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JAMA Network Open Jun 2024The US Supreme Court Dobbs v Jackson Women's Health Organization decision allowed states to strengthen restrictions on abortion access, triggering the closure of family...
IMPORTANCE
The US Supreme Court Dobbs v Jackson Women's Health Organization decision allowed states to strengthen restrictions on abortion access, triggering the closure of family planning clinics and leading to confusion about the legality of emergency contraceptives (ECs).
OBJECTIVES
To evaluate the association between the Dobbs decision and fills for oral and emergency contraceptives in states that enacted the most restrictive abortion policies after Dobbs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data on contraceptive fills for women of reproductive age (15-49 years) in the US from IQVIA's National Prescription Audit PayerTrak and data from the Guttmacher Institute were used to categorize changes in abortion restrictions in each state. A difference-in-differences analysis compared changes in monthly fill rates for daily oral contraceptive pills (OCPs) and ECs in states that became most restrictive (implemented a full abortion ban after Dobbs) and comparison states (kept a medium level of abortion restrictions after Dobbs) before (March 2021 to November 2021) and after (July 2022 to October 2023) the Dobbs decision.
EXPOSURE
State-level abortion restrictions.
MAIN OUTCOMES AND MEASURES
Monthly fills of OCPs and ECs per 100 000 women of reproductive age.
RESULTS
Between March 2021 and October 2023, 142.8 million prescriptions for OCPs and 904 269 prescriptions for ECs were dispensed at US retail pharmacies. Before Dobbs, trends in monthly fill rates were similar for OCPs and ECs between the most restrictive and comparison states. After the Dobbs decision, states that became the most restrictive experienced an additional 4.1% decline in OCP fills with 285.9 fewer fills per 100 000 (95% CI, -495.8 to -6.8; P = .04). In contrast to OCPs, fills for ECs increased during the first year after Dobbs (July 2022 to June 2023) in both groups of states. However, 1 year after Dobbs (July 2023 to October 2023), the most restrictive states experienced an additional 65% decrease in emergency contraceptive fills with 13.2 fewer fills per 100 000 (95% CI, -27.2 to -4.1; P = .01).
CONCLUSIONS AND RELEVANCE
In this cohort study of prescriptions filled at US pharmacies, the Dobbs decision was associated with declines in oral contraceptives, particularly ECs, in states enacting the most restrictive abortion policies. Given the important role of OCPs and ECs in preventing pregnancy and the need for abortion, efforts to improve access may be needed, especially in states where legal abortion is no longer an option.
Topics: Humans; Female; United States; Adult; Adolescent; Young Adult; Contraceptives, Postcoital; Middle Aged; Supreme Court Decisions; Contraceptives, Oral; Abortion, Induced; Cohort Studies; Pregnancy; Contraception, Postcoital
PubMed: 38922616
DOI: 10.1001/jamanetworkopen.2024.18620 -
Neurology International Jun 2024The tau protein is a microtubule-associated protein that promotes microtubule stabilization. The phosphorylation of the tau protein has been linked to its dissociation...
The tau protein is a microtubule-associated protein that promotes microtubule stabilization. The phosphorylation of the tau protein has been linked to its dissociation from microtubules. Here, we examined the relationship between neuronal depolarization activity and tau protein phosphorylation by employing model systems in culture as well as in vivo. The KCl-evoked depolarization of cultured neurons has often been used to investigate the effects of neuronal activity. We found dephosphorylation at AT8 sites (S202, T205), T212, AT180 sites (T231, S235), and S396 in KCl-simulated cultured neurons. We also found that the KCl-induced tau protein dephosphorylation increases the level of the tau protein fractionated with stable microtubules. In an in vivo experiment, we demonstrated that the exposure of mice to a new environment activates protein phosphatase 1 in the mouse hippocampus and induces tau protein dephosphorylation. We also found an increased amount of the tau protein in a stable microtubule fraction, suggesting that the dephosphorylation of the tau protein may lead to its increased microtubule association in vivo. These results suggest that the association of microtubules with tau proteins may be regulated by the tau protein phosphorylation status affected by neuronal electrical activity.
PubMed: 38921953
DOI: 10.3390/neurolint16030049 -
Medicines (Basel, Switzerland) Jun 2024Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 10/L...
An Unusual Case of Immune Complex-Mediated Membranoproliferative Glomerulonephritis as Renal Manifestation of Idiopathic Hypereosinophilic Syndrome: A Case Report and Literature Review.
BACKGROUND
Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 10/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition.
CASE PRESENTATION
We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature.
PubMed: 38921600
DOI: 10.3390/medicines11060013 -
Current Oncology (Toronto, Ont.) Jun 2024Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of...
The Effect of Hemithyroidectomy in Papillary Thyroid Carcinoma with an Exclusive Involvement of the Recurrent Laryngeal Nerve: A Retrospective Study with a Propensity Score-Matched Analysis.
BACKGROUND
Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons.
METHODS
A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan-Meier method was used for a comparison of recurrence outcomes.
RESULTS
In the baseline data of the 163 PTC patients, tumor size ( < 0.001), multifocality ( = 0.011), CLNM ( < 0.001), and RLN resection ( < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group ( < 0.001 and = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups ( = 0.092).
CONCLUSION
Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.
Topics: Humans; Male; Retrospective Studies; Female; Thyroid Cancer, Papillary; Propensity Score; Thyroidectomy; Middle Aged; Adult; Thyroid Neoplasms; Recurrent Laryngeal Nerve; Neoplasm Recurrence, Local; Aged
PubMed: 38920748
DOI: 10.3390/curroncol31060265 -
Cells Jun 2024Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with...
Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SC tumors, whereas SC tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of mutation and copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SC tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.
Topics: Humans; Tumor Microenvironment; Squamous Cell Carcinoma of Head and Neck; Phosphatidylinositol 3-Kinases; Signal Transduction; Peripheral Nerves; Head and Neck Neoplasms; Mutation; TOR Serine-Threonine Kinases; Class I Phosphatidylinositol 3-Kinases; Schwann Cells; PTEN Phosphohydrolase; Gene Expression Regulation, Neoplastic; Tumor Suppressor Protein p53
PubMed: 38920662
DOI: 10.3390/cells13121033 -
Cells Jun 2024The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the...
The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the regulatory relationship between the cytosolic chaperonin CCT, key insulin pathway genes, and an E3 ubiquitin ligase (Cullin1) in dendritic development. CCT loss of function (LOF) results in dendritic hypotrophy in Class IV (CIV) multi-dendritic larval sensory neurons, and CCT has recently been shown to fold components of the TOR (Target of Rapamycin) complex 1 (TORC1) in vitro. Through targeted genetic manipulations, we confirm that an LOF of CCT and the TORC1 pathway reduces dendritic complexity, while overexpression of key TORC1 pathway genes increases the dendritic complexity in CIV neurons. Furthermore, both CCT and TORC1 LOF significantly reduce microtubule (MT) stability. CCT has been previously implicated in regulating proteinopathic aggregation, thus, we examine CIV dendritic development in disease conditions as well. The expression of mutant Huntingtin leads to dendritic hypotrophy in a repeat-length-dependent manner, which can be rescued by Cullin1 LOF. Together, our data suggest that Cullin1 and CCT influence dendritic arborization through the regulation of TORC1 in both health and disease.
Topics: Animals; Cullin Proteins; Dendrites; Drosophila melanogaster; Drosophila Proteins; Huntingtin Protein; Larva; Mechanistic Target of Rapamycin Complex 1; Microtubules; Sensory Receptor Cells; Signal Transduction; Transcription Factors; Chaperonin Containing TCP-1
PubMed: 38920658
DOI: 10.3390/cells13121029 -
Cells Jun 2024Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While... (Review)
Review
Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.
Topics: Humans; Remyelination; Animals; Oligodendrocyte Precursor Cells; Cicatrix; Neuroglia; Oligodendroglia; Myelin Sheath; Cell Differentiation
PubMed: 38920654
DOI: 10.3390/cells13121024 -
Drug Design, Development and Therapy 2024Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.
PURPOSE
Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM).
PATIENTS AND METHODS
This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes.
RESULTS
The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05).
CONCLUSION
Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.
Topics: Humans; Propofol; Male; Middle Aged; Female; Single-Blind Method; Microvascular Decompression Surgery; Intraoperative Neurophysiological Monitoring; Facial Nerve; Anesthesia, Intravenous; Anesthetics, Intravenous; Aged; Adult
PubMed: 38919963
DOI: 10.2147/DDDT.S459618 -
Neuropsychiatric Disease and Treatment 2024We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to...
PURPOSE
We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action.
PATIENTS AND METHODS
This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively.
RESULTS
The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas.
CONCLUSION
Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.
PubMed: 38919562
DOI: 10.2147/NDT.S465650 -
Frontiers in Cellular Neuroscience 2024Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with a ubiquitous distribution in numerous tissues and with various functions in both neuronal and...
Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with a ubiquitous distribution in numerous tissues and with various functions in both neuronal and non-neuronal cells. IGF-1 provides trophic support for many neurons of both the central and peripheral nervous systems. In the central nervous system (CNS), IGF-1R signaling regulates brain development, increases neuronal firing and modulates synaptic transmission. IGF-1 and IGF-IR are not only expressed in CNS neurons but also in sensory dorsal root ganglion (DRG) nociceptive neurons that convey pain signals. DRG nociceptive neurons express a variety of receptors and ion channels that are essential players of neuronal excitability, notably the ligand-gated cation channel TRPV1 and the voltage-gated M-type K channel, which, respectively, triggers and dampens sensory neuron excitability. Although many lines of evidence suggest that IGF-IR signaling contributes to pain sensitivity, its possible modulation of TRPV1 and M-type K channel remains largely unexplored. In this study, we examined the impact of IGF-1R signaling on DRG neuron excitability and its modulation of TRPV1 and M-type K channel activities in cultured rat DRG neurons. Acute application of IGF-1 to DRG neurons triggered hyper-excitability by inducing spontaneous firing or by increasing the frequency of spikes evoked by depolarizing current injection. These effects were prevented by the IGF-1R antagonist NVP-AEW541 and by the PI3Kinase blocker wortmannin. Surprisingly, acute exposure to IGF-1 profoundly inhibited both the TRPV1 current and the spike burst evoked by capsaicin. The Src kinase inhibitor PP2 potently depressed the capsaicin-evoked spike burst but did not alter the IGF-1 inhibition of the hyperexcitability triggered by capsaicin. Chronic IGF-1 treatment (24 h) reduced the spike firing evoked by depolarizing current injection and upregulated the M-current density. In contrast, chronic IGF-1 markedly increased the spike burst evoked by capsaicin. In all, our data suggest that IGF-1 exerts complex effects on DRG neuron excitability as revealed by its dual and opposite actions upon acute and chronic exposures.
PubMed: 38919332
DOI: 10.3389/fncel.2024.1391858