Dengue Infection During Pregnancy and Adverse Birth Outcomes: A Systematic Review and Meta-Analysis.

Dengue is a rapidly spreading mosquito-borne viral disease, posing significant public health challenges in tropical and subtropical regions. This systematic review and meta-analysis aimed to evaluate the relationship between maternal dengue virus infection and adverse birth outcomes. A literature search was conducted in PubMed, Embase, and web of science databases until April 2024. Observational studies examining the association between laboratory-confirmed maternal dengue infection and adverse birth outcomes such as preterm birth, low birth weight (LBW), small for gestational age (SGA), stillbirth, and postpartum haemorrhage were included. Data were extracted, and risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to pool data in R software (V 4.3). Twenty studies met the inclusion criteria. The pooled prevalence of preterm birth among dengue-affected pregnancies was 18.3% (95% CI: 12.6%-25.8%), with an OR of 1.21 (95% CI: 0.78-1.89). For LBW, the pooled prevalence was 17.1% (95% CI: 10.4%-26.6%), with an OR of 1.00 (95% CI: 0.69-1.41). SGA had a pooled prevalence of 11.2% (95% CI: 2.7%-36.9%) and an OR of 0.93 (95% CI: 0.41-2.14). The prevalence of stillbirth was 3.3% (95% CI: 1.6%-6.8%), with significant associations found in some studies (RR: 2.67; 95% CI: 1.09-6.57). Postpartum haemorrhage had an OR of 1.97 (95% CI: 0.53-2.69). While maternal dengue infection was associated with a higher prevalence of preterm birth and LBW, the associations were not statistically significant. Significant associations were observed for stillbirth in specific studies. Further research with standardized methodologies is needed to clarify these relationships and identify potential mechanisms.

An atlas of combinatorial transcriptional regulation in mouse and man.

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

Most recent advances and applications of extracellular vesicles in tackling neurological challenges.

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use in the CNS. This review article aims to provide a comprehensive introduction to EVs, encompassing various aspects such as their diverse isolation methods, characterization, handling, storage, and different routes for EV administration. Additionally, it underscores the recent advances in their potential applications in neurodegenerative disorder therapeutics. By exploring their unique capabilities, this study sheds light on the promising future of EVs in clinical research. It considers the inherent challenges and limitations of these emerging applications while incorporating the most recent updates in the field.

Cholesteryl ester transfer protein knock-down in conjunction with a cholesterol-depleting agent decreases tamoxifen resistance in breast cancer cells.

The cholesterogenic phenotype, encompassing de novo biosynthesis and accumulation of cholesterol, aids cancer cell proliferation and survival. Previously, the role of cholesteryl ester (CE) transfer protein (CETP) has been implicated in breast cancer aggressiveness, but the molecular basis of this observation is not clearly understood, which this study aims to elucidate. CETP knock-down resulted in a >50% decrease in cell proliferation in both 'estrogen receptor-positive' (ER+; Michigan Cancer Foundation-7 (MCF7) breast cancer cells) and 'triple-negative' breast cancer (TNBC; MDA-MB-231) cell lines. Intriguingly, the abrogation of CETP together with the combination treatment of tamoxifen (5 µM) and acetyl plumbagin (a cholesterol-depleting agent) (5 µM) resulted in twofold to threefold increase in apoptosis in both cell lines. CETP knockdown also showed decreased intracellular CE levels, lipid raft and lipid droplets in both cell lines. In addition, RT2 Profiler PCR array (Qiagen, Germany)-based gene expression analysis revealed an overall downregulation of genes associated in cholesterol biosynthesis, lipid signalling and drug resistance in MCF7 cells post-CETP knock-down. On the contrary, resistance in MDA-MB-231 cells was reduced through increased expression in cholesterol efflux genes and the expression of targetable surface receptors by endocrine therapy. The pilot xenograft mice study substantiated CETP's role as a cancer survival gene as knock-down of CETP stunted the growth of TNBC tumour by 86%. The principal findings of this study potentiate CETP as a driver in breast cancer growth and aggressiveness and thus targeting CETP could limit drug resistance via the reduction in cholesterol accumulation in breast cancer cells, thereby reducing cancer aggressiveness.

