Associations of hair dye and relaxer use with breast tumor clinicopathologic features: Findings from the Women's circle of Health Study.

BACKGROUND: Building upon our earlier findings of significant associations between hair dye and relaxer use with increased breast cancer risk, we evaluated associations of select characteristics of use with breast tumor clinicopathology. METHODS: Using multivariable-adjusted models we examined the associations of interest in a case-only study of 2998 women with breast cancer, overall and stratified by race and estrogen receptor (ER) status, addressing multiple comparisons using Bonferroni correction. RESULTS: Compared to salon application of permanent hair dye, home kit and combination application (both salon and home kit application) were associated with increased odds of poorly differentiated tumors in the overall sample. This association was consistent among Black (home kit: OR 2.22, 95 % CI: 1.21-5.00; combination: OR 2.46, 95 % CI: 1.21-5.00), but not White women, and among ER+ (home kit: OR 1.47, 95 % CI: 0.82-2.63; combination: OR 2.98, 95 % CI: 1.62-5.49) but not ER-cases. Combination application of relaxers was associated with increased odds of tumors >2.0 cm vs. <1.0 cm (OR = 1.82, 95 % CI: 1.23-2.69). Longer duration and earlier use of relaxers and combination application of permanent hair dyes and relaxers were associated with breast tumor features including higher tumor grade and larger tumor size, which often denote more aggressive phenotypes, although the findings did not maintain significance with Bonferroni correction. CONCLUSIONS: These novel data support reported associations between hair dye and relaxer use with breast cancer, showing for the first time, associations with breast tumor clinicopathologic features. Improved hair product exposure measurement is essential for fully understanding the impact of these environmental exposure with breast cancer and to guide risk reduction strategies in the future.

The impact of cigarette smoking and nicotine on traumatic brain injury: a review.

INTRODUCTION: Traumatic Brain Injury (TBI) and tobacco smoking are both serious public health problems. Many people with TBI also smoke. Nicotine, a component of tobacco smoke, has been identified as a premorbid neuroprotectant in other neurological disorders. This study aims to provide better understanding of relationships between tobacco smoking and nicotine use and effect on outcome/recovery from TBI. METHODS: PubMed database, SCOPUS, and PTSDpub were searched for relevant English-language papers. RESULTS: Twenty-nine human clinical studies and nine animal studies were included. No nicotine-replacement product use in human TBI clinical studies were identified. While smoking tobacco prior to injury can be harmful primarily due to systemic effects that can compromise brain function, animal studies suggest that nicotine as a pharmacological agent may augment recovery of cognitive deficits caused by TBI. CONCLUSIONS: While tobacco smoking before or after TBI has been associated with potential harms, many clinical studies downplay correlations for most expected domains. On the other hand, nicotine could provide potential treatment for cognitive deficits following TBI by reversing impaired signaling pathways in the brain including those involving nAChRs, TH, and dopamine. Future studies regarding the impact of cigarette smoking and vaping on patients with TBI are needed .

Phytochemical Modulation of Ion Channels in Oncologic Symptomatology and Treatment.

Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, 'self-resistance' to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor's genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment.

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

Advances in Focused Ultrasound for the Treatment of Brain Tumors.

Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood-brain and blood-tumor barriers. In physiologic states, the blood-brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits the penetrance of therapeutics into the tumor microenvironment. Focused ultrasound technology provides a method for overcoming the blood-brain and blood-tumor barriers through ultrasound frequency to transiently permeabilize or disrupt these barriers. Concomitant delivery of therapeutics has allowed for previously impermeable agents to reach the tumor microenvironment. This review details the advances in focused ultrasound in both preclinical models and clinical studies, with a focus on its safety profile. We then turn towards future directions in focused ultrasound-mediated therapies for brain tumors.

Theoretical characterisation of electron tunnelling from granular activated carbon to electron accepting organisms in direct interspecies electron transfer.

Direct interspecies electron transfer (DIET) has been identified as an efficient metabolism between symbiotically interacting organisms. One method of DIET uses conductive materials (e.g., granular activated carbon (GAC)) as a medium to shuttle electrons from electron donating organisms (eg., Geobacter metallireducens) to electron accepting organisms (e.g., Geobacter sulfurreducens and Methanosarcina barkeri). Conductive materials such as GAC, become negatively charged in DIET processes due to reduction by electron donating organisms. This high excess electron density in GAC leads to quantum tunnelling of electrons being a significant electron transfer mechanism for DIET. Thus, a theoretical model obeying the Wentzel-Kramers-Brillouin (WKB) approximation and Fermi-Dirac statistics was developed and simulated. In the model, the electron tunnelling transfer barrier was described by an effective rectangular barrier. The result of our 1D tunnelling simulations indicates that within 29.4 nm of the GAC, tunnelling can sufficiently supply electrons from GAC to G. sulfurreducens and M. barkeri. The phenomenon of tunnelling may also have significance as a stimulant of chemotaxis for G. sulfurreducens and other electron accepting microbes when attempting to adsorb onto GAC. This study sheds light on quantum tunnelling's significant potential in both bacterium and archaeon DIET-centric processes.

COVID-19 Vaccine Mandates for Healthcare Professionals in the United States.

