Does performing manipulation of nasal bones under local anaesthetic beyond two weeks after injury affect outcomes? A prospective study during the SARS-CoV-2 pandemic.

Introduction: ENTUK guidelines recommend that manipulation of nasal bones (MNB) should be performed within 14 days of injury. However, evidence suggests treatment under general anaesthetic remains effective up to 5 weeks after injury. With the SARS-CoV-2 pandemic leading to delays in referral and limited access to theatre, local practice changed to offer delayed MNB under local anaesthetic. This prospective study assesses the effectiveness of MNB delayed until 3 weeks or later from time of injury when performed mostly under local anaesthetic. Methods: Data was prospectively collected between April and November 2020. All patients referred to ENT with a new nasal bone deformity presenting more than 21 days after injury were included. Demographic information, injury details and patient satisfaction was recorded for each patient. Results: 11 patients were included. Average age was 32.6 years (Range 8-65 years). 10 procedures (91%) were performed under local anaesthetic, with 1 (9%) performed under general anaesthetic. 9 patients (82%) gained complete reduction of the deformity, and 1 patient (9%) gaining partial reduction. 10 patients (91%) patients were satisfied with the cosmetic outcome. Conclusion: This study supports the small volume of recent literature showing that delayed manipulation of nasal bones is effective and additionally demonstrates that efficacy is maintained when performed under local anaesthetic.

Selective short-term memory impairment for verbalizable visual objects in children with Developmental Language Disorder.

BACKGROUND: Developmental language disorder (DLD) affects the ability to acquire and make use of native language. Possible underlying cognitive mechanisms are related to memory functions. AIMS: The aim was examination of the relationship between visual short-term memory of objects as well as audiovisual short-term memory, and particular nonverbal and language abilities. METHODS AND PROCEDURES: The study included 7-9-year-old children with DLD and matched control group. Participants completed the Language Development Test, the Stanford-Binet IQ scale (SB5), and two short-term memory tasks: immediate recall of the visually presented pictograms and immediate recall of audiovisually presented sequences of syllables. OUTCOMES AND RESULTS: The results revealed diminished levels of short-term visual memory for objects as well as audiovisual memory in children with DLD. However, there were no group differences in the control task of WM. CONCLUSIONS AND IMPLICATIONS: Results supported the idea of diminished abilities in children with DLD to perform mental operations on verbalizable visual objects. Importantly non-verbal working memory ability, which cannot easily be supported by verbal representations, is at typical levels. This suggests that verbalization ability should be taken into account in the assessment of seemingly non-verbal cognitive functions among children with DLD.

The Impact of Palliative Chemotherapy on the Survival of Patients With Metastatic Colorectal Cancer in Jordan.

Background In Jordan, managing metastatic colorectal cancer (mCRC) is particularly complex, considering limited resources, access to advanced therapies, and unique patient demographics. Palliative chemotherapy, an approach aimed at relieving symptoms and improving the quality of life in patients with advanced cancer, including mCRC, has gained attention as a treatment strategy. While palliative chemotherapy may not aim for complete cancer eradication, it can extend survival, manage disease-related symptoms, and enhance the patient's overall well-being. However, deciding to pursue palliative chemotherapy for mCRC patients involves individual patient characteristics, performance status, disease aggressiveness, potential treatment-related adverse effects, and available healthcare resources. Given the need for region-specific insights into treatment outcomes, the proposed study seeks to investigate the impact of palliative chemotherapy on overall survival (OS), specifically within Jordan's healthcare landscape. Our study aims to showcase palliative chemotherapy's effectiveness on OS in first-line settings. Materials and methods This study is a retrospective analysis conducted at the Military Cancer Center (MCAC) in Jordan. It includes 73 patients diagnosed with mCRC between January 1, 2018, and January 1, 2020. Data were obtained from electronic medical records, and patients were monitored until June 10, 2023. Various patient characteristics were analyzed, including age, sex, primary tumor site, metastatic site, and treatment options for mCRC. The study evaluated the effectiveness of palliative chemotherapy in improving survival rates compared to BSC. Result We conducted a study with 73 participants, whose mean age was 60.37 ±13.5 years and a median of 63. Of these patients, 51 (69.9%) were male, and 22 (30.1%) were female. The primary site of the tumor was located on the left side in 32 patients (43.9%), on the right side in 26 patients (35.6%), and rectal cancer in 15 patients (20.5%). The most common site of the tumor was the sigmoid (17 patients, 23.3%). The liver was the most common site of metastasis (52 patients, 71.2%). Of the patients, 47 (64.4%) received palliative chemotherapy, while 26 (35.6%) were kept on best supportive care (BSC). Of those who received chemotherapy, FOLFIRI was administered to 32 patients (43.8%) and FOLFOX to 15 patients (20.5%). Based on the Kaplan-Meier curve, palliative chemotherapy patients had a significantly longer OS than those who only received BSC. Patients with palliative chemotherapy had a median OS of 12.4 months, while those who only had BSC survived for 5.3 months. The HR was 0.36 with a 95% confidence interval of 0.2-0.62, and the P-value was less than 0.001. Conclusion This study shows that palliative chemotherapy offers a notable advantage and a significant survival benefit compared to BSC.

