Endovascular Treatment for Ruptured Proximal Anterior Cerebral Artery Dissecting Aneurysm: A Case Series.

Subarachnoid hemorrhage due to the A1 segment of an anterior cerebral artery dissecting aneurysm is rare. Therefore, a standard treatment has not been established. Though several case reports of direct surgery exist, there are few reports on endovascular treatment. This is the first study to describe five patients who underwent endovascular treatment for ruptured A1 dissecting aneurysms. Between January 2001 and December 2022 in our affiliated centers, five cases of SAH-onset A1 dissecting aneurysms were treated with endovascular treatment. We describe in detail two representative cases, briefly summarize the other three, and analyze their complications and outcomes. In the five cases, four were female. Four were in their 50s, and one was in her 80s. The WFNS grades were as follows: three were 2, one was 4, and one was 5. No re-ruptures or symptomatic complications were observed. The modified Rankin Scale scores at the time of discharge were as follows; one was 0, one was 1, two were 2, and one was 5. One in five patients needed retreatment after endovascular trapping because of recanalization. Endovascular treatment may be an effective and viable treatment option for ruptured A1 dissecting aneurysms. Further studies are needed to collect detailed data on complications and outcomes.

Impact of cancer history on long-term outcome after elective neuro-endovascular treatment in patients aged 80 years or older: A retrospective multicenter observational study.

AIM: Assessing the indication for elective neuro-endovascular treatment (EVT) in older patients requires consideration of the impact of systemic comorbidities on their overall reduced life expectancy. The objective of this study was to determine the long-term outcomes of elective neuro-EVT in patients aged ≥80 years, and to investigate the impact of pre-existing cancer on their long-term outcomes. METHODS: Of the patients enrolled in multicenter observational registry, those aged ≥80 years undergoing elective neuro-EVT between 2011 and 2020 were enrolled. A history of cancer was defined as a pre-existing solid or hematologic malignancy at the time of EVT. The primary outcome was time to death from elective neuro-EVT. RESULTS: Of the 6183 neuro-EVT cases implemented at 10 stroke centers, a total of 289 patients (median age, 82 years [interquartile range 81-84 years]) were analyzed. A total of 58 (20.1%) patients had a history of cancer. A total of 78 patients (27.0%) died during follow up. The 5-year survival rate of enrolled patients was 64.6%. Compared with patients without a history of cancer, those with a history of cancer showed significantly worse survival (log-rank test, P = 0.001). Multivariate Cox proportional hazards analysis showed history of cancer was an independent predictor of time to death from elective neuro-EVT (HR 1.74, 95% CI 1.01-3.00, P = 0.047). Cancer was the leading cause of death, accounting for 25.6% of all deaths. CONCLUSIONS: The present study showed that history of cancer has a significant impact on time to death from elective neuro-EVT in patients aged ≥80 years. Geriatr Gerontol Int 2024; 24: 211-217.

A novel FOXP3 knockout-humanized mouse model for pre-clinical safety and efficacy evaluation of Treg-like cell products.

Forkhead box P3 (FOXP3) is an essential transcription factor for regulatory T cell (Treg) function. Defects in Tregs mediate many immune diseases including the monogenic autoimmune disease immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), which is caused by FOXP3 mutations. Treg cell products are a promising modality to induce allograft tolerance or reduce the use of immunosuppressive drugs to prevent rejection, as well as in the treatment of acquired autoimmune diseases. We have recently opened a phase I clinical trial for IPEX patients using autologous engineered Treg-like cells, CD4LVFOXP3. To facilitate the pre-clinical studies, a novel humanized-mouse (hu-mouse) model was developed whereby immune-deficient mice were transplanted with human hematopoietic stem progenitor cells (HSPCs) in which the FOXP3 gene was knocked out (FOXP3KO) using CRISPR-Cas9. Mice transplanted with FOXP3KO HSPCs had impaired survival, developed lymphoproliferation 10-12 weeks post-transplant and T cell infiltration of the gut, resembling human IPEX. Strikingly, injection of CD4LVFOXP3 into the FOXP3KO hu-mice restored in vivo regulatory functions, including control of lymphoproliferation and inhibition of T cell infiltration in the colon. This hu-mouse disease model can be reproducibly established and constitutes an ideal model to assess pre-clinical efficacy of human Treg cell investigational products.

