A Case of Severe Organ Dysfunction and Skin Lesions Due to Methotrexate Toxicity.

Methotrexate is an anti-inflammatory and immunomodulatory drug, widely used for moderate to severe psoriasis and other rheumatological conditions such as rheumatoid arthritis, besides some types of malignancies. Side effects are more prevalent in high acute doses but can also be seen in low-dose chronic use, especially in cases of drug-dosing errors. Possible symptoms of toxicity include gastrointestinal, hepatic, hematologic and renal dysfunctions, but may also include mucositis and worsening of the psoriatic lesions. Here, we describe a case involving methotrexate toxicity in an elderly patient with psoriasis, detailing the management.

The Role of Vitamin D in the Treatment of Carpal Tunnel Syndrome: Clinical and Electroneuromyographic Responses.

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.

Investigation of an Mpox Outbreak Affecting Many Vaccinated Persons in Chicago, Illinois-March 2023-June 2023.

BACKGROUND: After months of few mpox cases, an increase in cases was reported in Chicago during May 2023, predominantly among fully vaccinated (FV) patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. METHODS: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics; mpox vaccine status; and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered the vaccine associated with breakthrough infections. RESULTS: During 18 March-27 June 2023, we identified 49 mpox cases; 57% of these mpox patients were FV. FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3; interquartile range [IQR] = 1-4) versus not fully vaccinated patients (1; IQR = 1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. CONCLUSIONS: Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Sexual Behavior and Sexual Decision-Making Among Gay, Bisexual, and Other Men Who Have Sex with Men During the COVID-19 Pandemic: Observations from a Rapid Ethnographic Assessment in Marion County, Indiana, October-November 2021.

From 2020 to 2021, Marion County, Indiana, USA, saw an increase in early syphilis diagnoses, primarily among gay, bisexual, and other men who have sex with men (GBMSM). This rapid ethnographic assessment combines survey data from GBMSM with data from key informant interviews with multiple groups of stakeholders, including GBMSM, to describe how COVID-19 impacted sexual behaviors, sexual decision-making, and access to sexually transmitted disease (STD) services among GBMSM in Marion County, Indiana. A total of 62 virtual, semi-structured qualitative interviews with 72 key respondents including health department staff, medical providers, community-based organization staff, and GBMSM were conducted from October 14 to November 22, 2021. Modifications to partner-seeking and sexual behaviors attributable to the pandemic were associated with the way in which individuals reacted to the pandemic in general. Some GBMSM adopted mitigation strategies to avoid COVID-19 when meeting sex partners, such as creating a "sex pod." Effects on mental health included increased loneliness, heightened anxiety, and a sense of hopelessness regarding the perceived inevitability of acquiring COVID-19. For some, the latter prompted decreased engagement in preventive measures when engaging in sexual activity. The pandemic decreased access to STD services and significantly curtailed public health outreach efforts, which may have limited access to needed STD treatment and care. Efforts focusing on ongoing public health concerns during extreme health events like COVID-19 may want to consider the many ways these events affect ancillary behaviors, such sexual decision-making and sexual behaviors. The role of mental health is key; messaging and guidance may benefit from a trauma-informed approach.

Oxytocin attenuates microglial activation and restores social and non-social memory in APP/PS1 Alzheimer model mice.

Alzheimer's disease (AD) is characterized by neurodegeneration, memory loss, and social withdrawal. Brain inflammation has emerged as a key pathogenic mechanism in AD. We hypothesized that oxytocin, a pro-social hypothalamic neuropeptide with anti-inflammatory properties, could have therapeutic actions in AD. Here, we investigated oxytocin expression in experimental models of AD, and evaluated the therapeutic potential of treatment with oxytocin. Amyloid-ß peptide oligomers (AßOs) reduced oxytocin expression in vitro and in vivo, and treatment with oxytocin prevented microglial activation induced by AßOs in purified microglial cultures. Treatment of aged APP/PS1 mice, a mouse model of AD, with intranasal oxytocin attenuated microglial activation and favored deposition of Aß in dense core plaques, a potentially neuroprotective mechanism. Remarkably, treatment with oxytocin alleviated social and non-social memory impairments in aged APP/PS1 mice. Our findings point to oxytocin as a potential therapeutic target to reduce brain inflammation and correct memory deficits in AD.

Nearly half of adults with symptoms of sexually transmitted infections (STIs) did not seek clinical care: A population-based study of treatment-seeking behavior among adults in Rakai, Uganda.

