Psychological distress, vaccine, and booster acceptance in women considering or undergoing fertility treatments during the Omicron surge of the COVID-19 pandemic.

OBJECTIVE: Follow-up study to evaluate perceptions of COVID-19 vaccination and booster with psychological distress during the COVID-19 pandemic and Omicron surge in women considering or undergoing fertility treatment. MATERIALS AND METHODS: Cross-sectional anonymous survey (N = 2558) from a single academic fertility center. Five hundred forty patients completed the survey (response rate = 21.1%). Participants were randomized 1:1 to a one-page evidence-based graphic with information and benefits regarding COVID-19 vaccination. Mental health and vaccine hesitancy were assessed via the Patient Health Questionnaire Depression (PHQ-8), the Generalized Anxiety Disorder (GAD-7) scales, and the Medical Mistrust Index (MMI). RESULTS: Majority of participants were nulliparous, fully vaccinated with a booster dose, with > 1 year of infertility and mild to moderate distress. Patients with vaccine hesitancy had higher medical mistrust scores (r = .21,  p < .001). Higher MMI scores were not associated with vaccination during pregnancy. Participants that had higher PHQ-8 and GAD-7 scores were more likely to believe the omicron variant would cause delay in fertility treatments, would have impact on fertility outcome, and were more likely exhibiting medical system distrust (p < .001). Participants who received educational material were more likely to know pregnant women with COVID-19 had increased risk of death, stillbirth, and preterm birth (p < .05). CONCLUSION: The majority of women in this study were vaccinated and had received their booster dose but also with clinically significant levels of depression. Patients with higher levels of distress and greatest medical mistrust demonstrated a concern that the Omicron variant would delay treatment, lead to suboptimal fertility outcomes, and COVID-19 vaccination would impact risk of miscarriages.

Vaccine hesitancy, distress, and medical mistrust in women considering or undergoing fertility treatment during the COVID-19 pandemic.

OBJECTIVE: To evaluate perceptions of COVID-19 vaccination and psychological distress during the COVID-19 pandemic in women considering or undergoing fertility treatment. MATERIALS AND METHODS: Cross-sectional anonymous survey (n= 3558) from a single academic fertility center. A total of 1103 patients completed the survey (response rate = 31% of those emailed, 97.6% of those who opened the email). Participants were randomized 1:1 to a one-page educational graphic providing facts and benefits regarding COVID-19 vaccination. Assessment of vaccine hesitancy was conducted via the Medical Mistrust Index (MMI). Mental health was assessed via the Patient Health Questionnaire Depression Scale (PHQ-8) and the Generalized Anxiety Disorder-7 (GAD-7). RESULTS: The majority of participants were married, nulliparous, white women with > 1 year of infertility and moderate to severe distress. As compared to the non-intervention group, participants in the intervention group believed that COVID-19 vaccination does not cause genetic abnormalities in a fetus (98.0% v. 94.2%) and infertility (99% v. 96.2%) and that severe infection has been associated with pregnancy (81.3% v. 74.6%) (P <0.05). Higher MMI scores were associated with vaccine hesitancy (P = 0.01), higher GAD-7 scores (P = 0.01), and greater concerns about side effects of the vaccine (P < 0.05). GAD-7 and PHQ-8 scores were not associated with vaccine hesitancy. Nearly a quarter of participants initiated psychiatric treatment after March 2020. CONCLUSION: Vaccine hesitancy was associated with mistrust of the medical system. Psychological distress was highly prevalent in this study. Efforts should be made to improve patient trust and provide psychological support for fertility patients.

Body mass index, not race, may be associated with an alteration in early embryo morphokinetics during in vitro fertilization.