The Capacity of HIV Care Facilities to Implement Strategies Recommended by the Ending the HIV Epidemic Initiative: The Medical Monitoring Project Facility Survey.

BACKGROUND: Data are needed to assess the capacity of HIV care facilities to implement recommended Ending the HIV Epidemic activities. SETTING: US HIV care facilities. METHODS: We analyzed 2021 survey data from 514 facilities that were recruited from a census of facilities providing care to a national probability sample of US adults with HIV. We present weighted estimates of facility characteristics, services, and policies and estimates of the proportion of all US HIV patients attending these facilities. RESULTS: Among HIV care facilities, 37% were private practices, 72% were in areas with population >1 million, and 21% had more than 1000 HIV patients. Most provided preexposure prophylaxis (83%) and postexposure prophylaxis (84%). More than 67% of facilities provided HIV-specific stigma or discrimination training for all staff (covering 70% of patients) and 66% provided training on cultural competency (covering 74% of patients). A majority of patients attended facilities that provided on-site access to HIV/sexually transmitted infection (STI) transmission risk reduction counseling (89%); fewer had on-site access to treatment for substance use disorders (35%). We found low provision of on-site assistance with food banks or meal delivery (14%) and housing (33%). Approximately 71% of facilities reported using data to systematically monitor patient retention in care. On-site access to adherence tools was available at 58% of facilities; 29% reported notifying patients of missed prescription pickups. CONCLUSION: Results indicate some strengths that support Ending the HIV Epidemic-recommended strategies among HIV care facilities, such as high availability of preexposure prophylaxis/postexposure prophylaxis, as well as areas for improvement, such as provision of staff antistigma trainings and adherence supports.

Central role of Tim17 in mitochondrial presequence protein translocation.

The presequence translocase of the mitochondrial inner membrane (TIM23) represents the major route for the import of nuclear-encoded proteins into mitochondria1,2. About 60% of more than 1,000 different mitochondrial proteins are synthesized with amino-terminal targeting signals, termed presequences, which form positively charged amphiphilic α-helices3,4. TIM23 sorts the presequence proteins into the inner membrane or matrix. Various views, including regulatory and coupling functions, have been reported on the essential TIM23 subunit Tim17 (refs. 5-7). Here we mapped the interaction of Tim17 with matrix-targeted and inner membrane-sorted preproteins during translocation in the native membrane environment. We show that Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins. The amphiphilic character of mitochondrial presequences directly matches this Tim17-dependent translocation mechanism. This mechanism permits direct lateral release of transmembrane segments of inner membrane-sorted precursors into the inner membrane.

Telehealth and Public Health Practice in the United States-Before, During, and After the COVID-19 Pandemic.

Telehealth is the use of electronic information and telecommunication technologies to provide care when the patient and the provider are not in the same room at the same time. Telehealth accounted for less than 1% of all Medicare Fee-for-Service outpatient visits in the United States in 2019 but grew to account for 46% of all visits in April 2020. Changes in reimbursement and licensure policies during the COVID-19 pandemic appeared to greatly facilitate this increased use. Telehealth will continue to account for a substantial portion of care provided in the United States and globally. A better understanding of telehealth approaches and their evidence base by public health practitioners may help improve their ability to collaborate with health care organizations to improve population health. The article summarizes the Centers for Disease Control and Prevention's (CDC's) approach to understanding the evidence base for telehealth in public health practice, possible applications for telehealth in public health practice, and CDC's use of telehealth to improve population health.

