Search

Bacterial meningitis, an infection of the membranes (meninges) and cerebrospinal fluid (CSF) surrounding the brain and spinal cord, is one of the major causes of death and disability worldwide. Higher case-fatality rates and short survival times have been reported in developing countries. Hence, a quick, straightforward, and low-cost approach is in great demand for the diagnosis of meningitis. In this research, a microfluidic fully paper-based analytical device (μFPAD) integrated with loop-mediated isothermal amplification (LAMP) and ssDNA-functionalized graphene oxide (GO) nano-biosensors was developed for the first time for a simple, rapid, low-cost, and quantitative detection of the main meningitis-causing bacteria

Introduction Around 50%-70% of all women, at any moment of their lives, will undergo pelvic surgery such as abdominal and vaginal hysterectomies, laparoscopic or robotic-assisted hysterectomies, and exploratory laparotomies for multiple reasons. These reasons include; endometriosis, chronic pelvic pain, pelvic adhesions secondary to pelvic inflammatory disease, infected or perforated IUDs, previous surgeries, abscesses or cysts, peritonitis, and genital prolapses such as cystoceles, rectoceles, uterine prolapse or vaginal prolapse in patients with previous hysterectomies, urinary and fecal incontinence, and total procidentia. The general public knowledge, distorted sexual education curriculum, and the influence of this inappropriate sexual education (produced by religions and cultures) affect the medical practice and investigations at scientific levels. These influences have expanded the beliefs that sexual activity is deteriorated for all of these kinds of procedures. Few American publications and many Asian publications report the frank deterioration of the sexual response in women who have had pelvic surgeries. Objective To show how a very high percentage of women, that have had pelvic surgeries, have an improvement in their sexual activity after these kinds of procedures. Methods This investigation analyzed the postoperative sexual function of hundreds of patients at our two centers in which all the procedures previously named were practiced. Results We found an improvement in sexual activity, not only in the women but also in the couples in more than 95% of the cases. The pre and post-procedure evaluations were done. Conclusions Contradictory to what several studies have shown regarding how pelvic surgeries produced deterioration in sexual activity, we have demonstrated the opposite. We found that in more than 95% of the cases, sexual activity was improved. These procedures included repairing total procidentia, cystocele, rectocele, urinary incontinence or rectal incontinence, fibroid uterus, or chronic pelvic pain. Disclosure No

Introduction Premature ejaculation (PE), according to the ISSM Committee, is defined as ejaculation with vaginal penetration that always or nearly always occurs prior to or within about one minute from the beginning of a sexual encounter, together with the inability to retard ejaculation with vaginal penetration. As a result, the personal life of an affected individual may be negatively impacted, with the consequences of distress, bother, frustrations, and/or avoidance of sexual intimacy. However, there are multiple factors to consider and not all sexologists, psychologists, and therapists agree about a clear and complete definition of PE. This, in turn, makes it more difficult to have clear statistics of the incidence, prevalence, and frequency of this disorder. On the other hand, Female Orgasmic Disorder (FOD) is defined as difficulty, delay, or inability for a woman to reach orgasm in a sexual encounter or the reduced frequency and/or intensity of orgasm. While PE and FOD are usually described separately in the medical literature, we have found in both the sexological literature and in practice that women with FOD are frequently the partners of men with PE. Objective The objective of this review is to address the increased incidence of FOD secondary to PE in the South Florida Latin-American population, its impact in the sexual function of both male and female partners in their relationship, and the possible reasons for the difference between the Latin-American community and the General population of the United States of America. Methods This is a retrospective review of the sexological literature and the statistics we have collected from patients over the last 20 years, in which around 80% of cases of women with FOD are due to PE in their partner. Results Nationally speaking, the frequency of FOD secondary to PE has been reported to generally run between 35-50% in reproductive aged women. Throughout the years we have noticed that this frequency is markedly higher in the Latin-American population of South Florida, reaching 79.6% of cases. Conclusions We do not have a clear explanation for this important difference between the General population of the United States and the Latin-American population of South Florida, but we know that the Latin-American population in this area is exposed to a great number of stressors. One such set of stressors that may be a contributing to the increased incidence is known as the “Immigrant’s Syndrome,” a set of circumstances which includes sexual dysfunction as one of its components. Disclosure No

