Tob Regulates the Timing of Sleep Onset at Night in Drosophila.

Sleep is regulated by homeostatic sleep drive and the circadian clock. While tremendous progress has been made in elucidating the molecular components of the core circadian oscillator, the output mechanisms by which this robust oscillator generates rhythmic sleep behavior remain poorly understood. At the cellular level, growing evidence suggests that subcircuits in the master circadian pacemaker suprachiasmatic nucleus (SCN) in mammals and in the clock network in Drosophila regulate distinct aspects of sleep. Thus, to identify novel molecules regulating the circadian timing of sleep, we conducted a large-scale screen of mouse SCN-enriched genes in Drosophila Here, we show that Tob (Transducer of ERB-B2) regulates the timing of sleep onset at night in female fruit flies. Knockdown of Tob pan-neuronally, either constitutively or conditionally, advances sleep onset at night. We show that Tob is specifically required in "evening neurons" (the LNds and the fifth s-LNv) of the clock network for proper timing of sleep onset. Tob levels cycle in a clock-dependent manner in these neurons. Silencing of these "evening" clock neurons results in an advanced sleep onset at night, similar to that seen with Tob knockdown. Finally, sharp intracellular recordings demonstrate that the amplitude and kinetics of LNd postsynaptic potentials (PSPs) cycle between day and night, and this cycling is attenuated with Tob knockdown in these cells. Our data suggest that Tob acts as a clock output molecule in a subset of clock neurons to potentiate their activity in the evening and enable the proper timing of sleep onset at night.

Case Report: Unilateral Cranial Nerve VI Palsy Secondary to Intracranial Hypotension.

SIGNIFICANCE: Intracranial hypotension is a condition that occurs from a cerebrospinal fluid leak. Various visual symptoms have been associated with this condition. Cranial nerve VI (CN VI) palsies are the most common ocular manifestation, as the abducens nerve is prone to injury because of its intracranial anatomical course. PURPOSE: This case report presents a CN VI palsy secondary to intracranial hypotension from ventriculoperitoneal shunt overfiltration. Diagnosis, treatment, and management considerations are discussed. No identifiable health information was included in this case report. CASE REPORT: A 70-year-old White man was referred to the eye clinic for evaluation of binocular horizontal diplopia. The patient had a recent history of a left ventriculoperitoneal shunt for a persistent cerebrospinal fluid leak after complex mastoid surgery. The patient was also symptomatic for positional headaches, which improved in a recumbent position. He was diagnosed with a left CN VI palsy secondary to intracranial hypotension from a ventriculoperitoneal shunt overfiltration. The patient was followed up by neurosurgery for shunt adjustments to resolve the overfiltration. Binocular horizontal diplopia was managed conservatively with Fresnel prism. CONCLUSIONS: Intracranial hypotension should be considered in patients presenting with cranial nerve palsies and positional headaches. Obtaining neuroimaging and comanaging with neurology or neurosurgery are advised to make prompt diagnosis and treatment. Careful clinical monitoring and conservative diplopia therapy are recommended as visual symptoms improve upon resolution of the cerebrospinal fluid leak.

Assessment of ethanol exposure from hand sanitizer use and potential for developmental toxicity in nursing infants.

Ingestion of ethanol during pregnancy is known to have detrimental effects on the fetus. Although the potential developmental effects of maternal ethanol intake during lactation are less well characterized, public health guidelines recommend avoidance of alcohol or, if alcohol is consumed, to allow for 1-2 h to pass before nursing. A proposal to classify ethanol as potentially harmful to breast-fed children warrants an investigation of the potential adverse neurodevelopmental effects of low-dose ethanol exposure during lactation. There currently are no studies that have examined neurodevelopmental outcomes from lactational exposure to ethanol from the use of topical products that contain ethanol, such as alcohol-based hand sanitizers (ABHS). Furthermore, the epidemiological literature of lactational ethanol exposures from maternal alcohol consumption is limited in design, provides equivocal evidence of neurological effects in infants, and is insufficient to characterize a dose-response relationship for developmental effects. Toxicological studies that observed neurodevelopmental effects in pups from ethanol via lactation did so at exceedingly high doses that also caused maternal toxicity. In this investigation, blood ethanol concentrations (BECs) of breastfeeding women following typical-to-intense ABHS use were computationally predicted and compared to health benchmarks to quantify the risk for developmental outcomes. Margins of 2.2 to 1000 exist between BECs associated with ABHS use compared to BECs associated with neurotoxicity adverse effect levels in the toxicology literature or oral ethanol intake per public health guidelines. Neurodevelopmental effects are not likely to occur in infants due to ABHS use by breastfeeding women, even when ABHSs are used at intense frequencies.

