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Introduction: In an interview-based study performed by our lab of women who use methamphetamine (meth), we previously found that the drug, when delivered intravenously (IV), produces a feeling indistinguishable from an orgasm, which is accompanied by a flushing sensation and the production of excessive vaginal lubrication. We have also reported meth-induced vaginal lubrication in an anesthetized animal model. This production of vaginal transudate was dependent on the dose of meth used and the potent vasodilator nitric oxide. Objective: The objective of the current study was to assess meth-induced vaginal lubrication across different stages of the estrous cycle and following ovariectomy (ovx) in anesthetized rats, and to assess plasma levels of two signaling molecules associated with sexual arousal. Methods: Anesthetized rats, each previously implanted with a chronic indwelling jugular catheter, were anesthetized and given one IV infusion of meth (0.24 mg/kg) and vaginal lubrication was measured. A pre-weighed cotton-tipped swab, inserted into the vaginal canal, collected fluid secreted following the administration of meth. Blood was withdrawn before and at ten and fifteen minutes after meth administration either via the jugular catheter or via a small tail snip to measure plasma levels of estradiol and nitric oxide. Testing was completed at each stage of the estrous cycle as well as before and after ovariectomy. Results: Estradiol and nitric oxide increased following meth infusion similarly across all stages of the estrous cycle. Vaginal lubrication increased more with meth treatment than with saline treatment. This was true across all stages of the estrous cycle and despite ovariectomy. Conclusions: These findings have far-reaching implications for those who suffer from vaginal dryness. The mechanism underlying this phenomenon may present a novel pharmacotherapeutic target to treat vaginal dryness. Since meth still produced vaginal secretions in anesthetized rats, these results suggest that targeting this mechanism may even prove beneficial in post-menopausal women, a patient group likely at highest risk for experiencing vaginal dryness. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Embera Neuurotherapeutics & JanOne. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms within this physiology. Previous research from our lab has demonstrated that female methamphetamine (meth) users experience the immediate production of excessive vaginal lubrication, accompanied by a warmth or flushing sensation spreading from the chest areas to the pelvic region, when using the drug intravenously (IV). The physiological source of this previously undescribed effect of meth could present a potential mechanism to enhance a woman's natural production of vaginal lubrication, providing a potentially life-changing option to patients experiencing vaginal dryness. Objectives: The purpose of the current study was to determine if vaginal lubrication induced by IV meth use reported in a previous study from our lab occurs in rats, and if this effect is dose-dependent. This study also sought to begin to uncover the mechanism behind this phenomenon. Methods: Adult female Wistar rats (n=8) were implanted with chronic indwelling jugular catheters and allowed at least one week to recover from surgery. Rats anesthetized with isoflurane gas were intravenously infused with one of seven doses of meth ranging from 0.015-0.96 mg/kg meth or saline IV via the implanted catheter. Pre-weighed cotton-tipped swabs inserted into the vaginal canal collected fluid secreted following drug administration. The change in weight of the swab was taken as the weight of fluid produced. Consequent studies examined several signaling molecules in plasma known to have an influence on vaginal lubrication, including the steroid hormones estradiol, progesterone and testosterone, as well as the gaseous vasodilator nitric oxide. These molecules were measured at time points up to 60 minutes after meth administration. Results: As hypothesized, meth increased vaginal lubrication in a dose-dependent manner. Doses of 0.06 and 0.24 mg/kg of meth induced significant increases in vaginal lubrication compared to saline. Further, compared to pre-meth levels, significant increases in estradiol were seen at two and 15 minutes after meth administration. Significant increases in progesterone, testosterone and nitric oxide were seen ten minutes after meth administration. Conclusions: This study has far-reaching implications since the majority of women will experience vaginal dryness at least once, if not recurrently. The underlying mechanism of meth-induced vaginal lubrication, when elucidated, may provide a pharmacological target in treating not only meth use disorder, but also the millions of women suffering from vaginal dryness. Disclosure: No. [ABSTRACT FROM AUTHOR]

Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance. [ABSTRACT FROM AUTHOR]

We describe the case of a returned traveler to the United States from Ecuador who had an acute febrile illness, initially diagnosed as Oropouche fever. This illness was later confirmed to be a rare infection with Iquitos virus, a related bunyavirus that shares 2 of 3 genome segments with Oropouche virus.

