Search Results (35)

Background: The number of women veterans has been rising steadily since the Gulf War and many assume the functions of their male counterparts. Women face unique obstacles in their service, and it is imperative that differences in physiology not be overlooked so as to provide better and appropriate care to our women in uniform. Despite this influx and incorporation of female talent, dedicated reports contrasting female and male veterans are rare, outside of specific psychological studies. We therefore attempt to contrast gut constituents, absorption, innate immune system, and nutritional differences to provide a comprehensive account of similarities and differences between female and male veterans, from our single-center perspective, as this has not been carried out previously. Herein, we obtained a detailed roster of commonly used biomedical tests and some novel entities to detect differences between female and male veterans. The objective of this study was to detect differences in the innate immune system and other ancillary test results to seek differences that may impact the health of female and male veterans differently. Methods: To contrast biochemical and sociomedical parameters in female and male veterans, we studied the data collected on 450 female veterans and contrasted them to a group of approximately 1642 males, sequentially from 1995 to 2022, all selected because of above-average risk for CRC. As part of this colorectal cancer (CRC) screening cross-sectional and longitudinal study, we also collected stool, urine, saliva, and serum specimens. We used ELISA testing to detect stool p87 shedding by the Adnab-9 monoclonal and urinary organ-specific antigen using the BAC18.1 monoclonal. We used the FERAD ratio (blood ferritin/fecal p87), a measure of the innate immune system to gauge the activity of the innate immune system (InImS) by dividing the denominator p87 (10% N-linked glycoprotein detected by ELISA) into the ferritin level (the enumerator, a common lab test to assess anemia). FERAD ratios have not been performed elsewhere despite past Adnab-9 commercial availability so we have had to auto-cite our published data where appropriate. Results: Many differences between female and males were detected. The most impressive differences were those of the InImS where males clearly had the higher numbers (54,957 ± 120,095) in contrast to a much lower level in females (28,621 ± 66,869), which was highly significantly different (p < 0.004). Mortality was higher in males than females (49.4% vs. 24.1%; OR 3.08 [2.40–3.94]; p < 0.0001). Stool p87, which is secreted by Paneth cells and may have a protective function, was lower in males (0.044 ± 0.083) but higher in females (0.063 ± 0.116; p < 0.031). Immunohistochemistry of the Paneth cell-fixed p87 antigen was also higher in females (in the descending colon and rectum). In contrast, male ferritin levels were significantly higher (206.3 ± 255.9 vs. 141.1 ± 211.00 ng/mL; p < 0.0006). Females were less likely to be diabetic (29.4 vs. 37.3%; OR 0.7 [0.55–0.90]; p < 0.006). Females were also more likely to use NSAIDs (14.7 vs. 10.7%, OR 1.08 [1.08–2.00]; p < 0.015). Females also had borderline less GI bleeding by fecal immune tests (FITs), with 13.2% as opposed to 18.2% in males (OR 0.68 [0.46–1.01]; p = 0.057), but were less inclined to have available flexible sigmoidoscopy (OR 0.68 [0.53–0.89]; p < 0.004). Females also had more GI symptomatology, a higher rate of smoking, and were significantly younger than their male counterparts. Conclusions: This study shows significant differences with multiple parameters in female and male veterans. Full article

Background: The perspective of inflammatory bowel disease (IBD) has changed radically since the first decade of the 21st century, and the formerly monolithic components of IBD, ulcerative colitis (UC), and Crohn’s disease (CD) have undergone a fundamental convergence, with realization that there is likely an element of shared pathogenesis. The ground shift began with genomic revelation but with the current emergence of the innate immune system (InImS) as a key player, allowing for improved understanding of the associations between the immune underpinnings of IBD. Methods: Using unique ferritin/fecal p87 (FERAD) or using colonoscopic effluent as denominator (FEREFF) and other ratios to test this hypothesis, we prospectively enrolled 2185 patients with increased risk of colorectal cancer, of whom 31 had UC and 18 CD, with 2136 controls and brought to bear in a convenient measure for the InImS, the FERAD ratio. The FERAD, FEREFF, and NLR ratios have been shown to be effective measures of the InImS in COVID-19 and various cancers. p87 is expressed in gut Paneth cells known to modulate the microbiome by secretion of alpha-defensins, a natural antibiotic. Other related parameters were also evaluated. Results: There was no significant difference between the FERAD ratio in UC and CD. However, differences between IBD entities and controls were substantial. Conclusions: InImS settings in IBD are similar between CD and UC. p87 tissue immunohistochemistry (IHC) is also shared. Other InImS markers, such as the absolute neutrophil/lymphocyte ratio, are also confluent between the two IBD forms. Full article