Antibody Light Chains: Key to Increased Monoclonal Antibody Yields in Expi293 Cells?

When constructing isogenic recombinant IgM-IgG pairs, we discovered that µ heavy chains strongly prefer partnering with λ light chains for optimal IgM expression in transiently cotransfected Expi293 cells. When µ chains were paired with κ light chains, IgM yields were low but increased by logs-up to 20,000 X-by using λ chains instead. Switching light chains did not alter epitope specificity. For dimeric IgA2, optimal expression involved pairing with λ chains, whereas light-chain preference varied for other immunoglobulin classes. In summary, recombinant IgM production can be drastically increased by using λ chains, an important finding in the use of IgM for mucosal immunoprophylaxis.

Emergency Department and Intensive Care Unit Overcrowding and Ventilator Shortages in US Hospitals During the COVID-19 Pandemic, 2020-2021.

OBJECTIVE: In 2020, the COVID-19 pandemic overburdened the US health care system because of extended and unprecedented patient surges and supply shortages in hospitals. We investigated the extent to which several US hospitals experienced emergency department (ED) and intensive care unit (ICU) overcrowding and ventilator shortages during the COVID-19 pandemic. METHODS: We analyzed Health Pulse data to assess the extent to which US hospitals reported alerts when experiencing ED overcrowding, ICU overcrowding, and ventilator shortages from March 7, 2020, through April 30, 2021. RESULTS: Of 625 participating hospitals in 29 states, 393 (63%) reported at least 1 hospital alert during the study period: 246 (63%) reported ED overcrowding, 239 (61%) reported ICU overcrowding, and 48 (12%) reported ventilator shortages. The number of alerts for overcrowding in EDs and ICUs increased as the number of COVID-19 cases surged. CONCLUSIONS: Timely assessment and communication about critical factors such as ED and ICU overcrowding and ventilator shortages during public health emergencies can guide public health response efforts in supporting federal, state, and local public health agencies.

Telehealth Expansion During the COVID-19 Pandemic and Beyond.

Information and resources for health care providers.

Effects of cardiovascular arousal on emotional experience.

Studies of arousal and emotion show that generalized physiological arousal can enhance emotional experience for a range of different emotions. Other research shows that different emotions may be associated with specific patterns of physiological reactivity. Together these findings suggest that while nonspecific autonomic activation can be sufficient in the generation of emotion, specific patterns of reactivity may appear once the emotion is established. This study aimed to test this hypothesis by examining the effects of generalized arousal on emotional experience, as well as the physiological responses associated with positive and negative emotions. One hundred and nine participants either sat or stood during the viewing of positive and negative film clips while emotion ratings and cardiorespiratory measures were taken. Those who stood during the videos reported greater levels of emotion than those who sat, indicating that generalized arousal due to standing heightened emotional experience. In addition, participants exhibited greater high-frequency heart rate variability and lower respiration rate during the negative video than the positive video, indicating that physiological reactivity differed between the positive and negative emotions. These results suggest that while patterns of physiological reactivity may be specific to individual emotions, nonspecific arousal is sufficient to enhance diverse emotions.

Microbial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells.