Understanding treatment-seeking behavior is critical to the treatment and control of sexually transmitted infections (STIs), yet current data on STI treatment seeking in low-resource settings is rare. This population-based study aimed to describe STI treatment-seeking behavior and identify factors associated with seeking treatment at a clinic among adults with STI-related symptoms in rural Uganda. The STI prevalence study (STIPS) conducted a survey and STI testing among all consenting adults aged 18-49 in two communities in rural south-central Uganda. Of 1,825 participants, 962 individuals self-reported STI symptoms in the past six months; we present descriptive data on treatment seeking and STI prevalence among these individuals. We used multivariable Poisson regressions with robust variance to determine the sociodemographic and symptom-related factors independently associated with seeking STI treatment at a clinic and assessed the association with previous clinic treatment seeking and current STI diagnosis. Forty-three percent of adults who reported STI-related symptoms in the past six months said they did not seek any treatment. Among those who did, 58% sought treatment at a private clinic, 28% at a government clinic, 9% at a pharmacy/drug store, 3% at a traditional healer, 2% at a market/shop, and 5% at another location. Among both males and females, having multiple STI related symptoms was positively associated with clinic treatment seeking (males = PRR: 1.73, 95%CI: 1.36-2.21; females = PR: 1.41, 95%CI: 1.12-1.78). Approximately one-third of males and females who reported previously seeking clinic treatment for their symptoms were diagnosed with a curable STI at the time of the survey. In this setting, nearly half of adults with STI-related symptoms are not seeking clinical care and many who report having sought treatment for recent STI symptoms have curable STIs. Future studies should explore barriers to care-seeking and strategies to improve STI services.

A Sore Subject? An Examination of National Case-Based Chancroid Surveillance.

BACKGROUND: Chancroid has been a nationally notifiable condition in the United States since 1944, with cases reported to Centers Disease Control and Prevention through the National Notifiable Diseases Surveillance System. Although frequently reported during the 1940s, <20 cases have been reported annually since 2011. We assessed the performance and utility of national case-based chancroid surveillance. METHODS: We reviewed the literature to contextualize chancroid surveillance through National Notifiable Diseases Surveillance System. We then assessed 4 system attributes, including data quality, sensitivity, usefulness, and representativeness: we reviewed chancroid cases reported during 2011-2020, conducted interviews with (a) sexually transmitted disease programs reporting ≥1 case in 2019 or 2020 (n = 9) and (b) Centers Disease Control and Prevention subject matter experts (n = 10), and reviewed published communicable disease reporting laws. RESULTS: Chancroid diagnostic testing is limited, which affects the surveillance case definition. National case-based surveillance has poor data quality; of the 2019 and preliminary 2020 cases (n = 14), only 3 were verified by jurisdictions as chancroid cases. Sexually transmitted disease programs report the system has low sensitivity given limited clinician knowledge and resources; experts report the system is not useful in guiding national control efforts. Review of reporting laws revealed it is not representative, as chancroid is not a reportable condition nationwide. CONCLUSIONS: Critical review of system attributes suggest that national case-based chancroid surveillance data have limited ability to help describe and monitor national trends, and chancroid's inclusion on the national notifiable list might need to be reconsidered. Alternative strategies might be needed to monitor national chancroid burden.

Evidence of Mpox Virus Infection Among Persons Without Characteristic Lesions or Rash Presenting for First Dose of JYNNEOS Vaccine-District of Columbia, August 2022.

We assessed mpox virus prevalence in blood, pharyngeal, and rectal specimens among persons without characteristic rash presenting for JYNNEOS vaccine. Our data indicate that the utility of risk-based screening for mpox in persons without skin lesions or rash via pharyngeal swabs, rectal swabs, and/or blood is likely limited.

The Acceptability of Self-Collected Samples for STI Testing: A Qualitative Study Among Adults in Rakai, Uganda.

Introduction: Self-collected samples (SCS) for sexually transmitted infection (STI) testing have been shown to be feasible and acceptable in high-resource settings. However, few studies have assessed the acceptability of SCS for STI testing in a general population in low-resource settings. This study explored the acceptability of SCS among adults in south-central Uganda. Methods: Nested within the Rakai Community Cohort Study, we conducted semi-structured interviews with 36 symptomatic and asymptomatic adults who self-collected samples for STI testing. We analyzed the data using an adapted version of the Framework Method. Results: Overall, participants did not find SCS physically uncomfortable. Reported acceptability did not meaningfully differ by gender or symptom status. Perceived advantages to SCS included increased privacy and confidentiality, gentleness, and efficiency. Disadvantages included the lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic. Most participants preferred provider-collected samples to SCS. Nevertheless, almost all said they would recommend SCS and would do it again in the future. Conclusion: Despite a preference for provider-collection, SCS are acceptable among adults in this setting and support expanded access to STI diagnostic services.

Monkeypox Outbreak - Nine States, May 2022.

