Deep-Sea Sponges and Corals off the Western Coast of Florida-Intracellular Mechanisms of Action of Bioactive Compounds and Technological Advances Supporting the Drug Discovery Pipeline.

The majority of natural products utilized to treat a diverse array of human conditions and diseases are derived from terrestrial sources. In recent years, marine ecosystems have proven to be a valuable resource of diverse natural products that are generated to defend and support their growth. Such marine sources offer a large opportunity for the identification of novel compounds that may guide the future development of new drugs and therapies. Using the National Oceanic and Atmospheric Administration (NOAA) portal, we explore deep-sea coral and sponge species inhabiting a segment of the U.S. Exclusive Economic Zone, specifically off the western coast of Florida. This area spans ~100,000 km2, containing coral and sponge species at sea depths up to 3000 m. Utilizing PubMed, we uncovered current knowledge on and gaps across a subset of these sessile organisms with regards to their natural products and mechanisms of altering cytoskeleton, protein trafficking, and signaling pathways. Since the exploitation of such marine organisms could disrupt the marine ecosystem leading to supply issues that would limit the quantities of bioactive compounds, we surveyed methods and technological advances that are necessary for sustaining the drug discovery pipeline including in vitro aquaculture systems and preserving our natural ecological community in the future. Collectively, our efforts establish the foundation for supporting future research on the identification of marine-based natural products and their mechanism of action to develop novel drugs and therapies for improving treatment regimens of human conditions and diseases.

Bipolar Disorder in Social Media: An Examination of Instagram's Role in Disseminating Accurate Information.

Introduction Bipolar disorder is a chronic and recurring condition marked by fluctuations in both energy and mood that can be debilitating to individuals without treatment. While physicians clinically diagnose the condition, patients frequently seek information from alternate channels. Social media platforms, such as Instagram, have facilitated more convenient access to supplementary information about bipolar disorder. Nevertheless, there is apprehension regarding the accuracy of publicly disseminated information through these platforms. The aim of this study is to evaluate the accuracy and dependability of information about Bipolar disorder found on the social media platform, Instagram. Methodology A cross-sectional observational study was conducted by gathering data from Instagram posts linked with popular bipolar disorder hashtags. To evaluate the credibility of the chosen entries, numerical ratings were assigned to each post using the established measurement scales of the Global Quality Score and Reliability Score. Results After analyzing 196 Instagram entries about Bipolar Disorder that fulfilled inclusion criteria, the study revealed that 70.4% (n=138) of these posts were shared by individuals diagnosed with bipolar disorder. Among the content posted by these individuals, a statistically significant global quality score of 2 and a reliability score of 1 were observed. Conclusions Verified medical information of superior global quality should be shared on social media platforms by accountable parties. Individuals with further inquiries about medical knowledge should be advised to reach out to local physicians.

A Very Unusual Presentation of Miliary Tuberculosis and Osteomyelitis as an Incidental Finding of Musculoskeletal Pain.

Tuberculosis (TB) is a highly infectious disease that takes the primary or latent route. In primary TB, the patient often presents with constitutional symptoms such as cough, fever, weight loss, and hemoptysis. This 83-year-old patient was sent to the emergency department (ED) by her primary care physician after abnormal imaging for acute back and neck pain. Imaging revealed pulmonary TB with possible tuberculosis osteomyelitis versus metastatic carcinoma to the cervical vertebrae. The case's unique presentation gives light to the need for more research on miliary TB and tuberculosis spondylitis/osteomyelitis in various populations and circumstances to ensure prompt and adequate patient care.

A Review of Pediatric Central Line-Associated Bloodstream Infections Reported to the National Healthcare Safety Network: United States, 2016-2022.

Central line-associated bloodstream infections (CLABSIs) are common healthcare-associated infections in pediatrics. Children's hospital CLABSI standardized infection ratios decreased when comparing 2016-2019 (-26%, 95% CI [-31%, -20%]), and increased from 2019 to 2022 (18%, 95% CI [9%, 26%]). Resilient pediatric CLABSI prevention initiatives are needed.

HIV Patient With a Complicated and Unique Presentation of the Monkeypox Virus.

Monkeypox virus presents a concerning challenge, as it is known for its ability to spread through a diverse range of transmission routes, including established pathways like direct contact and shared living spaces, with the spectrum of potential methods appearing to be limitless. This immunocompromised 43-year-old HIV patient presented to the emergency department (ED) in the United States with shortness of breath, cough, and painful lesions for several months. Numerous consults and a full panel of testing revealed an odd case of the monkeypox virus that strayed away from the predefined classifications for the disease. The case sheds light on the need for further research in immunocompromised patient populations as their presentations may be different from what research currently suggests.

