TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets.

The mouse thymus produces discrete γδ T cell subsets that make either interferon-γ (IFN-γ) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on γδ T cells. CD3DH mice had normal numbers and phenotypes of αß thymocyte subsets, but impaired differentiation of fetal Vγ6(+) (but not Vγ4(+)) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122(+) NK1.1(+) γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ(+) γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology.

Pelvic floor dysfunction after vaginal delivery: MOODS-a prospective study.

INTRODUCTION AND HYPOTHESIS: Labor is a known risk factor for pelvic floor dysfunction (PFD); however, the impact of operative vaginal delivery (OVD), particularly spatulas, remains unclear. The aim of this study was to compare postpartum PFD symptoms in women undergoing spontaneous vaginal delivery (SVD) and those undergoing OVD. METHODS: An observational prospective study (MOODS: Maternal-neonatal Outcomes in Operative Vaginal Delivery) was enrolled at Hospital de Braga from February to October 2018. All singleton term OVD (Thierry spatulas and vacuum extractor) and a convenience SVD sample were recruited, in a 2:1 ratio. To assess PFD symptoms Pelvic Floor Distress Inventory-20 (PFDI-20) was applied at 3, 6, and 12 months postpartum. The questionnaire is divided into three subscales: Urinary (UDI), Colorectal-Anal (CRADI), and Pelvic Organ Prolapse Distress Inventory (POPDI). RESULTS: Of the 304 women recruited, 207 were included, 34.3% with SVD and 65.7% with OVD. Thierry spatulas were used in 53.7% of women undergoing OVD. Frequency of nulliparous (p < 0.001), episiotomy (p < 0.001), neuraxial anesthesia (p < 0.001), postpartum pain (p = 0.001) and occiput-posterior fetal position (p < 0.001) were significantly higher in OVD. Second phase of labor duration was longer in OVD (p = 0.001). At 3 months postpartum, women undergoing OVD and spatula-assisted delivery had higher UDI score, POPDI score, and global score, with no differences at 6 months and 1 year. After controlling for confounding variables, OVD and spatulas were still associated with greater POPDI scores at 3 months postpartum. CONCLUSIONS: Operative vaginal delivery, particularly with spatulas, seems to be associated with a higher prevalence of early PFD symptoms, mainly regarding pelvic organ prolapse.

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress.

Interleukin 17 (IL-17)-producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vγ6+ γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27- γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27- Vγ6+ γδ17 T-cell proliferation in vivo. Moreover, human Vδ1+ γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.

The Role of Operative Vaginal Delivery in Postpartum Sexual Dysfunction: MOODS - A Prospective Study.