Bone mineral density in children with acute lymphoblastic leukemia.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) can develop reduced bone mineral density (BMD). However, data from patients who received treatment on a frontline regimen without cranial irradiation are limited, and no genome-wide analysis has been reported. METHODS: Lumbar BMD was evaluated by quantitative computed tomography at diagnosis, after 120 weeks of continuation therapy, and after 2 years off therapy in pediatric patients with ALL (ages 2-18 years at diagnosis) who were treated on the St. Jude Total XV Protocol. Clinical, pharmacokinetic, and genetic risk factors associated with decreased BMD Z-scores were evaluated. RESULTS: The median BMD Z-score in 363 patients was 0.06 at diagnosis, declined to -1.08 at week 120, but partly recovered to -0.72 after 2 years off therapy; BMD in patients with low BMD Z-scores at diagnosis remained low after therapy. Older age (≥10 years vs 2-9.9 years at diagnosis; P < .001), a higher BMD Z-score at diagnosis (P = .001), and a greater area under the plasma drug concentration-time curve for dexamethasone in weeks 7 and 8 of continuation therapy (P = .001) were associated with a greater decrease in BMD Z-score from diagnosis to week 120. Single-nucleotide polymorphisms in 2 genes important in osteogenesis and bone mineralization (COL11A1 [reference single-nucleotide polymorphism rs2622849]; P = 2.39 × 10-7 ] and NELL1 [rs11025915]; P = 4.07 × 10-6 ]) were associated with a decreased BMD Z-score. NELL1 (P = .003) also was associated with a greater dexamethasone area under the plasma drug concentration-time curve. CONCLUSIONS: BMD Z-scores decreased during therapy, especially in patients who had clinical, pharmacokinetic, and genetic risk factors. Early recognition of BMD changes and strategies to optimize bone health are essential. Cancer 2018;124:1025-35. © 2017 American Cancer Society.

The impact of cytokine responses in the intra- and extracellular signaling network of a traumatic injury.

Investigations of cellular responses involved in injury and repair processes have generated valuable information contributing to the advancement of wound healing and treatments. Intra- and extracellular regulators of healing mechanisms, such as cytokines, signaling proteins, and growth factors, have been described to possess significant roles in facilitating optimal recovery. This study explored a collection of 30 spatiotemporal responses comprised of cytokines (IL-1α, IL-1ß, IL-2, IL-6, TNF-α, MIP-1α), intracellular proteins (Akt, c-Jun, CREB, ERK1/2, JNK, MEK1, p38, p53, p90RSK), phosphorylated proteins (p-Akt, p-c-Jun, p-CREB, p-ERK1/2, p-GSK-3α/ß, p-HSP27, p-IκBα, p-JNK, p-MEK1, p-p38, p-p70S6K, p-p90RSK, p-STAT2, p-STAT3), and a protease (Caspase-3), measured in skeletal muscle tissue following a traumatic injury (rodent Gustilo IIIB fracture). To optimize the analysis of context-specific data sets, a network centrality parameter approach was used to assess the impact of each response in relation to all other measured responses. This approach identified proteins that were substantially amplified and potentially central in the wound healing network by evaluation of their corresponding centrality parameter, radiality. Network analysis allowed us to distinguish the progression of healing that occurred at certain time points and regions of injury. Notably, new tissue formation was proposed to occur by 168 h post-injury in severely injured tissue, while tissue 1-cm away from the site of injury that experienced relatively minor injury appeared to exhibit signs of new tissue formation as early as 24 h post-injury. In particular, hallmarks of inflammation, cytokines IL-1ß, IL-6, and IL-2, appear to have a pronounced impact at earlier time points (0-24 h post-injury), while intracellular proteins involved in cell proliferation, differentiation, or proteolysis (c-Jun, CREB, JNK, p38, p-c-Jun; p-MEK1, p-p38, p-STAT3) are more significant at later times (24-168 h). Overall, this study demonstrates the feasibility of a network analysis approach to extract significant information and also offers a spatiotemporal visualization of the intra- and extracellular signaling responses that regulate healing mechanisms.

