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Ulipristal acetate (UPA) is an effective drug for the treatment of symptomatic uterine fibroids. The drug is highly effective in controlling bleeding control and in the recovery of anemia. Here, we report the case of a woman with severe menorrhagia due to a uterine fibroid and with concomitant pulmonary embolism, a serious life-threatening condition. UPA was shown to be effective in reducing fibroid volume and controlling symptoms, without worsening the underlying embolic disease. No adverse events were observed, and the patient has completely recovered. [ABSTRACT FROM AUTHOR]

We studied the expression of adhesion molecules affecting recirculation and homing on peripheral blood CD4+ T cells of patients with systemic sclerosis (SSc), in order to evaluate whether the distribution of tissue targeted subsets could reflect the participation of internal organs or the extent of cutaneous involvement[i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age-matched controls were investigated by cytofluorimetric analysis for lymphocyte subpopulations carrying the following surface molecules: CD3, CD4, CLA,α4β7 andα4β1. Standard routine biochemistry and clinical examinations were also performed in all patients. We found that bothα4β1+ andα4β7+ cells within the CD4+ T cell population were significantly increased, while CLA+ CD4+ T cells were significantly reduced in SSc, compared to healthy donors. Significantly lower absolute numbers ofα4β7+ cells were found in lc- compared to dc-SSc. Patients with oesophageal involvement had high numbers ofα4β7+ cells, while those with nephritis also showed low levels of CLA+ cells. Lung involvement was related directly toα4β1+ cell numbers and inversely toα4β7+ CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4+ T cell populations with selective homing properties show changes from normal distribution in SSc, and such changes are related to clinical expression and organ involvement in the course of the disease. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate the prevalence of symptomatic yeast vaginitis caused by non-albicans species among patients attending a vaginitis clinic over an 8-year period.Study Design: A retrospective study of 1263 patients with symptomatic yeast vaginitis confirmed by culture techniques was performed.Results: The prevalence of symptomatic fungal vaginitis caused by non-albicans species increased from 9.9% (10/101) in 1988 to 17.2% (36/209) in 1995 (chi 2 for trend = 9.33, p = 0.002). Non-albicans species were found more frequently in known human immunodeficiency virus-seropositive patients (23/102 vs 143/1161, odds ratio 2.07, 95% confidence interval 1.2 to 3.46) than in seronegative subjects or subjects of unknown status for the virus. Recurrent vaginal candidiasis was an additional risk factor for vaginitis caused by non-albicans species (odds ratio 2.47, 95% confidence interval 1.72 to 3.52). The increase in non-albicans isolates during the study period was confirmed in stratified analysis and in the subgroup of self-referred patients with no history of either human immunodeficiency virus infection or recurrent vaginal candidiasis.Conclusion: The prevalence of fungal vaginitis caused by non-albicans species has increased sharply in the setting of a vaginitis clinic. The characteristics of risk factors suggest that fungal cultures should be done routinely in human immunodeficiency virus-seropositive subjects with suspected vaginal candidiasis and in patients with recurrent vaginal infection. [ABSTRACT FROM AUTHOR]

Reports on a case of isolated acral Darier's disease successfully treated with adapalene 0.1% gel. Presence of multiple, moderately itchy, keratotic papules on the back of both hands; Association with hyperkeratosis of the soles; Intraepidermal suprabasal lacunae with reduced or absent desmosomal structure and altered desmosomal tonofilaments.

A letter to the editor is presented in response to the article concerning the possible antiaggressive effect of cyproterone acetate, published in the previous issue.

A letter to the editor is presented in response to an article on the effect of sulpiride on negative symptoms of schizophrenia.