BACKGROUND: Childbirth brings many changes to women's life and sexual health. The influence of operative vaginal delivery on sexual function has produced inconsistent results. AIM: To evaluate the effects of mode of vaginal delivery (spontaneous or operative) in postpartum sexual function. METHODS: Descriptive prospective study (MOODS- Maternal-neonatal Outcomes in Operative Vaginal Delivery) including 304 women who had a singleton term vaginal delivery (operative or spontaneous in a relation 2:1). Women were invited to answer a questionnaire at 3, 6 months and 1 year postpartum. OUTCOMES MEASUREMENT: A validated questionnaire was applied, the Female Sexual Function Index (FSFI) Score, to evaluate effects of operative delivery on sexual health. Sexual dysfunction was defined by FSFI score <26.55. RESULTS: 211 women answered at least one questionnaire. Overall rate of sexual dysfunction was 62%, 43% and 48% at 3, 6 and 12 months respectively. At 3 months, total FSFI score was significantly lower in operative vaginal delivery group (mean±SD, 21.3±8.6 vs 24.9±7.9, P = 0.015). Arousal (P = 0.028), orgasm (P = 0.029), satisfaction (P = 0.015) and pain (P = 0.007) FSFI domains were also significantly inferior. At this time, 44% women in spontaneous delivery group and 70% in operative delivery group had sexual dysfunction (P = 0.0002). At 6 months, there were no differences in FSFI scores according the type of delivery. At 12 months, total FSFI score was similar in both groups, but pain domain was significantly lower in operative delivery (P = 0.004). Considering type of instrument (Thierry's Spatulas or Kiwi Vacuum), no differences were found regarding episiotomy, perineal trauma, obstetric anal sphincter injury or postpartum complications. FSFI scores did not differ between the two instruments at any time point. A logistic regression showed that, when controlled for perineal trauma, mode of delivery was independently associated with sexual dysfunction at 3 months (P = 0.02). CLINICAL IMPLICATIONS: Clinicians should assess women's sexual health during pregnancy and postpartum period in order to enhance their wellbeing. STRENGTHS/LIMITATIONS: Strengths include its prospective design, standardized questionnaire and the new perspectives about a different obstetrical instrument (Thierry's spatulas). Limitations include the absence of pre-pregnancy sexual function data and considerable drop-out rate. CONCLUSION: Sexual dysfunction affects a great proportion of newly mothers and in postpartum period mode of delivery and perineal trauma seem to play an important role. Although there was a progressive reduction over time, prevalence of sexual dysfunction at 6 months and 1 year postpartum was still considerable. The type of obstetrical instrument does not seem to influence short or long-term sexual function. de Sousa NQ, Borges AC, Sarabando R, et al. The Role of Operative Vaginal Delivery in Postpartum Sexual Dysfunction: MOODS - A Prospective Study. J Sex Med 2021;18:1075-1082.

IL-23 drives differentiation of peripheral γδ17 T cells from adult bone marrow-derived precursors.

Pro-inflammatory interleukin (IL)-17-producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4+ γδ17 T cells can develop de novo in draining lymph nodes in response to innate stimuli. In vitro, γδ T cells from IL-17 fate-mapping reporter mice that had never activated the Il17 locus acquire IL-17 expression upon stimulation with IL-1ß and IL-23. Furthermore, IL-23R (but not IL-1R1) deficiency severely compromises the induction of γδ17 T cells in EAE, demonstrating the key role of IL-23 in the process. Finally, we show, in a composite model involving transfers of both adult bone marrow and neonatal thymocytes, that induced γδ17 T cells make up a substantial fraction of the total IL-17-producing Vγ4+ T-cell pool upon inflammation, which attests the relevance of this novel pathway of peripheral γδ17 T-cell differentiation.

Murine CD27(-) Vγ6(+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages.

Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include γδ T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-γ. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, γδ T cells promote tumor cell growth. γδ T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated γδ T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-γ. Consistent with this finding, both T cell receptor (TCR)δ-deficient and IL-17-deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by γδ T cells in the tumor environment was essentially restricted to a highly proliferative CD27((-)) subset that expressed Vγ6 instead of the more common Vγ1 and Vγ4 TCR chains. The preferential expansion of IL-17-secreting CD27((-)) Vγ6((+)) γδ T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17-dependent lymphoid/myeloid cross-talk involving γδ T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance.

Protective role of the inflammatory CCR2/CCL2 chemokine pathway through recruitment of type 1 cytotoxic γδ T lymphocytes to tumor beds.