Towards gene therapy for IPEX syndrome.

Immune dysregulation polyendocrinopathy enteropathy X linked (IPEX) syndrome is an uncurable disease of the immune system, with immune dysregulation that is caused by mutations in FOXP3. Current treatment options, such as pharmacological immune suppression and allogeneic hematopoietic stem cell transplantation, have been beneficial but present limitations, and their life-long consequences are ill-defined. Other similar blood monogenic diseases have been successfully treated using gene transfer in autologous patient cells, thus providing an effective and less invasive therapeutic. Development of gene therapy for patients with IPEX is particularly challenging because successful strategies must restore the complex expression profile of the transcription factor FOXP3, ensuring it is tightly regulated and its cell subset-specific roles are maintained. This review summarizes current efforts toward achieving gene therapy to treat immune dysregulation in IPEX patients.

Chronologic Analysis of Tear Dynamics on Blinking Using Quantitative Manometry in Healthy Humans.

PURPOSE: To analyze the tear dynamics during blinking by measuring the inner pressure of the upper lacrimal drainage system. METHODS: This observational study involved 11 healthy bi- or tricenarian volunteers. Direct manometry was performed using a fiber optic pressure sensor inserted into the conjunctival sac, upper/lower canaliculus (5 mm from punctum), and inferior lacrimal sac (15 mm from punctum) during both involuntary and intentional tight blinking. Pressure was measured 200 times/second during 3 separate blinks and then chronologically analyzed. RESULTS: In all subjects of all locations during both types of blinking, the inner pressures during the stationary eyelid closing/opening were positive/approximately zero, while a positive/negative pressure spike was observed during the eyelid closing/opening movement. The averages of the maximum pressure in the spike during the intentional tight blinking (tPmax: mm Hg) in the conjunctival sac, upper/lower canaliculus, and lacrimal sac were 8.00, 12.39/12.93, and 10.59, respectively, while for the minimum (tPmin: mm Hg), the pressures were -3.18, -3.91/-3.43, and -3.31, respectively. The tPmax and tPmin in the lacrimal duct were positively correlated with that of the conjunctival sac, which suggested synchronism of the drainage system. However, the tPmax in the canaliculus was significantly higher than that of the conjunctival sac, which suggested that tears do not flow from the conjunctival sac into the lacrimal duct during eyelid closure. CONCLUSIONS: The upper lacrimal drainage system functions as one united lumen in the lacrimal pump. The positive /negative pressure spike is essential for the lacrimal pump to efficiently eject/aspirate the tear from the lacrimal/conjunctival sac.

A randomized clinical trial of triamcinolone acetonide injection for suppression of inflammation after blepharoptosis surgery.

This study aimed to determine the effectiveness of triamcinolone acetonide in suppressing inflammation after blepharoptosis surgery. The study was designed as prospective, randomized, two medical centers' clinical trial. Thirty-two patients with involutional blepharoptosis of the same degree in both eyelids underwent bilateral transcutaneous levator advancement. At the end of the surgery, 4 mg/0.1 ml of triamcinolone acetonide was injected into a randomly selected upper eyelid. The fellow eyelid was not injected and was used as control. Facial photographs were taken on day 1, week 1, month 1, and month 3, and the degree of inflammation, the margin reflex distance 1 (MRD-1), and levator function (LF) between the two eyelids of each patient were compared. The primary outcome was the selection of the less inflamed eyelid decided by the majority of three individuals unrelated to the study. MRD-1 and LF were analyzed for secondary outcomes. As a result, the injected eyelid was judged to be the less inflamed eyelid in all cases. The MRD-1 in the postoperative period less than 1 month was significantly larger in the injected eyelids than the control eyelids (P<0.03). The postsurgical MRD-1 at month 3, the postsurgical LF at all postsurgical examination times were not statistically different. Adverse complications by the injection, including ptosis, levator dysfunction, increase of the intraocular pressure, and visual disturbance were not observed. In conclusion, a triamcinolone acetonide injection after ptosis surgery is both safe and effective in reducing the early postsurgical inflammation and helpful in an earlier return to a daily routine for the patients.

Adjustable Medial Epicanthoplasty Using a Rotational Flap for Epiblepharon Repair.