Healthcare workers (HCWs) need to be vaccinated against COVID-19 because they care for vulnerable patients. Hesitation to receiving the COVID-19 vaccine stems from the argument of bodily autonomy, novel mRNA vaccine technology, and conspiracy theories. However, vaccinations may prevent thousands of hospitalizations and deaths. HCWs have previously complied with other required vaccinations to care for children, elderly, and immunocompromised patients. Yet, COVID-19 vaccination mandates in the healthcare setting have been faced with resistance and subsequent staffing shortages. As HCWs display their hesitation to the vaccine, the community loses trust in its efficacy and safety. Speculation on pharmaceutical profiteering has also contributed to vaccine mistrust. As the pandemic continues, the healthcare field must decide on a course of action: adhere to vaccination mandates and cope with decreased staffing, repeal vaccination mandates to recover staff, rely on personal protective equipment (PPE) alone for protection, or do nothing and expect survival through herd immunity. To date, the United States has chosen to mandate COVID-19 vaccinations for any healthcare worker employed by Medicare and/or Medicaid-accepting facilities, allowing allergy and religious exemptions. This COVID-19 vaccination mandate for HCWs ethically protects the vulnerable people who HCWs vow to care for.

A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient.

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient's platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that the transcellular electrochemical gradient is finely tuned in eukaryotic cells, any disruption in this homeostasis can contribute to aberrancies, including altering the activity of pro-tumorigenic molecular pathways, such as the MAPK/ERK, RAS, and mTOR pathways. Ligand-gated ion channels therefore serve as a potential targetable system for cancer therapeutics. In this review, we analyze the role that each of the three ligand-gated ion channel superfamilies has concerning tumor proliferation and as a target for the treatment of cancer symptomatology.

Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers.

Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12-15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood-brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies.

Pearls & Oy-sters: Pivoting Treatment Regimens of Pediatric Atypical Teratoid Rhabdoid Tumors to Optimize Care in Adult ATRT: A Case Report.

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the CNS, largely affecting pediatric patients, with exceedingly rare cases in adults at an estimated annual incidence of 1/1,000,000. We report a unique case of ATRT in a 43-year-old female patient who first presented with progressive focal headaches. Imaging revealed a sellar mass with suprasellar extensions, which was partially removed via a transsphenoidal resection. The tumor aggressively recurred just 1 month postoperatively. Her care team pursued a novel treatment plan by using a slightly modified COG ACNS 0332 regimen, which involved radiation, followed by 4 cycles of monthly chemotherapy including vincristine, cyclophosphamide, and cisplatin. Hematopoietic stem cells were collected between radiation and chemotherapy in the event that the patient required stem cell salvage therapy postadjuvant chemotherapy. The MRIs taken at 2 and 4 months postrecurrence indicated a substantial decrease in tumor volume, with corresponding clinical improvements to cranial nerve deficits. Given the scarcity of literature on adult cases of ATRT and the lack of a standard of care for these cases, discussing the efficacy of our patient's treatment plan may aid clinical decision making for adult ATRT cases.

Dual orexin antagonist normalized sleep homeostatic drive, enhanced GABAergic inhibition, and suppressed seizures after traumatic brain injury.

STUDY OBJECTIVES: Traumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE. METHODS: CD-1 mice underwent controlled cortical impact (CCI), sham injury, or no craniotomy. Sham and CCI groups underwent a monthlong daily treatment with sleep aids including a dual orexin antagonist (DORA-22) or THIP (gaboxadol) or a respective vehicle starting on the day of CCI. We performed continuous EEG (electroencephalography) recordings at week 1 and months 1, 2, and 3 for ~1 week each time. Seizure analysis occurred at all-time points and sleep analysis occurred in week 1 and month-1/2 in all groups. Subsets of CCI and sham groups were subjected to voltageclamp experiments in hippocampal slices to evaluate GABAergic synaptic inhibition. RESULTS: DORA-22 treatment suppressed seizures in month 1-3 recordings. TBI reduced the amplitude and frequency of miniature inhibitory synaptic currents (mIPSCs) in dentate granule cells and these changes were rescued by DORA-22 treatment. Sleep analysis showed that DORA-22 increased nonrapid eye movement (NREM) sleep during lights-off whereas THIP increased REM sleep during lights-on in week 1. Both treatments displayed subtle changes in time spent in NREM or REM at month-1/2 as well. TBI not only increased normalized EEG delta power (NΔ) at week-1 and month-1 but also resulted in the loss of the homeostatic diurnal oscillation of NΔ, which was restored by DORA-22 but not THIP treatment. CONCLUSIONS: Dual orexin antagonists may have a therapeutic potential in suppressing PTE potentially by enhancing GABAergic inhibition and impacting sleep homeostatic drive.

Muscle stem cells and rotator cuff injury.

The incidence of reinjury after treatment of rotator cuff tears (RCTs) remains very high despite the variety of nonoperative treatments and the high volume of surgical interventions performed. Muscle stem cells (MuSCs), also known as satellite cells, have risen to the forefront of rotator cuff tear research as a potential adjuvant therapy to aid unsatisfactory surgical outcomes. MuSCs are adult stem cells exhibiting the capacity to proliferate and self-renew, both symmetrically and asymmetrically. As part of this niche, they have been shown to adopt an activated phenotype in response to musculoskeletal injury and decrease their cellular populations during aging, implicating them as key players in both pathologic and normal physiological processes. While commonly connected to the regenerative phase of muscle healing, MuSCs also have the potential to differentiate into adverse morphologies. For instance, if MuSCs differentiate into adipocytes, the ensuing fatty infiltration serves as an obstacle to proper muscle healing and has been associated with the failure of surgical management of RCTs. With the potential to both harm and heal, we have identified MuSCs as a key player in RCT repair. To better understand this dichotomy, the following review will identify key studies regarding the morphology, function, and behavior of MuSCs with respect to RCTs and healing.