Tumor-infiltrating lymphocytes (TILs) are important prognostic factors in cancer progression and key players in cancer immunotherapy. Although γδ T lymphocytes can target a diversity of tumor cell types, their clinical manipulation is hampered by our limited knowledge of the molecular cues that determine γδ T cell migration toward tumors in vivo. In this study we set out to identify the chemotactic signals that orchestrate tumor infiltration by γδ T cells. We have used the preclinical transplantable B16 melanoma model to profile chemokines in tumor lesions and assess their impact on γδ TIL recruitment in vivo. We show that the inflammatory chemokine CCL2 and its receptor CCR2 are necessary for the accumulation of γδ TILs in B16 lesions, where they produce IFN-γ and display potent cytotoxic functions. Moreover, CCL2 directed γδ T cell migration in vitro toward tumor extracts, which was abrogated by anti-CCL2 neutralizing Abs. Strikingly, the lack of γδ TILs in TCRδ-deficient but also in CCR2-deficient mice enhanced tumor growth in vivo, thus revealing an unanticipated protective role for CCR2/CCL2 through the recruitment of γδ T cells. Importantly, we demonstrate that human Vδ1 T cells, but not their Vδ2 counterparts, express CCR2 and migrate to CCL2, whose expression is strongly deregulated in multiple human tumors of diverse origin, such as lung, prostate, liver, or breast cancer. This work identifies a novel protective role for CCL2/CCR2 in the tumor microenvironment, while opening new perspectives for modulation of human Vδ1 T cells in cancer immunotherapy.

Effect of Perineal Massage and Warm Compresses Technique in Postpartum Pelvic Floor Dysfunction. A Secondary Analysis from a Randomised Controlled Trial.

Pelvic floor dysfunction (PFD) is common to be associated with pregnancy and birth. To date, no research has been done to understand whether the perineal massage and warm compresses technique has an impact on pelvic floor dysfunction. To assess the impact of perineal massage and warm compresses technique during the second stage of labor in pelvic floor dysfunction at 3 and 6 months postpartum. Of the 800 women recruited to randomised controlled trial to prevent perineal trauma, 496 were included in the study, with 242 (48.8%) assigned to the Perineal Massage and Warm Compresses (PeMWaC) group and 254 (51.2%) to the control group (hands-on). Used the Pelvic Floor Distress Inventory-20 (PFDI-20). The questionnaire is divided into three subscales: Urinary (UDI), Colorectal-Anal (CRADI), and Pelvic Organ Prolapse Distress Inventory (POPDI). The PeMWaC group had a significantly higher frequency of intact perineum (p < 0.001) and low-severity vaginal tears (tears without any other degree of perineal trauma) (p = 0.031) compared to the control group, while the control group had significantly more patients who suffered high-severity vaginal/perineal trauma (second degree perineal tears) (p = 0.031) and patients without spontaneous perineal trauma or vaginal tears who underwent episiotomy (p < 0.001). In addition, at 3 months postpartum, women in the control group had a higher Urinary Distress Inventory (UDI) score and global score, compared to the PeMWaC group, and after controlling for confounding variables, the perineal massage and warm compresses technique was associated with lower UDI scores at 3 months postpartum compared to control group. At 6 months postpartum, there were no differences in the UDI or global scores, indicating general recovery from perineal trauma. In addition to reducing perineal trauma during birth, the perineal massage and warm compresses technique was associated with a lower prevalence of early PFD symptoms, mainly urinary distress, at 3 months.Trial registration http://www.ClinicalTrials.gov NCT05854888, retrospectively registered.

Perineal massage and warm compresses - Randomised controlled trial for reduce perineal trauma during labor.

