The PrEP resource: a mobile app for clinicians to facilitate screening, prescription and follow up of pre-exposure prophylaxis in the prevention of HIV.

Background Over 2million people worldwide receive a new HIV diagnosis annually. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission, but is underprescribed, including in the US. Lack of clinician comfort and knowledge are the most cited reasons for this discrepancy. We aimed to develop a mobile application (app) to address these barriers and improve patient access to PrEP. Methods We established key criteria to develop a point-of-care app that could be utilised in low-resource settings by various clinicians poised to prescribe PrEP therapy. The app underwent two rounds of beta testing and improvement utilising anonymous survey feedback from US physicians in 2023. Results The PrEP Resource tool was developed. Eleven physicians completed the initial survey addressing prescribing practices and app functionality. A total of 27% (3/11) of participants were uncomfortable prescribing PrEP, with the most common reasons being lack of training, unfamiliarity with guidelines and infrequently prescribing the medication. Our follow-up survey, completed by eight physicians, showed that 100% of participants found the app easy to learn and comprehensive enough to initiate PrEP. Conclusion Clinician discomfort due to lack of knowledge and familiarity is the most common reason for not prescribing PrEP. The PrEP Resource is a free tool that guides healthcare professionals through common clinical scenarios regarding PrEP therapy and may improve clinician comfort levels. It can be used in low-resource and low-bandwidth settings typically encountered in lower-middle-income countries where HIV prevalence is the highest. Further study is required to validate its usefulness across different settings.

Sulfurized Two-Dimensional Conductive Metal-Organic Framework as a High-Performance Cathode Material for Rechargeable Mg Batteries.

Rechargeable Mg batteries are a promising energy storage technology to overcome the limitations inherent to Li ion batteries. A critical challenge in advancing Mg batteries is the lack of suitable cathode materials. In this work, we report a cathode design that incorporates S functionality into two-dimensional metal-organic-frameworks (2D-MOFs). This new cathode material enables good Mg2+ storage capacity and outstanding cyclability. It was found that upon the initial Mg2+ insertion and disinsertion, there is an apparent structural transformation that crumbles the layered 2D framework, leading to amorphization. The resulting material serves as the active material to host Mg2+ through reduction and/or oxidation of S and, to a limited extent, O. The reversible nature of S and O redox chemistry was confirmed by spectroscopic characterizations and validated by density functional calculations. Importantly, during the Mg2+ insertion and disinsertion process, the 2D nature of the framework was maintained, which plays a key role in enabling the high reversibility of the MOF cathode.

Contingency enables the formation of social expectations about an artificial agent.

What environmental regularities support infant communicative learning from social interactions? We propose that infants allocate their attention toward and learn from external events that are contingent on their own behaviors. We tested the robustness of the influence of contingency on communicative learning by using a non-biological stimulus, a remote-controlled car, as the social partner. The car approached infants and produced a speech sound either contingently to infants' vocalizations or on a yoked schedule. Two additional groups had an unfamiliar human experimenter as their social partner in contingent and yoked control conditions. We assessed whether infants formed expectations about their partner's responsiveness to their vocalizations. Expectations made based on contingent responsiveness would support the role of contingency in promoting plasticity in early communicative learning. Infants across all conditions increased their vocalization rates when their partner paused in responding, suggesting that they expected their vocalizations to influence their partners' behavior. Infants vocalized significantly more to the social partner than their caregiver if they received contingent rather than yoked responses from the social partner, regardless of if the partner was a human or non-biological agent. Contingent responses to prelinguistic vocalizations facilitated the formation of expectations for interactivity of social partners.

An exploration into the relationship between insomnia and repetitive negative thinking among cancer survivors.