Surveillance Strategies After Primary Treatment for Patients with Invasive Lobular Carcinoma of the Breast: Method of Local Recurrence Detection After Breast-Conserving Surgery.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer. Although mammography is known to have low sensitivity for ILC, there are no data to guide the optimal surveillance after treatment. We explored surveillance strategies after breast-conserving surgery (BCS) for ILC and determined the proportion of imaging-detected recurrences versus interval cancers. METHODS: From an institutional database of 813 women, we retrospectively identified patients who underwent BCS for stage I-III ILC and subsequently had a recurrence. We categorized patients by surveillance strategy and determined the modality of recurrence detection. Interval cancer rates for local recurrences were compared across surveillance strategies using the Chi-square test. We evaluated overall survival with the log-rank test and a Cox proportional hazards model. RESULTS: We included 58 patients with ILC who had a recurrence after BCS. Of these, 22 (37.9%) had local recurrence, 27 (46.6%) had distant recurrence, and 9 (15.5%) had both local and distant recurrence. Most patients underwent routine mammographic surveillance (65.2%), with 19.6% having supplemental breast magnetic resonance imaging (MRI) and 15.2% having no surveillance. The interval cancer rate was significantly higher in the mammographic surveillance group compared with the MRI surveillance group (61.9% vs. 16.7%; p < 0.001). CONCLUSION: In this study of patients with recurrence after BCS for primary treatment of stage I-III ILC, we found that most local recurrences were not detected by surveillance mammography. These data support further investigation of supplemental imaging beyond mammography specifically for patients with ILC who undergo BCS.

BICAAC-Derived Covalent and Cationic Ir(I) Complexes: Application of Ir(BICAAC)Cl(COD) Complexes as Catalysts for Transfer Hydrogenation and Hydrosilylation Reactions.

The ambiphilic bicyclic (alkyl)(amino)carbenes (Me/iPrBICAAC) upon reaction with [IrCl(COD)]2 smoothly afford mononuclear Ir(I) complexes that have been spectroscopically and structurally characterized. These complexes exhibit good catalytic activity for transfer hydrogenation (TH) of 4-chlorobenzaldehyde using isopropyl alcohol (iPrOH), with turnover frequency values ranging between 6269 and 8093 h-1. Choosing the covalent complex Ir(MeBICAAC)Cl(COD) as a catalyst, a wide array of carbonyls and imines functionalized with electron-withdrawing and electron-donating substituents have been surveyed and afforded their reduced products in moderate-to-good yields. No detachment of the BICAAC unit from the Ir center was observed upon prolonged heating of Ir(MeBICAAC)Cl(COD) in toluene-d8 or isopropyl alcohol-d8, which evidenced good thermal stability of the catalyst. Complex Ir(MeBICAAC)Cl(COD) was also found to be catalytically active for the hydrosilylation of a variety of aldehydes using triethylsilane (Et3SiH).

Synthesis and studies of new purines/pyrimidine derivatives as multi-targeted agents involving various receptor sites in the immune system.

Pro-inflammation, which is developed due to the increased production of cytokines, mainly interleukin-6 (IL-6), during the working of immune system pathways, becomes a major concern these days for many researchers. So, it is desired to design, screen, and synthesize new molecules with multi-parametric features showing their efficacy for Toll-like receptors (TLRs) and inhibiting the disease-causing receptor sites like viral infections, cancers, etc. along with controlling inflammation, fever, and other side effects during such pathways. Further, looking at the literature, curcumin a multi-targeted agent is showing its efficiency toward various receptor sites involved in many diseases as mentioned above. This fascinated us to build up new molecules which behave like curcumin with minimum side effects. In silico studies, involving ADMET studies, toxicological data, and docking analyses, of newly synthesized compounds (3-5) along with tautomers of curcumin i.e., (1-2), and some reported compounds like 9 and 10 have been studied in detail. Great emphasis has been made on analyzing binding energies, protein-ligand structural interactions, stabilization of newly synthesized molecules against various selected receptor sites using such computational tools. Compound 3 is the most efficient multifunctional agent, which has shown its potential toward most of the receptor sites in docking analysis. It has also responded well in Molecular dynamics (MD) simulation toward 5ZLN, 4RJ3, 4YO9, 4YOJ, and 1I1R sites. Finally, studies were extended to understand in vitro anti-inflammatory activity for particularly compound 3 in comparison to diclofenac and curcumin, which signifies the efficiency of compound 3.

Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.

Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer.