Background: Alopecia areata (AA) is a non-scarring disorder characterized by hair loss that greatly affects patients' quality of life and has a chronic, recurring course. This disease is marked by an inflammatory process, mainly on an autoimmune basis primarily regulated by Janus kinase (JAK)., Research Design and Methods: We conducted a retrospective study evaluating the safety of JAKi in a real-world setting in 91 AA patients, with a specific focus on the assessment of infectious events., Results: Overall, 34 infectious events were observed in 28 patients (30.8%), among them 17 patients (60.7%) suspended treatment with JAKi until the infection was clinically resolved. Only in one case the infectious event led to a permanent discontinuation of the treatment. The data we observed in the study are consistent with results reported in clinical trials., Conclusion: It can be stated that, during treatment with JAKi in AA patients, infectious events may occur, but in most cases these events are easily manageable and do not result in permanent discontinuation of the drug.

Objective: In Italy the percentage of repeated abortions is about 24%. Long-acting reversible contraceptive (LARC) methods are currently considered the most effective mode worldwide and are associated with the highest rate of 12-months continuation, with a potential reported reduction of recurrent abortions. The aim of this study was evaluating LARC continuation and the patients' satisfaction at two and twelve months in use., Materials and Methods: A longitudinal observational study collected women who underwent surgical abortion and placed a LARC method at the time of abortion in our hospital., Results: Totally 828 women underwent surgical abortion during the study period from which 434 choose a LARC method. After two months the rate of continuation of 52mg LNG IUD was 100% in women presenting for follow-up. Continuation rate at one year was approximately 70% for all LARC methods. More than 70% of women declared themselves satisfied or very satisfied with all LARC methods., Conclusion: Despite a high rate of patient loss at follow-up, LARC methods showed a high rate of continuation at two and twelve months, with a high degree of patients' satisfaction., Competing Interests: Conflict of Interests Authors declare no conflict of interests., (Copyright © 2024 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

The aim was to demonstrate that the technique of near infrared range/indocyanine green (NIR/ICG) could aid the detection of inguinal sentinel lymph nodes in patients with vulvar cancer, in addition to technetium-99m (Tc-99m) scanning. We present a case report of sentinel lymph node detection in a patient with vulvar cancer with two methods: Tc-99m scan and NIR/ICG. The video showed that bilateral inguinal lymph nodes were detected both by Tc gamma probe and NIR/ICG. NIR/ICG may be a safe and effective alternative method for identifying sentinel lymph nodes in cases of early-stage vulvar cancer, although more evidence is required., Competing Interests: Conflict of Interest: No conflict of interest is declared by the authors., (©Copyright 2023 by the Turkish-German Gynecological Education and Research Foundation. Journal of the Turkish-German Gynecological Association is published by Galenos Publishing House.)

The percentage of repeat abortion in Italy is about 25%. It is therefore important to implement the strategies that can facilitate the adoption of the most effective contraceptive methods. Long-acting reversible contraceptive methods are currently considered the most effective and with the highest rates of 12-months continuation, with a reported reduction of recurrent abortion. Our study has the aim to evaluate the contraceptive choice of women requesting abortion, when an accurate and dedicate counselling is offered and the availability of a LARC method is given immediately after pregnancy termination, both in case of surgical and medical abortion. LARC methods were chosen both in case of surgical and medical abortion, by an high percentage of patients. We reported no differences between the surgical and pharmacological groups on the choice of LARC and SARC. Our observational study shows the feasibility to perform an accurate, dedicate, and personalised counselling on contraception at time of abortion. This approach has enabled a high number of women to have a LARC method inserted at the time of abortion, as a valid strategy to prevent the risk unplanned pregnancy.

Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch's effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4β7 in conventional T cells while preserving α4β7 in regulatory T cells, with findings suggesting increased β1 competition for α4 binding in conventional T cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4β7 integrin in T cells after allo-HCT. Together, DLL4-Notch blockade decreased effector T cell infiltration into the gut, with increased regulatory to conventional T cell ratios early after allo-HCT. Our results identify a conserved, biologically unique, and targetable role of DLL4-Notch signaling in intestinal GVHD.

