Subjective Norms theoretical framework suggested that perceived barriers, subjective norms, and the opinions of spouses, friends, and family predicted HPV vaccination acceptance. Educational interventions targeting providers, spouses, family, and community members with influential effects on parents may positively affect HPV vaccination acceptance. Providers should note that this population welcomes the provider's recommendations.

The Economic Burden of Type 2 Diabetes Mellitus in Pakistan: A Cost of Illness Study.

Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease with a chronic nature and poses a significant health burden worldwide, with no exception in Pakistan. Hence, this study aimed to explore the financial burden of T2DM in Pakistan through cost of illness analysis. A prevalence-based, cross-sectional study was conducted using a structured data collection tool from the patient's perspective. Through structured interviews by trained data collectors, the data regarding direct medical costs, direct non-medical costs, and indirect costs were collected and further verified through prescriptions and bills. After testing the normality of data, mean and median with interquartile range were used to present cost data, while non-parametric tests, i.e., the Mann-Whitney U test and the Kruskal-Wallis test, were used to assess factors associated with costs, as cost data were not normally distributed. The study included 522 participants, with a majority being female (54%) and aged between 41 and 60 years (64%). The mean annual total cost per patient was USD 235.1 (median = USD 162.8), comprising direct medical costs, 93.2% (mean = USD 219.2; median = USD 150.0), direct non-medical costs, 5.3% (mean = USD 12.4; median = USD 7.1), and indirect costs, 1.5% (mean = USD 3.5; median = USD 1.9). Costs were significantly higher for patients with advanced age, high literacy, higher household incomes, duration of diabetes, more than one complication, and using combination therapy. The economic burden of T2DM in Pakistan is substantial, with medication costs being the largest component. Effective management strategies and policy interventions are crucial to mitigate this burden and improve the economic and health outcomes for diabetic patients.

Investigation of TMEM41A's function in breast cancer prognosis and its connection to immune cell infiltration.

Globally, breast cancer is the most common type of malignant tumor. It has been demonstrated that TMEM41A is abnormally expressed in a number of cancers and is linked to a dismal prognosis. TMEM41A's involvement in breast cancer remains unknown, though. Data from databases such as TCGA were used in this study. Expression differences were compared using non-parametric tests. Cox regression analysis was employed, and analyses such as Nomogram were used to assess the significance of TMEM41A in predicting the prognosis of breast cancer. Lastly, it was looked into how immune cell infiltration in breast cancer is related to TMEM41A expression levels. The results suggest that TMEM41A is overexpressed in breast cancer and correlates with poor prognosis (P = 0.01), particularly in early-stage and ductal A breast cancer (P < 0.01). Breast cancer patients' expression of TMEM41A was found to be an independent risk factor (HR = 1.132, 95% CI 1.036-1.237) by multifactorial Cox regression analysis. The Nomogram prediction model's c-index was 0.736 (95% CI 0.684-0.787). The results of GSEA biofunctional enrichment analysis included the B cell receptor signaling pathway (P < 0.05). Ultimately, there was a significant correlation (P < 0.05) between TMEM41A expression in breast cancer and an infiltration of twenty immune cells. Breast cancer tissues overexpress TMEM41A, which is linked to immune cell infiltration and prognosis (particularly in early stage and luminal A breast cancer). Overexpression of TMEM41A is anticipated to serve as a novel prognostic indicator and therapeutic target for breast cancer.

Effect of Curing Light with Different Intensities on the Penetration of Silver and Fluoride Ions and Dentin Hardness in Primary Carious Molars Following Silver Diamine Fluoride Application: A Comparative Microscopic Ex Vivo Study.

