tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance.

About 20% of breast cancer patients are positive for HER2. The efficacy of current treatments is limited by primary and secondary resistance to trastuzumab. tRNA-derived fragments (tRFs) have shown crucial regulatory roles in various cancers. This study aimed to evaluate the role of tRF-27 in regulating the resistance of HER2-positive breast cancer against trastuzumab. tRF-27 was highly expressed in trastuzumab-resistant cells, and its expression level could predict the resistance to trastuzumab. High expression of tRF-27 promoted the growth and proliferation of trastuzumab-exposed cells. RNA-pulldown assay and mass spectrometry were performed to identify Ras GTPase-activating protein-binding proteins 1 and 2 (G3BPs) (two proteins targeted by tRF-27); RNA-immunoprecipitation (RIP) to confirm their bindings; co-immunoprecipitation (co-IP) and RNA-pulldown assay to determine the binding domains between G3BPs and tRF-27.tRF-27 bound to the nuclear transport factor 2 like domain(NTF2 domain) of G3BPs through a specific sequence. tRF-27 relied on G3BPs and NTF2 domain to increase trastuzumab tolerance. tRF-27 competed with lysosomal associated membrane protein 1(LAMP1) for NTF2 domain, thereby inhibiting lysosomal localization of G3BPs and tuberous sclerosis complex (TSC). Overexpression of tRF-27 inhibited phosphorylation of TSCs and promoted the activation of mechanistic target of rapamycin complex 1(MTORC1) to enhance cell proliferation and entice the resistance of HER2-positive breast cancer against trastuzumab.

Occurrence and health risks of multiple emerging bisphenol S analogues in pregnant women from South China.

Recently, there has been increasing concern regarding the emergence of bisphenol S analogues (BPSs) due to their potential toxicity. However, their exposure levels and associated health risks in susceptible populations remain unknown. In our study, we analyzed bisphenol A (BPA), along with 11 common BPA analogues (BPAs), and nine emerging BPSs in urine samples collected from 381 pregnant women in South China. All nine BPSs were first detected in pregnant women's urine. In addition to BPA, two BPAs, three BPSs including Diphenylsulfone (DPS), Bis(phenylsulfonyl)phenol (DBSP) and Bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA), were identified as the predominant bisphenols, with detection frequencies ranging from 53-100 %. BPA still exhibited the highest median concentration at 0.624 ng/mL, followed by DPS (0.169 ng/mL), BPS (0.063 ng/mL) and DBSP (0.023 ng/mL). Importantly, mothers with higher levels of BPA, DBSP, DPS, and TGSA in their urine are statistically more likely to give birth to premature infants with shorter lengths at birth or smaller head circumference (p < 0.05). Although the median exposure to 21 bisphenols did not exceed the tolerable daily intake (TDI) of BPA, it did surpass the recently proposed BPA TDI (0.2 ng/kg bw/day) by a factor ranging from 1.1-99 times. This study signifies the first report unveiling the prevalence of multiple bisphenols, particularly emerging BPSs, in the urine of pregnant women in South China.

Indian and global scenarios of Bisphenol A distribution and its new analogues: Prevalence & probability exceedance.

We compare, the prevalence, fate, and sources of Bisphenol A both globally and in India. India has the highest concentration of BPA and Bisphenol S(BPS) in general, with vegetables, particularly corn, beans, strings, and raw or canned vegetables, being the largest contributors. Among all the matrices, bisphenols (BPs) are found in the highest concentration in food, followed by surface water, wastewater, and indoor dust. BPA, BPS, and BPF are the most commonly reported analogues in India, with BPA being the most dominant category used worldwide. The highest concentration of BPs is observed in Uttar Pradesh, Punjab and Haryana that are three major agricultural states of India however, there is still a research gap regarding the dietary exposure to BPs on an individual level. Environmentally detected BPA occurs in a range of below detection to 10636 ng. L-1, with significant geographic variations. Interestingly, the order of abundance in India was maximum for BPS, which is contrary to the global average, where BPA is observed as most abundant. BPS is found to be the most common BPs analogue in surface water worldwide, with limited removal efficiency by both naturally remediation and conventional treatment methods. Similar patterns were observed in the US-India and Japan-Korea regions in terms of their source-sink-prevalence-fate dynamics. The probability of exceeding safe concentrations of BPs is higher in India and Korea, suggesting that these countries are more vulnerable to high prevalence concentrations and the subsequent public health hazards.

