Implant Design and Cervical Spinal Biomechanics and Neurorehabilitation: A Finite Element Investigation.

INTRODUCTION: The cervical spine, pivotal for mobility and overall body function, can be affected by cervical spondylosis, a major contributor to neural disorders. Prevalent in both general and military populations, especially among pilots, cervical spondylosis induces pain and limits spinal capabilities. Anterior Cervical Discectomy and Fusion (ACDF) surgery, proposed by Cloward in the 1950s, is a promising solution for restoring natural cervical curvature. The study objective was to investigate the impacts of ACDF implant design on postsurgical cervical biomechanics and neurorehabilitation outcomes by utilizing a biofield head-neck finite element (FE) platform that can facilitate scenario-specific perturbations of neck muscle activations. This study addresses the critical need to enhance computational models, specifically FE modeling, for ACDF implant design. MATERIALS AND METHODS: We utilized a validated head-neck FE model to investigate spine-implant biomechanical interactions. An S-shaped dynamic cage incorporating titanium (Ti) and polyetheretherketone (PEEK) materials was modeled at the C4/C5 level. The loading conditions were carefully designed to mimic helmet-to-helmet impact in American football, providing a realistic and challenging scenario. The analysis included intervertebral joint motion, disk pressure, and implant von Mises stress. RESULTS: The PEEK implant demonstrated an increased motion in flexion and lateral bending at the contiguous spinal (C4/C5) level. In flexion, the Ti implant showed a modest 5% difference under 0% activation conditions, while PEEK exhibited a more substantial 14% difference. In bending, PEEK showed a 24% difference under 0% activation conditions, contrasting with Ti's 17%. The inclusion of the head resulted in an average increase of 18% in neck angle and 14% in C4/C5 angle. Disk pressure was influenced by implant material, muscle activation level, and the presence of the head. Polyetheretherketone exhibited lower stress values at all intervertebral disc levels, with a significant effect at the C6/C7 levels. Muscle activation level significantly influenced disk stress at all levels, with higher activation yielding higher stress. Titanium implant consistently showed higher disk stress values than PEEK, with an orders-of-magnitude difference in von Mises stress. Excluding the head significantly affected disk and implant stress, emphasizing its importance in accurate implant performance simulation. CONCLUSIONS: This study emphasized the use of a biofidelic head-neck model to assess ACDF implant designs. Our results indicated that including neck muscles and head structures improves biomechanical outcome measures. Furthermore, unlike Ti implants, our findings showed that PEEK implants maintain neck motion at the affected level and reduce disk stresses. Practitioners can use this information to enhance postsurgery outcomes and reduce the likelihood of secondary surgeries. Therefore, this study makes an important contribution to computational biomechanics and implant design domains by advancing computational modeling and theoretical knowledge on ACDF-spine interaction dynamics.

Channel assisted noise propagation in a two-step cascade.

Signal propagation in biochemical networks is characterized by the inherent randomness in gene expression and fluctuations of the environmental components, commonly known as intrinsic and extrinsic noise, respectively. We present a theoretical framework for noise propagation in a generic two-step cascade (S→X→Y) regarding intrinsic and extrinsic noise. We identify different channels of noise transmission that regulate the individual and the overall noise properties of each component. Our analysis shows that the intrinsic noise of S alleviates the general noise and information transmission capacity along the cascade. On the other hand, the intrinsic noise of X and Y acts as a bottleneck of information transmission. We also show a hierarchical relationship among the intrinsic noise levels of S, X, and Y, with S exhibiting the highest level of intrinsic noise, followed by X and then Y. This hierarchy is preserved within the two-step cascade, facilitating the highest information transmission from S to Y via X.

The gut-immune-liver axis in patients with alcohol use disorder and clinically low serum zinc levels.