A paradigm shift from surgical to medical approach for caries management has popularized silver diamine fluoride (SDF) as a preventive and interim caries arrest medicament. Few studies conducted have explored the effect of curing light on SDF's microbial property, its penetration, and effect on dentin. However, there is a research gap regarding the effect of different intensities of curing light on SDF performance. To determine the effect of different curing light intensities on SDF penetration depth and dentin hardness in carious lesions of primary molars. Silver diamine fluoride was applied on 30 extracted carious primary molars. Teeth were randomly allocated into three groups-(1) control group, no light curing after application of SDF; (2) light curing of SDF with low intensity (1000 mW/cm2); and (3) light curing of SDF with high intensity (2500 mW/cm2). A scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis was performed to check ion penetration after 1 week, and a Vickers hardness test was used to assess dentin hardness of both infected and affected dentin layers at 1-week and 1-month intervals. Based on the distribution of data, parametric and nonparametric tests were applied. Statistical Package for the Social Sciences (SPSS) version 26 was used for statistical analysis. The level of significance was set at 5%. Silver diamine fluoride penetrated beyond the carious lesion in all three groups. The mean silver ion precipitation in infected dentin in group III (16.90 ± 0.68) was maximum, whereas it was found to be minimum in group II (7.31 ± 0.63). The mean fluoride ion precipitation in affected dentin in group III (4.06 ± 0.41) was highest and least in group II (3.09 ± 0.58). A considerable increase in mean dentin hardness of infected dentin was observed in all three groups (214.00 ± 89.06, 218.00 ± 75.17, 231.00 ± 98.86, respectively; p < 0.001) after 1 month. Applying SDF to carious lesions using a high-intensity dental curing light induced more silver ion precipitation in infected dentin and increased its hardness. Bhatt R, Patel M, Thakkar A, et al. Effect of Curing Light with Different Intensities on the Penetration of Silver and Fluoride Ions and Dentin Hardness in Primary Carious Molars Following Silver Diamine Fluoride Application: A Comparative Microscopic Ex Vivo Study. Int J Clin Pediatr Dent 2024;17(7):766-772.

The impact of diabetes on bronchiectasis

Objective: To study the impact of diabetes on bronchiectasis. Methods: From January 1 2017 to December 31 2021, data of 1 310 inpatients with bronchiectasis were retrospectively collected from Shanghai Pulmonary Hospital, Tongji University. This cohort inclueded 78 patients with bronchiectasis and diabetes (bronchiectasis-diabetes group) and 1 232 patients of bronchiectasis without diabetes (simple bronchiectasis group). To mitigate confounding variables, 269 patients with bronchiectasis but without diabetes (bronchiectasis non-diabetes group) were matched with 78 patients of bronchiectasis with diabetes (bronchiectasis-diabetes group) using the propensity score method in a 1∶4 ratio. A comparative analysis of clinical characteristics, laboratory test results, pathogenic infections, and disease severity was performed between the two groups. Analysis of continuous variables was performed using either a t-test or non-parametric test, while categorical data was assessed using the chi-square test. Results: The mean age of individuals in the bronchiectasis-diabetes group (62.99±8.09 years) was significantly higher than that of subjects in the simple bronchiectasis group (57.05±13.07 years) (t=-6.012, P<0.001). After propensity score matching, the pre-albumin level in the bronchiectasis-diabetes group (188.44±71.65 g/L) was found to be lower than in the bronchiectasis non-diabetes group (208.17±62.50 g/L) (t=2.023, P=0.044). In addition, the hospitalization cost for the bronchiectasis-diabetes group [1.59 (1.34, 2.15) Ten thousand yuan] was higher than that in the bronchiectasis non-diabetes group [1.39 (1.23, 1.62) Ten thousand yuan] (U=-3.744, P<0.001).The severity of mMRC in the bronchiectasis-diabetes group was significantly higher than that in the bronchiectasis non-diabetes group (χ2=25.392, P<0.001), and the frequency of previous hospitalization due to aggravation and acute exacerbation within the previous year were higher than in bronchiectasis non-diabetes group (χ2=34.031, 40.841, respectively, P<0.001). In additional, the BSI score was significantly increased in patients with bronchiectasis-diabetes compared to those with bronchiectasis non-diabetes (8.07±4.07 vs. 10.44±3.82) (P<0.001). Furthermore, fasting blood glucose concentration, urine glucose level, and BSI score exhibited positive correlations, whereas pre-albumin concentration showed a negative correlation with the BSI score (all P<0.05). Conclusion: Compared to those without diabetes, patients of bronchiectasis with diabetes have poorer nutritional status, more severe symptoms, increased risk of acute exacerbation, higher BSI score severity, and greater financial burden.