OBJECTIVE: Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors. METHODS: This study analyzed survey data from 40 cancer survivors with insomnia who participated in a pilot randomized trial of CBT-I. Correlations and linear regression models were used to determine associations between aspects of RNT and related constructs (fear of cancer recurrence [FCR], cancer-specific rumination, worry, and intolerance of uncertainty) and sleep (insomnia and sleep quality), while accounting for psychiatric symptoms such as anxiety and depression. Treatment-related change in RNT was examined using a series of linear mixed models. RESULTS: Evidence for an association between RNT and insomnia among cancer survivors emerged. Higher levels of FCR and cancer-related rumination were correlated with more severe insomnia symptoms and worse sleep quality. Notably, FCR levels predicted insomnia, even after controlling for anxiety and depression. Results identified potential benefits and limitations of CBT-I in addressing RNT that should be examined more thoroughly in future research. CONCLUSIONS: RNT is a potential target to consider in insomnia treatment for cancer survivors.

CRISPR-Cas9 for selective targeting of somatic mutations in pancreatic cancers.

Somatic mutations are desirable targets for selective elimination of cancer, yet most are found within noncoding regions. We have adapted the CRISPR-Cas9 gene editing tool as a novel, cancer-specific killing strategy by targeting the subset of somatic mutations that create protospacer adjacent motifs (PAMs), which have evolutionally allowed bacterial cells to distinguish between self and non-self DNA for Cas9-induced double strand breaks. Whole genome sequencing (WGS) of paired tumor minus normal (T-N) samples from three pancreatic cancer patients (Panc480, Panc504, and Panc1002) showed an average of 417 somatic PAMs per tumor produced from single base substitutions. Further analyses of 591 paired T-N samples from The International Cancer Genome Consortium found medians of ∼455 somatic PAMs per tumor in pancreatic, ∼2800 in lung, and ∼3200 in esophageal cancer cohorts. Finally, we demonstrated 69-99% selective cell death of three targeted pancreatic cancer cell lines using 4-9 sgRNAs designed using the somatic PAM discovery approach. We also showed no off-target activity from these tumor-specific sgRNAs in either the patient's normal cells or an irrelevant cancer using WGS. This study demonstrates the potential of CRISPR-Cas9 as a novel and selective anti-cancer strategy, and supports the genetic targeting of adult cancers.

Caregiver reactions to babbling organize turn-taking interactions: Facilitative effects of vocal versus non-vocal responses.

Turn-taking interactions are foundational to the development of social, communicative, and cognitive skills. In infants, vocal turn-taking experience is predictive of infants' socioemotional and language development. However, different forms of turn-taking interactions may have different effects on infant vocalizing. It is presently unknown how caregiver vocal, non-vocal and multimodal responses to infant vocalizations compare in extending caregiver-infant vocal turn-taking bouts. In bouts that begin with an infant vocalization, responses that maintain versus change the communicative modality may differentially affect the likelihood of further infant vocalizing. No studies have examined how caregiver response modalities that either matched or differed from the infant acoustic (vocal) modality might affect the temporal structure of vocal turn-taking beyond the initial serve-and-return exchanges. We video-recorded free-play sessions of 51 caregivers with their 9-month-old infants. Caregivers responded to babbling most often with vocalizations. In turn, caregiver vocal responses were significantly more likely to elicit subsequent infant babbling. Bouts following an initial caregiver vocal response contained significantly more turns than those following a non-vocal or multimodal response. Thus prelinguistic turn-taking is sensitive to the modality of caregivers' responses. Future research should investigate if such sensitivity is grounded in attentional constraints, which may influence the structure of turn-taking interactions.

Early Real-World Patient and Staff Experience with an Intracanalicular Dexamethasone Insert.