The microbially-derived short-chain fatty acid butyrate is a central inhibitor of inflammatory innate and adaptive immune responses. Emerging evidence suggests that butyrate induces differentiation of IL-10-producing (IL-10+) regulatory B cells. However, the underlying mechanisms of butyrate-driven modulation of B cell differentiation are not fully defined. Given the dominant role of regulatory plasma cells (PCs) as the main source of anti-inflammatory cytokines including IL-10 and the observation that butyrate also induces the differentiation of PCs, we here investigated the effect of the microbial metabolite butyrate on the induction of regulatory IL-10+ PCs and underlying mechanisms. Here we show that butyrate induces the differentiation of IL-10+IgM+ PCs. Ex vivo, butyrate, but hardly propionate, another microbially-derived short-chain fatty acid, induced the differentiation of IL-10+IgM+ CD138high PCs from isolated splenic murine B cells. In vivo, administration of butyrate via drinking water or by daily intraperitoneal injection increased the number of IL-10+IgM+ CD138high PCs in the spleens of Ovalbumin (Ova)/complete Freund's adjuvant-immunized mice. The induction of these regulatory PCs was associated with an increase of anti-Ova IgM, but a reduction of anti-Ova class-switched pathogenic IgG2b serum antibodies. Based on the knowledge that butyrate inhibits histone deacetylases (HDACs) thereby increasing histone acetylation, we identified here that HDAC3 inhibition was sufficient to induce PC differentiation and IL-10+ expression. Furthermore, reduced mitochondrial superoxide levels following butyrate treatment and HDAC3 inhibition were necessary for PC differentiation, but not IL-10 expression. In summary, the microbial metabolite butyrate promotes the differentiation of IgM+ PCs and their expression of IL-10. HDAC3 inhibition may be involved as an underlying pathway for both PC differentiation and IL-10 expression, while reduced mitochondrial superoxide levels are crucial only for PC differentiation. The induction of regulatory IL-10+IgM+ PCs and the inhibition of class switching to antigen-specific pathogenic IgG subclasses might represent important pathways of butyrate to limit inflammation.

Impaired attentional bias toward one's own face in autism spectrum disorder: ERP evidence.

Converging lines of evidence seem to indicate reduced self-referential processing in individuals with autism spectrum disorder (ASD). However, processing of one's own face has rarely been investigated in the context of ASD. Thus, the aim of the present study was to elucidate the role of attentional biases in the processing of self- and other faces in ASD. To achieve this goal we presented participants with images of their own face, the face of a close-other, and famous and unknown faces in a Stroop-like paradigm. Participants (22 with ASD, 22 typically developing [TD]) were instructed to indicate the color of presented faces while EEG was recorded. Our event-related potential results clearly showed that self-face was associated with larger P3 amplitudes than all other faces in the TD group, thus indicating a strong attentional bias toward one's own face. In the ASD group, P3 to the self-face and the close-other's face did not differ, suggesting similar attentional biases in both cases. In line with these P3 findings, nonparametric cluster-based permutation tests showed an analogous pattern of results: significant clusters for the self-face compared with all other faces in the TD group, and no significant cluster in the ASD group. Overall, our findings revealed impaired attentional bias to one's own face and diminished self versus other differentiation in individuals with ASD. The similar neural underpinnings of the self-face and other faces supports previous findings indicating reduced self-prioritization among individuals with ASD.

HIV Stigma Among a National Probability Sample of Adults with Diagnosed HIV-United States, 2018-2019.

HIV stigma is a barrier to achieving the goals of the US Ending the HIV Epidemic initiative. We analyzed data from the Medical Monitoring Project (MMP) collected during 6/2018-5/2019 from 4050 US adults with diagnosed HIV. We reported national estimates of HIV stigma and assessed their associations with sociodemographic and clinical characteristics. Disclosure concerns and stigma related to negative public attitudes were common. Stigma was higher among younger age groups, women and transgender people, Black and Hispanic/Latino men and women, and Black and Hispanic/Latino men who have sex with men. Stigma was associated with lower antiretroviral therapy use and adherence, missed HIV care visits, and symptoms of depression or anxiety. The estimates presented provide a benchmark from which the nation can monitor its progress. The findings suggest the need for enhanced stigma-reduction efforts among specific groups and the importance of addressing stigma around disclosure and community attitudes.

A cross-sectional study of prevalence and correlates of self-harm and suicidal ideation in older adults with dual sensory loss.

BACKGROUND: Loss of vision and hearing (dual sensory loss: DSL) presents risk factors for self-harm and/or suicidal ideation, although this has rarely been examined for older adults. OBJECTIVES: This study estimated the prevalence of thoughts about self-harm and suicide ideation in a national sample of adults with DSL in Denmark. METHODS: All 513 people aged 50 years or older who were registered with the national provider of service for people with DSL in Denmark were eligible to participate. Surveys were returned by 290 participants. Participants were mostly female (70%) and aged 50-100 years (M = 81). Surveys contained questions related to thoughts of self-harm and suicide as well as physical, mental, and social wellbeing. RESULTS: In total, 17% of participants reported thoughts of self-harm and/or suicide in the past two weeks. Not participating in social activities, poorer self-rated health, and presence of more depressive symptoms were associated with self-harm and suicidal ideation. Factors that were associated with self-harm and suicidal ideation were lower levels of emotional support, non-participation in social activities, and symptoms of depression. CONCLUSIONS: These finding highlight the importance of ongoing mental health screening and support for older adults with DSL, especially in ensuring accessible mental health services.

mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine.