Current Reports on Perinatal Intimate Partner Violence.

PURPOSE OF REVIEW: The purpose of this study was to review the literature on perinatal intimate partner violence, focusing on recent knowledge to guide mental health professionals on the best approaches to identify and treat women exposed to perinatal intimate partner violence. RECENT FINDINGS: Risk factors have been broadened from individual victim and perpetrator factors to include relationship, community, and societal factors which interact together. Better information is now available on how to identify, document, and treat women exposed to violence around the time of conception, pregnancy, and the postpartum period. Recent information helps psychiatrists and other mental health professionals assist women exposed to violence related to the perinatal period; however, further research is needed to provide improved evidence for optimal interventions for better patient outcomes.

In vitro cytotoxicity assessment of a West Virginia chemical spill mixture involving 4-methylcyclohexanemethanol and propylene glycol phenyl ether.

Thousands of gallons of industrial chemicals, crude 4-methylcyclohexanemethanol (MCHM) and propylene glycol phenyl ether (PPh), leaked from industrial tanks into the Elk River in Charleston, West Virginia, USA, on January 9, 2014. A considerable number of people were reported to exhibit symptoms of chemical exposure and an estimated 300,000 residents were advised not to use or drink tap water. At the time of the spill, the existing toxicological data of the chemicals were limited for a full evaluation of the health risks, resulting in concern among those in the impacted regions. In this preliminary study, we assessed cell viability and plasma membrane degradation following a 24-h exposure to varying concentrations (0-1000 µM) of the two compounds, alone and in combination. Evaluation of different cell lines, HEK-293 (kidney), HepG2 (liver), H9c2 (heart), and GT1-7 (brain), provided insight regarding altered cellular responses in varying organ systems. Single exposure to MCHM or PPh did not affect cell viability, except at doses much higher than the estimated exposure levels. Certain co-exposures significantly reduced metabolic activity and increased plasma membrane degradation in GT1-7, HepG2, and H9c2 cells. These findings highlight the importance of examining co-exposures to fully understand the potential toxic effects.

Spatiotemporal phosphoprotein distribution and associated cytokine response of a traumatic injury.

Molecular mechanisms of wound healing have been extensively characterized, providing a better understanding of the processes involved in wound repair and offering advances in treatment methods. Both spatial and temporal investigations of injury biomarkers have helped to pinpoint significant time points and locations during the recovery process, which may be vital in managing the injury and making the appropriate diagnosis. This study addresses spatial and temporal differences of phosphoproteins found in skeletal muscle tissue following a traumatic femur fracture, which were further compared to co-localized cytokine responses. In particular, several proteins (Akt, ERK, c-Jun, CREB, JNK, MEK1, and p38) and post-translational phosphorylations (p-Akt, p-c-Jun, p-CREB, p-ERK1/2, p-MEK1, p-p38, p-GSK3α/ß, p-HSP27, p-p70S6K, and p-STAT3) associated with inflammation, new tissue formation, and remodeling were found to exhibit significant spatial and temporal differences in response to the traumatic injury. Quadratic discriminant analysis of all measured responses, including cytokine concentrations from previously published findings, was used to classify temporal and spatial observations at high predictive rates, further confirming that distinct spatiotemporal distributions for total protein, phosphorylation signaling, and cytokine (IL-1α, IL-1ß, IL2, IL6, TNF-α, and MIP-1α) responses exist. Finally, phosphoprotein measurements were found to be significantly correlated to cytokine concentrations, suggesting coordinated intracellular and extracellular activity during crucial periods of repair. This study represents a first attempt to monitor and assess integrated changes in extracellular and intracellular signaling in response to a traumatic injury in muscle tissues, which may provide a framework for future research to improve both our understanding of wounds and their treatment options.