Population aging resulting from demographic changes requires some challenging decisions and necessary steps to be taken by different stakeholders to manage current and future demand for assistance and support. The consequences of population aging can be mitigated to some extent by assisting technologies that can support the autonomous living of older individuals and persons in need of care in their private environments as long as possible. A variety of technical solutions are already available on the market, but privacy protection is a serious, often neglected, issue when using such (assisting) technology. Thus, privacy needs to be thoroughly taken under consideration in this context. In a three-year project PAAL ('Privacy-Aware and Acceptable Lifelogging Services for Older and Frail People'), researchers from different disciplines, such as law, rehabilitation, human-computer interaction, and computer science, investigated the phenomenon of privacy when using assistive lifelogging technologies. In concrete terms, the concept of Privacy by Design was realized using two exemplary lifelogging applications in private and professional environments. A user-centered empirical approach was applied to the lifelogging technologies, investigating the perceptions and attitudes of (older) users with different health-related and biographical profiles. The knowledge gained through the interdisciplinary collaboration can improve the implementation and optimization of assistive applications. In this paper, partners of the PAAL project present insights gained from their cross-national, interdisciplinary work regarding privacy-aware and acceptable lifelogging technologies., Competing Interests: Conflicts of Interest/Competing interestsThe authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (© The Author(s) 2022.)

The use of agro-industrial by-products in animal nutrition is a promising strategy to reduce the food-feed competition, the diet cost at farm level and the environmental impact of animal-derived food production. In this study, the suitability of cocoa bean shell (CBS), a by-product of the cocoa industry, as a feed ingredient in the diet of dairy goats was evaluated, with a focus on the related implications on feed intake, milk yield, milk main constituents, and fatty acid (FA) profile of milk fat. Twenty-two Camosciata delle Alpi goats were divided into two balanced groups. All the goats were fed mixed hay ad libitum . The control group (CTRL; n = 11) also received 1.20 kg/head × day of a commercial concentrate, while in the experimental group (CBS; n = 11) 200 g of the CTRL concentrate were replaced by the same amount of pelleted CBS. The total dry matter intake of the goats was reduced by the dietary inclusion of CBS ( P ≤ 0.01). The milk yield, as well as the milk fat, protein, and casein contents and yields were unaffected by the treatment. Milk from the CBS-fed goats showed decreased urea content when compared to the CTRL group ( P ≤ 0.001). Milk from the CBS group of goats also showed increased concentrations of total branched-chain FA (both iso and anteiso forms; P ≤ 0.001) and total monounsaturated FA ( P ≤ 0.05), as well as a decreased ∑ n 6/∑ n 3 FA ratio ( P ≤ 0.05). De novo saturated FA, total polyunsaturated FA, total conjugated linoleic acids, and the majority of ruminal biohydrogenation intermediates remained unaffected by the dietary treatment. These results suggest that CBS can be strategically used as an alternative non-conventional raw material in diets intended for lactating goats, with no detrimental effects on their milk production performance. The use of CBS in goat nutrition may be hindered by the presence of theobromine, a toxic alkaloid. Special attention is needed by nutritionists to avoid exceeding the theobromine limits imposed by the current legislation. Detheobromination treatments are also suggested in literature to prevent toxic phenomena., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Renna, Lussiana, Colonna, Malfatto, Mimosi and Cornale.)

