Home, but Homebound after Traumatic Brain Injury: Risk Factors and Associations with Nursing Home Entry and Death.

OBJECTIVE: To examine risk factors associated with homeboundness 1-year following traumatic brain injury (TBI) and to explore associations between homebound status and risk of future mortality and nursing home entry. DESIGN: Secondary analysis of a longitudinal prospective cohort study SETTING: TBI Model Systems (TBIMS) Centers PARTICIPANTS: Community-dwelling TBIMS participants (n=6,595) who sustained moderate-severe TBI between 2006-2016, and resided in a private residence 1-year post-injury. INTERVENTIONS: N/A MAIN OUTCOME MEASURES: Homebound status (leaving home ≤1-2 days per week), 5-year mortality, and 2- or 5-year nursing home entry. RESULTS: In our sample, 14.2% of individuals were homebound 1-year post-injury, including 2% who never left home. Older age, having less than a Bachelor's degree, Medicaid insurance, living in the Northeast or Midwest, dependence on others or special services for transportation, unemployment or retirement, and needing assistance for locomotion, bladder management, and social interactions at 1-year post-injury were associated with being homebound. After adjustment for potential confounders and an inverse probability weight for nonrandom attrition bias, being homebound was associated with a 1.69-times (95% CI: 1.35-2.11) greater risk of five-year mortality, and a non-significant but trending association with nursing home entry by 5 years post-injury (RR=1.90, 95% CI: 0.94, 3.87). Negative associations between homeboundness and mortality were consistent by age subgroup (± 65 years). CONCLUSIONS: The negative long-term health outcomes among persons with TBI who rarely leave home warrants the need to re-evaluate home discharge as unequivocally positive. The identified risk factors for homebound status, and its associated negative long-term outcomes, should be considered when preparing patients and their families for discharge from acute and post-acute rehabilitation care settings. Addressing modifiable risk factors for homeboundness, such as accessible public transportation options and home care to address mobility, could be targets for individual referrals and policy intervention.

Rising global temperatures and its impact on sleep behavior of male redheaded bunting (Emberiza bruniceps).

Anthropogenic global warming is one of the most pervasive threats to nature and biodiversity. The magnitude with which earths' temperature is rising is affecting every lifeform uniquely; however, the studies highlighting the impacts of global warming on avian sleep are scarce. To this end, the present study was aimed at analyzing the impact of global warming on sleep behavior of a nocturnal migrant, Emberiza bruniceps. For this purpose, the birds were divided into two groups (N = 15 each), subjected to high (35 ± 1 °C) and low (19 ± 1 °C) temperature schedule with concurrent exposure to 8L:16D (short day; SD) photoperiod followed by 13L:11D (long day; LD). The experiment continued till 7 cycles of zugunruhe (LD) in birds. The results reveal significant impact of temperature treatment on initiation and quality of zugunruhe. Temporal distribution of activity and rest varied according to the temperature provided. Focusing on rest and specifically on sleep of birds, high ambient temperatures resulted in greater sleep fragmentation (evident by increased awakenings during night), whereas low temperature created a sleep conducive environment (evident by abundance of back sleep). Besides postural differences, high temperature resulted in reduced sleep duration, sleep onset latency and circulating plasma melatonin levels in comparison with low temperature suggesting the negative impact of high temperature on different sleep attributes. Not only sleep, seasonal physiology of birds such as hyperphagia, gain in body mass, and fat stores showed significant reduction in high temperature condition. Besides behavioral and physiological alterations, high ambient temperature led to elevated expression of temperature sensitive (trpv4, trpm8, hspa8, and hsp70) genes. Enhanced expression of chrm3 (responsible for wakefulness) also affirms sleep fragmentation in response to high temperature. Thus, the study highlights the negative impact of high temperature on birds' sleep behavior and seasonal physiology.

Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells.

Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.

Changing Spectrum of Invasive Fungal Infections of the Anterior Skull Base.