Deguelin and Its Role in Chronic Diseases.

Deguelin is one of four major naturally occurring rotenoids isolated from root extracts and is best recognized as a NADH: ubiquinone oxidoreductase (complex I) inhibitor, resulting in significant alterations in mitochondrial function. Deguelin has also been implicated as a regulator of apoptosis through signaling pathways, such as the (PI3K)/Akt pathway, as well as an initiator of cell cycle arrest. Consequently, this compound has accrued great interest as a potential chemopreventive and chemotherapeutic. Additionally, deguelin exposure has been linked to Parkinson's disease (PD). PD is a neurodegenerative disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra, as well the manifestation of symptoms such as bradykinesia, rigidity, and rest tremor. While exploring the genetic impact of PD is imperative, environmental factors, such as exposure to pesticides, herbicides, and insecticides, have also been connected to the development of PD. The etiology and pathogenesis of PD are yet to be fully understood and elucidated, but mitochondrial dysfunction is gaining recognition as a molecular hallmark of PD. In fact, deguelin has been reported to elicit PD-like symptoms (degeneration of the dopaminergic pathway) in rats administered with deguelin (6 mg/kg/day for 6 days), possibly through the inhibition of mitochondrial complex I. Further research investigating the mechanisms by which deguelin inhibits central cellular processes is essential in order to advance any prospective research addressing potential applications and risks of deguelin.

An approach to investigate intracellular protein network responses.

Modern toxicological evaluations have evolved to consider toxicity as a perturbation of biological pathways or networks. As such, toxicity testing approaches are shifting from common end point evaluations to pathway based approaches, where the degree of perturbation of select biological pathways is monitored. These new approaches are greatly increasing the data available to toxicologists, but methods of analyses to determine the inter-relationships between potentially affected pathways are needed to fully understand the consequences of exposure. An approach to construct dose-response curves that use graph theory to describe network perturbations among three disparate mitogen-activated protein kinase (MAPK) pathways is presented. Mitochondrial stress was induced in human hepatocytes (HepG2) by exposing the cells to increasing doses of the complex I inhibitor, deguelin. The relative phosphorylation responses of proteins involved in the regulation of the stress response were measured. Graph theory was applied to the phosphorylation data to obtain parameters describing the network perturbations at each individual dose tested. The graph theory results depicted the dynamic nature of the relationship between p38, JNK, and ERK1/2 under conditions of mitochondrial stress and revealed shifts in the relationships between these MAPK pathways at low doses. The inter-relationship, or crosstalk, among these 3 traditionally linear MAPK cascades was further probed by coexposing cells to deguelin plus SB202190 (JNK and p38 inhibitor) or deguelin plus SB202474 (JNK inhibitor). The cells exposed to deguelin plus SB202474 resulted in significantly decreased viability, which could be visualized and attributed to the decrease of ERK1/2 network centrality. The approach presented here allows for the construction and visualization of dose-response curves that describe network perturbations induced by chemical stress, which provides an informative and sensitive means of assessing toxicological effects on biological systems.

The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

Catalytic azide reduction in biological environments.

In the quest for the identification of catalytic transformations to be used in chemical biology and medicinal chemistry, we identified iron(III) meso-tetraarylporphines as efficient catalysts for the reduction of aromatic azides to their amines. The reaction uses thiols as reducing agents and tolerates water, air, and other biological components. A caged fluorophore was employed to demonstrate that the reduction can be performed even in living mammalian cells. However, in vivo experiments in nematodes (Caenorhabditis elegans) and zebrafish (Danio rerio) revealed a limitation to this method: the metabolic reduction of aromatic azides.