Background: Familiarity breeds complacency. One case of sore throat can start to sound like another. However, even common viral and bacterial infections can lead to serious sequelae. Clinicians cannot make a diagnosis if they do not consider it in their differential. Case: The presentation - and subsequent hospitalization - of a septic 19 year-old male college student is described. Despite brief interval improvement, he became hypoxic one week after developing a sore throat and was ultimately diagnosed with Lemierre's syndrome (septic thrombophlebitis of the internal jugular vein) via blood cultures and advanced imaging. Conclusions: Though rare, Lemierre's syndrome carries a high mortality rate. It should be considered an emergent complication of head and neck infections, particularly in young adults.

Background: African Americans chronically managing their diabetes benefit from receiving support from peers with shared experiences. Peer support is known to improve the well-being of individuals receiving support, however, there is limited literature on the experiences of those providing the support. The Peers Supporting Health Literacy, Self-efficacy, Self-Advocacy, and Adherence (Peers LEAD) program pairs Peer Ambassadors who are adherent to their diabetes medication, with Peer Buddies who need support with their medication adherence. Peer Ambassadors engage with Peer Buddies as they receive diabetes information, develop the skills and motivation to address identified psychosocial/sociocultural issues to enhance their diabetes medication adherence. This study qualitatively explores the experiences of African Americans who provided peer support in the Peers LEAD medication adherence intervention., Methods: Two focus groups were conducted with twelve Peer Ambassadors to explore their experiences of providing peer support in the Peers LEAD medication adherence intervention. Qualitative content analysis was conducted using an inductive open coding approach., Results: Emergent themes provided insight into Peer Ambassador' rationale for providing peer support and the benefits and challenges they experienced in their roles. Themes regarding their rationale included: their desire to receive support for their diabetes self-management as well as to contribute to their communities in reducing the stigma associated with diabetes. The perceived benefits they gained centered on creating interpersonal connections, experiencing personal growth as they adapted to their roles, and experiencing opportunities to contribute to an intervention regardless of professional training. Peer Ambassadors reflected on the challenges which included difficulties on coming to terms with their role as Peer Ambassadors, seeing African Americans experience complications associated with diabetes, and navigating supporting Peer Buddies who are also burdened with the challenges their family members are experiencing with managing their diabetes., Conclusions: This study provides unique insight to what motivates individuals to provide peer support and what they gain from these experiences despite the challenges. Understanding the experiences of peers participating in such interventions may help inform the structure and content of programs that use peer support to focus on the benefits of and the motivation for participating in the program., (© 2023. The Author(s).)

Background: African Americans are twice as likely to die from diabetes, compared to other racial and ethnic groups in the USA. Poor adherence to diabetes medications is common among African Americans and contributes to these disproportionally worse outcomes. A pilot study was conducted to determine the feasibility and acceptability of a peer-supported intervention targeting diabetes and medication beliefs, communication, and self-efficacy skills to enhance medication adherence among African Americans with type 2 diabetes., Methods: Based on the extended self-regulatory model and information-motivation-behavioral skills model, this intervention was piloted using a single group pre/post-intervention study design at two sites. Seventeen African Americans who self-reported as adherent to diabetes medicines (ambassadors) were paired with 22 African Americans with self-reported poor medication adherence (buddies). Feasibility outcomes evaluated recruitment, retention, and intervention adherence. Measures assessed at baseline and 1-month post-intervention included glycemic control (hemoglobin A1c), self-reported medication adherence, diabetes beliefs, concerns about diabetes medicines, and diabetes self-efficacy. Wilcoxon signed-rank tests assessed for differences in mean scores of outcome variables at baseline compared with a 3-month follow-up. Semi-structured 60-min interviews were conducted with each buddy to explore their acceptability of the intervention. To ensure the rigor of the qualitative data, we focused on analytic criteria such as credibility, confirmability, and transferability., Results: Most buddies and ambassadors were female and about 56 years old. Feasibility outcomes included recruitment success rates of 73% for buddies and 85% for ambassadors relative to our goals. Retention rate for hemoglobin A1c and medication adherence outcome assessment was 95% for buddies. Both buddies and ambassadors had excellent intervention adherence, with buddies having a mean attendance of 7.76 out of 8 sessions/phone calls and ambassadors completing > 99% of the 105 intervention calls with Buddies. Results showed a signal of change in hemoglobin A1c (effect size = 0.14) and medication adherence (effect size = 0.35) among buddies, reduction in buddies' negative beliefs about diabetes and an increase in necessity beliefs of diabetes medicines. Summative interviews with buddies showed they valued ambassador's encouragement of self-management behaviors., Conclusions: Results support conduct of an efficacy trial to address medication adherence for African Americans with type 2 diabetes using a peer-supported tailored intervention., Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04028076 ., (© 2022. The Author(s).)