Objective To study the etiological and anatomical factors in pathophysiology of invasive fungal rhinosinusitis affecting the skull base. Design Retrospective clinical study over 5 years. Setting Single-center tertiary referral hospital. Materials and Methods All cases of invasive fungal rhinosinusitis with clinicoradiological and/or operative evidence of anterior and central skull base, orbit, and orbital apex involvement with or without intracranial disease were included in the study. Patients with a sinonasal-palatal disease without the involvement of the skull base or orbit were excluded from the study. In addition, we assessed the risk factors such as coronavirus disease 2019 (COVID-19) infection, diabetes mellitus (DM), and other immunocompromised conditions. Results There were 79 patients, of which 65.8% had skull base rhino-oribitocerebral mucormycosis (ROCM), and 34.2% had Aspergillus infection. The mean duration from onset of the symptom to presentation of ROCM was 36.75 ± 20.97 days, while for the Aspergillus group was 21 weeks. The majority of patients (66%) with ROCM presented after 30 days of symptom onset. Among ROCM patients, 88.7% had a history of COVID-19 infection, and 96% had DM. In 40.8% of patients with Aspergillus infection, the tissue diagnosis was unavailable, and galactomannan assay and clinicoradiological assessment were used for diagnosis. The most common area of the skull base involved was the pterygopalatine fossa (88.5%), followed by the infratemporal fossa (73.1%). The most common neurovascular structure (75%) involved was the pterygopalatine ganglion and the infraorbital nerve. Conclusion With the increasing incidence of invasive fungal infections worldwide, particularly after the COVID-19 pandemic, it is crucial to understand the evolving nature of this disease. ROCM, documented in the literature to cause fulminant disease, became a chronic illness, possibly due to the improvement of the patient's immunity during the disease course.

Exploring Incision Options for Mandibular Fractures: A Review of Vestibular and Crevicular Approach.

The approach to mandibular fractures remains a contentious topic, with the vestibular and crevicular approaches being prominent incision options, each offering distinct advantages. This review explores the comparative benefits of crevicular incisions over the vestibular approach, focusing on ease of surgical access, better fracture reduction, and enhanced soft tissue healing. Along with a thorough literature review, a case report is also presented to exemplify the successful implementation of crevicular incision in treating a mandibular fracture, emphasizing on its key advantages, which include decreased risk of nerve injury and enhanced patient comfort, underscoring the clinical benefits of this approach. By synthesizing existing literature and case report findings, this review supports the adoption of crevicular incision as a preferred approach for various mandibular fracture cases. This approach offers clinicians a reduced surgical time, good soft tissue adaptation, improved surgical outcomes, and patient well-being.

Glucose-Regulated Protein 78, via Releasing ß-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization.

Retinopathy due to neovascularization is one of the major causes of vision loss. To understand the mechanisms underlying retinal neovascularization, using the oxygen-induced retinopathy (OIR) model, we performed two-dimensional gel matrix-assisted laser desorption/ionization time-of-flight/time-of-flight analysis of normoxic and 24-hour post-OIR mice pups' retinas. Two-dimensional gel analysis revealed that glucose-regulated protein 78 (GRP78) is one of the several molecules induced by OIR in the retinal endothelial cells (ECs). Vascular endothelial growth factor A (VEGFA) also induced GRP78 expression independent of endoplasmic reticulum stress response in human retinal microvascular endothelial cells, and depletion of its levels reduced VEGFA-induced EC angiogenic responses. Consistent with these observations, EC-specific deletion of GRP78 inhibited OIR-induced retinal neovascularization. In exploring the mechanisms, we found that GRP78 binds with vascular endothelial-cadherin and releases adherens junction- but not Wnt-mediated ß-catenin and that ß-catenin, in turn, via interacting with STAT3, triggers cyclin D1 expression. Furthermore, depletion of ß-catenin or cyclin D1 levels negated VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. EC-specific deletion of GRP78 also suppressed OIR-induced vascular leakage. In elucidating the upstream signaling, we found that activating transcription factor 6 mediates GRP78 induction in the modulation of VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. Together, these observations reveal that GRP78, independent of its response to endoplasmic reticulum stress, is involved in mediating EC angiogenic responses by VEGFA and retinal neovascularization by OIR. In view of these findings, it appears that GRP78 could be a desirable target for drug development against diabetic retinopathy.