Purpose: To evaluate both the early experience of real-world patients treated with dexamethasone ophthalmic insert (0.4 mg; DEXTENZA®), hereafter referred to as DEX, after cataract surgery as well as staff/practice integration of DEX relative to eyedrops. Patients and Methods: This was a cross-sectional survey study of 23 cataract practices in the United States. Respondents were patients and practice staff who had experience with DEX following cataract surgery. Both patients and practice staff completed an online survey. Descriptive statistics summarized the survey responses to portray the experience of the respondents. Results: Surveys were completed by 62 patients and 19 practice staff. Almost all patients (93%) were satisfied or extremely satisfied with DEX. Patients highly preferred DEX (93%) to topical steroid drops (7%) based on past experiences with topical steroid drops. Most practice staff (95%) were satisfied or highly satisfied with DEX, reporting a 45% reduction in time spent educating patients on postoperative drop use and a 46% decrease in time spent addressing calls from pharmacies regarding postoperative medications. Conclusion: Incorporating the DEX insert into clinical practice in cataract surgery practices can improve patient adherence, while potentially providing significant savings to practices in terms of time spent educating patients and responding to patient and pharmacy call-backs.

Glycemic Management in Insulin-Naive Patients in the Inpatient Setting.

Objective: The ideal inpatient insulin regimen efficiently attains the target blood glucose range, effectively treats hyperglycemia, and minimizes the risk of hypoglycemia. The objective of this study was to compare glycemic targets achieved by using correctional monotherapy (CM) and basal-bolus therapy (BBT) in insulin-naive patients in the inpatient setting to determine optimal blood glucose management for these patients. Design: This was a retrospective observational cohort study of 792 patients with diabetes not on home insulin therapy who were admitted to an academic hospital over a 5.5-month period. The percentages of hyperglycemic and hypoglycemic values in each group were compared. Results: Among the 3,112 measured blood glucose values obtained from 792 patients within the first 24 hours of insulin administration, 28.5% were hyperglycemic in the BBT group compared with 23.5% in the CM group. When adjusted for covariates, there was a 23% decrease in hyperglycemia in the BBT group (incidence rate ratio = 0.77, 95% CI 0.64-0.95, P = 0.006). Increases in A1C and admission blood glucose, as well as decreases in admission creatinine and inpatient steroid use, were independently associated with higher rates of hyperglycemia, adjusted for all other covariates. There was no significant difference between the groups in the rate of hypoglycemia in the first 24 hours, which was 1.9% in the BBT group and 1.4% in the CM group (P = 0.301). Conclusion: Utilizing BBT in insulin-naive patients admitted to the hospital within the first 24 hours of insulin administration results in lower rates of hyperglycemia without higher rates of hypoglycemia when compared with CM.

Developmental cascades of vocal turn-taking connect prelinguistic vocalizing with early language.

Conversational turn-taking is ubiquitously found in caregiver-infant interactions, and robustly predictive of infant communicative development. Over the first year, infants take quick adult-like vocal turns with caregivers. Many studies have documented the consistency of caregiver responsiveness and its influence on infant rapid language growth. However, few have examined how caregiver responsiveness facilitates extended vocal turn-taking in real-time with infants over the first year. The influence of prelinguistic vocal turn-taking on the emergence of language has also been under-investigated. We analyzed free-play sessions of 30 caregivers and their infants at both 5 and 10 months, and obtained infant language outcomes at 18 months. We examined the developmental consistency (group-level continuity and dyad-order stability) and change of infant volubility, caregiver responses to babbling in vocal, non-vocal and multimodal modalities, and the influence of modality on caregiver-infant vocal turn-taking. Caregiver contingent responsiveness to infant babbling at 5 months predicted vocal turn-taking at 10 months. Developmental increases in prelinguistic vocalizing and vocal turn-taking from 5 to 10 months predicted infant language outcomes at 18 months. At both 5 and 10 months, caregiver vocal responses were more effective in extending turn-taking than non-vocal or multimodal responses. In summary, prelinguistic vocal turn-taking, facilitated by caregiver vocal responsiveness, is positively related to the emergence of early language.

Massive 4-Gland Parathyroid Hyperplasia Initially Detected as a Parathyroid Adenoma.

Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery. Abnormalities in the parathyroid glands can be identified with various imaging modalities including ultrasound (US), sestamibi scan (MIBI), 4-dimensional computed tomography (4D-CT), and positron emission tomography/computed tomography (PET/CT). While it is not uncommon for parathyroid pathology to be undetected on imaging, this is more typical of low-volume hyperplasia and smaller-sized adenomas. We present the case of a 65-year-old man with PHPT who initially had a solitary parathyroid mass detected by US, but who was ultimately discovered to have massive PH with hyperplastic glands not visualized on US or MIBI. This atypical presentation may help guide providers in decisions on ordering and interpreting various imaging modalities for patients with PHPT. In this case, 4D-CT was the only modality in which large hyperplastic glands were identified, suggesting superior sensitivity. This case also highlights the importance of intraoperative parathyroid hormone testing to aid in diagnostic prediction.

Polysulfides in Magnesium-Sulfur Batteries.

Mg-S batteries hold great promise as a potential alternative to Li-based technologies. Their further development hinges on solving a few key challenges, including the lower capacity and poorer cycling performance when compared to Li counterparts. At the heart of the issues is the lack of knowledge on polysulfide chemical behaviors in the Mg-S battery environment. In this Review, a comprehensive overview of the current understanding of polysulfide behaviors in Mg-S batteries is provided. First, a systematic summary of experimental and computational techniques for polysulfide characterization is provided. Next, conversion pathways for Mg polysulfide species within the battery environment are discussed, highlighting the important role of polysulfide solubility in determining reaction kinetics and overall battery performance. The focus then shifts to the negative effects of polysulfide shuttling on Mg-S batteries. The authors outline various strategies for achieving an optimal balance between polysulfide solubility and shuttling, including the use of electrolyte additives, polysulfide-trapping materials, and dual-functional catalysts. Based on the current understanding, the directions for further advancing knowledge of Mg polysulfide chemistry are identified, emphasizing the integration of experiment with computation as a powerful approach to accelerate the development of Mg-S battery technology.

Insulin Requirements in Untreated Acromegaly: From 200 to 0.

We describe a patient with acromegaly presenting in diabetic ketoacidosis who was able to achieve euglycemia despite discontinuation of all antihyperglycemic therapy prior to surgical or medical treatment for his acromegaly. No previous cases of acromegaly presenting in diabetic ketoacidosis have reported glycemic normalization without antihyperglycemic therapy prior to acromegaly treatment. Our case highlights this unique outcome and postulates that pancreatic ß-cell resiliency may be influential on insulin resistance since our patient achieved euglycemia despite a persistent state of excess growth hormone and insulin-like growth factor-1. Our case further emphasizes that consideration for acromegaly should be given in patients presenting with severe insulin resistance and pertinent medical history and physical examination features, and it emphasizes the dramatic range of insulin requirements in patients with acromegaly.

Effect of Transperineal Versus Transrectal Prostate Biopsy on the Quality of Hydrogel Spacer Placement in Men Prior to Radiation Therapy for Prostate Cancer.

OBJECTIVE: To determine whether prostate biopsy type affects spacer placement quality using a large sample of patients treated in the ambulatory setting. METHODS: A retrospective cohort study was conducted on patients diagnosed with prostate cancer who underwent hydrogel spacer placement before primary radiation treatment between 2018 and 2023 after transperineal (TP) or transrectal (TR) prostate biopsy. Study outcomes were Spacer Quality Score (SQS) (0-2, with greater values indicating better placement), Rectal Wall Infiltration (RWI) (0-3, with lower values indicating lack of RWI), and the occurrence of other hydrogel complications. RESULTS: A total of 395 patients were included. A pre-hydrogel TR biopsy was performed in 273 patients (69.1%), while TP biopsy was performed in 122 (30.9%). A SQS ≥1 occurred in 308 (77.9%) patients. A greater proportion of TP patients had a favorable SQS (≥1) compared to those who underwent TR (87.7 vs 73.5%, P <.002). An RWI score ≥2 was found in 180 (45.6%) patients. The proportion of patients with an unfavorable RWI score (≥2) did not differ significantly by type of biopsy performed. Patients who had an interval of >70 days between biopsy and hydrogel placement had significantly decreased odds of an RWI score ≥2 (odds ratio = 0.42, 95% confidence interval: 0.21-0.83). Only one infection was found after hydrogel placement. CONCLUSION: The quality of hydrogel placement was significantly better in men who had undergone TP biopsy. Rectal wall infiltration was more common than previously reported but did not differ between TP and TR biopsies.