ABSTRACT: This report aimed to introduce the new adjustable rotational skin flap for epicanthoplasty in combination with traditional epiblepharon repair by the modified Hotz procedure. This retrospective study involved 25 consecutive patients with superficial punctate keratitis secondary to epiblepharon complicated with epicanthal fold who underwent the combined surgery between 2019 and 2020. The mean patient age was 11.4 years in this study with a median follow-up was 8months (range, 3-12months). The rationale of the surgery was to release vertical tension of the eyelids by dissecting dense connective tissue beneath the epicanthal fold and to form a new medial canthus using a rotational skin flap supplied by the redundant the upper and/or lower eyelid skin excised during the epiblepharon repair. Postsurgical resolution ofsuperficial punctate keratitis and patient satisfaction was achieved in all patients. Additionally, there were no complications, and no revisional surgery was required in all patients for a median 8 months follow-up period. Utilizing a rotational skin flap during epiblepharon repair is a useful adjunct during epicanthoplasty surgery. This modification is well tolerated and allows for intraoperative adjustment, whereas minimizing scarring and allowing for improved tissue relaxation.

Co-Expression of FOXP3FL and FOXP3Δ2 Isoforms Is Required for Optimal Treg-Like Cell Phenotypes and Suppressive Function.

FOXP3 is the master transcription factor in both murine and human FOXP3+ regulatory T cells (Tregs), a T-cell subset with a central role in controlling immune responses. Loss of the functional Foxp3 protein in scurfy mice leads to acute early-onset lethal lymphoproliferation. Similarly, pathogenic FOXP3 mutations in humans lead to immunodysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which are characterized by systemic autoimmunity that typically begins in the first year of life. However, although pathogenic FOXP3 mutations lead to overlapping phenotypic consequences in both systems, FOXP3 in human Tregs, but not mouse, is expressed as two predominant isoforms, the full length (FOXP3FL) and the alternatively spliced isoform, delta 2 (FOXP3Δ2). Here, using CRISPR/Cas9 to generate FOXP3 knockout CD4+ T cells (FOXP3KOGFP CD4+ T cells), we restore the expression of each isoform by lentiviral gene transfer to delineate their functional roles in human Tregs. When compared to FOXP3FL or FOXP3Δ2 alone, or double transduction of the same isoform, co-expression of FOXP3FL and FOXP3Δ2 induced the highest overall FOXP3 protein expression in FOXP3KOGFP CD4+ T cells. This condition, in turn, led to optimal acquisition of Treg-like cell phenotypes including downregulation of cytokines, such as IL-17, and increased suppressive function. Our data confirm that co-expression of FOXP3FL and FOXP3Δ2 leads to optimal Treg-like cell function and supports the need to maintain the expression of both when engineering therapeutics designed to restore FOXP3 function in otherwise deficient cells.

Pre-clinical development and molecular characterization of an engineered type 1 regulatory T-cell product suitable for immunotherapy.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic approach for many hematological disorders. However, allo-HSCT is frequently accompanied by a serious side effect: graft-versus-host disease (GVHD). The clinical use of allo-HSCT is limited by the inability of current immunosuppressive regimens to adequately control GvHD without impairing the graft-versus-leukemia effect (GvL) conferred by transplanted healthy immune cells. To address this, the authors have developed an engineered type 1 regulatory T-cell product called CD4IL-10 cells. CD4IL-10 cells are obtained through lentiviral transduction, which delivers the human IL10 gene into purified polyclonal CD4+ T cells. CD4IL-10 cells may provide an advantage over standard-of-care immunosuppressants because of the ability to suppress GvHD through continuous secretion of IL-10 and enhance the GvL effect in myeloid malignancies through targeted killing of malignant myeloid cells. METHODS: Here the authors established a production process aimed at current Good Manufacturing Practice (cGMP) production for CD4IL-10 cells. RESULTS: The authors demonstrated that the CD4IL-10 cell product maintains the suppressive and cytotoxic functions of previously described CD4IL-10 cells. In addition, RNA sequencing analysis of CD4IL-10 identified novel transcriptome changes, indicating that CD4IL-10 cells primarily upregulate cytotoxicity-related genes. These include four molecules with described roles in CD8+ T and natural killer cell-mediated cytotoxicity: CD244, KLRD1, KLRC1 and FASLG. Finally, it was shown that CD4IL-10 cells upregulate IL-22, which mediates wound healing and tissue repair, particularly in the gut. CONCLUSIONS: Collectively, these results pave the way toward clinical translation of the cGMP-optimized CD4IL-10 cell product and uncover new molecules that have a role in the clinical application of CD4IL-10 cells.