Inflammatory bowel disease (IBD) has become a common global health problem as prevalence continues to rise. It is often associated with increased risk of colorectal cancer (CRC) development. Limitations in current IBD biomarker-based diagnosis hinder the accuracy of early detection of CRC progression. Therefore, in this study, we proposed the use of transcription factor (TF)-based biomarkers that can potentially detect the transition of IBD to CRC. Various bioinformatic analysis and online database validations, and RT-qPCR validations were performed to identify possible diagnostic TFs. RUNX1 was identified as a promising TF that regulates 106 IBD/CRC-related genes. The incorporation of RUNX1 in combination with currently known IBD biomarkers, FEV + NFKB1 + RELA, achieved a comparable sensitivity and specificity scores of 99% and 87%, respectively, while RUNX1 in combination with known CRC markers, CEA + TIMP1 + CA724 + CA199, achieved a sensitivity and specificity score of 97% and 99%, respectively. Furthermore, a small pilot RT-qPCR-based analysis confirmed a demarcated shift in expression profiles in CA724, CEA, RUNX1 and TIMP1 in IBD patients compared to CRC patients' tissue samples. Specifically, CA724 is noticeably elevated in IBD, while the levels of CEA, RUNX1 with TIMP1 are probable genes that may be employed in discerning IBD progression to CRC. Therefore, these preliminary results once validated in large patient cohorts could potentially have a significant impact on CRC disease stratification, resulting in a more precise prediction for treatment and treatment outcomes, especially in South African patients.

Skeletal muscle transcriptomics of sheep acclimated to cold desert and tropical regions identifies genes and pathways accentuating their diversity.

The current study attempts to investigate the differences in gene expression in longissimus thoracis muscles between sheep breeds acclimated to diverse environments. Changthangi sheep inhabits the cold arid plateau of Ladakh, at an altitude above 3000 m with prevalence of rarefied atmosphere. Muzzafarnagri sheep, on the other hand is found in the sub-tropical hot and humid plains at an altitude of about 250 m. Comparative transcriptomics was used to provide a molecular perspective of the differential adaptation of the two breeds. RNA sequencing data was generated from four biological replicates of the longissimus thoracis muscles from both breeds. The common genes expressed in both breeds were involved in muscle contraction and muscle fibre organization. The most significant pathways enriched in Changthangi muscles were glycogen metabolism, reduction of cytosolic Ca++ levels and NFE2L2 regulating anti-oxidant, while those in Muzzafarnagri were extracellular matrix organization and collagen formation. The hub genes identified in Changthangi were involved in hematopoiesis and HIF signaling pathway, suggesting the molecular acclimatization of Changthangi to the high altitude cold desert of Ladakh. The nodal genes discovered in Muzzafarnagri sheep were associated with the extracellular matrix which accentuates its significance in the development, growth and repair of muscles. The observed transcriptomic differences underscore the morphological and adaptive disparity between the two breeds. The candidate genes and pathways identified in this study will form the basis for future research on adaptation to high altitude and body size in small ruminants.

Review to Elucidate the Correlation between Cuproptosis-Related Genes and Immune Infiltration for Enhancing the Detection and Treatment of Cervical Cancer.

Copper is a vital trace element in oxidized and reduced forms. It plays crucial roles in numerous biological events such as redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy, and immune modulation. Maintaining the balance of copper in the body is essential because its deficiency and excess can be harmful. Abnormal copper metabolism has a two-fold impact on the development of tumors and cancer treatment. Cuproptosis is a form of cell death that occurs when there is excessive copper in the body, leading to proteotoxic stress and the activation of a specific pathway in the mitochondria. Research has been conducted on the advantageous role of copper ionophores and chelators in cancer management. This review presents recent progress in understanding copper metabolism, cuproptosis, and the molecular mechanisms involved in using copper for targeted therapy in cervical cancer. Integrating trace metals and minerals into nanoparticulate systems is a promising approach for controlling invasive tumors. Therefore, we have also included a concise overview of copper nanoformulations targeting cervical cancer cells. This review offers comprehensive insights into the correlation between cuproptosis-related genes and immune infiltration, as well as the prognosis of cervical cancer. These findings can be valuable for developing advanced clinical tools to enhance the detection and treatment of cervical cancer.

Dosimetric effect of collimator rotation on intensity modulated radiotherapy and volumetric modulated arc therapy for rectal cancer radiotherapy.