OBJECTIVE: The aim of this study is to evaluate the effect of perineal massage and warm compresses technique on the perineum integrity during second stage of labor. DESIGN AND SETTING: A single-center, prospective, randomized controlled trial was conducted between March 1st, 2019, and December 31st, 2020, at Hospital of Braga. PARTICIPANTS: Women with 18 years or older, between 37 weeks and 41 weeks pregnant, in whom a vaginal birth of a fetus in the cephalic presentation was planned were recruited. Eight hundred forty-eight women were randomly assigned (Perineal massage and warm compresses group, n = 424 and control group, n = 424), and 800 women, both perineal massage and warm compresses group (n = 400) and control group (n = 400) were included in the strict per protocol analysis. INTERVENTION: In the perineal massage and warm compresses group, women received perineal massage and warm compresses and in the control group, women received hands-on technique. RESULTS: The incidence of intact perineum was significantly higher in the perineal massage and warm compresses group [perineal massage and warm compresses group: 47% vs control group: 26.3%; OR 2.53, 95% CI 1.86-3.45, p<0.001], whereas second-degree tears and episiotomy rate were significantly lower in this group [perineal massage and warm compresses group: 7.2% vs control group: 12.3%; OR 1.96, 95% CI 1.17-3.29, p = 0.010 and perineal massage and warm compresses group: 9.5% vs control group: 28.5%; OR 3.478, 95% CI 2.236-5.409, p<0.001, respectively]. Also, obstetric anal sphincter injury with and without episiotomy and second-degree tears with episiotomy were significantly lower in the perineal massage and warm compresses group [perineal massage and warm compresses group: 0.5% vs control group: 2.3%; OR 5.404, 95% CI 1.077-27.126, p = 0.040 and perineal massage and warm compresses group: 0.3% vs control group: 1.8%; OR 9.253, 95% CI 1.083-79.015, p = 0.042, respectively]. CONCLUSIONS: The perineal massage and warm compresses technique increased the incidence of intact perineum and reduced the incidence of second-degree tear, episiotomy and obstetric anal sphincter injury. IMPLICATIONS FOR PRACTICE: Perineal massage and warm compresses technique is feasible, inexpensive and reproductible. Therefore, this technique should be taught and trained to midwives students and midwives team. Thus, women should have this information and have the option to decide whether they want to receive the perineal massage and warm compresses technique in the second stage of labor.

Primary retroperitoneal nodal endometrioid carcinoma associated with Lynch syndrome: A case report.

We report a rare case of primary nodal, poorly differentiated endometrioid carcinoma associated with Lynch syndrome. A 29-year-old female patient was referred by her general gynecologist for further imaging with suspected right-sided ovarian endometrioid cyst. Ultrasound examination by an expert gynecological sonographer at tertiary center revealed unremarkable findings in the abdomen and pelvis apart from three iliac lymph nodes showing signs of malignant infiltration in the right obturator fossa and two lesions in the 4b segment of the liver. During the same appointment ultrasound guided tru-cut biopsy was performed to differentiate hematological malignancy from carcinomatous lymph node infiltration. Based on the histological findings of endometrioid carcinoma from lymph node biopsy, primary debulking surgery including hysterectomy and salpingo-oophorectomy was performed. Endometrioid carcinoma was confirmed only in the three lymph nodes suspected on the expert scan and primary nodal origin of endometroid carcinoma developed from ectopic Müllerian tissue was considered. As a part of the pathological examination immunohistochemistry analysis for mismatch repair protein (MMR) expression was done. The findings of deficient mismatch repair proteins (dMMR) led to additional genetic testing, which revealed deletion of the entire EPCAM gene up to exon 1-8 of the MSH2 gene. This was unexpected considering her insignificant family history of cancer. We discuss the diagnostic work-up for patients presenting with metastatic lymph node infiltration by cancer of unknown primary and possible reasons for malignant lymph node transformation associated with Lynch syndrome.

Adapted Portuguese folk dance intervention for subacute rehabilitation post-stroke: study protocol.

Dance can be an innovative, well-accepted, and effective therapy for stroke survivors. The present protocol aims to assess the feasibility of adapted Portuguese folk dance as a post stroke rehabilitative activity. We will use a mixed-methods pilot study convenience sampling to recruit 16 stroke survivors with mild-moderate lower limb paresis from a rehabilitation center in Lisbon and Tagus Valley. In addition to usual care, participants will attend 3 days per week 1-h dance exercise for 8 weeks. The dance style used for this intervention will be an adaptation of the Portuguese folk dance. Assessment will be conducted before and immediately after the program intervention. Acceptability will be assessed by four key domains (enrollment, retention, satisfaction, and recommendation to others). Safety will be assessed based on the number and type of adverse events. Feasibility will be assessed based on balance performance and functional mobility. Quantitative data will be analyzed through descriptive statistics for sample characterization, followed by inferential statistics to evaluate differences in the balance recovery and functional mobility scores between the initial and final assessment. Qualitative data will be analyzed using an inductive process of content analysis. The Portuguese folk dance program has the potential to improve balance outcomes and functional mobility. Our results will help validate Portuguese folk dance as a tool for rehabilitation settings for stroke survivors. The potential of our program to enhance balance outcomes and functional mobility among stroke survivors bears implications for aging and public health initiatives. Positive results from this study could pave the way for integrating dance-based rehabilitative activities into standard stroke rehabilitation protocols, catering to older stroke survivors' specific needs and preferences.