BACKGROUND: Alcohol use disorder (AUD) with chronic and heavy alcohol consumption causes alcohol-associated liver disease (ALD). Early-stage ALD exhibits dyshomeostasis of zinc. We investigated the role of zinc deficiency in gut-barrier dysfunction, proinflammatory response, hepatocyte injury, and death, as well as potential sex differences in AUD patients. METHODS: Thirty-nine male and female AUD patients were grouped by normal [≥71 µg/dL (Group 1, number (n) = 26)] and low [<71 µg/dL (Group 2, n = 13)] serum zinc levels. Demographics, alcohol intake markers [Lifetime Drinking History (LTDH), heavy drinking days in the past 90-days (HDD90), total drinks in the past 90-days (TD90), number of drinking days in the past 90-days (NDD90), average drinks per day in the past 90 days (AvgDPD90)] were collected. Blood samples were tested for complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation markers, gut-barrier dysfunction markers, cytokines, and hepatocyte death markers. RESULTS: Group 2 females exhibited lower LTDH than Group 2 males (p = 0.028), but higher recent drinking. Aspartate transaminase: alanine transaminase (AST:ALT) ratio was higher (p = 0.049) in Group 2 males compared to Group 1 males. Overall, Group 2 showed threefold higher interleukin 8 (IL-8) levels than Group 1 (p = 0.92); these were sevenfold higher in Group 2 females than Group 1 females. Group 2 females also had higher K18M65, but lower K18M30 than Group 1 females. Necrotic type of cell death (K18M65) was well-described only in Group 2 by the arrangement of lipopolysaccharide (LPS), soluble cluster of differentiation 14 (sCD14), and tumor necrosis factor alpha (TNF-α) (R2 = 0.633, p = 0.037). CONCLUSION: Our findings demonstrated the role of the gut-immune-liver axis in describing hepatocyte injury and death in zinc-deficient AUD patients. These patients represented an arrangement of gut-barrier dysfunction and an exacerbated immune response. Shift in the cell-death mechanism from apoptosis in zinc-replete females to necrosis in zinc-deficient females suggests a subclinical to clinical transition of ALD associated with zinc status.

Monomeric Fe(III)-Hydroxo and Fe(III)-Aqua Complexes Display Oxidative Asynchronous Hydrogen Atom Abstraction Reactivity.

This paper presents the synthesis and characterization of a series of novel monomeric aqua-ligated iron(III) complexes, [FeIII(L5R)(OH2)]2+ (R=OMe, H, Cl, NO2), supported by an amide-containing pentadentate N5 donor ligand, L5R [HL5R=2-(((1-methyl-1H-imidazol-2-yl)methyl)(pyridin-2-yl-methyl)amino)-N-(5-R-quinolin-8-yl)acetamide]. The complexes were characterized by various spectroscopic and analytical techniques, including electrochemistry and magnetic measurements. The Fe(III)-hydroxo complexes, [FeIII(L5R)(OH)]1+, were generated in situ by deprotonating the corresponding aqua complexes in a pH ~7 aqueous medium. In another way, adding one equivalent of a base to a methanolic solution of the Fe(III)-aqua complexes also produced the Fe(III)-hydroxo complexes. The study uses linoleic fatty acid as a substrate to explore the hydrogen atom abstraction (HAA) reactivity of both hydroxo and aqua complexes. The investigation highlights the substitution effect of the L5R ligand on reactivity, revealing a higher rate when an electron-withdrawing group is present. Hammett analyses and(or) determination of the asynchronicity factor (η) suggest an oxidative asynchronous concerted proton-electron transfer (CPET) pathway for the HAA reactions. Aqua complexes exhibited a higher asynchronicity in CPET, resulting in higher reaction rates than their hydroxo analogs. Overall, the work provides insights into the beneficial role of a higher imbalance in electron-transfer-proton-transfer (ET-PT) contributions in HAA reactivity.

Synthesis, characterization and reactivity of a Mn(III)-hydroxido complex as a biomimetic model for lipoxygenase.