Background: Meningitis remains an important cause of morbi-mortality in adults in sub-Saharan Africa. Data on the etiological investigation of meningitis in adults in Mozambique is limited and most studies were conducted in southern Mozambique. Identification of the etiology of meningitis in adults are crucial to guide prevention and treatments strategies. In this study, we determine the burden of fungal and bacterial meningitis among adults at the three largest hospitals in Mozambique., Method: We performed analysis of data from the routine sentinel surveillance system for meningitis in Mozambique from January 2016 to December 2017. Cerebrospinal fluid (CSF) samples were collected from eligible adults (≥18 years old) who met World Health Organization (WHO) case definition criteria for Meningitis. All samples were tested by cryptococcal antigen (CrAg) lateral flow assay (LFA), culture and triplex real-time polymerase chain reaction (qPCR) assay and all patients were tested for human immunodeficiency virus (HIV) using the national algorithm for HIV testing., Results: Retrospective analysis of 1501 CSF samples from adults clinically suspected of meningitis revealed that 10.5% (158/1501) were positive for bacterial and fungal meningitis. Of these 158 confirmed cases, the proportion of Cryptococcal meningitis and pneumococcal meningitis was38.6% (95% CI: 31.0% to 46.7%) and 36.7% (95% CI: 29.2% to 44.7%), respectively. The other bacterial agents of meningitis identified include Neisseria meningitidis (8.9%; 14/158), Escherichia coli (6.3%; 10/158), Haemophilus influenzae (5.1%; 8/158) and S. aureus (4.4%; 7/158), which represent (24.7%; 39/158) of the total confirmed cases., Conclusion: Altogether, our findings show a high burden of Cryptococcal meningitis among adults in Mozambique, especially in people living with HIV, followed by pneumococcal meningitis. Our findings suggest that rollout of CrAg Lateral Flow Assay in the health system in Mozambique for early detection of cryptococcus neoformans is necessary to improve overall patient care., Competing Interests: The authors have declared that no competing interests exist.

Interactive narrative technologies for preventive health care offer significant potential for promoting health behavior change in adolescents. By improving adolescents' knowledge, personal efficacy, and self-regulatory skills these technologies hold great promise for realizing positive impacts on adolescent health. These potential benefits are enabled through story-centric learning experiences that provide opportunities for adolescents to practice strategies to reduce risky health behaviors in engaging game-based environments. A distinctive feature of interactive narrative that promotes engagement is players' ability to influence the story through the choices they make. In this paper, we present initial work investigating engagement in an interactive narrative that focuses on reducing adolescents' risky behaviors around alcohol use. Specifically, we consider how the short-term and long-term goals adolescents choose as being important to the protagonist character relates to their engagement with the interactive narrative. Leveraging interaction log data from a pilot study with 20 adolescents, we conduct a cluster-based analysis of the goals players selected. We then examine how engagement differs between the identified clusters. Results indicate that adolescents' choices for the protagonist's short-term and long-term goals can significantly impact their engagement with the interactive narrative.

Event-related potentials (ERPs) were used to explore the effects of iconicity and structural visual alignment between a picture-prime and a sign-target in a picture-sign matching task in American Sign Language (ASL). Half the targets were iconic signs and were presented after a) a matching visually-aligned picture (e.g., the shape and location of the hands in the sign COW align with the depiction of a cow with visible horns), b) a matching visually-nonaligned picture (e.g., the cow's horns were not clearly shown), and c) a non-matching picture (e.g., a picture of a swing instead of a cow). The other half of the targets were filler signs. Trials in the matching condition were responded to faster than those in the non-matching condition and were associated with smaller N400 amplitudes in deaf ASL signers. These effects were also observed for hearing non-signers performing the same task with spoken-English targets. Trials where the picture-prime was aligned with the sign target were responded to faster than non-aligned trials and were associated with a reduced P3 amplitude rather than a reduced N400, suggesting that picture-sign alignment facilitated the decision process, rather than lexical access. These ERP and behavioral effects of alignment were found only for the ASL signers. The results indicate that iconicity effects on sign comprehension may reflect a task-dependent strategic use of iconicity, rather than facilitation of lexical access., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