Background: The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination. Objective: However, the impact of these new vaccine formats with unclear effects on the long-term Ab response - including isotype, subclass, and their type of Fc glycosylation - is less explored. Methods: Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270. Results: We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses - the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations. Conclusion: In summary, the study suggests a comparable "adjuvant" potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

Crepidium sect. Crepidium (Orchidaceae, Malaxidinae)-Chemical and Morphological Study of Flower Structures in the Context of Pollination Processes.

Crepidium is a large genus of mainly pantropical orchids. The lips of its flowers are upwardly directed and do not serve as landing platforms for pollinators. This role is assumed by the dorsal sepal and/or gynostemium. Information about the pollination and floral morphology of this genus is scarce. To date, no papers have been published on these topics. Field observations have revealed that the flowers are visited by small flies, midges, fruit flies, other small dipterans, ants, spiders, and mites. Preliminary observations revealed at least two forms of small liquid droplets secreted on the lip surface of Crepidium species: simple secretions from epidermal cells, and cell sap released upon the rupturing of raphide-producing cells. Further research revealed that this was the first time liquid secretion was recorded in this genus. Floral secretions were subjected to sequential organic solvent extraction and gas chromatography-mass spectrometry (GC-MS). Floral parts were investigated by means of scanning (SEM) and transmission electron microscopy (TEM), and histochemical tests. The presence of liquid droplets on the lip of Crepidium, the presence of a food reward, and the sequence of raphide development are reported here for the first time.

Timed "Up & Go" Dual-Task Tests: Age- and Sex-Specific Reference Values and Test-Retest Reliability in Cognitively Healthy Controls.

OBJECTIVE: The purpose of the study was to establish reference values for the Uppsala-Dalarna Dementia and Gait (UDDGait) Timed "Up & Go" dual-task (TUGdt) test variables in cognitively healthy adults and to assess these variables' test-retest reliability. METHODS: For reference values, 166 participants were recruited with approximately equal numbers and proportions of women and men in the age groups 50 to 59, 60 to 69, 70 to 79, and 80+ years (mean age = 70 years, age range = 50-91 years, 51% women). For reliability testing, 43 individuals (mean age = 69 years, age range = 50-89 years, 51% women) were recruited. Two dt tests were carried out: TUGdt naming animals and TUGdt months backward, representing 8 test variables: time scores, costs (the relative difference between single-task and dt time scores), "number of animals," "number of months," "animals/10 seconds ," and "months/10 seconds ." Reference ranges for the variables were established by quantile regression in age- and sex-specific groups. For reliability, intraclass correlation coefficients (ICCs), standard error of measurement, minimal detectable change, and Bland-Altman plots were used. RESULTS: Reference values for the TUGdt test variables are presented for the 2.5th and 97.5th percentiles. The reliability of TUGdt time scores was excellent (ICCs between 0.85 and 0.86). "Number of animals" and "animals/10 seconds" as well as "months/10 seconds" showed fair to good levels of reliability (ICCs between 0.45 and 0.58), whereas the reliability for both cost measures and "number of months" was poor (ICCs between 0.34 and 0.39). CONCLUSION: Normative reference values, potentially useful for clinical and research purposes, were presented in 4 age- and sex-specific groups from 50 years and older. Reliability for the test variables varied between poor and excellent, the lower estimates partly explained by some variables being the ratio of 2 other variables. In UDDGait, TUGdt tests are intended for diagnostic and predictive purposes, for which these tests are promising and require further investigations. IMPACT: Normative reference values and test-retest reliability results for the UDDGait TUGdt test variables were presented. These results should be useful for both clinical and research purposes.

Real-Time CDC Consultation during the COVID-19 Pandemic-United States, March-July, 2020.

CONTEXT: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. OBJECTIVE: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. DESIGN: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. SETTING: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. PARTICIPANTS: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. MAIN OUTCOME MEASURES: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. RESULTS: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues involving healthcare workers (27.7%) and interpretation or application of CDC's COVID-19 guidance (44%). CONCLUSION: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is warranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities.