Complete genome sequence of Delftia tsuruhatensis strain HA60 isolated from a commercial hydroxyapatite nano-particle product (nano-hydroxyapatite).

Delftia tsuruhatensis is a Gram-negative rod-shaped aerobic bacterium with environmental remediation functions. D. tsuruhatensis strain HA60 was isolated from a commercial nano-particle product, nano-hydroxyapatite. We report that the genome of D. tsuruhatensis strain HA60 has a circular genome of 6,922,195 base pairs with a G+C content of 66.45%.

Complete genome sequence of two chromosomes of Vibrio metoecus strain ZF102 isolated from the abdominal cavity of moribund laboratory zebrafish (Danio rerio).

Vibrio metoecus was isolated from the abdominal cavity of moribund laboratory zebrafish. We report complete genomic sequences of V. metoecus strain ZF102 that has two circular chromosomes of 2,872,299 and 1,170,691 bp and two plasmids of 5,265 and 2,361 bp.

Differences in Connected Speech Outcomes Across Elicitation Methods.

Background: Connected speech is often used to assess many aspects of an individual's language abilities after stroke. However, it is unknown the degree to which elicitation methods differ in generating structural and syntactic aspects of connected speech, two critical components of successful communication. Quantifying the degree to which elicitation methods differ in eliciting structurally, syntactically, and lexically complex connected speech at the earliest stage of stroke before reorganization and rehabilitation of function independent of clinical diagnosis of aphasia has not been examined to date. Addressing this gap has implications for early clinical intervention as well as empirical studies of connected speech production. Aims: We compared two common elicitation methods, picture description and storytelling on lexical, structural, and syntactic measures of connected speech in speakers during the acute stage of left hemisphere stroke. Methods & Procedures: We measured connected speech using an automated quantitative production analysis approach (Fromm et al., 2021) in 71 native-English speaking participants (27 female; 59 ± 13 years) within an average 3.9 days from left hemisphere stroke onset. We tested the degree of agreement and consistency between elicitation methods for lexical, structural, and syntactic measures of connected speech, as well as the degree of concordance in classifying deficits across individuals. Outcomes & Results: Storytelling elicited significantly more words and more structurally complex, lexically diverse, and syntactically accurate speech in comparison to picture description. Elicitation methods differed in measuring outcomes across participants for the lexical and syntactic, but not structural complexity aspects of connected speech where storytelling classified more participants with impairments in comparison to picture description. Conclusions: These differences suggest storytelling provides assessment of connected speech abilities more reflective of real-world abilities where its use is particularly critical for examining individual differences and providing diagnoses of acute stroke language deficits. As a result, using storytelling as a connected speech elicitation method more effectively captures a patient's language capabilities after stroke, consequently informing clinical diagnosis and treatment.

Complete genome sequences of Campylobacter jejuni subsp. jejuni strain P4549 isolated from an asymptomatic rhesus monkey (Macaca mulatta).

Campylobacter jejuni subsp. jejuni is a leading bacterial cause of human gastroenteritis. C. jejuni strain P4549 was isolated from an asymptomatic rhesus monkey, Macaca mulatta. We report the genome sequences have a circular chromosome of 1,729,940 bp and two plasmids of 50,482 bp and 7,259 bp, respectively.

Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment.

Introduction: Both the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross-sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI). Methods: We included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. Anosognosia was defined as the study-partner having an ECog score ≥2.5/4 and the participant having an ECog score < 2.5/4 on their baseline measure and their last observation without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia. Results: Thirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline (p > 0.9), though participants with anosognosia had lower MMSE scores (p = 0.049) and a higher proportion of amyloid-positivity using PET (p < 0.001. At baseline, the frequencies of agitation (p = 0.029) and disinhibition (p < 0.001) were higher in the anosognosia group compared to the non-anosognosia group. Survival analyses showed earlier onset of seven of the 12 NPS in the anosognosia group (p's < 0.001). Discussion: Loss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.

Complete genome sequence of Parabacteroides distasonis strain GP102, isolated from the cecum of a morbid pregnant laboratory guinea pig (Cavia porcellus).

Parabacteroides distasonis is an anaerobic bacterium with ambivalent health effects. P. distasonis strain GP102 was isolated from the cecum content of a morbid pregnant laboratory guinea pig (Cavia porcellus). The genome consists of one circular 5.39-Mbp chromosome with a G + C content of 44.79%.

Genome sequence of Clostridium septicum strain WW106, isolated from influent wastewater at a research center with multiple-species research animal facilities.

Clostridium septicum is an anaerobic Gram-positive rod-shaped bacterial pathogen known as a lethal causative agent of progressive gas gangrene in animals and humans. We report the 3.43-Mbp genome sequence of C. septicum strain WW106, isolated from influent wastewater at a research center with multiple-species laboratory animal facilities.