Health Professionals' Motivational Strategies to Enhance Adherence in the Rehabilitation of People with Lower Limb Fractures: Scoping Review.

Patients with lower limb fractures require rehabilitation but often struggle with adherence to interventions. Adding motivational strategies to rehabilitation programs can increase patient adherence and enhance outcomes. This review aims to identify the motivational strategies used by health professionals in the rehabilitation of people with lower limb fractures. We used Arksey and O'Malley's methodological framework to structure and conduct this scoping review. The literature search was performed using the Scopus, CINAHL, MEDLINE, Nursing & Allied Health, and Cochrane Central Register of Controlled Trials databases. The final search was conducted in February 2023. A total of 1339 articles were identified. After selecting and analyzing the articles, twelve studies were included in this review. Health professionals use several strategies to motivate patients with lower limb fractures to adhere to rehabilitation programs. These strategies include building a therapeutic alliance, increasing patients' health literacy, setting achievable goals, personalizing the rehabilitation program, managing unpleasant sensations of exercise, using persuasion, providing positive reinforcement, avoiding negative emotional stimulation, and helping to seek support. The motivational strategies identified may help professionals to increase patient adherence to rehabilitation for lower limb fractures. This knowledge will allow these professionals to help patients overcome barriers to rehabilitation, enhance their motivation, and ultimately improve their recovery outcomes.

Landing wise program: feasibility study protocol for Parkinson's disease.

Regardless of the benefits of fall prevention programs, people with Parkinson's disease (PD) will still fall. Therefore, it is crucial to explore novel therapeutic approaches that are well-accepted and effective for addressing fall risk and the fear of falls among this population. The present study aims to assess the feasibility of the Landing Wise program as a therapeutic intervention for reducing the fear of falling in people with PD. A mixed-methods study will be conducted using convenience sampling to recruit 20 people with PD with a moderate concern of falling from a Parkinson's Patients Association. In addition to usual care, participants will attend 2 days per week, 90 min group sessions for 8 weeks. The intervention combines group cognitive behavioral intervention with the training of safe landing strategies. Feasibility will be assessed by six key domains (recruitment strategy and rates, enrollment, retention, acceptability, reasons for decline/withdrawal, and adverse events). Quantitative data will be analyzed using descriptive statistics to characterize the sample, followed by inferential statistics to evaluate differences in the Short Falls Efficacy Scale-International Scale, Movement Disorder Society Unified Parkinson's Disease Rating Scale, Timed Up Go, 6-Minutes Walking Distance, and fall frequency and severity scores between baseline and final assessment. Qualitative data will be analyzed using an inductive thematic analysis process. There is a growing interest in developing new effective therapeutic approaches for people with PD. If proven program feasibility, this study precedes a randomized controlled trial to establish the effectiveness of the Landing Wise program.

Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-dependent manner.

Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared with the progeny of γδ T cell-sufficient dams. Upon helminth infection, mice born from TCRδ-/- dams sustain an increased type 2 inflammatory response. This is independent of the genotype of the pups. Instead, the offspring of TCRδ-/- dams harbors a distinct intestinal microbiota, acquired during birth and fostering, and decreased levels of intestinal short-chain fatty acids (SCFAs), such as pentanoate and hexanoate. Importantly, exogenous SCFA supplementation inhibits type 2 innate lymphoid cell function and suppresses first-breath- and infection-induced inflammation. Taken together, our findings unravel a maternal γδ T cell-microbiota-SCFA axis regulating neonatal lung immunity.