Organ infiltration by donor T cells is critical to the development of acute graft-versus-host disease (aGVHD) in recipients after allogeneic hematopoietic stem cell transplant (allo-HCT). However, deconvoluting the transcriptional programs of newly recruited donor T cells from those of tissue-resident T cells in aGVHD target organs remains a challenge. Here, we combined the serial intravascular staining technique with single-cell RNA sequencing to dissect the tightly connected processes by which donor T cells initially infiltrate tissues and then establish a pathogenic tissue residency program in a rhesus macaque allo-HCT model that develops aGVHD. Our results enabled creation of a spatiotemporal map of the transcriptional programs controlling donor CD8 + T cell infiltration into the primary aGVHD target organ, the gastrointestinal (GI) tract. We identified the large and small intestines as the only two sites demonstrating allo-specific, rather than lymphodepletion-driven, T cell infiltration. GI-infiltrating donor CD8 + T cells demonstrated a highly activated, cytotoxic phenotype while simultaneously developing a canonical tissue-resident memory T cell (T RM ) transcriptional signature driven by interleukin-15 (IL-15)/IL-21 signaling. We found expression of a cluster of genes directly associated with tissue invasiveness, including those encoding adhesion molecules ( ITGB2 ), specific chemokines ( CCL3 and CCL4L1 ) and chemokine receptors ( CD74 ), as well as multiple cytoskeletal proteins. This tissue invasion transcriptional signature was validated by its ability to discriminate the CD8 + T cell transcriptome of patients with GI aGVHD from those of GVHD-free patients. These results provide insights into the mechanisms controlling tissue occupancy of target organs by pathogenic donor CD8 + T RM cells during aGVHD in primate transplant recipients., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Chimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies have rapidly emerged as a promising, novel therapy. In contrast, results from the few CAR T-cell studies for infectious diseases such as HIV-1 have been less convincing. These challenges are likely due to the low level of antigen present in antiretroviral therapy (ART)-suppressed patients in contrast to those with hematologic malignancies. Using our well-established nonhuman primate model of ART-suppressed HIV-1 infection, we tested strategies to overcome these limitations and challenges. We first optimized CAR T-cell production to maintain central memory subsets, consistent with current clinical paradigms. We hypothesized that additional exogenous antigen might be required in an ART-suppressed setting to aid expansion and persistence of CAR T cells. Thus, we studied 4 simian/HIV-infected, ART-suppressed rhesus macaques infused with virus-specific CD4CAR T cells, followed by supplemental infusion of cell-associated HIV-1 envelope (Env). Env boosting led to significant and unprecedented expansion of virus-specific CAR+ T cells in vivo; after ART treatment interruption, viral rebound was significantly delayed compared with controls (P = .014). In 2 animals with declining CAR T cells, rhesusized anti-programmed cell death protein 1 (PD-1) antibody was administered to reverse PD-1-dependent immune exhaustion. Immune checkpoint blockade triggered expansion of exhausted CAR T cells and concordantly lowered viral loads to undetectable levels. These results show that supplemental cell-associated antigen enables robust expansion of CAR T cells in an antigen-sparse environment. To our knowledge, this is the first study to show expansion of virus-specific CAR T cells in infected, suppressed hosts, and delay/control of viral recrudescence., (© 2020 by The American Society of Hematology.)