On May 17, 2022, the Massachusetts Department of Public Health (MDPH) Laboratory Response Network (LRN) laboratory confirmed the presence of orthopoxvirus DNA via real-time polymerase chain reaction (PCR) from lesion swabs obtained from a Massachusetts resident. Orthopoxviruses include Monkeypox virus, the causative agent of monkeypox. Subsequent real-time PCR testing at CDC on May 18 confirmed that the patient was infected with the West African clade of Monkeypox virus. Since then, confirmed cases* have been reported by nine states. In addition, 28 countries and territories,† none of which has endemic monkeypox, have reported laboratory-confirmed cases. On May 17, CDC, in coordination with state and local jurisdictions, initiated an emergency response to identify, monitor, and investigate additional monkeypox cases in the United States. This response has included releasing a Health Alert Network (HAN) Health Advisory, developing interim public health and clinical recommendations, releasing guidance for LRN testing, hosting clinician and public health partner outreach calls, disseminating health communication messages to the public, developing protocols for use and release of medical countermeasures, and facilitating delivery of vaccine postexposure prophylaxis (PEP) and antivirals that have been stockpiled by the U.S. government for preparedness and response purposes. On May 19, a call center was established to provide guidance to states for the evaluation of possible cases of monkeypox, including recommendations for clinical diagnosis and orthopoxvirus testing. The call center also gathers information about possible cases to identify interjurisdictional linkages. As of May 31, this investigation has identified 17§ cases in the United States; most cases (16) were diagnosed in persons who identify as gay, bisexual, or men who have sex with men (MSM). Ongoing investigation suggests person-to-person community transmission, and CDC urges health departments, clinicians, and the public to remain vigilant, institute appropriate infection prevention and control measures, and notify public health authorities of suspected cases to reduce disease spread. Public health authorities are identifying cases and conducting investigations to determine possible sources and prevent further spread. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.¶.

The Natural Alkaloid Tryptanthrin Induces Apoptosis-like Death in Leishmania spp.

Leishmaniasis is a vector-borne disease against which there are no approved vaccines, and the treatment is based on highly toxic drugs. The alkaloids consist of a chemical class of natural nitrogen-containing substances with a long history of antileishmanial activity. The present study aimed at determining the antileishmanial activity and in silico pharmacokinetic and toxicological potentials of tryptanthrin alkaloid. The anti-Leishmania amazonensis and anti-L. infantum assays were performed against both promastigotes and intracellular amastigotes. Cellular viability was determined by parasites' ability to grow (promastigotes) or differentiate (amastigotes) after incubation with tryptanthrin. The mechanisms of action were explored by mitochondrion dysfunction and apoptosis-like death evaluation. For the computational pharmacokinetics and toxicological analysis (ADMET), tryptanthrin was submitted to the PreADMET webserver. The alkaloid displayed anti-promastigote activity against L. amazonensis and L. infantum (IC50 = 11 and 8.0 µM, respectively). Tryptanthrin was active against intracellular amastigotes with IC50 values of 75 and 115 µM, respectively. Mitochondrial membrane depolarization was observed in tryptanthrin-treated promastigotes. In addition, parasites undergoing apoptosis-like death were detected after 18 h of exposure. In silico ADMET predictions revealed that tryptanthrin has pharmacokinetic and toxicological properties similar to miltefosine. The results presented herein demonstrate that tryptanthrin is an interesting drug candidate against leishmaniasis.

Impaired pulmonary function is associated with dynapenia, but not with abdominal obesity and dynapenic abdominal obesity in older adults.

PURPOSE: No studies have previously analyzed the association between dynapenic abdominal obesity (DAO) and pulmonary function in older adults. The aim of this study was to analyze whether there is an association between pulmonary function and abdominal obesity, dynapenia, and DAO in community-dwelling older adults. METHODS: A cross-sectional study was conducted with community-dwelling older adults (n = 383) of Macapá, Amapá, Brazil. Pulmonary function variables were evaluated with spirometry; and DAO was evaluated with the combination of dynapenia and abdominal obesity. Cutoff points for handgrip strength, 26 kg force for men and 16 kg force for women, were used to detect dynapenia; and cutoff points of abdominal circumference of > 102 cm for men and > 88 cm for women were used to identify abdominal obesity. RESULTS: Most of the studied pulmonary function variables (obtained values and obtained versus predicted values) were associated with abdominal obesity, dynapenia, and DAO. However, in the adjusted model, there was an association of FVC (ß = - 0.163; p < 0.001), FEV1 (ß = - 0.119; p = 0.006), and PEF (ß = - 0.110; p = 0.017) only with dynapenia. CONCLUSIONS: Older adults with abdominal obesity, dynapenia, and DAO presented impaired pulmonary function when compared to those without these conditions. Most of the pulmonary function variables were associated with abdominal obesity, dynapenia, and DAO conditions. However, in the adjusted model, there was an association of reduced FVC, FEV1, and PEF values only with dynapenia.