Introduction Traditionally, sex has been thought of as a function predominantly exercised for reproductive purposes. Likely, religion and culture have both failed to promote a healthy appreciation for the pleasure that sex can provide. Due to the heavy focus on the reproductive utility of sex, society has perpetuated the misconception that increased age reduces libido. As such, the health benefits of sex, particularly in older adults, has been largely ignored as an integral part of preventative medicine. Furthermore, recent studies in the field of neuroendocrinology have demonstrated an increase in the number of receptors for estrogen, progesterone, and testosterone in different tissues of our body, especially in vital organs as brain, heart, bone, and muscle. Objective To spread awareness on the importance of maintaining a healthy amount of sexual activity in order to decrease adverse health outcomes. Methods In this study, we review the literature extensively and use the sexual histories of patients in our office to assess the beneficial health outcomes. Results We present evidence associating increased sexual activity with decreased risk of many disease states. Populations with higher frequency of arousal and orgasms showed reduced rates of breast cancer, prostate cancer, obesity, vaginal atrophy, dyspareunia, dysmenorrhea, dysfunctional uterine bleeding, recurrent urinary tract infections, urinary stress incontinence, fecal incontinence, genitourinary symptoms of menopause, abnormal false pap smears, vulvar, labial, and vaginal obliteration, and cardiovascular disease. Conclusions Our findings suggest that increased sexual activity is an important factor for the maintenance of general good health. These findings indicate decline in sexual activity, desire or function, particularly in older patients, as potential risk factors for adverse health outcomes. Promotion of healthy sexual behaviors have been strongly linked to sexual ability at advanced ages, with studies since 1948 showing that over 80% of women with orgasmic dysfunction do not masturbate, while over 80% of women who regularly achieve orgasm do not have trouble masturbating. Sexual literacy and comfort are key factors that may promote healthy sexual activity during adulthood. As such, masturbation should be promoted in adolescent and young adults as part of routine sexual education. Furthermore, standard medical practice should encourage regular sexual activity, with or without a partner. Disclosure No

Introduction Urologist, gynecologist, surgeons, sexologists, and ER physicians are familiarized with some of the sexual emergencies that called the attention of everybody. However, the broad spectrum of those disorders is not well-known. Objective 1. Show the magnitude of sexual emergencies in an important hospital of South Florida. 2. Show the magnitude of sexual emergencies nationally and internationally. 3. Describe how they can vary according with the place, culture, and societies. 4. To learn the methods of diagnosis and treatment of these ample variety of conditions. Methods Based on the multiple cases seen in our ER in Hialeah Hospital in Miami, Florida, extensive review of the literature was done, and the cases are presented to show the magnitude, variety, and diversity of cases in the different areas of the medical field. Results The review includes: I. The common coital emergencies in neurology (benign coital headache, subarachnoid hemorrhage, intracerebral bleeding, subdural hemorrhage, cerebral vascular accidents), urology (penile fracture, priapism, preputial tears, penile vessel rupture, penile strangulation, penile necrosis, ureterovesical foreign bodies, epididymitis., obstructive uropathies), cardiology (sudden cardiac death, myocardial infarction), gynecology (vaginal laceration and/or evisceration with/without previous gynecological surgeries), obstetrical (postpartum dyspareunia secondary or not to episiotomy or vaginal lacerations; postcoital preterm labor), immunological (local or systemic, anaphylactic allergic reactions). II. Common autoerotic emergencies in gastroenterology (foreign objects in rectum, vagina, oropharyngeal/mandibular lesions), as well as “body packers” cases (swallowed latex balloons for smuggling in the GI tract, rectum, or vagina). III. Sexual assault IV. Sexual dysfunction: Hyperactive arousal disorders (compulsive hunt for orgasms with/without attempt or real suicide, hypersexuality related to SSRI use). V. Sociosexual issues: Killings for jealousy during sex, infidelity, castration like Lorena Bobbitt case. gynecologicalgynecological Conclusions The epidemiology of these pathologies varies from country to country and includes subjects of any age, sex, race, religion, and culture. Finally, a review of these diagnostic methods and treatment are presented. Disclosure No

Introduction Genitourinary syndrome of menopause (GSM) has been well described within medical literature and its effects have been well managed by physicians with an extensive understanding of the condition. However, the progression of medicine in each area continues to evolve. We propose new findings that are extremely important to have in consideration of GSM. Objective To describe new findings that are not traditionally associated with GSM, some with lethal consequences: * False abnormal pap smears * Total vulvovaginal obliteration and secondary renal damage * Undiagnosed recurrent urinary tract infections (UTI) in the geriatric population without hormone replacement therapy with secondary sepsis, pneumonia, and death. Methods Large review of recent literature, diagnosis, treatment and follow up of patients within our facility and nursing homes including geriatric females with and without hormone replacement therapy. Results `- Resolution of the abnormal pap smear with the use of local estrogens in more than 1500 cases. - Management of 6 cases of vulvovaginal obliteration with surgery, dilators, increasing penetrative sex, and local estrogens with great results. - Description of some dozens of patients seen and evaluated in home care facilities with undiagnosed UTI by the primary care, showed subsequent findings of sepsis, pneumonia, and even death. Conclusions Emphasize the need to inform and educate healthcare providers, especially primary care, internal medicine, OB/GYN physicians, and urologists the ample growing and potentially lethal spectrum of GSM. Disclosure No