Thalidomide-associated thrombosis in the treatment of HIV-associated severe aphthous disease: a case report and review of the literature.

Venous thrombosis is a well-described complication of thalidomide therapy in patients with multiple myeloma (MM). However, an association between thalidomide use and thrombosis in HIV-positive patients has not been previously described. We present the case of a 48-year-old HIV-positive man who developed a deep venous thrombosis while on thalidomide for the treatment of severe aphthous ulcers. We review the management of severe aphthous disease and the potential adverse effects of thalidomide therapy. We examine the association between thalidomide and thrombosis in patients with MM and discuss how the same relationship may or may not exist in HIV-positive patients. Although the strength of the association between thalidomide use and thrombosis in HIV-positive patients being treated for aphthous disease remains unclear, HIV providers should be aware of the potential risk of thrombosis in all patients receiving thalidomide.

Fungal Endocarditis With Severe Vegetations of the Aortic Valve and Septic Emboli Secondary to Total Parenteral Nutrition.

Fungal endocarditis is a rare but serious complication of fungemia. It is most commonly caused by Candida species. Risk factors include prosthetic heart valves, injection drug use, and indwelling central venous catheters. In comparison to bacterial endocarditis, fungal endocarditis is more commonly associated with arterial embolization, likely due to the larger size of vegetations. Unfortunately, diagnosis is often delayed, contributing to significant morbidity and mortality. Relapses are common, and extended treatment is often warranted. Antifungal agents and valve replacement are the recommended treatments. However, in-hospital mortality remains at 36%. For these reasons, it is critical to have a high index of suspicion and not delay appropriate therapy.

Healthcare personnel experiences implementing carbapenem-resistant Enterobacterales infection control measures at a ventilator-capable skilled nursing facility-A qualitative analysis.

OBJECTIVE: Ventilator-capable skilled nursing facilities (vSNFs) are critical to the epidemiology and control of antibiotic-resistant organisms. During an infection prevention intervention to control carbapenem-resistant Enterobacterales (CRE), we conducted a qualitative study to characterize vSNF healthcare personnel beliefs and experiences regarding infection control measures. DESIGN: A qualitative study involving semistructured interviews. SETTING: One vSNF in the Chicago, Illinois, metropolitan region. PARTICIPANTS: The study included 17 healthcare personnel representing management, nursing, and nursing assistants. METHODS: We used face-to-face, semistructured interviews to measure healthcare personnel experiences with infection control measures at the midpoint of a 2-year quality improvement project. RESULTS: Healthcare personnel characterized their facility as a home-like environment, yet they recognized that it is a setting where germs were 'invisible' and potentially 'threatening.' Healthcare personnel described elaborate self-protection measures to avoid acquisition or transfer of germs to their own household. Healthcare personnel were motivated to implement infection control measures to protect residents, but many identified structural barriers such as understaffing and time constraints, and some reported persistent preference for soap and water. CONCLUSIONS: Healthcare personnel in vSNFs, from management to frontline staff, understood germ theory and the significance of multidrug-resistant organism transmission. However, their ability to implement infection control measures was hampered by resource limitations and mixed beliefs regarding the effectiveness of infection control measures. Self-protection from acquiring multidrug-resistant organisms was a strong motivator for healthcare personnel both outside and inside the workplace, and it could explain variation in adherence to infection control measures such as a higher hand hygiene adherence after resident care than before resident care.

Persistent SARS-CoV-2 infectivity greater than 50 days in a case series of allogeneic peripheral blood stem cell transplant recipients.