Fowl aviadenovirus (FAdV) species D and E are associated with inclusion body hepatitis (IBH); species C, serotype 4 (hereafter, FAdV4) is associated with hepatitis-hydropericardium syndrome (HHS) in young chickens. Outbreaks of HHS have led to significant losses in the poultry industry in several countries, predominantly in China. In April 2020, FAdV4 was detected in a remote backyard flock in California. In a mixed flock of chickens of various breeds and ages (6 mo to 2 y old), 7 of 30 were found dead within a week without premonitory signs. One additional bird died after the flock was relocated to fresh pasture, bringing the total mortality to 8 of 30 (27%). Postmortem examination of 3 birds revealed good body condition scores and active laying. One chicken had subtle hemorrhages throughout the liver, and the other 2 had diffusely dark mahogany livers. On histopathology, 2 chickens had hepatic necrosis with hepatocytes containing large, mostly basophilic, intranuclear inclusion bodies, identified by electron microscopy as 82.2-nm diameter adenoviral particles. Virus isolation and genomic sequencing performed on a liver sample revealed strains with 99.9% homology to FAdV4 isolates reported from China. To our knowledge, FAdV4 has not been reported in the United States to date. Furthermore, the chickens affected here were all adults and exhibited a variation of serotype 4 disease in which IBH was present but not hydropericardium.

Therapeutic options for infections caused by Carbapenem-resistant Enterobacterales (CRE) are restricted and include polymyxins-centred schemes. Evaluation of in vitro susceptibility is difficult and time consuming. Agar-based methodologies are an alternative to broth microdilution (BMD) and we aimed to evaluate the accuracy of those methods among Enterobacterales. A total of 137 non-duplicated CRE were subjected to polymyxin B BMD, agar screening test (Mueller Hinton plates containing 3 µg ml -1 of polymyxin B) and agar dilution (antibiotic serially diluted 0·25-64 µg ml -1 ). CRE of 42·3% were resistant to polymyxin B (MICs range: 0·25->64 µg ml -1 ) and 16·8% presented borderline MICs. Sensitivity, specificity, PPV and NPV were 86·2, 98·7, 98 and 90·7% for screening test and 86·2, 97·5, 96·1 and 90·6% for agar dilution. ME was 0·73 and 1·5% for screening and agar dilution respectively; VME was 5·8% for both techniques. In general, agar-based methods had a good performance. As far as we know, this is the first study to propose an agar screening test using polymyxin B instead of colistin., (© 2021 The Society for Applied Microbiology.)

A picture-naming task and ERPs were used to investigate effects of iconicity and visual alignment between signs and pictures in American Sign Language (ASL). For iconic signs, half the pictures visually overlapped with phonological features of the sign (e.g., the fingers of CAT align with a picture of a cat with prominent whiskers), while half did not (whiskers are not shown). Iconic signs were produced numerically faster than non-iconic signs and were associated with larger N400 amplitudes, akin to concreteness effects. Pictures aligned with iconic signs were named faster than non-aligned pictures, and there was a reduction in N400 amplitude. No behavioral effects were observed for the control group (English speakers). We conclude that sensory-motoric semantic features are represented more robustly for iconic than non-iconic signs (eliciting a concreteness-like N400 effect) and visual overlap between pictures and the phonological form of iconic signs facilitates lexical retrieval (eliciting a reduced N400).

The picture word interference (PWI) paradigm and ERPs were used to investigate whether lexical selection in deaf and hearing ASL-English bilinguals occurs via lexical competition or whether the response exclusion hypothesis (REH) for PWI effects is supported. The REH predicts that semantic interference should not occur for bimodal bilinguals because sign and word responses do not compete within an output buffer. Bimodal bilinguals named pictures in ASL, preceded by either a translation equivalent, semantically-related, or unrelated English written word. In both the translation and semantically-related conditions bimodal bilinguals showed facilitation effects: reduced RTs and N400 amplitudes for related compared to unrelated prime conditions. We also observed an unexpected focal left anterior positivity that was stronger in the translation condition, which we speculate may be due to articulatory priming. Overall, the results support the REH and models of bilingual language production that assume lexical selection occurs without competition between languages.