Introduction Between Dec. 2018 & June 2020, 5 cases of Vulvovaginal Obliteration, also known as Labial Adhesion were diagnosed, evaluated and treated. All of the presenting cases had a history which shared certain features, including more than 2 decades without sexual activity, no history of masturbation, no use of hormone replacement therapy and chronic urinary tract symptoms. The most severe case had the longest period without vaginal penetration (>30years). In 3 of the 5 cases the patients didn't have a partner, while the other 2 patients were not sexually active with their partner in any way. Objective To add new cases to the literature about this rarely described disorder. To show this condition is one of the most extreme consequences of Genitourinary Syndrome of Menopause. To demonstrate the importance of vaginal penetration and hormone replacement therapy (HRT) to prevent postmenopausal labial adhesion. Methods This is a case series reviewing the effective management of labial adhesion in post-menopausal women. Results In 2 of the cases the patients main complaint was their inability to urinate due to obstruction of the urethral outlet by the fused labia. This obstruction caused urocolpos, extremely distended urinary bladder, megaloureters, & bilateral hydronephrosis. Leakage of urine also occurred at the posterior fourchette. All of these urinary symptoms disappeared after an urgent introital incision was performed in the OR. In both cases the exclusive use of local estrogens postoperatively failed to prevent recurrent closure. Only the combined use of local estrogens and the regular use of dilators (3-4 times/day/2 weeks, then 1-2 times /day/2 weeks, then PRN) prevented recurrence. In 3 of the 5 cases, regular use of the dilators caused them to reach orgasm for the first time in their lives. The ages of these women were between 76 & 92 years old. The last 2, and more mild cases had 50% labial fusion, without urinary retention. The use of progressively increasing sizes of dilators and estrogen cream resolved the problem without surgical interventions. Conclusions Labial adhesion is one of the worst consequences of GSM, due to progression towards urinary retention. It is caused by insufficient maintenance of sexual activity after menopause, combined with lack of prevention with HRT, and is successfully managed with surgery, dilators and topical estrogens. Disclosure No

Introduction In 1948 Alfred Kinsey’s investigation of female and male sexuality found that 80% of women reached orgasm mainly through non-coital sexual experiences, such as oral and physical manipulation of the genitals or through sex toys. After that many peer-reviewed studies confirmed these data as well as in our practice. However, the question remains; what happened with the other 20% that reached orgasm through vaginal penetration. Objective To describe the epidemiological sexual characteristics of the 20% of women who reached orgasm mainly through vaginal penetration. Methods Over 3000 sexual histories were done in our medical center and were used to collect data regarding the reasons for the orgasm obtained through vaginal penetration. This study includes retrospective and prospective questionnaires applied to all patients seen in our centers. Results The epidemiological sexual characteristic of this specific group of women are: - 75% have had only one sexual partner in their lives - 20% of them have had two sexual partners in their life and - 5% of them have more than two. It has been very scantly found that women with a history of multiple sexual partners enjoy sexual penetration. The orgasmic response resulting from coital sex was more persistent and presently found while the number of sexual partners was less. Increased orgasmic responsiveness was also present when the initiation of the sexual activity with the partner was earlier in life. Conclusions When the sexual development of a woman is allowed to mature in the presence of a lifelong partner. Their response to penetrative vaginal stimuli is better and the obtention of sexual pleasure and orgasm reinforce this response that persists throughout life and is more attainable over any other form of vaginal stimulation. Disclosure No

Introduction Hormone Replacement Therapy (HRT) use has recently been a topic of debate amongst clinicians. The discussion has been most prevalent in the fields of gynecology, urology, and endocrinology. Current research suggests HRT can prevent the development of lethal diseases such as myocardial infarction, osteoporosis, diabetes mellitus, Alzheimer's disease, Parkinson’s disease, and genitourinary syndrome of menopause. Objective To raise awareness of HRT as a prophylactic measure to treat a variety of diseases in multiple organ systems, we recommend providing this information across multiple medical specialties to warrant the use of HRT amongst patients. Specialists including obstetricians and gynecologists, urologists, cardiologists, neurologists, dermatologists, psychiatrists, ophthalmologists, orthopedics, wound care specialists, sexologists, sex therapists, psychologists, rheumatologists, immunologists, infectious disease specialists, cosmetic surgeons, endocrinologists, and geriatricians should be aware of the benefits of HRT and how they can incorporate it into patient care. Methods Based on our own experience, for more than 40 years and the continued management of postmenopausal women, we have realized the importance that physicians, in specialties other than obstetrics and gynecology must be aware of the use of this therapy in their specific field. For example, approximately 60% of depression diagnoses in perimenopausal years can be treated with greater efficacy with hormone replacement therapy rather than antidepressants prescribed by psychiatrists. These findings have been confirmed in the current literature, however awareness amongst the various specialties is very poor. Results HRT plays a significant role in treating silent killers such as myocardial infarction, osteoporosis, diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, and Genitourinary syndrome of menopause. Conclusions Previously, the role of HRT was not clearly established. Current data suggests HRT provides many benefits including a reduction in mortality. Through recent research and published literature, the consensus of the benefits and strategies of HRT have been established. However, the use of HRT is currently under-prescribed. This creates an opportunity to bring awareness to clinicians, thereby improving the lives of patients. Disclosure No

Introduction Every year, two or more benefits of the use of hormone replacement therapy (HRT) in menopause and andropause appear in medical literature. We present an extensive review of the literature describing the classical and novel benefits of hormonal replacement therapy and sex in menopause. Additionally, we present recent findings from our own patient population. Objective To contribute to the presently known benefits of the use of HRTs, and additionally to present new findings from our own practice not previously described. Methods We conducted an extensive literature review and described our own experience and findings within our centers. Results `- In the area of prevention and treatment of genitourinary syndrome of menopause, we have found: - Prevention and treatment of false positive cervical dysplasia in perimenopause. - Prevention and treatment of vulvar, labial, and vaginal occlusion in late menopause. - Prevention and treatment of recurrent urinary tract infections in geriatric patients for prevention of sepsis, secondary pneumonia, and even death. - Prevention and treatment of clitoral atrophy, phimosis, and urethral caruncles - Dermatology: We have found: - Prevention and treatment of wrinkles, alopecia related, postmenopause. - Prevention in prostrated geriatric patients of decubitus ulcers. - Internal Medicine: prevention of obesity, decreased metabolic rate, and insulin resistance. - Ophthalmology: - Prevention and treatment of macular degeneration. - Prevention of glaucoma (increased intraocular pressure), most notably in primary open- angle glaucoma. - The prevention of aging of optic nerve and neuroprotection of retinal cells. - Oncology: - Prevention of kidney cancers, and breast cancer (only estrogen hormone replacement therapy). - Enhanced visualization of the transformation zone during cervical cancer screening - Gastroenterology: protection of the gut microbiome and serum metabolome, especially in premature ovarian insufficiency - Dentistry: prevention of tooth loss through decreased gingival inflammation and periodontitis, mandibular bone loss, and oral dysesthesia. - Neurology: - Protection against intracranial aneurysm rupture in ovariectomized mice. - The prevention of Parkinson’s and Alzheimer’s disease - Rheumatology: prevention of rheumatoid arthritis. Conclusions To demonstrate the number of studies with the anti-aging mechanism of the use of HRT. How this knowledge, alongside our own findings of hundreds of menopausal women within our centers justify the generalized use of this therapy. Disclosure No

Introduction Sexual emergencies in female patients are more common than people think. They represent medical curiosities more than pathologies for which we should be prepared to treat. This review and the presentation of our cases shows how extensive and important is this area in the medical practice and why every single physician should be prepared to confront them. Gynecologist, surgeons, sexologists, and ER physicians are familiarized with some of the sexual emergencies in women that called the attention of the medical community. However, the broad spectrum of those disorders is not well-known. Objective 1. Show the magnitude of sexual emergencies in women nationally and internationally. 2. Describe how they can vary according with the place, culture, and societies. 3. To learn the methods of diagnosis and treatment of these ample variety of conditions. Methods Based on the multiple cases seen in the ER of our facility, an extensive review of the literature was done, and the cases are presented to show the magnitude, variety, and diversity of cases in the different areas of the medical field. Results The review includes: I. The common coital emergencies in neurology (benign coital headache, subarachnoid hemorrhage, intracerebral bleeding, subdural hemorrhage, cerebral vascular accidents), urology (ureterovesical foreign bodies, obstructive uropathies), cardiology (sudden cardiac death, myocardial infarction), gynecology (vaginal lacerations and/or evisceration and death with/without previous gynecological surgeries), obstetrical (postpartum dyspareunia secondary or not to episiotomy or vaginal lacerations; postcoital preterm labor), immunological (local or systemic, anaphylactic allergic reactions). II. Common autoerotic emergencies in gastroenterology (foreign objects in rectum, vagina, oropharyngeal/mandibular lesions), as well as “body packers” cases (swallowed latex balloons for smuggling in the GI tract, rectum, or vagina). III. Sexual assault IV. Sexual dysfunction: Hyperactive arousal disorders (compulsive hunt for orgasms with/without attempt or real suicide, hypersexuality related to SSRI use). V. Sociosexual issues: Killings for jealousy during sex, infidelity, castration like Lorena Bobbitt case. Conclusions The epidemiology of these pathologies varies from country to country, and state to state, and includes women of any age, race, religion, and culture. Finally, a review of these diagnostic methods and treatment are presented. Disclosure No

Introduction Around 2010, we started to realize in our centers that we were receiving an increasing number of perimenopausal women with abnormal Pap smears (cervical dysplasia), going from ASCUS to low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions with or without positive HPV. With no previous history of cervical abnormality and almost all of them in a long-term stable sexual relationship with a maximum of 1 or 2 sexual partners. After talking with our pathologist, we asked if vaginal atrophy could produce such results. He answered affirmatively and provided us with a few recent articles that describe such findings. As an advocate for hormone replacement therapy, we decided to start using local vaginal estrogen for several months and then repeat the Pap smears. We were able to confirm that inclusively with those cases diagnosed with high-grade squamous intraepithelial lesions, the next Pap smear after the treatment with local estrogens was totally normal. The situation has been repeated in more than 96% of cases in around 1500 patients in the same conditions for the last 12 years. Objective Describe these new findings confirmed by a few articles in the pathology field and two articles on estrogen use, in women ranging between the ages of 30-70 years. Methods Prospective follow-up of perimenopausal patients with positive Pap smears and very low risk for STDs placed on local and/or systemic vaginal estrogen. A Pap smear was conducted at 4 months and then 1 year after, which was followed by the regular scheme of Pap smear follow-ups. Results 96.7% of all those patients with the described characteristics were successfully treated with local estrogens. During the study, we realized that the high number of patients who entered after the initial diagnosis of cervical dysplasia in the regular guidelines of colposcopies, biopsies, LEEP excisions, cryotherapy, and due to the persistence of the findings in more than 50% of those cases (because of the persistence of cervicovaginal atrophy) they finished having cone biopsies and/or hysterectomies. Conclusions We describe the early finding of another sign of genitourinary syndrome of menopause: false positive cervical dysplasias, secondary to cervicovaginal atrophy, due to the decrease in the level of estrogens that characterized the perimenopause. Also, how the management of local estrogens prevents a great number of interventions and patient procedures, saving billions of dollars per year, taking into account that the number of Pap smears in the named population is around 50-60% of all Pap smears practiced in the total population of women. Disclosure No