INTRODUCTION: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are the main radiotherapy techniques for treating and managing rectal cancer. Collimator rotation is one of the crucial parameters in radiotherapy planning, and its alteration can cause dosimetric variations. This study assessed the effect of collimator rotation on the dosimetric results of various IMRT and VMAT plans for rectal cancer. MATERIALS AND METHODS: Computed tomography (CT) images of 20 male patients with rectal cancer were utilized for IMRT and VMAT treatment planning with various collimator angles. Nine different IMRT techniques (5, 7, and 9 coplanar fields with collimator angles of 0°, 45°, and 90°) and six different VMAT techniques (1 and 2 full coplanar arcs with collimator angles of 0°, 45°, and 90°) were planned for each patient. The dosimetric results of various treatment techniques for target tissue (conformity index [CI] and homogeneity index [HI]) and organs at risk (OARs) sparing (parameters obtained from OARs dose-volume histograms [DVH]) as well as radiobiological findings were analyzed and compared. RESULTS: The 7-fields IMRT technique demonstrated lower bladder doses (V40Gy, V45Gy), unaffected by collimator rotation. The 9-fields IMRT and 2-arcs VMAT (excluding the 90-degree collimator) had the lowest V35Gy and V45Gy. A 90-degree collimator rotation in 2-arcs VMAT significantly increased small bowel and bladder V45Gy, femoral head doses, and HI values. Radiobiologically, the 90-degree rotation had adverse effects on small bowel NTCP (normal tissue complication probability). No superiority was found for a 45-degree collimator rotation over 0 or 30 degrees in VMAT techniques. CONCLUSION: Collimator rotation had minimal impact on dosimetric parameters in IMRT planning but is significant in VMAT techniques. A 90-degree rotation in VMAT, particularly in a 2-full arc technique, adversely affects PTV homogeneity index, bladder dose, and small bowel NTCP. Other evaluated collimator angles did not significantly affect VMAT dosimetrical or radiobiological outcomes.

Influence of Graft Type and Meniscal Involvement on Short-Term Outcomes Following Anterior Cruciate Ligament Reconstruction.

CONTEXT: The purpose of this study was to compare short-term clinical outcomes between meniscus procedures performed with anterior cruciate ligament reconstruction (ACLR), ACLR (ACLR-only), ACLR with meniscectomy/resection (ACLR-resect), and ACLR with meniscal repair (ACLR-repair) for bone patellar tendon bone grafts (BPTB) and hamstring tendon grafts, separately. DESIGN: This was a cross-sectional study conducted in a controlled laboratory setting as part of a large point-of-care collaborative research program. METHODS: This study included 314 participants (168 females; mean [SD]: age, 19.7 [4.8]) with primary unilateral ACLR with a BPTB or hamstring tendon. Patients were divided into 3 groups depending on meniscal procedure (ACLR-only, ACLR-resect, and ACLR-repair). Postsurgical testing included: isokinetic assessment of knee extension and flexion, single-leg hop tests, and patient-reported outcomes. Multivariate analysis of covariance compared differences between meniscal procedures on the battery of tests, and for each statistically significant variable an analysis of covariance assessed the effect of meniscal procedure within each graft type. Chi-square analysis assessed the influence of meniscal procedure on tests' pass rates defined as 90% of limb symmetry index. RESULTS: BPTB: ACLR-only had greater hamstring strength than ACLR-resect (P = .05) and ACLR-repair (P = .005). ACLR-only had the highest proportion of participants to pass the hamstring strength test (P = .02). Hamstring tendon: ACLR-only (P = .03) and ACLR-resect (P = .003) had higher International Knee Documentation Committee scale scores than ACLR-repair. There was a significant difference in the proportion of participants who scored >90% limb symmetry index on the timed hop test (P = .05). CONCLUSIONS: The influence of meniscal repair on clinical outcomes is dependent on the graft choice. Following an ACLR with BPTB and a meniscal procedure, hamstring function should be more closely monitored for optimal short-term recovery.

HER-2 low status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series.