Water and water transfer are the keys of the concrete durability problem; the non-uniform moisture transfer caused by the concrete micro–meso structure has a great effect on the drying shrinkage crack, transfers of inimical ions, etc. For the non-uniform moisture transfer problem, a multi-scale concrete moisture diffusion coefficient model which can consider the effect of Knudsen diffusion was established and verified based on the moisture transfer mechanism of porous medium and the concrete micro–meso structure characteristics. The effects of pore structure, the interfacial transition zone, and aggregate on the concrete moisture diffusion coefficient were studied based on the model, and the non-uniform moisture transfer characteristics and differences in concrete wetting and drying were analyzed via simulations. The results show that the moisture transfers more easily via the pores ranging from 10 nm to 100 nm, the effect of Knudsen diffusion increases with the increasing water-to-cement ratio and decreases with the increasing relative moisture, and Knudsen diffusion is also an effect factor which causes the moisture diffusion coefficient to increase with the increase in moisture. Moisture transfers more easily via the interfacial transition zone at the meso-level and causes a “flow around” phenomenon. The “S” growth relation between the moisture diffusion coefficient and relative moisture can consider the differences in the moisture diffusion coefficient under wetting and drying conditions to a certain extent, which makes concrete wet faster than dry. In addition, the jumping growth of the moisture diffusion coefficient in the relation also leads to an “inflection point” in the concrete moisture distribution. Full article

Cancer discovery is directed at the identification of a specific cancer type which allows for specific therapeutic interventions. Background/Objectives: Recently, similar immune checkpoint therapeutics have been applied with success across several cancer types, opening the field for other immune disruptive interventions that have practical applications. Methods: We have discovered an innate immune system (InImS) biomarker that allows for the characterization of allied cancer subtypes and outliers that might aid with diagnosis, treatment, and prognostication. Results: These InImS biomarkers are related to PD-L1 treatment outcomes and can be potentially manipulated by dietary means. Conclusions: The FERAD (ferritin–fecal p87) and absolute neutrophil/lymphocyte (aNLR) ratios are two such InImS biomarkers and we show herein, that they allow for the discovery of diagnosis and prognostication patterns, as demonstrated by this study. Full article

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett’s esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR. Full article

Background: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs). Methods: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA−CCR7+ (T-central memory, TCM), CD45RA−CCR7− (T-effector memory, TEM) and CD45RA+CCR7− (T-effector memory re-expressing CD45RA, T_EMRA, senescent), CD28− (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders. Results: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28− T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04]. Conclusion: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms. Full article

Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options—twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials. Full article

Conventional integral imaging (InIm) three-dimensional (3D) display has the defect of a small viewing angle and usually presents a single 3D image. In this paper, we propose a viewing-angle-enhanced and dual-view compatible InIm 3D display system. The crosstalk pixel areas within the conventional elemental images (EIs) that result in image crosstalk were effectively utilized either for viewing angle enhancement or for dual-view 3D display. In the viewing-angle-enhanced 3D display mode, a composite elemental image (CEI) that consisted of a normal EI and two view-enhanced EIs was imaged by a dual pinhole array and formed an extended 3D viewing area. A precisely designed mask array was introduced to block the overlapped rays between adjacent viewing areas to eliminate image crosstalk. While in the dual-view 3D display mode, a CEI was composed of image information of two different 3D scenes. With the help of the dual pinhole array and mask array, two different 3D images were reconstructed for the left and right perspectives. Experiments demonstrated that both the left and right sides were increased by 6 degrees from the conventional 3D viewing angle, and also, a dual-view 3D display effect that retains the same viewing angle as the conventional system was achieved. The proposed system has a compact structure and can be freely switched between two display modes. Full article

Background: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. Methods: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP−) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. Results: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP− group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP− with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP− group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. Conclusion: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP− phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP− group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival. Full article

The ability of the indole–imidazole hybrid ligands to coordinate with the Zn(II) ion and the resulting structures of this new class of coordination compounds were analyzed in order to determine their structural properties and biological functionalities. For this purpose, six novel Zn(II) complexes, [Zn(InIm)₂Cl₂] (1), [Zn(InMeIm)₂Cl₂] (2), [Zn(IniPrIm)₂Cl₂] (3), [Zn(InEtMeIm)₂Cl₂] (4), [Zn(InPhIm)₂Cl₂] (5) and [Zn₂(InBzIm)₂Cl₂] (6) (where InIm is 3-((1H-imidazol-1-yl)methyl)-1H-indole), were synthesized by the reactions of ZnCl₂ and the corresponding ligand in a 1:2 molar ratio in methanol solvent at an ambient temperature. The structural and spectral characterization of these complexes was performed using NMR, FT–IR and ESI–MS spectrometry and elemental analysis, and the crystal structures of 1–5 were determined using single-crystal X-ray diffraction. Complexes 1–5 form polar supramolecular aggregates by utilizing, for this purpose, the N-H(indole)∙∙∙Cl(chloride) intermolecular hydrogen bonds. The assemblies thus formed differ depending on the distinctive molecular shape, which can be either compact or extended. All complexes were screened for their hemolytic, cytoprotective, antifungal, and antibacterial activities. The results show that the cytoprotective activity of the indole/imidazole ligand significantly increases upon its complexation with ZnCl₂ up to a value comparable with the standard antioxidant Trolox, while the response of its substituted analogues is diverse and less pronounced. Full article