The coronavirus disease 19 (COVID-19) pandemic has infected tens of millions across the world, but there is a significant gap in our understanding about COVID-19 in the hematopoietic stem transplant (HSCT) recipient population. Prolonged viral shedding is frequently observed with severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), but studies suggest viral loads decline 10 days after symptom onset. Current CDC guidance suggests that severely ill and immunocompromised hosts are no longer infectious after 20 days from symptom onset. Cycle threshold (Ct) values are inversely proportional to the viral load and are used to detect SARS-CoV-2 RNA concentration. Specimens with reverse transcriptase PCR (RT-PCR) Ct values > 33-34 have been associated with inability to culture virus, and have been used as a surrogate for diminished infectivity. We report two cases of  allogeneic peripheral blood stem cell transplant (PBSCT) recipients who had prolonged durations of infectivity with SARSCov-2, based on culture positivity and persistently low Ct values for greater than 50 days.

Early Tocilizumab Dosing Is Associated With Improved Survival in Critically Ill Patients Infected With Severe Acute Respiratory Syndrome Coronavirus-2.

To identify the most efficacious timing for tocilizumab administration in critically ill patients infected with severe acute respiratory syndrome coronavirus-2. DESIGN: Observational multicenter cohort study. SETTING: A total of 23 acute care hospitals in four states. PATIENTS: One-hundred eighteen patients admitted between March 13, 2020, and April 16, 2020. Eighty-one patients received tocilizumab, and 37 were untreated and served as a control group. MEASUREMENTS AND MAIN RESULTS: The main outcome was mortality and was analyzed by timing of tocilizumab dosing. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered greater than 1 day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was used for comparison. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p = 0.003). Dosing tocilizumab late was associated with an increased mortality compared with the untreated group (p = 0.006). CONCLUSIONS: Early tocilizumab administration was associated with decreased mortality in critically ill severe acute respiratory syndrome coronavirus-2 patients, but a potential detriment was suggested by dosing later in a patient's course.

Episodic, severe abdominal pain due to isolated jejunal Crohn's disease.

Small bowel Crohn's disease can present with episodic, relapsing, and remitting symptoms and delays in the diagnosis are common. We present a case of a young woman with three years of intermittent abdominal pain and nausea with negative previous evaluations. On presentation, inflammatory markers were elevated, and repeat imaging showed jejunal inflammation, with histopathological examination showing non-caseating granulomas of the small bowel consistent with Crohn's disease. This case highlights the importance of gastroenterologist recognizing the alarm signs in a patient with unexplained symptoms and adds to the literature on the clinical presentation of a rare diagnosis of isolated jejunal Crohn's disease.

Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).

Sexual assault as a risk factor for gynaecological morbidity: An exploratory systematic review and meta-analysis.

Among Australian females, sexual assault affects 1 in 5 Australian women [1], and 1 in 10 girls [2]. While it is well known that females who experience sexual assault have an increased risk of future pelvic pain, there is limited knowledge regarding the occurrence of other gynaecological morbidity. We performed systematic review and meta-analysis for the relationship between sexual assault and gynaecological morbidity. We searched online electronic databases for observational studies on the subject published between 1993 and 2018. Search terms included variants of 'sexual abuse', 'sexual assault' and a range of gynaecological morbidity. Two independent reviewers completed study selection, quality assessment and data extraction. For each gynaecological symptom we calculated common odds ratios and 95 % confidence intervals in relation to sexual abuse history. Our search identified 1846 studies, of which 38 studies were included. A history of sexual assault was significantly associated with overall gynaecological morbidity (RR 1.42; 95%CI, 1.27-1.59), pelvic pain (RR 1.60; 95%CI, 1.36-1.89), 'dyspareunia' (pooled RR 1.74, 95%CI, 1.50-2.02); 'dysmenorrhea' (pooled RR 1.20; 95%CI, 1.11-1.29); 'abnormal menstrual bleeding' (pooled RR 1.29; 95%CI, 1.12-1.49)) and 'urinary incontinence' (pooled RR 1.31; 95%CI, 1.12-1.53)), while association was not statistically significant for 'vaginismus'(pooled RR 1.71; 95%CI, 0.87-3.36) and 'vulvodynia' (pooled RR 1.49; 95%CI, 0.76-2.91). There was no relation with 'prolapse' (pooled RR 1.10; 95%CI, 0.53-2.30). Females with a history of sexual assault have a significantly increased risk of different gynaecological disorders later in life.