Genome sequence of Gordonia alkaliphila strain WW102, isolated from influent wastewater at a research center with multiple-species research animal facilities.

Gordonia alkaliphila is a little known mesophilic Gram-positive rod-shaped bacterium. We report the 3.85-Mbp genome sequence of G. alkaliphila strain WW102, isolated from wastewater at a research center with multiple-species laboratory animal facilities. The genome predicted FadD32 gene clusters that are involved in the biosynthesis of mycolic acids as found in Mycobacterium tuberculosis.

Complete Genome Sequence of Invasive MLST-Untypeable Serotype 3 xpt-Deficient Streptococcus pneumoniae Strain B1900, Isolated from the Brain of an Infant Rhesus Monkey (Macaca mulatta) That Died of Meningitis.

Serotype 3 Streptococcus pneumoniae is associated with major invasive pneumococcal diseases in humans. We report the circularized 2.0-Mbp complete genome sequence of invasive serotype 3 S. pneumoniae strain B1900, untypeable by multilocus sequence typing (MLST). This strain was isolated from the brain of an infant rhesus monkey (Macaca mulatta) that suddenly died of meningitis with no clinical symptoms.

Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings.

BACKGROUND: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical. OBJECTIVE: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults. METHODS: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid. RESULTS: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone. CONCLUSION: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting.

A prospective longitudinal study of multidomain resilience among youths with and without maltreatment histories.

The majority of children with maltreatment histories do not go on to develop depression in their adolescent and adult years. These individuals are often identified as being "resilient", but this characterization may conceal difficulties that individuals with maltreatment histories might face in their interpersonal relationships, substance use, physical health, and/or socioeconomic outcomes in their later lives. This study examined how adolescents with maltreatment histories who exhibit low levels of depression function in other domains during their adult years. Longitudinal trajectories of depression (across ages 13-32) in individuals with (n = 3,809) and without (n = 8,249) maltreatment histories were modeled in the National Longitudinal Study of Adolescent to Adult Health. The same "Low," "increasing," and "declining" depression trajectories in both individuals with and without maltreatment histories were identified. Youths with maltreatment histories in the "low" depression trajectory reported lower romantic relationship satisfaction, more exposure to intimate partner and sexual violence, more alcohol abuse/dependency, and poorer general physical health compared to individuals without maltreatment histories in the same "low" depression trajectory in adulthood. Findings add further caution against labeling individuals as "resilient" based on a just single domain of functioning (low depression), as childhood maltreatment has harmful effects on a broad spectrum of functional domains.

Valley fever, mimicker of malignancy.

Coccidioidomycosis rates in endemic areas such as California and Arizona have been increasing in recent years. Most common manifestations in symptomatic individuals involve the lungs. Disseminated disease occurs when the infection spreads beyond the lungs. Disseminated disease occurs in about 1% of all coccidiomycosis cases. Diagnosis in classically non-endemic regions can be difficult as coccidiomycosis can mimic a variety of other illnesses which can lead to delays in initiating appropriate therapy. We report a case of severe disseminated coccidiomycosis involving the soft tissue, bone, and intra-abdominal organs in a previously healthy individual that was initially thought to be a malignancy. With climate change possibly altering the traditional endemic regions and expanding Coccidioides to new territories, this case reinforces the importance of maintaining a broad differential as well as awareness of disease manifestations for healthcare providers who do not regularly treat Coccidioides.

Double-stranded RNA reduction by chaotropic agents during in vitro transcription of messenger RNA.

In-vitro-transcribed messenger RNA (mRNA) has recently shown increasing significance in the development of vaccines and therapeutics. Immunogenic double-stranded RNA (dsRNA) is an undesired byproduct formed during in vitro transcription (IVT), and it is challenging to reduce dsRNA byproduct from mRNA due to their similar sizes and intrinsic characteristics. Removal of dsRNA relies heavily on post-IVT chromatography purifications, such as reverse-phase high-pressure liquid chromatography, which increase manufacturing costs, reduce yield, and often decrease integrity, especially for long mRNA. Thus, it would be ideal to reduce and control the level of dsRNA during IVT. We herein present a simple, scalable, and controllable method to reduce the formation of dsRNA byproducts during IVT. Selected chaotropic agents at optimized concentrations are included during IVT to create a mild denaturing environment to prevent the undesired intermolecular or intramolecular base-pairing that is thought to promote RNA-templated dsRNA formation by RNA polymerase. Compared with regular IVT, our improved method produces mRNA with significantly less dsRNA, much lower immuno-stimulation, and more efficient protein expression. Therefore, this method potentially eliminates dsRNA removal purification steps and does not require reduced magnesium concentration, elevated temperature, or custom reagents, enabling a straightforward, high-yield, and cost-effective scale-up approach for mRNA manufacturing.