This study used ERPs to a) assess the neural correlates of cross-linguistic, cross-modal translation priming in hearing beginning learners of American Sign Language (ASL) and deaf highly proficient signers and b) examine whether sign iconicity modulates these priming effects. Hearing learners exhibited translation priming for ASL signs preceded by English words (greater negativity for unrelated than translation primes) later in the ERP waveform than deaf signers and exhibited earlier and greater priming for iconic than non-iconic signs. Iconicity did not modulate translation priming effects either behaviorally or in the ERPs for deaf signers (except in a 800-1000 ms time window). Because deaf signers showed early translation priming effects (beginning at 400ms-600ms), we suggest that iconicity did not facilitate lexical access, but deaf signers may have recognized sign iconicity later in processing. Overall, the results indicate that iconicity speeds lexical access for L2 sign language learners, but not for proficient signers.

A domain-general monitoring mechanism is proposed to be involved in overt speech monitoring. This mechanism is reflected in a medial frontal component, the error negativity (Ne), present in both errors and correct trials (Ne-like wave) but larger in errors than correct trials. In overt speech production, this negativity starts to rise before speech onset and is therefore associated with inner speech monitoring. Here, we investigate whether the same monitoring mechanism is involved in sign language production. Twenty deaf signers (American Sign Language [ASL] dominant) and 16 hearing signers (English dominant) participated in a picture-word interference paradigm in ASL. As in previous studies, ASL naming latencies were measured using the keyboard release time. EEG results revealed a medial frontal negativity peaking within 15 msec after keyboard release in the deaf signers. This negativity was larger in errors than correct trials, as previously observed in spoken language production. No clear negativity was present in the hearing signers. In addition, the slope of the Ne was correlated with ASL proficiency (measured by the ASL Sentence Repetition Task) across signers. Our results indicate that a similar medial frontal mechanism is engaged in preoutput language monitoring in sign and spoken language production. These results suggest that the monitoring mechanism reflected by the Ne/Ne-like wave is independent of output modality (i.e., spoken or signed) and likely monitors prearticulatory representations of language. Differences between groups may be linked to several factors including differences in language proficiency or more variable lexical access to motor programming latencies for hearing than deaf signers.

Giant cell tumor is a relatively uncommon bone tumor rarely originating from the chest wall. Given its proximity to vital structures in the thoracic cavity, treatment options may be challenging. We report the case of a patient with a giant cell tumor of the posterolateral chest wall with invasion of the thoracic spine treated with neoadjuvant denosumab, followed by surgical resection., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose. Invasive pneumococcal disease (IPD) in the elderly is an important public health issue due to the increased proportion of this population in many countries including Brazil. We aimed to characterise pneumococci isolates in adults >50 years with IPD, following the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) as part of the National Childhood Immunisation Program for children ≤2 years in March 2010. Methodology. Between 2013 and 2015, pneumococcal isolates were collected and serotypes were determined using multiplex PCR and/or Quellung reaction. Antimicrobial susceptibility was defined by E-test (bioMérieux); genetic diversity was determined using Multiple-Locus Variable Number Tandem Repeat Analysis (MLVA) and, in selected isolates, Multi Locus Sequence Typing (MLST) was performed. Results/Key findings. Among 102 pneumococcal isolates, the most frequent serotypes were 19A, 13 of 102 (12.7 %) and 22F, 10 of 102 (9.8 %). Ninety-eight isolates were tested for antimicrobial susceptibility. Intermediate resistance to penicillin was present in 2/98 (2.0 %), ceftriaxone in 7/98 (7.1 %) and meropenem in 7/95 (7.4 %) of the isolates (non-meningitis breakpoint: 4 µg ml -1 /2 µg ml -1 /0.5 µg ml -1 , respectively). Resistance to penicillin (meningitis breakpoint ≥0.12 µg ml -1 ) was observed in 31/98 (31.6 %) of the isolates. Genetic analysis presented two relevant clonal groups, belonging to non-PCV10 serotypes: 19A (ST320, linked to non-susceptibility) and 22F (ST6403). Conclusion. Our data suggest a predominance of non-PCV10 serotypes among IPD in the elderly population in circulating strains ca. 3 to 5 years after the introduction of PCV10 in Brazil.