NT-proBNP as a neuroendocrine tumor biomarker: beyond heart failure.

Introduction: Neuroendocrine tumors (NETs) are rare neoplasms that occur in various locations throughout the body. Despite their usually benign character, they might manifest with distant metastases. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) has previously been described as a useful biomarker in diagnosing carcinoid heart disease (CHD), a common advanced NETs manifestation. We observed plasma concentrations of NT-proBNP in metastatic midgut NETs over a 4-year period. Objectives: We aimed to explore NT-proBNP concentrations in states of varying levels of cell proliferation and disease status. Our goal was to investigate NT-proBNP's role in predicting disease progression in relation to previous research and up-to-date scientific guidelines. Patients and methods: We performed a retrospective multivariate analysis of NT-proBNP concentrations in 41 midgut NETs patients treated with somatostatin analogs, all with liver metastases. NT-proBNP concentrations were measured in every patient across 16 evenly distanced time points over a 48-month period and were compared to variables such as sex, age, grading, Ki-67, primary tumor location, and CT findings. Results: NT-proBNP concentrations correlated positively with higher liver tumor burden, higher grading, high Ki-67 levels, and with progressive disease in CT. There were no differences in NT-proBNP levels with regard to primary location (ileum vs jejunum), sex, and age. Conclusion: We conclude that NT-proBNP is a useful analyte for monitoring NETs progression, due to its increased concentration in scenarios implying increased cellular proliferation. These long-term follow-up results align with previous findings and suggest an additional role for NT-proBNP in diagnostic algorithms, beyond a CHD biomarker.

Sepsis Program Activities in Acute Care Hospitals - National Healthcare Safety Network, United States, 2022.

Sepsis, life-threatening organ dysfunction secondary to infection, contributes to at least 1.7 million adult hospitalizations and at least 350,000 deaths annually in the United States. Sepsis care is complex, requiring the coordination of multiple hospital departments and disciplines. Sepsis programs can coordinate these efforts to optimize patient outcomes. The 2022 National Healthcare Safety Network (NHSN) annual survey evaluated the prevalence and characteristics of sepsis programs in acute care hospitals. Among 5,221 hospitals, 3,787 (73%) reported having a committee that monitors and reviews sepsis care. Prevalence of these committees varied by hospital size, ranging from 53% among hospitals with 0-25 beds to 95% among hospitals with >500 beds. Fifty-five percent of all hospitals provided dedicated time (including assigned protected time or job description requirements) for leaders of these committees to manage a program and conduct daily activities, and 55% of committees reported involvement with antibiotic stewardship programs. These data highlight opportunities, particularly in smaller hospitals, to improve the care and outcomes of patients with sepsis in the United States by ensuring that all hospitals have sepsis programs with protected time for program leaders, engagement of medical specialists, and integration with antimicrobial stewardship programs. CDC's Hospital Sepsis Program Core Elements provides a guide to assist hospitals in developing and implementing effective sepsis programs that complement and facilitate the implementation of existing clinical guidelines and improve patient care. Future NHSN annual surveys will monitor uptake of these sepsis core elements.

A comprehensive study on Industry 4.0 in the pharmaceutical industry for sustainable development.

The four evolutionary stages have brought us to Industry 4.0. Industry 4.0 is nothing but the 4th Industrial Revolution which will change the production processes. The implementation of Industry 4.0 in the pharmaceutical sector will make the manufacturing of complex drugs easier. The arrival of Industry 4.0 and its advanced technologies such as artificial intelligence (AI), robotics, and the Internet of Things (IoT) makes the processes flexible. Industry 4.0 was introduced to reduce the human workforce and make the complicated processes unchallenging. It is used in all aspects of pharmaceutical sector like analysis, diagnosis, manufacturing, and packaging. The main aim of this paper is to comprehensively elucidate how Industry 4.0 has played a significant role in sustainable development (SD). Industry 4.0 in sustainability decreases the research efforts and examines the research sector's opportunities. This paper also discusses the impact of Industry 4.0 on sustainable development. Industry 4.0 constructs a bridge between industry and sustainability leading to sustainable development. Sustainability can be achieved by adopting innovative techniques of Industry 4.0 in manufacturing. Moreover, Industry 4.0 provides potential benefits for enhancing pharmaceutical production concerning flexibility, expenses, standards, and safety. It is noticed that Industry 4.0 has a beneficial impact on sustainable development by implementing advanced technologies leading to flexible manufacturing processes.

Massive Life-Threatening Saddle Pulmonary Embolism in a Healthy 28-Year-Old.