Legionnaire's Disease Presenting With the Legionella Triad (Pneumonia, Rhabdomyolysis, and Renal Failure) and Cardiac Complications.

Legionella pneumonia is well-characterized as a cause of atypical, community-acquired pneumonia in susceptible individuals. In recent years, extrapulmonary manifestations, including an emerging triad of Legionella pneumonia, rhabdomyolysis, and renal failure, have been identified. Here we report a case of Legionnaire's disease that presented non-classically, with subclinical pneumonia and non-ST elevated myocardial infarction (NSTEMI). Although he received early treatment with antibiotics, he developed the Legionellatriad during admission. He had several episodes of cardiopulmonary decompensation during his hospital course, eventually ending in his passing. This case serves to highlight the importance of early identification and intervention in regard to extrapulmonary Legionella infection.

Prevalence of Central Line-Associated Bloodstream Infections (CLABSI) in Intensive Care and Medical-Surgical Units.

BACKGROUND:  Central line-associated bloodstream infections (CLABSIs) remain an important preventable healthcare-associated infection with a 2020 rate of 0.87 (per 1,000 central line days) in the United States intensive care units (ICU). METHODS:  This was a retrospective cohort study of all adult patients in our institution. The total number of central venous catheter (CVC) insertions and line days were determined using daily unit logs maintained by unit managers. Central line insertion practice (CLIP) compliance was calculated as the total number of CLIP forms submitted divided by the total number of newly-inserted CVCs with and without associated CLIP forms as determined by unit logs. RESULTS: A total of 1,125 CVCs were reviewed (448 - ICU and 677 - medical-surgical units). Of the 13 CLABSI, one patient had internal jugular (IJ), one patient had subclavian (SC), four patients had femoral, three patients had peripherally inserted central catheter (PICC) and four patients had hemodialysis catheters. Patients with CLABSI had CVC inserted for a range of five to 92 days with the average number of line days being 29 days. CONCLUSION:  Based on the analysis of our CLABSI patient population, we recommend our institution implement the following criteria to decrease the prevalence of CLABSI: All patients receiving a CVC must adhere to CLIP documentation in all units, any femoral or HD CVC placed without a CLIP form should have the line changed within 48 hours, those patients with a femoral CVC or hemodialysis catheter in place for four days or greater with an abnormal WBC (<4.0 or >11 mg/dL) or abnormal temperature (<97.0F or >100.4F) should be considered for catheter exchange, and those patients with an IJ, SC, or PICC CVC in place for seven days or greater with an abnormal WBC or abnormal temperature should have the catheter changed.

Antagonistic Antibody Targeting TNFR2 Inhibits Regulatory T Cell Function to Promote Anti-Tumor Activity.

Infiltration of regulatory T cells (Tregs) in the tumor microenvironment suppresses anti-tumor immune response, and promotes tumor progression. Tumor necrosis factor receptor-2 (TNFR2), which is highly expressed on Tregs, activates Tregs through nuclear factor kappa B (NF-κB) pathway. Moreover, TNFR2+ Tregs have been shown to be most suppressive among all Tregs populations in tumor. Due to the unique expression pattern and function of TNFR2 on Tregs, a TNFR2 blocking antibody is expected to compromise Tregs function, relieve Tregs-mediated immunosuppression, and hence to enhance anti-tumor immune response. AN3025 is an antagonistic anti-human TNFR2 (hTNFR2) antibody that is currently under preclinical development. This study investigates the immunomodulatory and anti-tumor activity of AN3025. AN3025 was generated through rabbit immunization with extracellular domain of human TNFR2 and subsequent humanization by complementarity-determining regions (CDRs) grafting. AN3025 binds to the extracellular domain of both human and cynomolgus with sub-nanomolar affinity and specificity, but not mouse or rat TNFR2. AN3025 inhibited tumor necrosis factor alpha (TNFα) induced cell death of hTNFR2-overexpressing Jurkat cells by competing with TNFα for binding to hTNFR2. In the Tregs/T effector co-culture assay, AN3025 increased T effector proliferation and enhanced interferon gamma (IFNγ) production. As a monotherapy, AN3025 significantly inhibited MC38 tumor growth in TNFR2 humanized mouse model. Subsequent flow cytometry (FACS) and immunohistochemistry (IHC) analysis revealed that administration of AN3025 led to decreased Tregs population, increased CD4+ and CD8+ T cell numbers in the tumor. The anti-tumor activity of AN3025 was dependent on the existence of CD4+ and CD8+ T cells, as depletion of CD4+ and CD8+ T cells abolished the anti-tumor activity of AN3025. In addition, AN3025 in combination with anti-PD-1 antibody demonstrated stronger in-vivo anti-tumor activity. The potent anti-tumor efficacy of AN3025, either as a monotherapy or in combination with anti-PD-1 antibody, supports its further clinical development for the treatment of various human tumors.