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility. Full article

In recent years, the coupling of structurally and functionally controllable polymers with biologically active protein materials to obtain polymer–protein conjugates with excellent overall properties and good biocompatibility has been important research in the field of polymers. In this study, the hyperbranched polymer hP(DEGMA-co-OEGMA) was first prepared by combining self-condensation vinyl polymerization (SCVP) with photo-induced metal-free atom transfer radical polymerization (ATRP), with 2-(2-bromo-2-methylpropanoyloxy) ethyl methacrylate (BMA) as inimer, and Di (ethylene glycol) methyl ether methacrylate (DEGMA) and (oligoethylene glycol) methacrylate (OEGMA, M_n = 300) as the copolymer monomer. Then, hP(DEGMA-co-OEGMA) was used as a macroinitiator to continue the polymerization of a segment of pyridyl disulfide ethyl methacrylate (DSMA) monomer to obtain the hyperbranched multiarm copolymers hP(DEGMA-co-OEGMA)-star-PDSMA. Finally, the lysozyme with sulfhydryl groups was affixed to the hyperbranched multiarm copolymers by the exchange reaction between sulfhydryl groups and disulfide bonds to obtain the copolymer protein conjugates hP(DEGMA-co-OEGMA)-star-PLZ. Three hyperbranched multiarm copolymers with relatively close molecular weights but different degrees of branching were prepared, and all three conjugates could self-assemble to form nanoscale vesicle assemblies with narrow dispersion. The biological activity and secondary structure of lysozyme on the assemblies remained essentially unchanged. Full article

Electronic communication of the Christian message—online preaching—raises distinct theological challenges. Notwithstanding the undeniable convenience and unlimited geographical reach of “virtual church”, electronic media have the potential to separate preacher from congregants, congregants from one another, and—potentially of greatest concern—the church from God, even while appearing to accomplish the opposite. Communication theorist Marshall McLuhan (1911–1980) argues provocatively that virtual representation is at the cost of authentic human identity (in which case it is inimical to community), while French sociologist and philosopher Jean Baudrillard (1929–2007) warns of substituting representation for reality, especially in matters of theology and the identity of God. The paradigm of Jesus’ Incarnation, by contrast, mandates un-mediated divine-human and human-to-human communication, requiring engagement between persons themselves rather than their avatars or provisional simulacra. With respect to electronically mediated communication itself, acknowledging divine initiative in the formation of identity (as a feature of soteriology) and of understanding (under the category of revelation) countermands the more dehumanizing and anti-theological influences that McLuhan and Baudrillard both identify, encouraging direct engagement with God in the person of the Holy Spirit rather than resorting to technological mediation. Full article

The influence of the rapidly changing business environment due to the COVID-19 global pandemic presents an important organizational challenge to fresh produce export supply chains in developing countries such as Ghana. Such an inimical supply chain problem highlights the relevance of supply chain agility as a potent methodological framework to measure, monitor and evaluate these challenges in stable as well as turbulent times. This review paper focuses on the applicability of a framework for Supply Chain Agility as a methodological framework in stable (pre-COVID-19) versus turbulent (COVID-19) business environments. We argue and propose that Supply Chain Agility Framework is a holistic framework which is efficacious in both stable and unstable supply chain environments. This is amply supported by the central plank of our proposition that the Supply Chain Agility Framework offers an adaptable tool that can serve as a panacea to fresh produce supply chain challenges not only in a stable (pre-COVID-19) business environment but also effective and applicable in a turbulent business environment, such as experienced during the COVID-19 pandemic. The implications of this proposition for the fresh produce export supply chain industry and relevant stakeholders are duly presented. Full article

The human gut harbors microbial ecology that is in a symbiotic relationship with its host and has a vital function in keeping host homeostasis. Inimical alterations in the composition of gut microbiota, known as gut dysbiosis, have been associated with cardiometabolic diseases. Studies have revealed the variation in gut microbiota composition in healthy individuals as compared to the composition of those with cardiometabolic diseases. Perturbation of host–microbial interaction attenuates physiological processes and may incite several cardiometabolic disease pathways. This imbalance contributes to cardiometabolic diseases via metabolism-independent and metabolite-dependent pathways. The aim of this review was to elucidate studies that have demonstrated the complex relationship between the intestinal microbiota as well as their metabolites and the development/progression of cardiometabolic diseases. Furthermore, we systematically itemized the potential therapeutic approaches for cardiometabolic diseases that target gut microbiota and/or their metabolites by following the pathophysiological pathways of disease development. These approaches include the use of diet, prebiotics, and probiotics. With the exposition of the link between gut microbiota and cardiometabolic diseases, the human gut microbiota therefore becomes a potential therapeutic target in the development of novel cardiometabolic agents. Full article