PURPOSE: HER2 overexpression has a central role in breast cancer carcinogenesis and is associated with poor prognosis if untreated. Lately, identification of HER2-low breast cancer has been proposed to select patients for novel HER2-directed chemotherapy and includes cancers with immunohistochemistry 1 + or 2 + with negative FISH, encompassing approximately 55-60% of all breast carcinomas. In early-stage breast cancer, the prognostic significance of HER2 low-disease is less well understood, with a particular paucity of data evaluating the prevalence and implications of HER2-low status in invasive lobular carcinoma (ILC). METHODS: We evaluated 666 stage I-III ILC tumors from a prospectively maintained institutional database, comparing clinicopathologic features and disease-free survival (DFS) using a multivariable Cox proportional hazards model. RESULTS: HER2-low status was common in this cohort of patients with ILC, but most clinicopathologic features did not differ between HER2-low and HER2-negative cases. However, when adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse disease-free survival (DFS) than those with HER2-negative tumors (hazard ratio 2.0, 95% confidence interval 1.0-4.1, p = 0.05). CONCLUSION: This difference in DFS supports the notion that HER2-low and HER2-negative early stage ILC may differ clinically, despite similar clinicopathologic features. Further investigation into the potential benefit of HER2 targeted therapy in HER2-low early-stage breast cancer, and specifically lobular cancer, is warranted to ensure optimal outcomes in this distinct tumor subtype.

Quantifying hormone receptor status in lobular breast cancer in an institutional series: the relationship between estrogen and progesterone receptor status and outcomes.

PURPOSE: Recent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort. METHODS: We searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10-69%, 70-89%, and ≥ 90% respectively. PR low and high tumors were defined by < 20%, or ≥ 20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models to evaluate associations between ER/PR categories and tumor characteristics or disease-free survival (DFS). RESULTS: The cohort consisted of 707 ILC cases, with 11% of cases categorized as ER low, 15.1% as medium, and 73.8% as high. The majority (67.6%) were PR high. Patients with ER low/medium expression were significantly younger, and more likely to also have PR low and/or HER2 positive tumors compared to those that were ER high. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and treatment, ER category was not prognostic for DFS, but PR negative and PR low status each had significantly worse DFS compared to PR high status (HR 3.5, 95% CI 1.8-6.7, p < 0.001; and HR 2.0, 95% CI 1.1-3.5, p = 0.015, respectively). CONCLUSION: These findings highlight the relevance of quantifying ER and PR within ILC.

miRNA-128 and miRNA-223 regulate cholesterol-mediated drug resistance in breast cancer.

BACKGROUND: Breast cancer is the second most common malignancy worldwide and 70% of all breast cancer cases are estrogen receptor-positive (ER+). Endocrine therapy, Tamoxifen (TAM), is a popular treatment for ER+ breast cancer patients; however, despite its success in reducing breast cancer mortality, cancer drug resistance remains a significant challenge. A major contributor to this resistance is the dysregulation of cholesterol homeostasis, where breast cancer cells have elevated cholesterol levels. MicroRNAs (miRNAs) are master regulators of cholesterol-related and cancer drug resistance pathways, and their aberrant expression often confers resistance. Therefore, we aimed to investigate the roles of miRNA-128 and miRNA-223 in cholesterol-mediated TAM resistance. METHODS: Three breast cancer cell lines were treated with a combination of 1 µM TAM and 10 µM of a cholesterol depleting agent (Acetyl Plumbagin: AP) following transfection with a miR-128 inhibitor or a miR-223 mimic. Cell viability and cholesterol levels were assessed using an MTT assay and fluorescence staining, respectively. In addition, expression levels of several genes and proteins involved in cancer drug resistance and cholesterol homeostasis were also assessed using RT-qPCR and western blotting. RESULTS: The combination treatment with altered miRNA expression led to reduced cell viability due to a reduction in free cholesterol and lipid rafts in MCF-7, MDA-MB-231, and long-term estrogen-deprived cells (resistant breast cancer cells). Moreover, reduced miR-128 expression was favoured in all breast cancer cell lines as this alteration lowered the expression of genes involved in cholesterol synthesis and transport, drug resistance, and cell signalling. CONCLUSIONS: Investigating the gene expression profiles in different breast cancer cell lines was important to elucidate further the molecular mechanisms involved in miRNA-regulated cholesterol homeostasis and cancer drug resistance. Therefore, our findings demonstrated that miR-128 and miR-223 could be potential targets in reducing TAM resistance through the depletion of excess cholesterol.

Successful Breast Conservation After Neoadjuvant Chemotherapy in Lobular Breast Cancer: The Role of Menopausal Status in Response to Treatment.