Introduction Hyposexuality is a well-defined and prevalent side effect of individuals prescribed SSRI medication. However, hypersexuality has never been found in patients taking SSRI and antitypical antidepressant medications. We present two new case reports to the scanty literature found up to now in this area. This condition needs to be differentiated from the hyperactive arousal disorder already described in the sexological literature. This demands further study. With several documented reports of these side effects, failure to examine and develop therapy options for our patients would be a disservice. Objective The objective of this care report is to educate both patients and medical providers of this side effect as well as further investigation to include the pharmacological mechanism involved. Methods Two patients presented to the office complaining of hypersexuality. These patients were then followed for four months before completing analysis. Results Of the two patients presenting on the drug regimen specified, both experienced hypersexuality. Conclusions This case study illustrates that the use of Bupropion and Fluoxetine/Sertraline concomitantly can cause hypersexuality in perimenopausal women. This is an area that needs to be studied more to conclude the mechanism of action. Disclosure No

Introduction Dyspareunia has been defined by the American College of Obstetricians and Gynecologists as pain with sexual intercourse. While dyspareunia has been described as only a part of the symptomatology spectrum of interstitial cystitis, it has never been used as a primary symptom to diagnose uncomplicated or complicated UTIs. Dyspareunia and lower abdominal pain are the most common symptoms followed by dysuria, urodynia, pollakiuria, urgency, nocturia, tenesmus, headache and fever. Increased awareness of the association of dyspareunia with UTI’s will improve the diagnosis of UTIs. Objective UTI’s are under-diagnosed in emergency rooms, as clinicians increasingly rely on urinalysis rather than symptomatology. The presence of dyspareunia is rarely inquired during an evaluation of the patient. The objective of this research is to inform clinicians that dyspareunia is a common symptom of urinary tract infections. By increasing awareness of the association between UTI’s and dyspareunia, clinicians will include it in the assessment of a patient, rather than relying solely on a urinalysis. Additionally, our objective is to educate the patient population that dyspareunia is not normal, and it is a medical condition that can be resolved and investigated. Methods In 2009-2010, a review of 3,000 charts was conducted to determine the sexual attitudes and behaviors of the female Latin American community in South Florida. Analysis of the data shows a correlation between dyspareunia and urinary tract infections, a finding that has not been described before. Results The association between a UTI and dyspareunia was found to be approximately 80% in premenopausal women of reproductive age. In post menopausal women, UTIs are the second most common cause of dyspareunia following vaginal dryness. Conclusions This analysis has determined that dyspareunia is a significant aspect of the semiology of a UTI, thus clinicians should be aware of this association in order to accurately diagnose UTIs in patients. Disclosure No

Introduction We present two cases of hypersexuality in perimenopausal women evaluated, diagnosed, and being managed at this time for what seems to be a sexual dysfunction recently described as a consequence of the use of a combination of 2 kinds of medications: Bupropion, a Norepinephrine Dopamine Reuptake Inhibitor (NDRI), and Sertraline/Fluoxetine, a Selective Serotonin Receptor Inhibitor (SSRI), used as an anti-depressant and anxiolytics for psychiatric conditions. Both cases arrived at our centers referred by their primary care physicians or a psychiatrist for sexual therapy and sexological evaluation. Objective To show a new sexual dysfunction related to the use of SSRI medications. Methods The analysis of 2 cases of a new described sexual dysfunction related with the use of SSRI medications: Bupropion at 150 mg PO bid, and Fluoxetine at 125 mg PO qd. Results The first case, one week after the initiation of Fluoxetine, having been taking Bupropion for months, started to develop uncontrolled need for sex, having sex with multiple men, in addition to her husband. Her husband accepted to have sexual relationships in trios, a situation that lasted for several months. However, after 4-6 weeks, she started to look for additional partners other than her husband. He left. She arrived with extreme anxiety during her first visit. Neither her, nor the psychiatrist understood why this was happening. At that moment, she was having sex with several men on a daily basis. She wanted to preserve her marriage but her sexual compulsion was an impediment. The second patient decided to be unfaithful to her husband of 10 years. In this case, she decided to have hidden sexual relations with several men at the same time with just one. She was also undergoing psychiatric treatment with both medications, Fluoxetine and Bupropion. There was a temporal correlation between the initiation of Fluoxetine and the appearance of the sexual dysfunction. We suspended both medications and around 10 days after this therapeutic step, there was a frank decline in the compulsive sexual behavior. However, due to depression and anxiety symptoms, the psychiatrist decided to restart only Bupropion without the Fluoxetine that was the medication with which the appearance of symptoms have been related. Now, she is okay. Conclusions We describe the possible pharmacological mechanisms involved in the pathophysiology of this disorder and the way in which we have managed the two cases up to now. This condition needs to be differentiated from the hyperactive sexual arousal disorder, previously described in the sexological literature and we need to determine if this is a variant of that kind of syndrome. We have never encountered this kind of reaction before and have only found one publication describing a similar case. Disclosure No