OBJECTIVE: To assess the relationship between maternal body mass index (BMI) and embryo morphokinetics on time-lapse microscopy (TLM). DESIGN: Retrospective cohort study. METHODS: All IVF cycles between June 2015 and April 2017 were reviewed. Female BMI prior to egg retrieval was collected through chart review. BMI (kg/m2) classification included underweight (< 18.5), normal weight (18.5-25), overweight (25-30), and obese (≥ 30). Embryos' morphokinetic parameters were assessed with TLM and included time to syngamy, 2-cell, 3-cell, 4-cell, and 8-cell. A generalized linear mixed model was used to control for potential confounders and multiple embryos resulting from a single IVF cycle. RESULTS: A total of 2150 embryos from 589 IVF cycles were reviewed and included in the analysis. Classification based on BMI was as follows: underweight (N = 56), normal weight (N = 1252), overweight (N = 502), and obese (N = 340). After adjusting for race and use of intracytoplasmic sperm injection, the mean time to the 8-cell stage in the underweight group was 4.3 (95% CI: - 8.31, - 0.21) h less than in the normal weight group (P = 0.025) and 4.6 (95% CI: - 8.8, - 0.21) h less than in the obese group (p = 0.022). No significant difference was noted between race and TLM after controlling for possible confounders. CONCLUSIONS: Embryos from underweight women were demonstrated to have a faster time to the 8-cell stage than normal weight or obese women. No significant difference was noted for race. This study demonstrates that weight can be a factor contributing to embryo development as observed with TLM.

Arginine Metabolism in Supragingival Oral Biofilms as a Potential Predictor of Caries Risk.

INTRODUCTION: Ammonia production via the arginine deiminase system (ADS) of oral bacteria can function to reduce the cariogenicity of oral biofilms by neutralizing glycolytic acids that cause tooth demineralization. OBJECTIVES: This cohort study investigated the relationship between ADS activity and bacterial profile changes of supragingival biofilms with caries experience among children over time. METHODS: A total of 79 children aged 2 to 7 y at baseline were assessed every 6 mo for a period of 18 mo. Children were grouped as caries free (CF), caries active with enamel lesions (CAE), or caries active with dentin lesions (CA). Supragingival plaque samples were collected from caries-free surfaces (PF) and from enamel (PE) and dentin (PD) lesions. Plaque ADS activity was measured by monitoring citrulline production from arginine and compared with ribosomal 16S rRNA-derived taxonomic profiles for the same samples. RESULTS: At baseline, 37% of the children were CF, 34% CAE, and 29% CA. At 18 mo, 26% were CF, 41% CAE, 23% CA, and 10% were caries experienced (new restorations but no caries activity). Throughout the study period, ADS activity was significantly higher in the CF group than the CA group (P < 0.0001), and ADS activity in the PF samples was significantly higher than in the PE and PD samples (P < 0.0001). Distance-based redundancy analysis showed that the bacterial communities could be differentiated when plaque samples are grouped into levels of high and low ADS activity. CONCLUSIONS: There is a positive correlation between caries activity and low arginolytic capacity of the supragingival oral biofilms of children and tooth surfaces over time. Measurements of arginine metabolism via ADS may be useful to differentiate the caries risk of individuals and tooth surfaces. KNOWLEDGE TRANSFER STATEMENT: Findings from this study support the development of new strategies for caries risk assessment and prevention based on modulation of the virulence of the oral microbiome through arginine metabolism in supragingival biofilms.

Enhanced coupling of broadband light into amorphous silicon via periodic nanoplasmonic arrays.

Achieving enhanced coupling of solar radiation over the full range of the silicon absorption spectrum up to the bandgap is essential for increased efficiency of solar cells, especially thin film versions. While many designs for enhancing trapping of radiation have been explored, detailed measurements of light scattering inside silicon cells is still lacking. Here, we demonstrate experimentally and computationally that plasmonic-assisted localized and traveling modes can efficiently couple red and infrared radiation into ultrathin amorphous silicon (a-Si) layers. Utilizing patterned periodic arrays of aluminum nanostructures on thin a-Si, we perform specular and diffuse reflectivity and transmission measurements over a broad spectrum. Based on these results, we are able to separate parasitic absorption in aluminum plasmonic arrays from enhanced light absorption in the 200 nm thick amorphous silicon layer, as compared to a blank silicon layer. We discover a very efficient near-infrared a-Si absorption mechanism that occurs at the transition from the radiative to evanescent diffractive coupling, analogous to earlier surface-enhanced infrared studies. These results represent a direct demonstration of enhanced radiation coupling into silicon due to large angle scattering and show a path forward to improved ultrathin solar cell efficiency.