Bisphenol S and Its Chlorinated Derivatives in Indoor Dust and Human Exposure.

Bisphenol S (BPS), an environmental endocrine disruptor, has been identified in global environmental matrices. Nevertheless, limited studies have investigated the presence of chlorinated analogues of BPS (Clx-BPSs) with potential estrogenic activities in environmental matrices. In this study, the occurrence of BPS and five types of Clx-BPSs was characterized in indoor dust (n = 178) from Hangzhou City. BPS was measurable in 94% of indoor dust samples, with an average level of 0.63 µg/g (

Evaluation of the teratogenic potency of bulk zinc oxide and its nanoparticles on embryos of the freshwater snail, Helisoma duryi.

Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.

Occurrence of bisphenol analogues and their conjugated metabolites in foodstuff.

Bisphenol analogues (BPs) are prevalent in diverse foodstuff samples worldwide. However, the occurrence of conjugated bisphenol A (BPA) and bisphenol S (BPS) metabolites in foodstuff remains poorly understood. This study analyzed eight BPs, and four conjugated BPA and BPS metabolites, in three animal-derived foodstuff and five plant-derived foodstuff samples from China. Results showed that fish foodstuff (9.7 ng/g ww) contained the highest mean concentration of BPA, followed by rice (5.1 ng/g ww) and beans foodstuff (3.6 ng/g ww). BPA-sulfate had higher mean concentrations than BPA-glucuronide in different foodstuff categories, except that in eggs foodstuff (p < 0.05). Compared with other foodstuff items, fish (3.4 ng/g ww) and vegetable (1.6 ng/g ww) foodstuff samples exhibited comparatively higher mean concentrations of BPS. Mean concentrations of BPS-sulfate were consistently higher than BPS-glucuronide in vegetables, meats, and fish foodstuff (p < 0.05). BPA contributed the major total dietary intake (DI) of BPs, with the mean DI of 435 ng/kg bw/day for women and 374 ng/kg bw/day for men, respectively. To our knowledge, this study is the first to investigate the occurrence of conjugated BPA and BPS metabolites in foodstuff, which enhances our comprehension of the origins of these conjugated metabolites in the human body.

Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP)).

OBJECTIVE: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). DESIGN: Cross-sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. SETTING: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). POPULATION OR SAMPLE: A total of 100 participants. METHODS: Descriptive and comparative analysis from flares questionnaire. MAIN OUTCOME MEASURES: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. RESULTS: We received 100 responses of 104 questionnaires sent. Seventy-six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non-painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. CONCLUSIONS: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.

Disruptive effects of plasticizers bisphenol A, F, and S on steroidogenesis of adrenocortical cells.