Introduction In 2014, the Genitourinary Syndrome of Menopause replaced the previous concept of vaginal and genital atrophy. The spectrum of this syndrome includes and is not limited to atrophy, dryness, recurrent UTI, dyspareunia, anal incontinence, pelvic organ prolapse, vaginal stenosis, labial fusion, and/or vulvar obliteration. However, with time and the continuous exposure to women who have reached more advanced ages, such as centenarians, the spectrum of the GSM has been increasingly showing new entities and disorders never described before. Objective To update and expand the literature on the spectrum of GSM affecting the well-being, sexual functioning, and quality of life of postmenopausal women including the new observations seen in centenarians. Methods Multiple peer reviewed articles of both cohort and observational studies were evaluated to assess the increased spectrum of GSM symptoms in the centenarian women population. Results Nearly 60% of women in menopause experience GSM. Despite a vast majority of signs and symptoms, only 7% of providers ask women about this condition implying that GSM continues to be underdiagnosed and undertreated. In the early extreme of the spectrum of GSM, we show the new finding of the presence of false abnormal cervical dysplasia in women who have never had an abnormal PAP smear and have maintained a stable sexual relationship with their partner. This misconstrue is due to early vaginal and cervical atrophy which produces cells that, under the microscope, are very similar to dysplastic cells to the pathologist. This scenario is frequently seen in more than 80% of cases with those epidemiological characteristics, which is extremely easy to resolve with 4 months of regular local estrogen therapy. In the other extreme of the spectrum of GSM, in the elderly, the combination of lack of HRT and sex for prolonged periods of times produced the partial or total obliteration of the labia majora or minora with fusion in several women. Thus, preventing the exit of urine through the urethra with significant retention of fluid affecting the urinary bladder, ureters, and kidneys. Finally, having been exposed to the care of centenarian women in home care (women over 90 years old), we have realized that a significant number of them died with the diagnosis of pneumonia. However, when reviewing the analyzed cases retrospectively, we found that the real diagnosis was undiagnosed recurrent UTIs with poor clinical manifestations (which is common in these types of patients). The algorithm goes as follows: undiagnosed recurrent UTIs with poor clinical manifestations such as fever, leukocytosis, and poor verbal manifestations due to the age of patients, that progress to sepsis and the pneumonia that has been the part that really draws the attention of the physician. Conclusions The new findings of this review highlight the clinical implications when analyzing the two extremes of the spectrum of GSM throughout women’s lives. In all these cases, local or systemic HRT was never used. Appropriate management of GSM will enhance the quality of life and sexual function of these women. Disclosure No

Introduction Between December 2018 and July 2022, six cases of vulvovaginal fusion (obliteration) were diagnosed, evaluated, and treated at our centers. Less than 30 cases have been reported according to our reviews of the medical literature. All of the cases presented shared certain features such as more than 2 decades without sex or masturbation, no use of hormone replacement therapy, and a history of chronic urinary tract infections. Objective 1. Present information from 6 cases of a rare genitourinary disorder, its diagnosis, medical & surgical management, follow-up, and resolution. 2. Place vulvovaginal obliteration or labial fusion as one of the most extreme late consequences of untreated genitourinary syndrome of menopause. 3. Emphasize not only the importance of the use of local estrogen in all women going through menopause but also clarify and promote the importance of the maintenance of penetrative sexual activity in the lives of older women. This can be achieved either naturally or with the use of dilators and sexual toys. Methods We analyzed 6 cases of patients with vulvo-vaginal obliteration that presented in our facilities. Results Analysis of the 6 cases showed: In 3 out of the 6 cases, the patient didn’t have a partner, while in the other 3 cases, they were not sexually active with their partner in any way. In 2 of the cases, the patient’s main complaint was the inability to urinate due to obstruction of the urethral outlet by a fused labia. In both cases, urinary leakage from overflow was present in the area of the posterior fourchette, along with urocolpos, an extremely distended urinary bladder, bilateral megaureter, and hydronephrosis. The ages of these 6 women were between 72 to 94. The most severe case involved a patient with the longest time without penetration (> 30 years). Conclusions Total and partial vulvovaginal obliteration is a disease that hasn’t been commonly described. By obtaining the sexual history of each patient and the practice of geriatric gynecology, we have been able to diagnose this disorder. There is no doubt that vulvovaginal obliteration, also known as labial fusion, is one of the most extreme complications of the genitourinary syndrome of menopause but has not been medically described as part of its findings up till now. The prevention and treatment include not only the local use of estrogen but also the education of the patients on the need to maintain penetrative sexual activity in order to prevent the atrophy of the genitourinary area and maintain its functional ability. This can be done with a partner, penetrative dilators, or sexual toys. Disclosure No