BACKGROUND: While neoadjuvant chemotherapy (NAC) has been shown to increase rates of breast conservation surgery (BCS) for breast cancer, response rates in invasive lobular carcinoma (ILC) appear lower than other histologic subtypes. Some data suggest higher response rates to NAC in premenopausal versus postmenopausal patients, but this has not been studied in ILC. We evaluated the rates of successful BCS after NAC in patients with ILC stratified by menopausal status. PATIENTS AND METHODS: We analyzed data from a single-institution cohort of 666 patients with stage I-III hormone receptor positive HER-2 negative ILC. We used t-tests, chi-squared tests, and multivariable logistic regression to investigate rates of NAC use, attempted BCS, and associations between NAC and successful BCS by menopausal status. RESULTS: In 217 premenopausal and 449 postmenopausal patients, NAC was used more often in the premenopausal group (15.2% vs. 9.8%, respectively, p = 0.041). Among those who attempted breast conservation (51.3% of pre- and 64.8% of postmenopausal cohorts), NAC was not associated with successful BCS in either group. Interestingly, for postmenopausal patients, receipt of NAC was significantly associated with increased rates of completion mastectomy in those who had positive margins at the first attempt at BCS. CONCLUSION: NAC was not associated with successful BCS in either premenopausal or postmenopausal patients with ILC. Although premenopausal patients were more likely to receive NAC, these data suggest that menopausal status may not be a good predictor of response to chemotherapy. Better predictors of response and more efficacious treatment for patients with ILC are needed.

Highly Electrophilic Mononuclear Cationic Aluminium Alkoxide Complexes: Syntheses, Reactivity and Catalytic Applications.

Herein, we report the synthesis of ß-diketiminate-supported aluminium complexes bearing terminal alkoxide and mono-thiol functional groups: LAlOMe(Et) (2), LAlOtBu(Et) (3), and LAlSH(Et) (4), (L=[HC{C(Me)N-(2,6-iPr2 C6 H3 )}2 ]). Complexes 2 and 3 are further used as synthons to generate the fascinating cationic aluminium alkoxide complexes, [LAlOMe(µ-OMe)-Al(Et)L][EtB(C6 F5 )3 ] (5), [LAlOMe(OEt2 )][EtB(C6 F5 )3 ] (6), and [LAlOtBu(OEt2 )][EtB(C6 F5 )3 ] (8). These electrophilic cationic species are well characterized by spectroscopic and crystallographic techniques. The assessment of Lewis acidity by the Gutmann-Beckett method revealed superior Lewis acidity of the cations substituted with electron-demanding alkoxy groups in comparison to the known methyl analogue [LAlMe][B(C6 F5 )4 ]. This has been further endorsed by computational calculations to determine the NBO charges and hydride ion affinity for complexes 6 and 8. These complexes are also capable of activating triethylsilane in stoichiometric reactions. The applicability of these complexes has been realized in the hydrosilylation of ethers, carbonyls, and olefines. Additionally, the solid-state structure of a new THF stabilized aluminium halide cation [LAlCl(THF)][B(C6 F5 )4 ] (11) has also been reported.

Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer's Disease.

The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.

The pathogenic and spoilage bacteria associated with red meat and application of different approaches of high CO2 packaging to extend product shelf-life.

With the fast-global development of packaging techniques, the potential antimicrobial effect of CO2, as a safe, cheap and readily available gas, makes it the integral component for packaging of meat products. The associated spoilage and/or pathogenic bacteria on raw meat may respond in different ways to elevated CO2 concentrations. The growth of some aerobic Gram-negative bacteria such as Pseudomonas spp. is significantly inhibited but some LAB bacteria may be allowed to grow faster and dominate the product. The antimicrobial efficacy of enriched CO2 packaging is attributed to the rate of CO2 solubility in the product which is itself affected by the level of headspace CO2, product pH, temperature and the ratio of headspace gas to product (G:P). This review, first, explores the varied range of beef and sheep meat spoilage and pathogenic bacteria and the intrinsic and extrinsic parameters that may influence the pattern of microbial growth and meat spoilage rate during storage. Then, the antimicrobial mechanism of elevated CO2 packaging will be discussed and the different approaches of achieving enriched CO2 packaging i.e. the traditional technique of flushing a desired gas mixture and/or using the new commercially developed CO2 emitters will then be compared in terms of their strengths, limitations and technical mode of action.