Introduction: Endocrine disrupting chemicals (EDCs) are known to interfere with endocrine homeostasis. Their impact on the adrenal cortex and steroidogenesis has not yet been sufficiently elucidated. This applies in particular to the ubiquitously available bisphenols A (BPA), F (BPF), and S (BPS). Methods: NCI-H295R adrenocortical cells were exposed to different concentrations (1nM-1mM) of BPA, BPF, BPS, and an equimolar mixture of them (BPmix). After 72 hours, 15 endogenous steroids were measured using LC-MS/MS. Ratios of substrate and product of CYP-regulated steps were calculated to identify most influenced steps of steroidogenesis. mRNA expression of steroidogenic enzymes was determined by real-time PCR. Results: Cell viability remained unaffected at bisphenol concentrations lower than 250 µM. All tested bisphenols and their combination led to extensive alterations in the quantified steroid levels. The most profound fold changes (FC) in steroid concentrations after exposure to BPA (>10µM) were seen for androstenedione, e.g. a 0.37±0.11-fold decrease at 25µM (p≤0.0001) compared to vehicle-treated controls. For BPF, levels of 17-hydroxyprogesterone were significantly increased by 25µM (FC 2.57±0.49, p≤0.001) and 50µM (FC 2.65±0.61, p≤0.0001). BPS treatment led to a dose-dependent decrease of 11-deoxycorticosterone at >1µM (e.g. FC 0.24±0.14, p≤0.0001 at 10µM). However, when combining all three bisphenols, additive effects were detected: e.g. 11-deoxycortisosterone was decreased at doses >10µM (FC 0.27±0.04, p≤0.0001, at 25µM), whereas 21-deoxycortisol was increased by 2.92±0.20 (p≤0.01) at 10µM, and by 3.21±0.45 (p≤0.001) at 50µM. While every measured androgen (DHEA, DHEAS, androstenedione, testosterone, DHT) was lowered in all experiments, estradiol levels were significantly increased by BPA, BPF, BPS, and BPmix (e.g. FC 3.60±0.54, p≤0.0001 at 100µM BPF). Calculated substrate-product ratios indicated an inhibition of CYP17A1-, and CYP21A2 mediated conversions, whereas CYP11B1 and CYP19A1 showed higher activity in the presence of bisphenols. Based on these findings, most relevant mRNA expression of CYP genes were analysed. mRNA levels of StAR, CYP11B1, and CYP17A1 were significantly increased by BPF, BPS, and BPmix. Discussion: In cell culture, bisphenols interfere with steroidogenesis at non-cytotoxic levels, leading to compound-specific patterns of significantly altered hormone levels. These results justify and call for additional in-vivo studies to evaluate effects of EDCs on adrenal gland functionality.

Bisphenol S (BPS) induces glioblastoma progression via regulation of EZH2-mediated PI3K/AKT/mTOR pathway in U87-MG cells.

Bisphenol S (BPS), an alternative to bisphenol A (BPA), exerts proliferative effects similar to those of BPA. BPS is a representative endocrine disruptor associated with cancer progression. However, the mechanisms underlying BPS-induced glioblastoma progression are not fully understood. To investigate the effects of BPS on glioblastoma, U-87 MG cancer cell lines were exposed to BPS. The study focused on analyzing the proliferation and migration of U-87 MG cells. Furthermore, the involvement of the enhancer of the zeste homolog 2 (EZH2)-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) pathway was examined. Pharmacological approaches were employed to inhibit EZH2 activity and observe its effects on BPS-induced changes. The results indicated that BPS promoted the proliferation and migration of U-87 MG cells at a concentration of 0.1 µM. These changes appeared to be linked to the activation of the EZH2-mediated PI3K/AKT/mTOR pathway. Moreover, inhibiting EZH2 activity using pharmacological approaches restored the BPS-mediated induction of proliferation and migration. In conclusion, the results of this study indicated that BPS induces glioblastoma progression through EZH2 upregulation. Therefore, targeting the EZH2-mediated PI3K/AKT/mTOR pathway could be considered a potential therapeutic strategy for the treatment of glioblastoma.

How Intravesical Platelet-Rich Plasma Can Help Patients with Interstitial Cystitis/Bladder Pain Syndrome: A Comprehensive Scoping Review.

INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. METHODS: We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. RESULTS: Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. CONCLUSION: The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.

Conjugated metabolites of bisphenol A and bisphenol S in indoor dust, outdoor dust, and human urine.

Bisphenol A (BPA) and bisphenol S (BPS) have been widely spread in the global environment. However, for conjugated BPA and BPS metabolites, limited studies have investigated their occurrence in environmental matrices. We collected paired indoor and outdoor dust (n = 97), as well as human urine (n = 153) samples, from residential houses in Quzhou, China, and measured these samples for 8 conjugated BPA and BPS metabolites. Three BPA metabolites were found in collected indoor and outdoor dust, with BPA sulfate (mean 0.75 and 1.3 ng/g, respectively) and BPA glucuronide (0.13 and 0.26 ng/g) being more abundant. BPA conjugates accounted for a mean of 42 and 56% of total BPA (sum of conjugated BPA and BPA metabolites) in indoor and outdoor dust, respectively. BPS sulfate (mean 0.29 and 0.82 ng/g, respectively) had consistently higher concentrations than BPS glucuronide (0.13 and 0.27 ng/g) in indoor and outdoor samples. BPS conjugates contributed a mean 32% and 45% of total BPS (sum of BPS and BPS metabolites) in indoor and outdoor dust, respectively. Moreover, conjugated BPA and BPS metabolites in indoor or outdoor dust were not significantly correlated with those in urine from residents. Overall, this study first demonstrates the wide presence of conjugated BPA and BPS metabolites, besides BPA and BPS, in indoor and outdoor dust. These data are important for elucidating the sources of conjugated BPA and BPS metabolites in the human body.