Diffuse large B-cell lymphoma (DLBCL) exhibits significant genetic heterogeneity which contributes to drug resistance, necessitating development of novel therapeutic approaches. Pharmacological inhibitors of cyclin-dependent kinases (CDK) demonstrated pre-clinical activity in DLBCL, however many stalled in clinical development. Here we show that AZD4573, a selective inhibitor of CDK9, restricted growth of DLBCL cells. CDK9 inhibition (CDK9i) resulted in rapid changes in the transcriptome and proteome, with downmodulation of multiple oncoproteins (eg, MYC, Mcl-1, JunB, PIM3) and deregulation of phosphoinotiside-3 kinase (PI3K) and senescence pathways. Following initial transcriptional repression due to RNAPII pausing, we observed transcriptional recovery of several oncogenes, including MYC and PIM3. ATAC-Seq and ChIP-Seq experiments revealed that CDK9i induced epigenetic remodeling with bi-directional changes in chromatin accessibility, suppressed promoter activation and led to sustained reprograming of the super-enhancer landscape. A CRISPR library screen suggested that SE-associated genes in the Mediator complex, as well as AKT1, confer resistance to CDK9i. Consistent with this, sgRNA-mediated knockout of MED12 sensitized cells to CDK9i. Informed by our mechanistic findings, we combined AZD4573 with either PIM kinase or PI3K inhibitors. Both combinations decreased proliferation and induced apoptosis in DLBCL and primary lymphoma cells in vitro as well as resulted in delayed tumor progression and extended survival of mice xenografted with DLBCL in vivo. Thus, CDK9i induces reprogramming of the epigenetic landscape, and super-enhancer driven recovery of select oncogenes may contribute to resistance to CDK9i. PIM and PI3K represent potential targets to circumvent resistance to CDK9i in the heterogeneous landscape of DLBCL.

Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure–volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure–volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.

Whereas moist-tamped specimens of silts and sands are most used in engineering practice to characterize tailings, offshore sediments, and fluvial/alluvial deposits, design parameters derived from moist-tamping data sets can be significantly different from those obtained from slurry or underwater deposition. This study shows that moist-tamped silty and sandy specimens may exhibit phase transformation at stress ratios that are 25% to 50% lower than those observed for slurry-deposited specimens. Conversely, the small-strain stiffness of the moist-tamped specimens tested can be 50% higher than those from slurry deposition. With tailings dams’ performance receiving increased worldwide attention due to recent dam failures in several parts of the world, this study provides new, specific, and concerning insights about the crucial impact that the selection of moist tamping can have on design parameters. More realistic and rigorous laboratory testing procedures involving tailings remain a key requirement for engineering assessments of tailings behavior. A novel slurry-deposition setup is presented that allows underwater reconstitution of silts, sands, and their mixtures, yielding high-quality uniform specimens. Systematic uniformity checks, which are mandatory to avoid segregation of silty materials, are described. A detailed analysis of typical errors affecting initial void ratio evaluation is also presented to ensure that comparisons between different methods are done with the highest degree of confidence possible.

Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke being more harmful to developing cells than mainstream smoke. Furthermore, first reports are emerging to suggest a differential impact of conventional versus harm-reduction tobacco products on bone tissue as it develops in the embryo or in vitro. To gather first insight into the molecular mechanism of such differences, we assessed the effect of sidestream smoke solutions from Camel (conventional) and Camel Blue (harm-reduction) cigarettes using a human embryonic stem cell osteogenic differentiation model. Sidestream smoke from the conventional Camel cigarettes concentration-dependently inhibited in vitro calcification triggered by high levels of mitochondrially generated oxidative stress, loss of mitochondrial membrane potential, and reduced ATP production. Camel sidestream smoke also induced DNA damage and caspase 9-dependent apoptosis. Camel Blue-exposed cells, in contrast, invoked only intermediate levels of reactive oxygen species insufficient to activate caspase 3/7. Despite the absence of apoptotic gene activation, damage to the mitochondrial phenotype was still noted concomitant with activation of an anti-inflammatory gene signature and inhibited mineralization. Collectively, the presented findings in differentiating pluripotent stem cells imply that embryos may exhibit low bone mineral density if exposed to environmental smoke during development.