Manganese hydroxido (Mn-OH) complexes supported by a tripodal N,N',N″-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat]3-) ligand have been synthesized and characterized by spectroscopic techniques including UV-vis and electron paramagnetic resonance (EPR) spectroscopies. X-ray diffraction (XRD) methods were used to confirm the solid-state molecular structures of {Na2[MnIIpoat(OH)]}2 and {Na[MnIIIpoat(OH)]}2 as clusters that are linked by the electrostatic interactions between the sodium counterions and the oxygen atom of the ligated hydroxido unit and the phosphinic (P=O) amide groups of [poat]3-. Both clusters feature two independent monoanionic fragments in which each contains a trigonal bipyramidal Mn center that is comprised of three equatorial deprotonated amide nitrogen atoms, an apical tertiary amine, and an axial hydroxido ligand. XRD analyses of {Na[MnIIIpoat(OH)]}2 also showed an intramolecular hydrogen bonding interaction between the MnIII-OH unit and P=O group of [poat]3-. Crystalline {Na[MnIIIpoat(OH)]}2 remains as clusters with Na+---O interactions in solution and is unreactive toward external substrates. However, conductivity studies indicated that [MnIIIpoat(OH)]- generated in situ is monomeric and reactivity studies found that it is capable of cleaving C-H bonds, illustrating the importance of solution-phase speciation and its direct effect on chemical reactivity. Synopsis: Manganese-hydroxido complexes were synthesized to study the influence of H-bonds in the secondary coordination sphere and their effects on the oxidative cleavage of substrates containing C-H bonds.

Evaluating postoperative outcome assessment tools in hepato-pancreato-biliary surgery: A comparative analysis of the comprehensive complication index and Clavien-Dindo classification in a cohort of 1240 patients at a tertiary care center.

Introduction: The comprehensive complication index (CCI) has emerged as a new tool for reporting postoperative complications. The aim of this study is to evaluate and compare the efficacy of CCI and Clavien-Dindo Classification (CDC) in measuring postoperative outcomes in patients undergoing hepato-pancreato-biliary (HPB) surgery. Materials and methods: In this single-centered, prospective, comparative study conducted between January 2022 and March 2023, 1240 patients underwent HPB surgery, including laparoscopic cholecystectomies and complex HPB surgery. Postoperative complications were evaluated utilizing the CCI and CDC indices, and their relationships with length of ICU stay, hospital stay, and return to activity were compared. Results: A total of 117 patients (9.44%) experienced complications of varying grades. There was a strong correlation between CCI and CDC (r=0.982, P <0.001). Both CCI and CDC demonstrated a strong correlation with the length of hospital stay, ICU stay, and return to normal activity. While CCI showed a better correlation with the length of hospital stay (r=0.706 vs. 0.695) and return to normal activity (r=0.620 vs. 0.611) than CDC, the difference was not statistically significant. Conclusion: CCI exhibited a stronger correlation with the length of stay and return to activity; however, no statistically significant advantage was observed over CDC.

Supported-amine-catalyzed cascade synthesis of spiro-thiazolone-tetrahydrothiophenes: assessing HSA binding activity.

We have devised a supported-amine-catalyzed efficient synthesis of spiro-thiazolone-tetrahydrothiophenes via a sulfa-Michael/aldol cascade approach. The catalyst demonstrated sustained efficacy over 21 cycles. These derivatives were found to exhibit excellent binding abilities with purified human serum albumin as indicated by both in silico and in vitro-based experiments.

Edge-functionalized coal-derived graphene oxide in bacterial nanocellulose hydrogel for active wound healing.