The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay. Despite their apparent behavioral rescue, synapse formation in these fish was significantly altered as a result of delayed AChR expression. Motor neuron innervation determined the sites for AChR clustering, a complete reversal of normal neuromuscular junction (NMJ) development where AChR clustering precedes innervation. Most importantly, among the three modes of presynaptic vesicle release, only the spontaneous release machinery was strongly suppressed in these fish, while evoked vesicle release remained relatively unaffected. Such a specific presynaptic change, which may constitute a part of the compensatory mechanism in response to the absence of postsynaptic AChRs, may underlie symptoms of neuromuscular diseases characterized by reduced AChRs, such as myasthenia gravis.

Superficial CD34-positive fibroblastic tumor is a low-grade mesenchymal neoplasm of superficial soft tissues characterized by fascicles of spindle to epithelioid cells displaying nuclear pleomorphism and strong diffuse CD34 immunoreactivity. The intraoperative imprint cytology preparations (ICP) of a superficial CD34-positive fibroblastic tumor from a 50-year-old female are described. To the best of our knowledge, there is no report of the cytologic findings of superficial CD34-positive fibroblastic tumor in the English medical literature. The ICP, differential diagnosis, tissue correlation, and ancillary studies of this fascinating entity are discussed. Diagn. Cytopathol. 2016;44:926-930. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Case: Atypical presentations of Ewing sarcoma (ES) can lead to misdiagnosis and delays in treatment. We present a rare case of ES in the hand of an adult woman who underwent multiple interventions prior to referral to our institution. At 22 months after definitive treatment, the patient remained pleased with the result and had no evidence of recurrence., Conclusion: To our knowledge, ES of the hand in an adult woman has not yet been reported in the literature, and a lack of recognition of this condition might be secondary to the absence of features traditionally associated with malignant bone neoplasms. A broader differential diagnosis after intervention failures offers the opportunity for diagnosis and appropriate treatment.

Background: Although serogroup 20 is not part of any conjugate pneumococcal vaccine, its serotype 20A, but not 20B, belongs to the polysaccharide 23-valent formula. Little is known about its clinical, laboratorial and epidemiological characteristics., Methods: The purpose of this study was to evaluate the bacterial genotypes (by PFGE and MLST), clinical characteristics of patients (from review of medical records) and antimicrobial susceptibility of serogroup 20 isolates which were recovered from patients with invasive pneumococcal disease (IPD) from 2007 to 2012. Subtyping to determine 20A and 20B types was also performed by sequencing the genes of the cps locus., Results: Sixteen isolates were genotyped and were highly related. All pneumococci were resistant to tetracycline and 31 % were non-susceptible to trimethoprim/sulfamethoxazole. Penicillin MIC ranged from 0.004 to 1 μg/mL and non-susceptibility (MIC ≥ 0.12 μg/mL) was observed in 5/16 isolates (31 %). All isolates belonged to subtype 20B. Most patients were male with a median age of 62 years and presented at least one underlying disease (mostly respiratory conditions). All isolates belonged to ST8889 and to a unique PFGE clone., Conclusions: A high clonal occurrence of serotype 20B pneumococci recovered from patients with IPD in Brazil was observed. As a non-PCV10 serotype, selective pressure may be responsible for this unusual occurrence of serogroup 20. However, temporal variation effect should not be underestimated; therefore it is an issue that warrants continued monitoring.

This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. NINDS supports early- and late-stage therapy development funding programs to accelerate preclinical discovery and the development of new therapeutic interventions for neurological disorders. The NINDS Office of Translational Research facilitates and funds the movement of discoveries from the laboratory to patients. Its grantees include academics, often with partnerships with the private sector, as well as small businesses, which, by Congressional mandate, receive > 3% of the NINDS budget for small business innovation research. This article provides an overview of NINDS-funded therapy development programs offered by the NINDS Office of Translational Research.

Streptococcus pneumoniae is a rare cause of appendicitis.We report apneumococcal appendicitis with secondary peritonitis in a human immunodeficiency virus–positive adult, with favorable outcome after surgery and antibiotic therapy. Secondary peritonitis is frequently complication of S pneumoniae appendicitis in the few reported cases,and no specific risk factor has been identified so far.