This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., The merger of two compact objects of which at least one is a neutron star is signalled by transient electromagnetic emission in a kilonova (KN). This event is accompanied by gravitational waves and possibly other radiation messengers such as neutrinos or cosmic rays. The electromagnetic emission arises from the radioactive decay of heavy r-process elements synthesized in the material ejected during and after the merger. In this paper we show that the analysis of KNe light curves can provide cosmological distance measurements and constrain the properties of the ejecta. In this respect, MAAT, the new Integral Field Unit in the OSIRIS spectrograph on the 10.4 m Gran Telescopio CANARIAS (GTC), is well suited for the study of KNe by performing absolute spectro-photometry over the entire 3600 − 10 000 Å spectral range. Here, we study the most representative cases regarding the scientific interest of KNe from binary neutron stars, and we evaluate the observational prospects and performance of MAAT on the GTC to do the following: (a) study the impact of the equation of state on the KN light curve, and determine to what extent bounds on neutron star (NS) radii or compactness deriving from KN peak magnitudes can be identified and (b) measure the Hubble constant, H0, with precision improved by up to 40%, when both gravitational wave data and photometric-light curves are used. In this context we discuss how the equation of state, the viewing angle, and the distance affect the precision and estimated value of H0. © M. A. Pérez-García et al., M.A.P.G. and C.A. acknowledge financial support from Junta de Castilla y León through the grant SA096P20, Agencia Estatal de Investigación through the grant PID2019-107778GB-100. D.B. acknowledges support from the program Ayudas para Financiar la Contratación Predoctoral de Personal Investigador (Orden EDU/1508/2020) funded by Consejería de Educación de la Junta de Castilla y León and European Social Fund. L.I., A.A., C.R.A., C.G. and J.H. were supported by grants from VILLUM FONDEN (project number 16599, 25501 and 36225). The Oskar Klein Centre authors acknowledge support from the G.R.E.A.T. research environment, funded by Vetenskapsrådet, the Swedish Research Council, project number 2016-06012. M.B. acknowledges support from the Swedish Research Council (Reg. no. 2020-03330). The IAA-CSIC authors acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). E.P. and C.D.T. thank support from the Agencia Estatal de Investigación through the grant AYA2016-77846-P. F.P. and C.D.T. thank the support of the Spanish Ministry of Science and Innovation funding grant PGC2018-101931-B-I00.CDT thanks the Instituto de Astrofísica de Canarias for the use of its facilities while carrying out this work. D.J. acknowledges support from the Erasmus+ programme of the European Union under grant number 2020-1-CZ01-KA203-078200. S.D. acknowledges support from the Marie Curie Individual Fellowship under grant ID 890695 and a junior research fellowship at Lucy Cavendish Fellowship. AA’s research is funded by Villum Experiment Grant Cosmic Beacons project number 36225. The MAAT instrument project consists of a partnership of member institutes in Spain (Instituto de Astrofísica de Andalucía CSIC, Instituto de Astrofísica de Canarias), Denmark (DARK, Niels Bohr Institute, University of Copenhagen), and Sweden (The Oskar Klein Centre for Cosmoparticle Physics, Stockholm University).

Pulmonary diseases alter lung mechanical properties, can cause loss of function, and necessitate use of mechanical ventilation, which can be detrimental. Investigations of lung tissue (local) scale mechanical properties are sparse compared to that of the whole organ (global) level, despite connections between regional strain injury and ventilation. We examine ex vivo mouse lung mechanics by investigating strain values, local compliance, tissue surface heterogeneity, and strain evolutionary behavior for various inflation rates and volumes. A custom electromechanical, pressure-volume ventilator is coupled with digital image correlation to measure regional lung strains and associate local to global mechanics by analyzing novel pressure-strain evolutionary measures. Mean strains at 5 breaths per minute (BPM) for applied volumes of 0.3, 0.5, and 0.7 ml are 5.0, 7.8, and 11.3%, respectively, and 4.7, 8.8, and 12.2% for 20 BPM. Similarly, maximum strains among all rate and volume combinations range 10.7%-22.4%. Strain values (mean, range, mode, and maximum) at peak inflation often exhibit significant volume dependencies. Additionally, select evolutionary behavior (e.g., local lung compliance quantification) and tissue heterogeneity show significant volume dependence. Rate dependencies are generally found to be insignificant; however, strain values and surface lobe heterogeneity tend to increase with increasing rates. By quantifying strain evolutionary behavior in relation to pressure-volume measures, we associate time-continuous local to global mouse lung mechanics for the first time and further examine the role of volume and rate dependency. The interplay of multiscale deformations evaluated in this work can offer insights for clinical applications, such as ventilator-induced lung injury.

Type-Ia supernovae (SNe Ia) are among the best standard candles for obtaining an accurate measurement of the Hubble constant (H0) in late times, and can help us to shed light on the reported discrepancy with the estimated value in the opposite edge of the universe, early times. We propose to use NOTCam mounted on the 2.5 m NOT telescope to obtain near-IR photometry of the nearby SNe (z < 0.06) included in our "SN2 Project" sample, and observed in the optical at the Sierra Nevada Observatory (OSN). By including the NIR light curves (LCs) of the SNe we can obtain accurate values of the main luminosity SN parameters. Furthermore, we can determine the extinction curves of the host galaxies for each SN Ia, which is of paramount importance to unravel possible systematics related to their physical properties. The proposed NIR observations and the optical data obtained through the SN2 project allow us to constrain the main physical properties of nearby type-Ia SNe, and provide accurate systematic estimates in the luminosity distance measurements, which will contribute to understanding the origin of the “Hubble tension”.

In the evaluation of any political strategy, it is essential to carry out the collection and analysis of the available data. The presentation of a complex phenomenon by means of synthetic measures ...

We have provided an overview on the profound impact of COVID‐19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health‐care settings, including hospital, out‐patient, care homes, and the community during the COVID‐19 pandemic. We have also proposed a conceptual framework and practical suggestions for health‐care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health‐care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD‐19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.