When Virchow's triad is disrupted, a deep vein thrombosis (DVT) can often occur and progress into a pulmonary embolism, and in rare cases, a saddle pulmonary embolism. This 28-year-old male patient showed up at the emergency department (ED) with shortness of breath, chest palpitations, and right calf pain. Additional imaging showed a massive saddle pulmonary embolism, and he was taken to immediate right femoral catheterization for thrombectomy. Though this patient presents with no known risk factors in his history or workup, he stretches the predefined boundaries with his cavalier presentation.

Chemical neurolysis of the genicular nerves for chronic refractory knee pain: an observational cohort study.

OBJECTIVE: Evaluate outcomes of genicular nerve chemical neurolysis (GChN) in a real-world population with chronic knee pain. DESIGN: Restrospective, observational cohort study. SETTING: Tertiary academic medical center. SUBJECTS: Consecutive patients who had undergone GChN ≥3 months prior. METHODS: Standardized surveys were collected by telephone and included the numerical rating scale, opioid analgesic use, and Patient Global Impression of Change. Age, sex, body mass index, duration of pain, history of arthroplasty, lack of effect from previous radiofrequency ablation, percentage relief from a prognostic block, and volume of phenol used at each injection site were extracted from charts. Descriptive statistics were calculated, and logistic regression analyses were performed to identify factors influencing treatment outcome. RESULTS: At the time of follow-up after GChN (mean ± SD: 9.9 ± 6.1 months), 43.5% (95% CI = 33.5-54.1) of participants reported ≥50% sustained pain reduction. On the Patient Global Impression of Change assessment, 45.9% (95% CI = 35.5-56.7) of participants reported themselves to be "very much improved" or "much improved." Of 40 participants taking opioids at baseline, 11 (27.5%; 95% CI = 14.6-43.9) ceased use. Of participants with a native knee treated, 46.3% reported ≥50% pain reduction, whereas of participants with an arthroplasty in the treated knee, 33.3% reported this threshold of pain reduction (P = .326). Logistic regression analyses did not reveal associations between treatment success and any of the factors that we evaluated. CONCLUSIONS: GChN could provide a robust and durable treatment effect in a subset of individuals with chronic knee pain with complicating factors traditionally associated with poor treatment outcomes, such as those with pain refractory to radiofrequency ablation or those who have undergone arthroplasty.

Sex work, gender transition, family rejection and depressive symptoms among transgender women in India.

Background: Transgender women in India face unique stressors associated with minority experiences, such as experiences of gender transition and participation in sex work. However, the relationship between sex work, transition and mental health outcomes is understudied in this population. Aims: This article aims to examine the association between gender transition status, sex work, family rejection and depressive symptoms among transgender women in India. Methods: Data comes from a cross-sectional epidemiological study with transgender women from three states of India; Karnataka, Maharashtra and Tamil Nadu (N = 1366). Multivariate regressions were used to examine the association between sex work status and gender transition and how gender transition, and sex work are associated with depressive symptoms. Results: 70% of the sample reported being in sex work and over 82% endorsed taking some form of gender transition service. Those who reported being in sex work were significantly more likely to have undergone breast augmentation, hormonal therapy and gender affirming surgery. Those who reported ever being married were less likely to report gender affirming surgery and were more likely to report hormonal therapy. Additionally, being in sex work, undergoing transition, leaving home because of sexual orientation, and being married were significantly associated with depressive symptoms. Discussion: Community-led organizations and other service agencies must incorporate intersectional experiences and identities, including sex work and gender transition, in their programs to further social and health justice for transgender women in India. Policy and programmatic implications are discussed. Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1939220.

Black fungus outbreak in India - A direct consequence of COVID-19 surge: A myth or reality.

The deadly second wave of COVID-19 has seen an unprecedented surge in mucormycosis associated mortality in India, overwhelming the heath authorities with challenges beyond measure. Also known as black fungus, this life-threatening fungal infection usually manifests in the nose, spreads to the eyes, and in some cases also to the brain. Immune suppression, pre-existing conditions, prolonged and indiscriminate use of steroids, and unhygienic environments are some of the widely recognized risk factors for contracting black fungus in individuals recovered from COVID-19. However, diagnosis of the infection remains insufficient due to the lack a holistic understanding of the possible risks, symptoms, and exposure pathways and therefore no definite protocol exists for managing this fatal infection. Here, we synthesize the current state of knowledge on black fungus outbreak in India and identify key gaps in its understanding with respect to potential risk factors leading to the widespread infection. We looked at 3354 black fungus cases in India, enlisting ailment history (particularly diabetes) and steroid usage in COVID-19 patients as the key factors responsible for exacerbating risks associated with the disease. However, we also press on the possibilities that other less studied non-traditional risk factors may also have a role in causing the infection. Black fungus is therefore a reality of COVID-19, with or without diabetes or steroid use needs to be investigated. We believe such a review is imperative for making informed decisions specially around timely diagnosis and channelizing efforts in controlling the spread of COVID-19 associated mucormycosis.