Bisphenol S exposure induces intestinal inflammation via altering gut microbiome.

Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium, and decreased anti-inflammatory genera such as Lactobacillus, Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity.

Emerging regulatory roles of noncoding RNAs induced by bisphenol a (BPA) and its alternatives in human diseases.

Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly utilized to produce epoxy resins, polycarbonate plastics, and other products. Mounting evidence has shown that BPs, especially BPA, may enter into the human body and participate in the development of human diseases mediated by nuclear hormone receptors. Moreover, BPA may negatively affect human health at the epigenetic level through processes such as DNA methylation and histone acetylation. Recent studies have demonstrated that, as part of epigenetics, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), have vital impacts on BP-related diseases, such as reproductive system diseases, nervous system diseases, digestive system diseases, endocrine system diseases, and other diseases. Moreover, based on the bioinformatic analysis, changes in ncRNAs may be relevant to normal activities and functions and BP-induced diseases. Thus, we conducted a meta-analysis to identify more promising ncRNAs as biomarkers and therapeutic targets for BP exposure and relevant human diseases. In this review, we summarize the regulatory functions of ncRNAs induced by BPs in human diseases and latent molecular mechanisms, as well as identify prospective biomarkers and therapeutic targets for BP exposure and upper diseases.

Cdk1/p53/p21 feedback loop mechanisms in the pathogenesis of interstitial cystitis/bladder pain syndrome.

PURPOSE: This study aimed to elucidate the role of the Cdk1/p53/p21 feedback loop in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). MATERIALS AND METHODS: An IC/BPS cell model was established. Cell viability was determined using the CCK-8 assay. Flow cytometry was adopted to assess cell apoptosis rates. ELISA was employed to measure secretion levels of inflammatory factors (IL-6, IL-8, and TNF-α). Gene expressions were assessed using PCR, while protein expressions were analyzed through Western blotting analysis. Epithelial permeability was demonstrated using the phenol red leakage experiment and FITC-dextran permeability assay. The interaction between proteins was determined using co-immunoprecipitation, and protein localization was investigated using immunofluorescence. RESULTS: The CCK-8 assay revealed a significantly reduced viability of IC/BPS cells compared to normal epithelial cells (p < 0.05). Elevated levels of IL-6, IL-8, and TNF-α were detected in IC/BPS cells. Changes in the expressions of E-cadherin and ZO-1 were evident, leading to increased epithelial permeability in IC/BPS cells. Furthermore, within IC/BPS cells, Cdk1 phosphorylated p53 in the nucleus. The Cdk1/p53/p21 feedback loop was established to influence urothelial permeability. Both p21 and Cdk1 inhibitors notably reduced the epithelial permeability in IC/BPS cells. CONCLUSION: The Cdk1/p53/p21 feedback loop was instrumental in IC/BPS, acting as a regulator of urothelial permeability. This discovery offered a novel therapeutic approach for IC/BPS management.

Unveiling the intricacies of BPA and BPS: comprehensive insights into its toxic effects using a cutting-edge microphysiological system.

Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function. Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.

Aquablation versus HoLEP in patients with benign prostatic hyperplasia: a comparative prospective non-randomized study.