This work presents a comparison of physicochemical and in vitro active wound healing properties of two distinct Graphene Oxides (GOs) from graphite and coal. These GOs are incorporated in Bacterial Nanocellulose (BNC) to form hydrogels. The performance and limitations of the loading fraction of both GOs in BNC are controlled by the processing technology and the source materials from which GOs are derived. Edge functionalization with C-GO offers the advantage of facilitating face-to-edge assembly in the hydrogel leading to better dispersion than the face-to-face assembly of basal functionalized G-GO. The latter leads to more aggregation of G-GO, resulting in a lower optimal loading fraction. Our investigation into the antibacterial properties of the BNC and BNC/GO hydrogels against gram-negative E. coli revealed inhibitory effects of the BNC/GO hydrogels that intensified with an increase in the concentration of GO. Furthermore, an in vitro wound scratch assay demonstrated that BNC/C-GO hydrogels promote better cell migration, confirming their superior biocompatibility and suitability as active wound dressings, albeit limited by loading fraction due to agglomeration. These findings shed light on the performance and limitations of GOs for diverse applications, emphasizing the significance of exploring the influence of different methods and source materials of GOs.

Lipidomic Analysis Reveals Systemic Alterations in Servicemen Exposed to Repeated Occupational Low-Level Blast Waves.

INTRODUCTION: Occupational exposure to blast is a prevalent risk experienced by military personnel. While low-level exposure may not manifest immediate signs of illness, prolonged and repetitive exposure may result in neurophysiological dysfunction. Such repeated exposure to occupational blasts has been linked to structural and functional modifications in the brain, adversely affecting the performance of servicemen in the field. These neurological changes can give rise to symptoms resembling concussion and contribute to the development of post-traumatic stress disorder. MATERIALS AND METHODS: To understand long-term effects of blast exposure, the study was conducted to assess memory function, serum circulatory protein and lipid biomarkers, and associated concussive symptomology in servicemen. Concussion-like symptoms were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) along with memory function using PGI memory scale. The serum protein biomarkers were quantified using a sandwich ELISA assay, and the serum lipid profile was measured using liquid chromatography-mass spectrometer. RESULTS: The findings revealed that repeated low-level blast exposure resulted in impaired memory function, accompanied by elevated levels of serum neurofilament light chain (neuroaxonal injury) and C-reactive protein. Furthermore, alterations in the lipid profile were observed, with an increase in lipid species associated with immune activation. These changes collectively point to systemic inflammation, neuronal injury, and memory dysfunction as pathological characteristics of repeated low-level blast exposure. CONCLUSION: The results of our preliminary investigation offer valuable insights for further large-scale study and provide a guiding principle that necessitates a suitable mitigation approach to safeguard the health of personnel against blast overpressure.

In silico prediction of heme binding in proteins.

The process of heme binding to a protein is prevalent in almost all forms of life to control many important biological properties, such as O2-binding, electron transfer, gas sensing or to build catalytic power. In these cases, heme typically binds tightly (irreversibly) to a protein in a discrete heme binding pocket, with one or two heme ligands provided most commonly to the heme iron by His, Cys or Tyr residues. Heme binding can also be used as a regulatory mechanism, for example in transcriptional regulation or ion channel control. When used as a regulator, heme binds more weakly, with different heme ligations and without the need for a discrete heme pocket. This makes the characterization of heme regulatory proteins difficult, and new approaches are needed to predict and understand the heme-protein interactions. We apply a modified version of the ProFunc bioinformatics tool to identify heme-binding sites in a test set of heme-dependent regulatory proteins taken from the Protein Data Bank and AlphaFold models. The potential heme binding sites identified can be easily visualized in PyMol and, if necessary, optimized with RosettaDOCK. We demonstrate that the methodology can be used to identify heme-binding sites in proteins, including in cases where there is no crystal structure available, but the methodology is more accurate when the quality of the structural information is high. The ProFunc tool, with the modification used in this work, is publicly available at https://www.ebi.ac.uk/thornton-srv/databases/profunc and can be readily adopted for the examination of new heme binding targets.

Attributes of hypertension among industrial workers in Northern India - An alarming signal.