Uterocervical angle in predicting spontaneous preterm birth: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the uterocervical angles in term and spontaneous preterm birth cohorts and to compare the test characteristics of the uterocervical angle and cervical length in the prediction of spontaneous preterm birth. DATA SOURCES: A systematic search of published literature from January 1, 1945, to May 15, 2022, was performed using the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, World Health Organization International Clinical Trials Registry Platform, Web of Science, and ClinicalTrials.gov. The search was not restricted. The references of all relevant articles were reviewed. STUDY ELIGIBILITY CRITERIA: Randomized control trials, nonrandomized control trials, and observational studies were evaluated for primary comparisons. Included studies compared the uterocervical angles in term and spontaneous preterm birth cohorts and compared the uterocervical angle with cervical length in the prediction of spontaneous preterm birth. METHODS: Of note, 2 researchers independently selected studies and evaluated the risk of bias with the Newcastle-Ottawa Scale for cohort and case-control studies. Mean differences and odds ratios were calculated using a random effects model for inclusion and methodological quality. The primary outcomes were uterocervical angle and successful prediction of spontaneous preterm birth. Moreover, posthoc analysis comparing the uterocervical angle and cervical length together was performed. RESULTS: A total of 15 cohort studies with 6218 patients were included. The uterocervical angle was larger in the spontaneous preterm birth cohorts (mean difference, 13.76; 95% confidence interval, 10.61-16.91; P<.00001; I2=90%). Sensitivity and specificity analyses demonstrated lower sensitivities with cervical length alone and uterocervical angle plus cervical length than with uterocervical angle alone. Pooled sensitivities for uterocervical angle and cervical length alone were 0.70 (95% confidence interval, 0.66-0.73; I2=90%) and 0.46 (95% confidence interval, 0.42-0.49; I2=96%), respectively. Pooled specificities for uterocervical angle and cervical length were 0.67 (95% confidence interval, 0.66-0.68; I2=97%) and 0.90 (95% confidence interval, 0.89-0.91; I2=99%), respectively. The areas under the curve for uterocervical angle and cervical length were 0.77 and 0.82, respectively. CONCLUSION: Uterocervical angle alone or with cervical length was not superior to cervical length alone in predicting spontaneous preterm birth.

Curiosity constructs communicative competence through social feedback loops.

One of the most important challenges for a developing infant is learning how best to allocate their attention and forage for information in the midst of a great deal of novel stimulation. We propose that infants of altricial species solve this challenge by learning selectively from events that are contingent on their immature behavior, such as babbling. Such a contingency filter would focus attention and learning on the behavior of social partners, because social behavior reliably fits infants' sensitivity to contingency. In this way a contingent response by a caregiver to an immature behavior becomes a source of learnable information - feedback - to the infant. Social interactions with responsive caregivers afford infants opportunities to explore the impacts of their immature behavior on their environment, which facilitates the development of socially guided learning. Furthermore, contingent interactions are opportunities to make and test predictions about the efficacy of their social behaviors and those of others. In this chapter, we will use prelinguistic vocal learning to exemplify how infants use their developing vocal abilities to elicit learnable information about language from their social partners. Specifically, we review how caregivers' contingent responses to babbling create information that facilitates infant vocal learning and drives the development of communication. Infants play an active role in this process, as their developing predictions about the consequences of their actions serve to further refine their allocation of attention and drive increases in the maturity of their vocal behavior.