Continued increases in the incidence of healthcare-associated infection (HAI) during the second year of the coronavirus disease 2019 (COVID-19) pandemic.

Data from the National Healthcare Safety Network were analyzed to assess the impact of COVID-19 on the incidence of healthcare-associated infections (HAI) during 2021. Standardized infection ratios were significantly higher than those during the prepandemic period, particularly during 2021-Q1 and 2021-Q3. The incidence of HAI was elevated during periods of high COVID-19 hospitalizations.

Hemoglobin Wayne: A Rare Variant That Can Cause Falsely Elevated Hemoglobin A1c.

Hemoglobin A1c (HbA1c) can be unreliable (falsely elevated or lowered) in certain conditions, including hemoglobinopathies, anemia, lead poisoning, chronic alcoholism, and opioid use. Hemoglobin Wayne is a rare variant of hemoglobin (Hgb) that can also result in a false elevation of HbA1c. Hence, clinicians should be aware of these underlying causes before diagnosing and treating diabetes mellitus to avoid unexpected consequences. We are reporting a case of falsely elevated HbA1c in a female in her early 60s due to a rare variant of Hgb called hemoglobin Wayne. The patient presented with a consistently elevated HbA1c ranging from 10.3% to 10.7% for two years, which did not correlate with her fasting blood glucose levels ranging between 80 and 100. The continuous glucose monitoring (CGM) profile was also within the normal range. The hemoglobin electrophoresis technique was used to confirm the diagnosis of hemoglobin Wayne in this patient and the initial treatment of metformin was discontinued upon confirmation.

Interaction of bottom-up and top-down neural mechanisms in spatial multi-talker speech perception.

How the human auditory cortex represents spatially separated simultaneous talkers and how talkers' locations and voices modulate the neural representations of attended and unattended speech are unclear. Here, we measured the neural responses from electrodes implanted in neurosurgical patients as they performed single-talker and multi-talker speech perception tasks. We found that spatial separation between talkers caused a preferential encoding of the contralateral speech in Heschl's gyrus (HG), planum temporale (PT), and superior temporal gyrus (STG). Location and spectrotemporal features were encoded in different aspects of the neural response. Specifically, the talker's location changed the mean response level, whereas the talker's spectrotemporal features altered the variation of response around response's baseline. These components were differentially modulated by the attended talker's voice or location, which improved the population decoding of attended speech features. Attentional modulation due to the talker's voice only appeared in the auditory areas with longer latencies, but attentional modulation due to location was present throughout. Our results show that spatial multi-talker speech perception relies upon a separable pre-attentive neural representation, which could be further tuned by top-down attention to the location and voice of the talker.

Surgical Outcomes of Endoscopic Transsphenoidal Pituitary Adenoma Resection in Elderly Versus Younger Patients.

Introduction Pituitary adenomas (PAs) are one of the most common types of intracranial neoplasm with increased incidence in elderly patients. The outcomes of endoscopic transsphenoidal surgery (ETS) specifically on elderly patients remain unclear. Methods We performed a retrospective cohort study to compare elderly patients (age ≥65 years) with nonelderly patients (age <65 years) who underwent ETS for PA from January 2005 to December 2020. Surgical outcomes, including extent of resection, complication profile, length of stay, and endocrinopathy rates, were compared between elderly and nonelderly patients. Results A total of 690 patients were included, with 197 (29%) being elderly patients. Elderly patients showed higher rates of hypertension ( p < 0.05), myocardial infarction ( p < 0.01), and atrial fibrillation ( p = 0.01) but not other comorbidities. Elderly patients also had more frequent optic nerve involvement (72 vs. 61% of cases, p = 0.01). Tumor characteristics and other patient variables were otherwise similar between younger and elderly patients. Postoperative cerebrospinal fluid (CSF) leaks (2 vs. 2%, p = 0.8), 30-day readmission, reoperation, postoperative complications, and postoperative endocrinopathies were similar between younger and older patients. Subdividing patients into age <65, 65 to 79, and >80 years also did not demonstrate a worsening of surgical outcomes with age. Conclusion For well-selected elderly patients in experienced endoscopic skull base centers, good surgical outcomes similarly to younger patients may be achieved.