Context: There has been an increasing prevalence of hypertension (HTN) affecting all populations of the world including the special occupational groups and industries workers. Aims: To estimate the prevalence of hypertension and to determine the associated factors among industrial workers in the Haryana state of India. Settings and Design: A cross-sectional study was conducted among 323 industrial workers of Faridabad, Haryana. Materials and Methods: A semi-structured and validated questionnaire was used to collect information regarding sociodemographic characteristics of the workers, their personal habits, and occupational history. The investigator also recorded the height, weight, blood pressure, blood glucose, and lipid profile of the workers. Statistical Analysis Used: Analysis of the data was done using SPSS Vs 21. Results: The prevalence of hypertension among industrial workers was 48.6%. Age of the worker, presence of smoking or alcohol consumption, having a longer duration of employment, and having deranged total cholesterol/TG/LDL-C levels, diabetes, or obesity were found to be independently associated with hypertension. Conclusion: Screening is required for early detection and prevention of complications. Lifestyle modification is of utmost importance. Employers should implement guidelines issued by the government to protect the health of the productive population.

Finding the Ajoene Sweet-Spot: Structure-Activity Relations that Govern its Blood Stability and Cancer Cytotoxicity.

Ajoene is an organosulfur compound found in crushed garlic that exerts its anti-cancer activity by S-thiolating cysteine residues on proteins. Its development is hampered due to limited bioavailability, so in this study, we synthesised analogues of ajoene to probe the significance of the ajoene vinyl disulfide/sulfoxide core with respect to cytotoxicity and blood stability. Polar side groups were also incorporated to improve aqueous solubility. It was found that derivatives containing a vinyl disulfide functional group (4-7, as in ajoene), were more cytotoxic compared to analogues in which the double bond was removed, although the latter showed superior blood stability. It was also found that the allyl-S sulfur of the disulfide was more electrophilic to S-thiolysis based on the global electrophilicity index (ω) and the condensed electrophilic Fukui function f k + ${{ f}_{\rm{k}}^{\rm{ + }} }$ . S-Thiolysis was found to be exergonic for the vinyl disulfides based on entropy and enthalpy computations with a deprotonated thiolate. Derivatisation to the dihydro (10, 12) and deoxydihydroajoenes (9, 11) produced analogues that were slightly less potent but with greatly improved blood stability. Taken together, the deoxydihydroajoenes present themselves as good candidates for further therapeutic development.

Screening and Evaluation of Sleep Disturbances and Sleep Disorders in Children and Adolescents.

Sleep disturbances and sleep disorders are prevalent in children/adolescents and have a bidirectional relationship with pediatric medical and mental health disorders. Screening tools and mechanisms for the evaluation and treatment of sleep disturbances and sleep disorders in the pediatric mental health clinic are less well-known; hence, sleep disturbances and disorders are under-recognized in the pediatric clinics. We present specific, validated screening and evaluation tools to identify sleep disturbances and sleep disorders in children/adolescents. We offer guidance related to the use of consumer wearables for sleep assessments and use of sleep telemedicine in pediatric mental health and primary care clinics.

Multi-faceted dysregulated immune response for COVID-19 infection explaining clinical heterogeneity.

Clinical heterogeneity and varied prognosis are well noted for SARS-CoV-2 infection. Altered immune response is a major feature for the adverse prognosis however focus on altered immune response has been primarily limited to hyper-inflammatory responses like Cytokine storm. A deeper understanding of viral pathobiology and the interplay of innate and adaptive immune cells against SARS-CoV-2 infection is essential to optimize intervention strategy and future preparedness for SARS-CoV-2 or its related viral diseases. To uncover the immunological signatures driving the progression of SARS-CoV-2 infection, we performed an extensive immunophenotype on blood samples from 79 hospitalized patients with mild/moderate to severe infections as well as from healthy controls and recovered donors to understand the interplay between innate and adaptive responses impacting severity and prognosis. We observed multifarious immune dysregulation, varied across patients of the clinical spectrum. We observed 4 major dysregulations of immune phenotypes 1) depletion of M1φ (impaired antiviral response as APC), 2) immune suppression/exhaustion via activation of repressor like CD4+/CD8+PD1, TIM3, LAG3 3) inappropriate differentiation of lymphocyte (extreme elevated proportion of CD4 naive, memory B and T cells along with reduction of inflammatory activator like TLR2/4/TIGIT) and 4) cytokine storm. Our results show the identification of biomarkers to differentiate the different trajectories for SARS-CoV-2 infection.

Evaluation of an Objective MRI-Based Tumor Regression Grade (mrTRG) Score and a Subjective Likert Score for Assessing Treatment Response in Locally Advanced Rectal Cancers-A Retrospective Study.

Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.

Determination of sputum eosinophil count and serum absolute eosinophil count in patients with bronchial asthma and its correlation with disease severity and response to treatment.

Background: Sputum eosinophils can be used to assess severity of disease and response to treatment in bronchial asthma. Eosinophilic inflammation in the airways can also be marked by blood eosinophilia. In this study, we tried to determine the sputum eosinophil count and serum absolute eosinophil count in patients with asthma and correlate them with disease severity and treatment response. Materials and Methods: It was a cross-sectional intervention study including all consecutive cases with a diagnosis of bronchial asthma based on spirometry and clinical history. An induced sputum sample and blood were sent for eosinophil count to the laboratory. All the patients were started on inhaled corticosteroids and followed up at the end of 1 month with spirometry, sputum eosinophil count and AEC. Statistical Package for the Social Sciences for Windows v20.0 (IBM SPSS Corp.; Armonk, NY, USA) was used for statistical analysis. Results: There was no significant difference in the mean sputum eosinophil count (%) in mild, moderate and severe disease (f = 0.24; P = 0.79) or in AEC (f = 1.48; P = 0.24). At follow-up, all patients with moderate and severe disease showed significant improvement in FEV1 (P = 0.0001). The mean sputum eosinophil count and AEC (%) in the three subgroups was also seen to decrease at the end of the follow-up period (f = 0.08; P = 0.9 and f = 2.75; P = 0.07, respectively). Conclusion: Sputum eosinophils and AEC are important markers of airway inflammation. All our patients showed improvement in FEV1, sputum eosinophil count and AEC after 1 month of treatment thus confirming the role of ICS in the treatment of eosinophilic asthma.

An Uncommon Side Effect of Rivaroxaban: A Drug-Induced Liver Injury.

Rivaroxaban is rarely associated with drug-induced liver injury (DILI). A 57-year-old male was sent to the emergency room from an endocrine clinic for a presyncope evaluation. His exam was non-focal, and his laboratory work was remarkable for the hepatocellular pattern of liver injury. Upon detailed assessment, he was found to have DILI due to rivaroxaban. The liver function tests improved after its discontinuation. This case emphasizes the need for early recognition and timely intervention to prevent further hepatotoxicity from the culprit drug.

A Rare Case of Elevated Transaminases With Incomplete Abortion Due to Cytomegalovirus Infection: An Experience From a Resource-Limited Setting.

Cytomegalovirus (CMV) infection during pregnancy may cause spontaneous abortion, stillbirth, and death of newborns. CMV is the most common congenital infection in newborns. It generally has a benign course in immunocompetent individuals, while the severe disease is usually seen in immunocompromised patients. Most of the published studies about CMV infection describe congenital abnormalities in newborns. Only a handful of case reports mention CMV infection associated with elevated transaminases during pregnancy. Here, we present a case of incomplete abortion with elevated liver enzymes in a 26-year-old female caused by CMV infection. Our case report illustrates the importance of considering CMV infection as a differential in an incomplete abortion associated with elevated liver enzymes.

Recyclable Polymer Supported DMAP Catalyzed Cascade Synthesis of α-Pyrones.

Polymer-supported catalysts have emerged as one of the sustainable and cost-effective alternatives in organic synthetic chemistry. We have developed the first polymer-supported DMAP catalyzed one-pot synthesis of diversely substituted α-pyrones. The cascade approach involves C5 conjugate addition of 5H-oxazol-4-ones to α,ß-unsaturated-ß-ketoesters followed by lactonization/elimination.