PURPOSE: The question of best surgical treatment for lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH) remains controversial. We compared the outcomes of aquablation and holmium laser enucleation of the prostate ("HoLEP") in a prospective cohort. METHODS: Patients with BPH underwent aquablation or HoLEP according to their preference between June 2020 and April 2022. Prostate volume ("PV"), laboratory results, postvoid residual volume, uroflowmetry, IPSS, ICIQ-SF, MSHQ-EjD, EES and IIEF were evaluated preoperatively and at three, six and 12 months postoperatively. We also analyzed perioperative characteristics and complications via the Clavien Dindo ("CD") classification. RESULTS: We included 40 patients, 16 of whom underwent aquablation and 24 HoLEP. Mean age was 67 years (SD 7.4). Baseline characteristics were balanced across groups, except the HoLEP patients' larger PV. IPSS fell from 20.3 (SD 7.1) at baseline to 6.3 (SD 4.2) at 12 months (p < 0.001) without differences between aquablation and HoLEP. HoLEP was associated with shorter operation time (59.5 (SD 18.6) vs. 87.2 (SD 14.8) minutes, p < 0.001) and led to better PV reduction over all timepoints. At three months, aquablation's results were better regarding ejaculatory (p = 0.02, MSHQ-EjD) and continence function (p < 0.001, ICIQ-SF). Beyond three months, erectile, ejaculatory, continence function and LUTS reduction did not differ significantly between aquablation and HoLEP. CD ≥ grade 3b complications were noted in six patients in aquablation group while only one in HoLEP group (p = < 0.01). CONCLUSIONS: While aquablation revealed temporary benefits regarding ejaculation and continence at three months, HoLEP was superior concerning operation time, the safety profile and volumetric results.

Interstitial cystitis/bladder pain syndrome: when part of the posterior fornix syndrome is potentially curable surgically.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as chronic pelvic pain plus a bladder symptom, usually urge. Evidence is offered to show IC/BPS forms part of the posterior fornix syndrome (PFS), which was defined in 1993 as: chronic pelvic pain (CPP), urge, frequency, nocturia, abnormal emptying, post-void residual urine, caused by uterosacral ligament (USL) laxity and cured or improved by USL repair. The IC/BPS definition implies that the urge and pain of IC/BPS is from a single (as yet unknown) pathogenic origin. However, when urge and pain are viewed from the perspective of the PFS, though both have the same lax USL origin, the anatomical pathway from lax USL to symptom manifestation is very different manifestation. For CPP the anatomical pathway is the inability of loose USLs to support pelvic visceral plexuses (VPs); it is hypothesized that inability of weak USLs to mechanically supports VPs, the afferent nerve synapse from end organs may fire off autologous afferent impulses to the brain which interprets them as pain from end organs such as urothelium, vulva, lower abdomen. For urge, the anatomical pathway is very different: lax USLs weaken the directional pelvic muscle forces which stretch the vagina to support the urothelial stretch receptors. The receptors fire off afferent impulses to the cortex at a lower bladder volume, and these are interpreted as "urge to go". Mechanical support of USLs relieves both pain and urge, as does USL repair.

A rare tale of an extralobar pulmonary sequestration as a cause of hemoptysis not often contemplated: a case report.

Background: A rare congenital malformation of the respiratory tract, bronchopulmonary sequestration (BPS), may present symptomatically early on in childhood or adolescent years. Adult BPS is typically an incidental finding found on thoracic imaging. There are currently four known types of BPS. Intralobar sequestrations (ILSs) are the most common of them and the most commonly reported form in literature. In our case report, we report of a healthy adult female who presented with hemoptysis that resulted in the diagnosis of the rarest form of BPSs; extralobar sequestration (ELS). One that is not commonly described in literature, especially of one reported in late adulthood. This case report aims to educate and elude clinicians to this rare cause as a differential and guidance on its investigation and management. Case Description: In this case report, a 56-year-old woman who presented to an outpatient respiratory clinic after being referred by her general practitioner (GP) of a queried BPS. A thorough workup was done by the respiratory team that derived at the final diagnosis of an ELS. The patient's autonomy was adhered to along with risks and benefits which resulted in a non-surgical approach to management. One that she remarkably achieved a resolution of her symptoms. Conclusions: An awareness and familiarity of this rare disease, ELS, should prompt one to consider its' diagnosis when no other common causes are apparent. Often the diagnosis can be made radiologically. Treatment of ELSs should depend on multiple factors.