Racial and socioeconomic status differences in stress, posttraumatic growth, and mental health in an older adult cohort during the COVID-19 pandemic.

Background: The COVID-19 pandemic has disproportionately impacted the most vulnerable and widened the health disparity gap in both physical and mental well-being. Consequentially, it is vital to understand how to best support elderly individuals, particularly Black Americans and people of low socioeconomic status, in navigating stressful situations during the COVID-19 pandemic and beyond. The aim of this study was to investigate perceived levels of stress, posttraumatic growth, coping strategies, socioeconomic status, and mental health between Black and non-Hispanic, White older adults, the majority over the age of 70. Additionally, we investigated which variables, if any, were associated with posttraumatic growth in these populations. Methods: One hundred seventy-six community dwelling older adults (mean age = 76.30 ±8.94), part of two observational studies (The Harvard Aging Brain Study and Instrumental Activities of Daily Living Study) in Massachusetts, US, were included in this cross-sectional study. The survey, conducted from March 23, 2021 to May 13, 2021, measured perceived stress, behavioral coping strategies, posttraumatic growth, and mental health during the COVID-19 pandemic. We investigated associations with post-traumatic growth in a multiple linear regression model and examined their differences by race with t-tests, Wilcoxon rank-sum tests, and Fisher's exact tests. A second multiple linear regression model was used to examine which coping strategies were associated with posttraumatic growth. Findings: Our results indicated no significant difference between the groups in terms of mental health or stress. However, Black participants showed significantly greater posttraumatic growth compared to non-Hispanic, White participants. Additionally, the coping strategies of religion and positive reframing were found to be significantly associated with posttraumatic growth. Furthermore, even with the effects of stress and coping strategies controlled for, race remained significantly associated with posttraumatic growth. Interpretation: The COVID-19 pandemic has differentially impacted Black and non-Hispanic White older adults. These results may help encourage further analysis on geriatric psychiatry as well as understanding how cultural values and adaptations impact posttraumatic growth and mental health in diverse populations. Funding: The Harvard Aging Brain Study (HABS) has been funded by NIH-NIA P01 AG036694 (PI: Reisa Sperling). The IADL study is funded by the National Institute on Aging (R01 AG053184, PI: Gad A. Marshall).

Tracheobronchitis Due to Invasive Aspergillus fumigatus in a Male With HIV With Minimal Imaging Findings.

Aspergillus tracheobronchitis (AT) is a rare manifestation of invasive aspergillosis. We present a case of tracheobronchitis caused by Aspergillus fumigatus in a 33-year-old male with neutropenia and known human immunodeficiency virus (HIV) infection with acquired immunodeficiency syndrome (AIDS). A 33-year-old male with HIV/AIDS presented to the hospital with symptoms of productive cough for over two months associated with subjective fevers, chills, and body aches. Computed tomography (CT) of the chest was significant for scattered sub-centimeter bilateral upper lobe nodules but otherwise normal. The patient underwent an extensive evaluation for his respiratory symptoms, including an initial sputum culture, which grew Haemophilus parainfluenzae in addition to preliminary fungal growth, prompting further evaluation with bronchoscopy. Bronchoscopy revealed diffuse adherent obstructive pseudomembranous plaques in the trachea and bilateral upper lobe segmental bronchi. Bronchoalveolar lavage cultures later grew Aspergillus fumigatus. Tracheobronchitis due to Aspergillus species is a rare cause of infection in patients with HIV. We believe that this case underscores the importance of further evaluation utilizing bronchoscopy in patients with AIDS who have respiratory symptoms despite mild abnormalities on chest CT. This approach can be used to rule out atypical endobronchial infections such as tracheobronchitis due to Aspergillus species.

Emergent Inpatient Administration of Casirivimab and Imdevimab Antibody Cocktail for the Treatment of COVID-19 Pneumonia.

Infection by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is known to have the highest mortality rate among the elderly and those with pre-existing medical conditions. Viral load has been directly correlated with increased risk of mortality in hospitalized patients. Once infected, symptoms first arise approximately six to seven days later followed by immunoglobulin M (IgM) antibodies appearing 8-12 days after onset of clinical symptoms. Recent studies have noted that the monoclonal antibody combination of casirivimab and imdevimab (REGN-COV2) effectively reduces viral load in infected seronegative non-hospitalized patients. However, research supporting the use of REGN-COV2 in an inpatient setting is limited. We present the case of a 45-year-old male with confirmed SARS-CoV-2 infection with moderate dyspnea and progressive worsening of his symptoms over a week period. The patient showed drastic improvement of his symptoms after a single low-dose regimen of REGN-COV2 infusion while admitted to the hospital and was subsequently discharged without further medical complications.