Impact of habitual swimming on the success of lacrimal surgery.

PURPOSE: To elucidate how factors associated with swimming affect the lacrimal ducts of swimmers. STUDY DESIGN: Prospective, interventional cohort study, METHODS: Five hundred seventy four consecutive epiphora patients were surveyed via a questionnaire regarding details of their swimming-pool usage; i.e., frequency, swim-goggles' wear, and type of pool activity (i.e., swimming vs. waist-depth walking). In this cohort, all the swimmers over 20 years old with anatomical lacrimal duct obstruction underwent surgical reconstruction. The surgical success rates at 12-months postoperative were compared using multivariable logistic regression analyses between swimmer/non-swimmer patients, those with a history of high/low frequency of pool usage, and those with high/low amount of conjunctival contact with the swimming-pool water. RESULTS: Of the patients with anatomical lacrimal duct obstruction, 6.4% were habitual swimmers; nasolacrimal duct obstruction was more common in the swimmers than in the non-swimmers' controls (89.1%/66.7%, P = 0.025). The success rate of lacrimal surgery for the swimmers with anatomical nasolacrimal duct obstruction was lower (60.6%) than of the non-swimmers (83.3%, P = 0.048). A receiver operating characteristic curve analysis of the frequency for the prediction of surgical failure showed that the threshold was 4 days/week. The success rate was statistically lower (26.7%) in the high-frequency swimmers compared to the low-frequency swimmers (88.9%, P = 0.037). However, no statistical difference in the high/low ocular surface contact to the swimming-pool water was observed (71.4%/57.7%, P = 0.56). CONCLUSION: Habitual swimmers have a high risk of nasolacrimal-duct damage retrogradely from the nasal cavity that lowers lacrimal surgery's success rate.

Compressive optic neuropathy (CON) in Graves' disease caused by hypertrophy of levator and superior rectus muscles: A case report.

RATIONALE: Enlargemento of the medial rectus is the most predominant factor of compressive optic neuropathy (CON) in Graves' disease. This case report indicates that CON could develop only from the hypertrophic superior levator and superior rectus (SL/SR) muscle in a patient with poorly controlled Graves' disease, and described the possible risk of FT3-thyrotoxicosis with a prominent goiter to develop the current rare case with a review of the literature. PATIENT CONCERNS: A 66-year-old woman undergoing endocrine management of hyperthyroidism with prominent goiter visited the Department of Ophthalmology due to right-eye upper-eyelid retraction. DIAGNOSES: At initial presentation, the right and left margin reflex distance-1 (MRD-1) was 3.2 mm and 2.1 mm, respectively, and no proptosis or visual dysfunction was observed. Despite insufficient hormonal regulation, she refused to undergo goiter removal. The upper eyelid retraction gradually worsened to 7.7 mm of MRD-1, followed by the onset of 20 prism diopters (PD) of the right hypertropia, resulting in right-eye CON after 6 months. Her free thyroxin level was 3.88 ng/dl and free triiodothyronine was 24.90 pg/ml. Computed tomography and magnetic resonance imaging showed only SL/SR enlargement in the right orbit. INTERVENTIONS: Intravenous steroid and radiation therapy resulted in visual improvement; however, a prominent upper eyelid retraction and 35PD of hypertropia remained in her right eye. Orbital decompression, upper retraction repair, and superior rectus recession were performed to prevent the recurrence of CON and correct any disfigurement. OUTCOMES: The combination of conventional intravenous steroid pulse therapy, radiotherapy, and orbital decompression was effective, and no recurrence was observed for more than 1.5-years postoperatively. LESSONS: Enlargement of the SL/SR muscle complex may independently induce the CON. We believe that strict attention should be paid to patients with triiodothyronine thyrotoxicosis with progressive eyelid retraction and hypertropia.

Development of a scoring system to predict outcomes of i.v. corticosteroid pulse therapy in rapidly progressive alopecia areata adopting digital image analysis of hair recovery.

Alopecia areata (AA) is a common autoimmune disease manifesting varying degrees of hair loss. Rapidly progressive AA (RP-AA) is a severe subtype of AA and often resistant to skin-directed treatments. i.v. corticosteroid pulse therapy has been applied for RP-AA; however, the treatment outcome can only become evaluable several months after the intervention, discomposing the patients. In this study, we attempted to develop a scoring system to predict treatment outcomes based on statistical correlations between newly identified predictors and the recovery rates calculated by digital image analysis. Thirty RP-AA patients (15 men and 15 women) who underwent pulse therapy and demonstrated total hair loss during the clinical course were included. The percentages of hair regrowth (%HR) at 6 months after the treatment were quantitatively calculated by image analysis software. The correlation between %HR and clinicopathological and immunological variables were statistically assessed. The analysis identified four confirmatory contributors including female sex (P = 0.015), absence of previous AA history (P = 0.02), lower peripheral blood eosinophil count (P = 0.02) and mild to moderate cell infiltration around the hair bulb (P = 0.034), together with a potential contributor, namely absence of atopic dermatitis in their medical history (P = 0.08). The scoring system was developed by double counting confirmatory variables and single counting a potential variable. Importantly, the scores obtained by this system demonstrated significant correlation with %HR (r = 0.61, P < 0.001). The usefulness of this scoring system was further validated by assessing additional 20 cases of RP-AA. When combined with a recently published algorithm for early detection of self-healing subset, the current scoring system may help strategize the therapeutic approach for RP-AA.

Human-engineered Treg-like cells suppress FOXP3-deficient T cells but preserve adaptive immune responses in vivo.

OBJECTIVES: Genetic or acquired defects in FOXP3+ regulatory T cells (Tregs) play a key role in many immune-mediated diseases including immune dysregulation polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Previously, we demonstrated CD4+ T cells from healthy donors and IPEX patients can be converted into functional Treg-like cells by lentiviral transfer of FOXP3 (CD4LVFOXP3). These CD4LVFOXP3 cells have potent regulatory function, suggesting their potential as an innovative therapeutic. Here, we present molecular and preclinical in vivo data supporting CD4LVFOXP3 cell clinical progression. METHODS: The molecular characterisation of CD4LVFOXP3 cells included flow cytometry, qPCR, RNA-seq and TCR-seq. The in vivo suppressive function of CD4LVFOXP3 cells was assessed in xenograft-versus-host disease (xeno-GvHD) and FOXP3-deficient IPEX-like humanised mouse models. The safety of CD4LVFOXP3 cells was evaluated using peripheral blood (PB) humanised (hu)- mice testing their impact on immune response against pathogens, and immune surveillance against tumor antigens. RESULTS: We demonstrate that the conversion of CD4+ T cells to CD4LVFOXP3 cells leads to specific transcriptional changes as compared to CD4+ T-cell transduction in the absence of FOXP3, including upregulation of Treg-related genes. Furthermore, we observe specific preservation of a polyclonal TCR repertoire during in vitro cell production. Both allogeneic and autologous CD4LVFOXP3 cells protect from xeno-GvHD after two sequential infusions of effector T cells. CD4LVFOXP3 cells prevent hyper-proliferation of CD4+ memory T cells in the FOXP3-deficient IPEX-like hu-mice. CD4LVFOXP3 cells do not impede in vivo expansion of antigen-primed T cells or tumor clearance in the PB hu-mice. CONCLUSION: These data support the clinical readiness of CD4LVFOXP3 cells to treat IPEX syndrome and other immune-mediated diseases caused by insufficient or dysfunctional FOXP3+ Tregs.

Intracellular accumulation of PD-1 molecules in circulating T lymphocytes in advanced malignant melanoma: an implication for immune evasion mechanism.

BACKGROUND: The blockade of cell surface PD-1 ((sur)PD-1) by monoclonal antibodies, represented by nivolumab, provides the strategy to treat advanced malignant melanoma (AMM). The intracellular presence of PD-1 molecules have been reported in some T cell subsets, however, their kinetic association with those expressed on the cell surface, let alone their significance in antitumor immunity has been ill-investigated. METHODS: Intracellular PD-1 expression status in T cell subsets in AMM cases during nivolumab administration was chronologically characterized. The kinetics of PD-1 molecules within AMM-derived T cells was assessed in vitro in conjunction with their functional properties. RESULTS: Increase in (sur)PD-1 and intracellular PD-1 ((int)PD-1+) expression was characteristic for AMM T cells. After short-term culture, virtually (sur)PD-1- nivolumab-treated AMM T cells restore (sur)PD-1 expression, which could not be explained by the detachment of nivolumab from PD-1 epitopes alone. The blockade of trans-Golgi network resulted in the decrease in the extent of (sur)PD-1 recovery, suggesting the translocation of accumulated (int)PD-1 to the cell surface. Antigen-specific PD-1+ T cells significantly increased in (int)PD-1+ cells after treatment. In addition, a surge in (int)PD-1+CD4+ T cells was observed prior to the emergence of skin rash as an immune-related adverse event (irAE). CONCLUSIONS: Accumulated (int)PD-1 in T cells may contribute to enhanced immune evasion in AMM. Evaluation of intracellular PD-1 expression would be useful for better management of nivolumab-treated AMM patients in view of predicting treatment response and the incidence of irAE. Our findings further support the necessity of periodical administration of nivolumab for treating AMM.

Spontaneous disappearance and recurrence of impending macular hole: a case report.

BACKGROUND: There have been several reports of spontaneous closure and reopening of a macular hole, however, in most of those cases, it was observed in eyes post vitrectomy. Here, we report a case of multiple episodes of spontaneous disappearance and recurrence of impending macular hole (stage 1B macular hole) with no history of previous surgery. CASE PRESENTATION: A 76-year-old Japanese man presented with a primary complaint of reduced visual acuity in his right eye. On initial examination, the visual acuity in his right and left eye was 0.4 and 0.01, respectively. He had previously been diagnosed as having macular degeneration of unknown origin in his left eye. Optical coherence tomography imaging confirmed vitreomacular traction and impending macular hole in his right eye. After a 1-week follow-up period, posterior vitreous detachment was detected, and the impending macular hole appeared to be resolved. Two months later, the impending macular hole had completely disappeared and his visual acuity had improved to 0.9. Six months later, he again noticed decreased vision in his right eye. An examination revealed that his visual acuity had dropped to 0.4, and there was a recurrence of impending macular hole. An optical coherence tomography examination showed no definitive findings of vitreous traction, and, 1 month later, spontaneous disappearance was observed again and his visual acuity improved to 0.7. CONCLUSIONS: In this case, both the initial onset and the recurrence involved impending macular hole, however, the optical coherence tomography findings differed at each examination. These findings suggest that some causes other than vitreous traction were responsible for both the spontaneous disappearance and recurrence of the impending macular hole in this present case.

Design and control of gas diffusion process in a nanoporous soft crystal.

Design of the gas-diffusion process in a porous material is challenging because a contracted pore aperture is a prerequisite, whereas the channel traffic of guest molecules is regulated by the flexible and dynamic motions of nanochannels. Here, we present the rational design of a diffusion-regulatory system in a porous coordination polymer (PCP) in which flip-flop molecular motions within the framework structure provide kinetic gate functions that enable efficient gas separation and storage. The PCP shows substantial temperature-responsive adsorption in which the adsorbate molecules are differentiated by each gate-admission temperature, facilitating kinetics-based gas separations of oxygen/argon and ethylene/ethane with high selectivities of ~350 and ~75, respectively. Additionally, we demonstrate the long-lasting physical encapsulation of ethylene at ambient conditions, owing to strongly impeded diffusion in distinctive nanochannels.

Gas-responsive porous magnet distinguishes the electron spin of molecular oxygen.

Gas-sensing materials are becoming increasingly important in our society, requiring high sensitivity to differentiate similar gases like N2 and O2. For the design of such materials, the driving force of electronic host-guest interaction or host-framework changes during the sorption process has commonly been considered necessary; however, this work demonstrates the use of the magnetic characteristics intrinsic to the guest molecules for distinguishing between diamagnetic N2 and CO2 gases from paramagnetic O2 gas. While the uptake of N2 and CO2 leads to an increase in TC through ferrimagnetic behavior, the uptake of O2 results in an O2 pressure-dependent continuous phase change from a ferrimagnet to an antiferromagnet, eventually leading to a novel ferrimagnet with aligned O2 spins following application of a magnetic field. This chameleonic material, the first with switchable magnetism that can discriminate between similarly sized N2 and O2 gases, provides wide scope for new gas-responsive porous magnets.