New Hybrid Copper Nanoparticles/Conjugated Polyelectrolyte Composite with Antibacterial Activity.

In the search for new materials to fight against antibiotic-resistant bacteria, a hybrid composite from metallic copper nanoparticles (CuNPs) and a novel cationic π-conjugated polyelectrolyte (CPE) were designed, synthesized, and characterized. The CuNPs were prepared by chemical reduction in the presence of CPE, which acts as a stabilizing agent. Spectroscopic analysis and electron microscopy showed the distinctive band of the metallic CuNP surface plasmon and their random distribution on the CPE laminar surface, respectively. Theoretical calculations on CuNP/CPE deposits suggest that the interaction between both materials occurs through polyelectrolyte side chains, with a small contribution of its backbone electron density. The CuNP/CPE composite showed antibacterial activity against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative (Escherichia coli and Salmonella enteritidis) bacteria, mainly attributed to the CuNPs' effect and, to a lesser extent, to the cationic CPE.

Adenovirus-Mediated Transduction of Insulin-Like Growth Factor 1 Protects Hippocampal Neurons from the Toxicity of Aß Oligomers and Prevents Memory Loss in an Alzheimer Mouse Model.

Alzheimer's disease (AD) is the main cause of dementia in the elderly. Although activation of brain insulin signaling has been shown to be neuroprotective, to preserve memory in AD models, and appears beneficial in patients, the role of insulin-like growth factor 1 (IGF1) remains incompletely understood. We found reduced active/inactive IGF1 ratio and increased IGF1R expression in postmortem hippocampal tissue from AD patients, suggesting impaired brain IGF1 signaling in AD. Active/inactive IGF-1 ratio was also reduced in the brains of mouse models of AD. We next investigated the possible protective role of IGF1 in AD models. We used a recombinant adenoviral vector, RAd-IGF1, to drive the expression of IGF1 in primary hippocampal neuronal cultures prior to exposure to AßOs, toxins that accumulate in AD brains and have been implicated in early synapse dysfunction and memory impairment. Cultures transduced with RAd-IGF1 showed decreased binding of AßOs to neurons and were protected against AßO-induced neuronal oxidative stress and loss of dendritic spines. Significantly, in vivo transduction with RAd-IGF1 blocked memory impairment caused by intracerebroventricular (i.c.v.) infusion of AßOs in mice. Our results demonstrate altered active IGF1 and IGF1R levels in AD hippocampi, and suggest that boosting brain expression of IGF1 may comprise an approach to prevent neuronal damage and memory loss in AD.

Home tonometry in childhood glaucoma: clinical indications and physician and parental attitudes.

Home rebound tonometry is a beneficial tool for the management of childhood glaucoma, yet is not commonly used. In this study, 29 childhood glaucoma patients were recruited for twice daily home intraocular pressure (IOP) monitoring using an Icare rebound tonometer. Home rebound tonometry data prompted and/or validated glaucoma-related surgery in 16 patients (55%) and medication change in 22 patients (76%). According to survey responses, 84% of parents or patients (n = 83) would be interested in home tonometry, and 80% of physicians (n = 48) agreed that home tonometry would improve their ability to manage patients; however, only 14% of physicians currently lend tonometers for this purpose, largely due to financial concerns.

Natural history of asymptomatic gallstones: differential behaviour in male and female subjects.

OBJECTIVE: The natural history of asymptomatic (silent) gallstones has been inadequately studied. Existing information derives from studies based on oral cholecystography or relatively small sample sizes. We planned a retrospective cohort study in subjects with gallstones to determine conversion rates from asymptomatic to symptomatic. METHODS: We extracted data from computerised databases of one government hospital and two private clinics in Malaysia. Files were scrutinised to ensure that criteria for asymptomatic gallstones were fulfilled. Patients were called on telephone, further questioned to confirm that the gallstones at detection were truly asymptomatic, and asked about symptoms that were consistent with previously defined criteria for biliary colic. Appropriate ethical clearances were taken. RESULTS: 213 (112 males) patients fulfilled the criteria for asymptomatic gallstones and could be contacted. 23 (10.8%) developed pain after an average follow up interval of 4.02 years (range 0.1-11 years). Conversion rates from asymptomatic to symptomatic gallstones were high in the first two years of follow up, averaging 4.03±0.965 per year. Over time the conversion rates slowed, and by year 10 the annual conversion rate averaged only 1.38±0.29. Conversion rates were much higher for females compared to males (F:M hazard ratio 3.23, SE 1.54, p>z 0.014). The lifetime risks for conversion approached 6.15% for males, and 22.1% for females. CONCLUSION: In conclusion, asymptomatic gallstones are much more likely to convert to symptomatic in females than in males. Males in whom asymptomatic stones are discovered should be advised conservative treatment. Surgery may be preferable to conservative management if the subject is a young female.