Transferrin-Targeted Nanoparticles Containing Zoledronic Acid as a Potential Tool to Inhibit Glioblastoma Growth.

The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted self-assembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Hydroxypropyl-ß-cyclodextrin impacts renal and systemic hemodynamics in the anesthetized dog.

Hydroxypropyl-ß-cyclodextrin (HPßCD) is a complexation agent used to enhance drug solubilization and formulation stability. Although its toxicity is well characterized, its cardiovascular effects are less known. To investigate them, HPßCD was infused intravenously over 10 min in anesthetized dogs (10-40% (w/v, i.e. 200-800 mg/kg) in non-denervated animals and at 40% in denervated animals). HPßCD increased renal arteriolar resistance and decreased renal blood flow at all doses, almost immediately after infusion start, more drastically in females. A less pronounced increase in total peripheral resistance occurred in females only due to sex difference in sympathetic tone. Pulmonary hemodynamic parameters remained unaffected, suggesting that the renal effect was rather selective. As a consequence of the increased systemic blood pressure, heart rate decreased in normal animals without direct effect on cardiac conductance. This effect was abolished in denervated animals. This suggests that autonomous nervous feedback loops are functional in normal animals and that HPßCD has no direct chronotropic effect. In conclusion, systemic and renal hemodynamic changes should be considered as potential background effects at 200-400 mg/kg. At higher doses (800 mg/kg), changes are more pronounced and could mask/exacerbate hemodynamic response of drug candidate; such doses should be avoided in nonclinical safety studies.

Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: a comparison of cefazolin and ceftriaxone.

PURPOSE: Although the antistaphylococcal penicillins remain the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, cefazolin and ceftriaxone are often prescribed due to their less frequent dosing and reduced cost. The purpose of this study was to compare clinical outcomes and adverse events in patients receiving outpatient parenteral antimicrobial therapy (OPAT) with ceftriaxone or cefazolin for the treatment of MSSA infections. METHODS: A retrospective study was carried out of 122 patients evaluated at Ben Taub and Lyndon B. Johnson General Hospitals in Houston, Texas, between January 1, 2006, and March 31, 2012, with a documented MSSA infection who received cefazolin or ceftriaxone as OPAT. A favorable clinical outcome was determined by their primary care physician's assessment at follow-up in the clinic. RESULTS: Out of 122 patients, 78 (64 %) were treated with cefazolin and 44 (36 %) with ceftriaxone. Patients were predominantly young (median age 46 years), male (54.2 %), and Hispanic (51.2 %). Patients were similar in terms of baseline demographics, types of infections, and management of infections. Favorable clinical outcomes were similar between cefazolin and ceftriaxone (67.9 versus 79.8 %, p = 0.17), along with a similar incidence of adverse events and complications (5.1 versus 2.3 %, p = 0.65, and 26.9 versus 18.2 %, p = 0.38, respectively). CONCLUSIONS: OPAT with either cefazolin or ceftriaxone is similar in terms of favorable outcomes, adverse events, and complications when treating MSSA infections. A randomized clinical trial is needed in order to confirm these results.

Rivastigmine in the treatment of parkinsonian psychosis and cognitive impairment: preliminary findings from an open trial.

This open study assessed the ability of rivastigmine to treat the neuropsychiatric complications of advanced Parkinson's disease. In a group of 12 patients, hallucinations, sleep disturbance, and carer distress were all improved and cognitive performance significantly enhanced by the drug.

How do memory clinics compare with traditional old age psychiatry services?