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common treatment for patients suffering from different hematological disorders. Allo-HCT in combination with hematopoietic stem cell (HSC) gene therapy is considered a promising treatment option for millions of patients with HIV+ and acute myeloid leukemia. Most currently available HSC gene therapy approaches target CD34-enriched cell fractions, a heterogeneous mix of mostly progenitor cells and only very few HSCs with long-term multilineage engraftment potential. As a consequence, gene therapy approaches are currently limited in their HSC targeting efficiency, very expensive consuming huge quantities of modifying reagents, and can lead to unwanted side effects in nontarget cells. We have previously shown that purified CD34 + CD90 + CD45RA - cells are enriched for multipotent HSCs with long-term multilineage engraftment potential, which can reconstitute the entire hematopoietic system in an autologous nonhuman primate transplant model. Here, we tested the feasibility of transplantation with purified CD34 + CD90 + CD45RA - cells in the allogeneic setting in a nonhuman primate model., Methods: To evaluate the feasibility of this approach, CD34 + CD90 + CD45RA - cells from 2 fully major histocompatibility complex-matched, full sibling rhesus macaques were sort-purified, quality controlled, and transplanted. Engraftment and donor chimerism were evaluated in the peripheral blood and bone marrow of both animals., Results: Despite limited survival due to infectious complications, we show that the large-scale sort-purification and transplantation of CD34 + CD90 + CD45RA - cells is technically feasible and leads to rapid engraftment of cells in bone marrow in the allogeneic setting and absence of cotransferred T cells., Conclusions: We show that purification of an HSC-enriched CD34 + subset can serve as a potential stem cell source for allo-HCTs. Most importantly, the combination of allo-HCT and HSC gene therapy has the potential to treat a wide array of hematologic and nonhematologic disorders., Competing Interests: S.R. is a consultant to Forty Seven Inc (Gilead Sciences). H.-P.K. is a consultant to and has ownership interests with Rocket Pharma and Homology Medicines. H.-P.K. is a consultant to CSL Behring and Magenta Therapeutics. S.R. and H.-P.K. are inventors on patent applications (nos. 62/351 761, 62/428 994, and PCT/US2017/037967) submitted by the Fred Hutchinson Cancer Research Center that covers the selection and use of cell populations for research and therapeutic purposes as well as strategies to assess and/or produce cell populations with predictive engraftment potential. The other authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection., Competing Interests: Declaration of Interests A.R. is an SAB member of ThermoFisher Scientific, Neogene Therapeutics, Asimov, and Syros Pharmaceuticals; a co-founder of and equity holder in Celsius Therapeutics; and an equity holder in Immunitas Therapeutics. A.K.S. reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Cellarity, Cogen Therapeutics, Orche Bio, and Dahlia Biosciences. L.S.K. is on the SAB for HiFiBio; she reports research funding from Kymab Limited, Bristol Meyers Squibb, Magenta Therapeutics, BlueBird Bio, and Regeneron Pharmaceuticals and consulting fees from Equillium, FortySeven, Inc, Novartis, Inc, EMD Serono, Gilead Sciences, and Takeda Pharmaceuticals. A.S. is an employee of Johnson and Johnson. N.K. is an inventor on a patent using thyroid hormone mimetics in acute lung injury that is now being considered for intervention in COVID-19 patients. J.L. is a scientific consultant for 10X Genomics, Inc. O.R.R, is a co-inventor on patent applications filed by the Broad Institute to inventions relating to single-cell genomics applications, such as in PCT/US2018/060860 and US Provisional Application No. 62/745,259. S.T. in the last three years was a consultant at Genentech, Biogen, and Roche and is a member of the SAB of Foresite Labs. M.H.W. is now an employee of Pfizer. F.J.T. reports receiving consulting fees from Roche Diagnostics GmbH and ownership interest in Cellarity, Inc. P.H. is a co-inventor on a patent using artificial intelligence and high-resolution microscopy for COVID-19 infection testing based on serology., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Lupus nephritis (LN) is a major contributor to morbidity and mortality in lupus patients, but the mechanisms of kidney damage remain unclear. In this study, we introduce, to our knowledge, novel models of LN designed to resemble the polygenic nature of human lupus by embodying three key genetic alterations: the Sle1 interval leading to anti-chromatin autoantibodies; Mfge8 -/- , leading to defective clearance of apoptotic cells; and either C1q -/- or C3 -/- , leading to low complement levels. We report that proliferative glomerulonephritis arose only in the presence of all three abnormalities (i.e., in Sle1.Mfge8 -/- C1q -/- and Sle1.Mfge8 -/- C3 -/- triple-mutant [TM] strains [ C1q -/- TM and C3 -/- TM, respectively]), with structural kidney changes resembling those in LN patients. Unexpectedly, both TM strains had significant increases in autoantibody titers, Ag spread, and IgG deposition in the kidneys. Despite the early complement component deficiencies, we observed assembly of the pathogenic terminal complement membrane attack complex in both TM strains. In C1q -/- TM mice, colocalization of MASP-2 and C3 in both the glomeruli and tubules indicated that the lectin pathway likely contributed to complement activation and tissue injury in this strain. Interestingly, enhanced thrombin activation in C3 -/- TM mice and reduction of kidney injury following attenuation of thrombin generation by argatroban in a serum-transfer nephrotoxic model identified thrombin as a surrogate pathway for complement activation in C3-deficient mice. These novel mouse models of human lupus inform the requirements for nephritis and provide targets for intervention., (Copyright © 2020 by The American Association of Immunologists, Inc.)