Cognitive Performance is Associated With 1-Year Participation and Life Satisfaction Outcomes: A Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To determine, in persons with traumatic brain injury (TBI), the association between cognitive change after inpatient rehabilitation discharge and 1-year participation and life satisfaction outcomes. DESIGN: Secondary analysis of prospectively collected TBI Model Systems (TBIMS) data. SETTING: Inpatient rehabilitation and community. PARTICIPANTS: 499 individuals with TBI requiring inpatient rehabilitation who completed the Brief Test of Adult Cognition by Telephone (BTACT) at inpatient rehabilitation discharge (ie, baseline) and 1-year postinjury. MAIN OUTCOME MEASURES: Participation Assessment with Recombined Tools-Objective (PART-O) and Satisfaction with Life Scale (SWLS). RESULTS: Of 2,840 TBIMS participants with baseline BTACT, 499 met inclusion criteria (mean [standard deviation] age = 45 [19] years; 72% male). Change in BTACT executive function (EF) was not associated with 1-year participation (PART-O; ß = 0.087, 95% CI [-0.004, 0.178], P = .061) when it was the sole model predictor. Change in BTACT episodic memory (EM) was associated with 1-year participation (ß = 0.096, [0.007, 0.184], P = .035), but not after adjusting for demographic, clinical, and functional status covariates (ß = 0.067, 95% CI [-0.010, 0.145], P = .089). Change in BTACT EF was not associated with life satisfaction total scores (SWLS) when it was the sole model predictor (ß = 0.091, 95% CI [-0.001, 0.182], P = .0503). Change in BTACT EM was associated with 1-year life satisfaction before (ß = 0.114, 95% CI [0.025, 0.202], P = .012) and after adjusting for covariates (ß = 0.103, [0.014, 0.191], P = .023). In secondary analyses, change in BTACT EF was associated with PART-O Social Relations and Out and About subdomains before (Social Relations: ß = 0.127, 95% CI [0.036, 0.217], P = .006; Out and About: ß = 0.141, 95% CI [0.051, 0.232], P = .002) and after (Social Relations: ß = 0.168, 95% CI [0.072, 0.265], P < .002; Out and About: ß = 0.156, 95% CI [0.061, 0.252], P < .002) adjusting for functional status and further adjusting for covariates (Social Relations: ß = 0.127, 95% CI [0.040, 0.214], P = .004; Out and About: ß = 0.136, 95% CI [0.043, 0.229], P = .004). However, only the models adjusting for functional status remained significant after multiple comparison correction (ie, Bonferroni-adjusted alpha level = 0.002). CONCLUSION: EF gains during the first year after TBI were related to 1-year social and community participation. Gains in EM were associated with 1-year life satisfaction. These results highlight the potential benefit of cognitive rehabilitation after inpatient rehabilitation discharge and the need for interventions targeting specific cognitive functions that may contribute to participation and life satisfaction after TBI.

A cub and sushi domain-containing protein with esterase-like activity confers insecticide resistance in the Indian malaria vector Anopheles stephensi.