Tregopathies: Monogenic diseases resulting in regulatory T-cell deficiency.

Monogenic diseases of the immune system, also known as inborn errors of immunity, are caused by single-gene mutations resulting in immune deficiency and dysregulation. More than 350 diseases have been described to date, and the number is rapidly expanding, with increasing availability of next-generation sequencing facilitating the diagnosis. The spectrum of immune dysregulation is wide, encompassing deficiencies in humoral, cellular, innate, and adaptive immunity; phagocytosis; and the complement system, which lead to autoinflammation and autoimmunity. Multiorgan autoimmunity is a dominant symptom when genetic mutations lead to defects in molecules essential for the development, survival, and/or function of regulatory T (Treg) cells. Studies of "Tregopathies" are providing critical mechanistic information on Treg cell biology, the role of Treg cell-associated molecules, and regulation of peripheral tolerance in human subjects. The pathogenic immune networks underlying these diseases need to be dissected to apply and develop immunomodulatory treatments and design curative treatments using cell and gene therapy. Here we review the pathogenetic mechanisms, clinical presentation, diagnosis, and current and future treatments of major known Tregopathies caused by mutations in FOXP3, CD25, cytotoxic T lymphocyte-associated antigen 4 (CTLA4), LPS-responsive and beige-like anchor protein (LRBA), and BTB domain and CNC homolog 2 (BACH2) and gain-of-function mutations in signal transducer and activator of transcription 3 (STAT3). We also discuss deficiencies in genes encoding STAT5b and IL-10 or IL-10 receptor as potential Tregopathies.

Association between Delirium and Prehospitalization Medication in Poststroke Patients.

PURPOSE: Medication is an important risk factor for delirium; however, the association between delirium and prehospitalization medication is unclear. We investigated the association between prestroke medication and poststroke delirium. MATERIALS AND METHODS: All patients hospitalized in the stroke care unit from September 2011 to September 2012 were selected, and their delirium symptoms, patient information, and pre- and poststroke medications were analyzed. Delirium was defined as a score of 4 or higher on the Intensive Care Delirium Screening Checklist. Factors that were related to delirium were extracted using univariate analysis, and the independent risk factors were determined using multivariate analysis. RESULTS: Of the 269 patients analyzed, 97 (36%) experienced delirium. Univariate analysis revealed significant differences between the delirium and nondelirium groups in age, dementia, previous cerebrovascular disease, craniotomy, all insertion-tube types, and 6 categories of prestroke medication. Prestroke polypharmacy was associated with poststroke delirium (P = .002). Multivariate analysis showed that taking antianxiety agents or sleep aids was an independent risk factor for delirium (odds ratio: 3.17, 95% confidence interval: 1.16-8.82). CONCLUSIONS: The present study suggests that prestroke medication affects the onset of poststroke delirium. These findings can contribute to the prediction and prevention of this condition.

Immunohistochemical dissection of cystic panfolliculoma focusing on the expression of multiple hair follicle lineage markers with an insight into the pathogenesis.

Panfolliculoma (PF) is a rare benign tumor with signs of differentiation toward all components of the hair follicle (HF). Cystic panfolliculoma (CPF) is a subset of PF with histological similarity to trichofolliculoma making the differential diagnosis difficult in some cases. Immunohistopathological investigations of PF have been reported; however, previous studies focused mostly on the expression profile of the outer root sheath markers. Herein, we report a case of CPF. A panel of antibodies was developed and used for the detection of the expression of cytokeratin (CK) 10, CK13, CK14, CK15, hair-hard keratin (AE13) and EpCAM within the lesion, supporting the differentiation of all epithelial lineages of the HF and the diagnosis of CPF. Immunohistopathological examinations clearly showed the spatial distribution pattern of each subset of tumor cells with distinct HF differentiation marker expression. Intriguingly, fibroblastic dermal cells were distributed preferentially near CK15-negative epithelium or CK13-positive HF-like structures, suggesting a role for epithelial-mesenchymal interactions (EMIs) in CPF pathogenesis. Further characterization of EMIs between the tumor and surrounding mesenchymal cells in CPF may provide an explanation for immature HF differentiation. These findings suggest that the more intense and coordinated EMI in the analogous tumorigenesis gives rise to mature HF structures, resulting in trichofolliculoma, which may explain their histological resemblance.