Identifying neural correlates of balance impairment in traumatic brain injury using partial least squares correlation analysis

Objective.Balance impairment is one of the most debilitating consequences of traumatic brain injury (TBI). To study the neurophysiological underpinnings of balance impairment, the brain functional connectivity during perturbation tasks can provide new insights. To better characterize the association between the task-relevant functional connectivity and the degree of balance deficits in TBI, the analysis needs to be performed on the data stratified based on the balance impairment. However, such stratification is not straightforward, and it warrants a data-driven approach.Approach.We conducted a study to assess the balance control using a computerized posturography platform in 17 individuals with TBI and 15 age-matched healthy controls. We stratified the TBI participants into balance-impaired and non-impaired TBI usingk-means clustering of either center of pressure (COP) displacement during a balance perturbation task or Berg Balance Scale score as a functional outcome measure. We analyzed brain functional connectivity using the imaginary part of coherence across different cortical regions in various frequency bands. These connectivity features are then studied using the mean-centered partial least squares correlation analysis, which is a multivariate statistical framework with the advantage of handling more features than the number of samples, thus making it suitable for a small-sample study.Main results.Based on the nonparametric significance testing using permutation and bootstrap procedure, we noticed that the weakened theta-band connectivity strength in the following regions of interest significantly contributed to distinguishing balance impaired from non-impaired population, regardless of the type of stratification:left middle frontal gyrus, right paracentral lobule, precuneus, andbilateral middle occipital gyri. Significance.Identifying neural regions linked to balance impairment enhances our understanding of TBI-related balance dysfunction and could inform new treatment strategies. Future work will explore the impact of balance platform training on sensorimotor and visuomotor connectivity.

Transamniotic Delivery of Surfactant Protein B mRNA in a Healthy Model

Introduction: We sought to determine whether exogenous surfactant protein B (SPB) mRNA could be incorporated and translated by the fetal lung after simple transamniotic administration. Methods: Fetuses (n = 149) of twelve time-dated dams underwent intra-amniotic injections of either human SPB (hSPB) mRNA encapsulated into lipopolyplex (mRNA, n = 99) or lipopolyplex without mRNA (control; n = 50) on gestational day 17 (E17, term = E21–22). Lungs were screened for hSPB by enzyme-linked immunosorbent assay daily until term. Phosphatidylcholine (PC) (a surrogate for surfactant production) was measured in the amniotic fluid by fluorometric assay. Statistical analysis included nonparametric Wilcoxon rank sum test. Results: Significantly improved survival in the mRNA group compared to controls was observed at E18 (100% vs. 85.7%) and E20 (100% vs. 83.3%) (both p < 0.001). When controlled by mRNA-free injections, hSPB protein was detected in the mRNA group’s lungs at E18, 19, and term (p = 0.002 to <0.001). Amniotic fluid PC levels were increased compared to control at term [285.9 (251.1, 363.9) μM versus 263.1 (222.8, 309.1) μM]; however, this did not reach significance (p = 0.33). Conclusions: Encapsulated exogenous SPB mRNA can be incorporated and translated by fetal lung cells following intra-amniotic injection in a healthy rat model. Transamniotic mRNA delivery could become a novel strategy for perinatal surfactant protein replacement.

The impact of socio-demographic factors on web credibility assessment

The aim of this study is to investigate the relationship between web credibility evaluation and socio-demographic variables. A sample of 380 students from Ferdowsi University of Mashhad, Iran, was selected using stratified sampling methods. Data was collected through a questionnaire encompassing socio-demographic information and Choi items. The collected data was analysed using Spearman and Kruskal–Wallis non-parametric tests, guided by the data's characteristics (type and distribution). The findings reveal a significant association between interest, experience and academic level in determining web credibility assessments. Conversely, expertise, income, gender and age were not found to be influential factors. This is a first attempt to determine the impact of socio-demographic variables on web credibility assessment. The findings suggest that individuals from diverse age, gender and income groups could benefit from acquiring knowledge pertaining to web credibility and engaging in workshops related to this domain. Additionally, those with lower levels of experience, education and interest may derive greater value from participating in web-credibility-evaluation workshops.

Nonparametric isotropy test for spatial point processes using random rotations

In spatial statistics, point processes are often assumed to be isotropic meaning that their distribution is invariant under rotations. Statistical tests for the null hypothesis of isotropy found in the literature are based either on asymptotics or on Monte Carlo simulation of a parametric null model. Here, we present a nonparametric test based on resampling the Fry points of the observed point pattern. Empirical levels and powers of the test are investigated in a simulation study for four point process models with anisotropy induced by different mechanisms. Finally, a real data set is tested for isotropy.