Cutting edge: adaptive versus innate receptor signals selectively control the pool sizes of murine IFN-γ- or IL-17-producing γδ T cells upon infection.

γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27((-)), IL-17A-producing γδ T cells, but not of IFN-γ-producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27((+)), IFN-γ-secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review.

Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.

Inhibition of murine gammadelta lymphocyte expansion and effector function by regulatory alphabeta T cells is cell-contact-dependent and sensitive to GITR modulation.

Gammadelta T cells are highly cytolytic lymphocytes that produce large amounts of pro-inflammatory cytokines during immune responses to multiple pathogens. Furthermore, their ability to kill tumor cells has fueled the development of gammadelta-T-cell-based cancer therapies. Thus, the regulation of gammadelta-T-cell activity is of great biological and clinical relevance. Here, we show that murine CD4+CD25+ alphabeta T cells, the vast majority of which express the Treg marker, Foxp3, abolish key effector functions of gammadelta T cells, namely the production of the pro-inflammatory cytokines, IFN-gamma and IL-17, cytotoxicity, and lymphocyte proliferation in vitro and in vivo. We further show that suppression is dependent on cellular contact between Treg and gammadelta T cells, results in the induction of an anergic state in gammadelta lymphocytes, and can be partially reversed by manipulating glucocorticoid-induced TNF receptor-related protein (GITR) signals. Our data collectively dissect a novel mechanism by which the expansion and pro-inflammatory functions of gammadelta T cells are regulated.

Analysis of invasiveness of pneumococcal serotypes and clones circulating in Portugal before widespread use of conjugate vaccines reveals heterogeneous behavior of clones expressing the same serotype.

To estimate the invasive disease potential of serotypes and clones circulating in Portugal before extensive use of the seven-valent pneumococcal conjugate vaccine, we analyzed 475 invasive isolates recovered from children and adults and 769 carriage isolates recovered from children between 2001 and 2003. Isolates were serotyped and genotyped by pulsed-field gel electrophoresis, and a selection of isolates were also characterized by multilocus sequence typing. We found that the diversities of serotypes and genotypes of pneumococci responsible for invasive infections and carriage were identical and that most carried clones could also be detected as causes of invasive disease. Their ability to do so, however, varied substantially. Serotypes 1, 3, 4, 5, 7F, 8, 9N, 9L, 12B, 14, 18C, and 20 were found to have an enhanced propensity to cause invasive disease, while serotypes 6A, 6B, 11A, 15B/C, 16F, 19F, 23F, 34, 35F, and 37 were associated with carriage. In addition, significant differences in invasive disease potential between clones sharing the same serotype were found among several serotypes, namely, 3, 6A, 6B, 11A, 14, 19A, 19F, 22F, 23F, 34, and NT. This heterogeneous behavior of the clones was found irrespective of the serotype's overall invasive disease potential. Our results highlight the importance of the genetic background when analyzing the invasive disease potential of certain serotypes and provide an important baseline for its monitoring following conjugate vaccine use. Continuous surveillance should be maintained, and current research should focus on uncovering the genetic determinants that contribute to the heterogeneity of invasive disease potential of clones sharing the same serotype.

Multidisciplinary management of idiopathic intracranial hypertension in pregnancy: case series and narrative review

Abstract Idiopathic intracranial hypertension (IIH) is a neurological condition characterized by raised intracranial pressure of unknown etiology with normal cerebrospinal fluid (CSF) composition and no brain lesions. It occurs in pregnant patients at approximately the same frequency as in general population, but obstetric and anesthetic management of the pregnancy and labor remains controversial. In this article we provide a multidisciplinary review of the main aspects of IIH in pregnancy including treatment options, mode of delivery and anesthetic techniques. Additionally, we report three cases of pregnant women diagnosed with IIH between 2012 and 2019 in our institution.