METHODS: 100 consecutive referrals to the Northern Memory Clinic (NMC) were compared with 100 referrals to a traditional Old Age Psychiatry (OAPsych) service in the same city in terms of demographic variables, cognitive function (assessed by the Mini-Mental State Examination), and diagnosis. The study also examined the ability of psychometric assessments (CAMCOG, MMSE, Trail-Making Tests A & B, Word Fluency) and CT scans included in the NMC assessment to differentiate between those with and without DSM-IV dementia. RESULTS: NMC patients were significantly younger than OAPsych patients, had lower levels of cognitive impairment, and had a wider range of diagnoses. The NMC patients who were diagnosed as having dementia were found to be at least 2 years earlier in the course of the disease than those seen by the OAPsych team. The CAMCOG and MMSE were proved to be effective at distinguishing between patients diagnosed as dementing versus non-dementing with cut-offs of 82/83 and 23/24 respectively, confirming previous findings. The Memory subscale of the CAMCOG, though much shorter, was equally as effective using a cut-off of 20/21. Trail-Making Tests, Word Fluency (FAS), and measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans were poor indicators of dementia in this sample. CONCLUSIONS: This study confirms that the memory clinic is targeting a distinct patient group compared to traditional old age psychiatry services, is identifying cases of dementia much earlier, and as such has potential to make valuable contributions to patient care.

A randomized controlled trial of Moderation-Oriented Cue Exposure.

OBJECTIVE: A randomized controlled trial was conducted to examine the effectiveness of Moderation-Oriented Cue Exposure (MOCE) in comparison to Behavioral Self-Control Training (BSCT). The main hypothesis was that MOCE would be more effective than BSCT among a sample of problem drinkers aiming at moderate drinking. A subsidiary hypothesis was that MOCE would be relatively more effective than BSCT among problem drinkers with higher levels of alcohol dependence. METHOD: Clients (N = 91; 75% men) were randomly allocated to either MOCE or BSCT. Treatment was delivered in weekly sessions by two trained therapists, in a nested design in which therapists switched to the alternative treatment modality approximately halfway through the trial. Follow-up was carried out 6 months following posttreatment assessment, with 85% successful contact. RESULTS: There was no evidence for the general superiority of MOCE over BSCT. The subsidiary hypothesis was not confirmed. A subsample of clients (n = 14) showing levels of dependence at baseline above the commonly accepted cut-point for a moderation goal (Severity of Alcohol Dependence Questionnaire [SADQ] > 29) showed outcomes at least as favorable as those below the cut-point. The validity of self-reports of alcohol consumption and problems was supported by significant relationships with liver function tests (gamma-glutamyl transferase and alanine transferase). CONCLUSIONS: These results provide no grounds for the replacement of BSCT by MOCE in routine, moderation-oriented treatment practice. Assuming they prefer it to abstinence and that it is not contra-indicated on other grounds, there seems no reason why clients showing a higher level of dependence (SADQ = 30-45) should not be offered a moderation goal.

Impaired Control Scale: cross-validation and relationships with treatment outcome.

AIMS: (1) To cross-validate Australian findings on the Impaired Control Scale (ICS) in an English sample of problem drinkers. (2) To examine a possible improvement to the scoring of the ICS. (3) To explore the relationship of the ICS to treatment outcome. DESIGN: In a repeated measures design, questionnaires and interviews were administered by trained staff during treatment and again at 6 months follow-up. SETTING: Two alcohol and drug treatment services in Newcastle and Liverpool (UK). PARTICIPANTS: Two hundred and twenty-nine problem drinkers attending as in- or outpatients, with abstinence or moderation treatment goals. MEASUREMENTS: ICS scores; typical weekly alcohol consumption (units); degree of alcohol-related problems; severity of alcohol dependence; and classification of outcome using consumption levels and current alcohol-related problems, with collateral confirmation of self-reports. FINDINGS: The satisfactory reliability and validity of the ICS was confirmed in an English sample of problem drinkers in treatment. An improved "substitution method" of scoring was developed to give a single measure of impaired control for all subjects irrespective of degree of attempted control. ICS scores were significantly correlated with treatment outcome and, among a subgroup of subjects who had aimed at abstinence but failed, predicted outcome status after the effects of degree of dependence had been extracted. CONCLUSIONS: Impaired control over alcohol consumption can be measured in a reliable and valid fashion by the ICS. The ICS has potential uses in research on impaired control and as a clinical assessment tool.