Chemical insecticides (organophosphates and pyrethroids) in the form of IRS (Indoor Residual Sprays) and LLINs (Long Lasting Insecticidal Nets) are the cornerstone for vector control, globally. However, their incessant use has resulted in widespread development of resistance in mosquito vectors, warranting continuous monitoring and investigation of the underlying mechanisms of resistance. Here, we identified a previously uncharacterized- Cub and Sushi Domain containing Insecticide Resistance (CSDIR) protein and generated evidence for its role in mediating insecticide resistance in the Anopheles stephensi. A strong binding affinity of the CSDIR protein towards different classes of insecticide molecules-malathion (KD 6.43 µM) and deltamethrin (KD 46.7 µM) were demonstrated using MD simulation studies and Surface Plasmon Resonance (SPR) experiments. Further, the recombinant CSDIR913-1190 protein exhibited potent esterase-like activity (α-naphthyl acetate (α-NA)- 1.356 ± 0.262 mM/min/mg and ß-naphthyl acetate (ß -NA)- 1.777 ± 0.220 mM/min/mg). Interestingly, dsRNA-mediated gene silencing of the CSDIR transcripts caused >60% mortality in resistant An. stephensi upon 1-h exposure to deltamethrin and malathion insecticides, compared to the control group. A significant reduction in the esterase-like activity was also observed against α-NA (p = 0.004) and ß-NA (p = 0.025) in CSDIR silenced mosquitoes compared to the control group. Using computational analysis and experimental data, our results provided significant evidence of the involvement of the CSDIR protein in mediating insecticide resistance in Anopheles mosquitoes. Thereby making the CSDIR protein, a novel candidate for exploration of novel insecticide molecules. These data would also be helpful in further understanding the development of metabolic resistance by the Anopheles vector.

Structural proteomics defines a sequential priming mechanism for the progesterone receptor.

The progesterone receptor (PR) is a steroid-responsive nuclear receptor, expressed as two isoforms: PR-A and PR-B. The isoforms display distinct expression patterns and biological actions in reproductive target tissues and disruption of PR-A:PR-B signaling is associated with breast cancer development potentially by altering interactions with oncogenic co-regulatory protein (CoRs). However, the molecular details of isoform-specific PR-CoR interactions that influence progesterone signaling remain poorly understood. We employed structural mass spectrometry in this study to investigate the sequential binding mechanism of purified full-length PR and full-length CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes with target DNA. Our findings reveal selective CoR NR-box binding by PR and novel interaction surfaces between PR, SRC3, and p300, which change during complex assembly. This provides a structural model for a sequential priming mechanism that activates PR. Comparisons of PR bound to progesterone agonist versus antagonist challenges the classical model of nuclear receptor activation and repression. Collectively, we offer a peptide-level perspective on the organization of the PR transcriptional complex and elucidate the mechanisms behind the interactions of these proteins, both in active and inactive conformations.

Epigenetic regulation of NKG2D ligand and the rise of NK cell-based immunotherapy for cancer treatment.

Epigenetic modifications influence gene expression and effects cancer initiation and progression. Therefore, they serve as diagnostic and prognostic biomarkers and potential therapeutic targets. Natural Killer (NK) cells, integral to the innate immune system, exhibit anti-tumor effect by recognizing and eliminating cancerous cells through the balance of activating and inhibitory ligands. Understanding the epigenetic regulation of NK cell ligands offers insights into enhancing NK cell-mediated tumor eradication. This review explores the epigenetic modifications governing the expression of activating NKG2D ligands and discusses clinical trials investigating NK cell-based immunotherapies, highlighting their potential as effective cancer treatment strategies. Case studies examining the safety and effectiveness of NK cell therapies in different cancer types, such as acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC), demonstrate promising outcomes with minimal toxicity. These findings underscore the therapeutic prospects of epigenetic modulation of NKG2D ligands and NK cell-based immunotherapies as effective cancer treatment strategies. Future research in the advancement of personalized medicine approaches and novel combination therapies with NK cell will further improve treatment outcomes and provide new therapeutic options for treating patients with various types of cancer.

The TBI Model Systems Neighborhood Socioeconomic Disadvantage Index (TBIMS-NSDI): Development and Comparison to Individual Socioeconomic Characteristics.

OBJECTIVE: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: People enrolled in the TBI Model Systems National Database (TBIMS NDB). DESIGN: Secondary analysis of a longitudinal cohort study. MAIN MEASURES: The TBIMS-NSDI was calculated at the census tract level for the United States population based on a principal components analysis of eight census tract-level variables from the American Community Survey. Individual socioeconomic characteristics from the TBIMS NDB were personal household income, education (years), and unemployment status. Neighborhood:Individual NSDI residuals represent the difference between predicted neighborhood disadvantage based on individual socioeconomic characteristics versus observed neighborhood disadvantage based on the TBIMS-NSDI. RESULTS: A single principal component was found to encompass the eight socioeconomic neighborhood-level variables. It was normally distributed across follow-up years 2, 5, and 10 post-injury in the TBIMS NDB. In all years, the TBIMS-NDSI was significantly associated with individual-level measures of household income and education but not unemployment status. Males, persons of Black and Hispanic background, Medicaid recipients, persons with TBI caused by violence, and those living in urban areas, as well as in the Northeast or Southern regions of the United States, were more likely to have greater neighborhood disadvantage than predicted based on their individual socioeconomic characteristics. CONCLUSIONS: The TBIMS-NSDI provides a neighborhood-level indicator of socioeconomic disadvantage, an important social determinant of outcomes from TBI. The Neighborhood:Individual NSDI residual adds another dimension to the TBIMS-NSDI by summarizing how a person's socioeconomic status aligns with their neighborhood socioeconomics. Future studies should evaluate how both measures affect TBI recovery and life quality. Research studying neighborhood socioeconomic disadvantage may improve our understanding of how systemic adversity influences outcomes after TBI.

Isolation and Molecular Characterization of the LTA precursor molecule Glc2-DAG, a potential target for antibiotics.

Bacterial infections present a major global health threat, often displaying resistance to various antibiotics. Lipoteichoic acid (LTA) is a vital component of bacterial cell envelopes of Gram-positive bacteria, crucial for cell integrity, cell division, and host inflammation. Due to its essential role for bacteria, LTA and its biosynthesis are also attractive drug targets, however, there is only scant molecular knowledge on LTA and its precursor molecules in membranes. Here, we report the isolation and molecular characterization of diglucosyldiacylglycerol (Glc2-DAG), the glycolipid precursor molecule that anchors LTA in the bacterial plasma-membrane. Using a tailored growth medium and purification protocols, we isolated 13C-isotope labelled Glc2-DAG from bacteria, which can then be used for high-resolution NMR studies. Using solution-state and solid-state NMR, we show an in-depth molecular characterization of Glc2-DAG, including in native-like membranes. Our approach may help to identify antibiotics that directly target LTA precursor molecules, and it offers a tool for future investigations into the role of Glc2-DAG in bacterial physiology.

Pediatric Lumbosacral Spondylolisthesis: Overcoming the Disability!

BACKGROUND: Congenital spondylolisthesis is characterized by dysplasia of the facet joint or congenital defect in the pars. OBJECTIVE: Our study highlights the clinical and radiological profile, various treatment options, and outcomes in patients with pediatric congenital lumbar and lumbosacral spondylolisthesis. METHODS: A retrospective analysis and follow-up of 22 patients were conducted presented with radiological diagnosis of congenital lumbar/lumbosacral spondylolisthesis (2018-2021). RESULTS: Twenty patients (91%) had L5-S1 listhesis and two patients (9%) had L4-L5 listhesis. Six (27.3%) patients had low-grade listhesis (grades 1-2), 16 (72.7%) had high-grade listhesis (grades 3-5). Seventeen (77.3%) had S1, three (13.6%) had L5, and two (9%) had both L4-L5 radiculopathy. All patients had neurogenic claudication. One had an associated spina bifida occulta. Six (27.3%) patients underwent two-level fixation, and 16 (72.7%) underwent three-level fixation. Minimally Invasive Transforaminal Lumbar Interbody Fusion (MIS TLIF) was done in two patients. Revision of at least one screw was done in three patients. After one year of follow-up, all the patients had 75-100% relief in radicular pain and neurogenic claudication. The Oswestry Disability Index (ODI) score in preop for all patients was 41-60% and postoperatively they showed an improvement in ODI score (0-20). The postoperative low back pain score on the Numeric Rating Scale was 0-1 for all patients. CONCLUSION: Congenital lumbar spondylolisthesis usually presents with high-grade listhesis. Management of such cases is a surgical challenge but posterior decompression resulted in relief of pain in all patients. However, in situ fixation without reduction is also effective in selective cases where attempts to reduce the listhesis result in a decline in intraoperative neuromonitoring parameters.

Potential and Pitfalls of Postoperative Volumetric Assessment of Extent of Resection in High-Grade Glioma in Resource-Constrained Settings.

BACKGROUND: While literature suggests the need for routine postoperative volumetric estimation of the EOR and residual tumour volume (RTV) in all cases of gliomas, the utility and feasibility of this protocol in resource-constrained centers remain underinvestigated. OBJECTIVES: Our objective was to study the feasibility of volumetric EOR in routine neurosurgical practice and determine correlation with surgeons' intraoperative estimation of EOR. The secondary objective was to determine the survival impact of EOR and RTV on survival. METHODS AND MATERIALS: A prospective study of pathologically proven high-grade gliomas (WHO grades 3 and 4) in adults was conducted at a tertiary care center. Pre- and postoperative magnetic resonance imaging (MRI) was obtained for volumetric analysis using OsiriX software and manual segmentation. Overall survival and predictors were studied using Kaplan-Meier and Cox regression analysis. RESULTS: Postoperative volumetry was feasible in 31% patients (n = 25) of study eligible patients (n = 84). The median EOR, CE-PTV, and CE-RTV were 79.1%, 69.8 cm3, and 8.7 cm3, respectively. There was a poor correlation of surgeons' intraoperative impression and volumetric data (P = 0.359). Interestingly, the EOR was not significantly associated with the survival time (P = 0.920), while tumor grade, molecular profile, Ki 67 score, and postoperative functional status showed statistically significant impact. CONCLUSION: Logistic difficulties impede routine implementation of this protocol in developing countries. MRI volumetry is clearly more accurate than surgeons' intraoperative estimation of EOR. Notwithstanding the role of EOR in survival, our study reveals a perhaps bigger impact of tumor biology and postoperative functional status in this equation.

Carcinosarcoma of breast - A chimera among breast neoplasms.

Malignant phyllodes, along with ductal carcinoma, is known as metaplastic cancer of the breast. This tumor is additionally known as breast carcinosarcoma. Malignant phyllodes in conjunction with ductal carcinoma is a rare finding in routine clinical practice. We describe the case report of a 47-year-old female patient who arrived with a large right breast mass. A core biopsy was performed, and histopathological examination indicated that the tumor was a malignant phyllodes tumor. A positron emission tomography (PET) scan revealed hyper-metabolic and hypo-metabolic tumors with perilesional stranding and satellite nodularity. There were a few metastatic right axillary nodes visible. There was no indication of distant metastases. Due to the presence of both components, a modified radical mastectomy surgery with axillary dissection was undertaken for this patient. Histopathological analysis of paraffin sections revealed ductal carcinoma in situ (DCIS) comedo-epithelial component and spindle-shaped cells with hyper-chromatic oval nuclei and scanty cytoplasm.

Effect of cold arid high-altitude environment on bioactive phytochemical compounds of organically grown Brassicaceae vegetables for nutri-health security in mountainous regions.

High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter. The open field study was conducted as a two-factorial randomized block design. The first factor was treatment (T1-FYM, T2-Azotobacter, T3-FYM + Azotobacter, and T4-control) while the second was locations (HA and LA). Among all these treatments, the application of treatment T3 in HA-grown cabbage showed the highest total phenolic content (TPC; 9.56 µg/mg), total flavonoids content (TFC; 14.48 µg/mg), and antioxidant potential using 2,2-diphenyl-1-picrylhydrazyl (DPPH; 85.97%) and ferric reducing antioxidant power (FRAP; 30.77 µg/mg) compared to LA grown samples. Reverse Phase high performance liquid chromatography (RP-HPLC) analysis showed that treatment T3 at HA led to significantly high kaempferol (0.92 µg/mg) and sulforaphane (8.94 µg/mg) contents in cabbage whereas, indole-3-carbinol (1.31 µg/mg) was higher in HA grown cauliflower. The present study provides scientific evidence for the enrichment of health-promoting phytochemical compounds in Brassicaceae vegetables grown with T3 treatment specifically at HA.

Erratum to "Branching out: Feasibility of examining the effects of greenspace on mental health after traumatic brain injury" [Dialogues in Health, Volume 2, 2023, 100129].

[This corrects the article DOI: 10.1016/j.dialog.2023.100129.].

Design, synthesis, and anticancer assessment of structural analogues of (E)-1-((3,4,5-trimethoxybenzylidene)amino)-4-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]quinoxaline-2-carbonitrile (6b), an imidazo[1,2-a]quinoxaline-based non-covalent EGFR inhibitor.

In our quest to find improved anticancer therapeutics, we expedite the lead optimization of (E)-1-((3,4,5-trimethoxybenzylidene)amino)-4-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]quinoxaline-2-carbonitrile (6b), an EGFR inhibitor previously discovered in our laboratory through an in-house screening program. The lead optimization was rationally initiated considering the catalytic site of EGFR. We synthesized twenty-nine new analogues of 6b and assessed their anticancer activities. SAR studies highlighted the role of important groups in controlling anticancer activities. Among all, 5a and 5l were found to exhibit improved EGFR inhibition with anticancer asset potential. In silico studies corroborated with in vitro EGFR inhibitory results. The deeper analysis of 5a and 5l revealed that these synthetics could alter the MMP (ΔΨ m) and significantly reduce the ROS levels in lung cancer cells. This is a vital prerequisite for better plausible EGFR inhibitors devoid of cardiotoxicity. qPCR analysis further revealed that the investigational compounds 5a and 5l were able to downregulate the expression of key oncogenes, viz., KRAS, MAP2K, and EGFR. The downregulation of these genes suggests that the investigational compounds could interact and inhibit key players in the signalling cascade along with the EGFR, which may lead to the inhibition of the growth and prognosis of cancer cells via a holistic approach.

Longitudinal associations of time-varying homeboundness and life satisfaction after traumatic brain injury.

PURPOSE/OBJECTIVE: To examine the association of changes in homebound status (i.e., never/rarely leaving the home) with life satisfaction in the first 10 years after traumatic brain injury (TBI). RESEARCH METHOD/DESIGN: We analyzed data from 2,294 individuals with moderate-to-severe TBI from the TBI Model Systems National Database using a longitudinal multilevel model with time-varying predictors to account for within-person changes over time as well as between-person differences. We measured homebound status (defined as leaving the home ≤ 2 days/week) and life satisfaction (defined as the total score on the Satisfaction With Life Scale) at 1, 2, 5, and 10 years post-TBI. We adjusted the models for demographic and injury-related covariates and used inverse probability weighting to account for selection bias. RESULTS: Forty-five (2%) individuals were homebound at all follow-up visits, 523 (22.8%) were homebound at least one follow-up visit, and 1,726 (75.2%) were never homebound. Individuals with TBI who were consistently homebound had > 1 SD lower life satisfaction compared to those who were never homebound, ß = -8.07, 95% confidence interval (CI) = [-9.39, -6.76], p < .001. Individuals who became homebound experienced a significant, but modest, decline in life satisfaction (ß = -2.13, 95% CI = [-2.66, -1.61], p < .001). CONCLUSIONS/IMPLICATIONS: Our results indicate that being homebound and becoming homebound are associated with decreased life satisfaction. Homeboundness is a potentially modifiable target to improve life satisfaction, and elucidation of contributing factors to homebound status will help develop interventions to ameliorate post-TBI homeboundness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictors of Multidimensional Profiles of Participation After Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury. DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury). MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control). RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and Functional Independence Measure Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity. CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.