Comparison of a Novel, Flavor-optimized, Polyethylene Glycol and Sulfate Bowel Preparation With Oral Sulfate Solution in Adults Undergoing Colonoscopy.

INTRODUCTION: A new bowel preparation for colonoscopy has been developed containing poorly absorbed sulfate salts and polyethylene glycol 3350, which retain water within the intestinal lumen resulting in copious diarrhea, thereby cleansing the bowel. The product was formulated to be safe and effective with a sports drink-like flavor. This study evaluated the new flavored polyethylene glycol and sulfate solution (FPSS) compared with a Food and Drug Administration-approved bowel preparation containing sulfate salts only [oral sulfate solution (OSS)]. METHODS: Five hundred adults were enrolled in this multicenter, noninferiority study. Subjects were assigned FPSS or OSS administered in split-dose regimens (PM/AM). FPSS subjects took 2 L of the flavored osmotic solution (1 L at night and 1 L in the morning). OSS was taken according to its approved labeling. Colonoscopies were graded globally and segmentally by blinded local investigators using a 4-point scale (excellent, good, fair, and poor), with "good" and "excellent" considered successful. Safety was assessed by adverse events (AEs) and laboratory testing. RESULTS: A high rate of cleansing success was seen with FPSS (94%), which was noninferior to OSS (94%). This conclusion was confirmed by blinded central readers. Segmental success rates were >90% for both preparations, including the right colon. Questionnaire ratings indicated the FPSS experience was preferred over OSS with 87% of FPSS subjects noting their preparation was "tolerable" to "very easy" to consume versus 74% for OSS. The majority of FPSS subjects agreed their preparation tasted like a sports drink. Gastrointestinal symptoms were the most common AEs. There was no difference between preparations for any AE and no clinically significant differences in laboratory parameters. CONCLUSIONS: The new sports drink-like flavored preparation achieved a high level of cleansing in the study, demonstrating noninferiority to OSS. FPSS was well-tolerated with low rates of expected gastrointestinal symptoms. The optimized flavor of FPSS resulted in significantly better acceptance ratings.

CMV-associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity among immunocompromised patients who have undergone kidney transplantation and is known to rarely induce collapsing focal segmental glomerulosclerosis (FSGS) among adults. METHODS: We present the first reported case of CMV-induced collapsing FSGS in a pediatric patient after kidney transplant. RESULTS: Our patient underwent a deceased donor kidney transplant due to end-stage renal disease secondary to lupus nephritis. Approximately 4 months after transplantation, he developed signs of worsening kidney function in the setting of CMV viremia and was found to have collapsing features of FSGS on kidney transplant biopsy. He was managed with a prompt escalation of antiviral therapy along with a reduction of immunosuppression and recovered without significant complication. At follow-up, he continued to have undetectable CMV titers, creatinine within normal limits, and no significant proteinuria. CONCLUSION: This report demonstrates CMV as a cause of collapsing FSGS and should be considered among pediatric transplant recipients who present with acute kidney injury, as should early assessment of APOL1 genetic status in both donor and recipient.

Effects of Punctal Occlusion on Ocular Itching and Conjunctival Redness Associated with Allergic Conjunctivitis.

PURPOSE: Punctal occlusion using punctal plugs has been successfully used to treat the signs and symptoms of dry eye disease. However, the effects of punctal occlusion on the symptoms of allergic conjunctivitis (AC) have been less well documented. There is some concern among clinicians that punctal occlusion may make signs/symptoms of allergic conjunctivitis worse by trapping allergens on the eye. The objective of this post hoc analysis was to address this question and thus assess the effect of punctal occlusion alone on ocular itching and conjunctival redness associated with AC. METHODS: This was a pooled post hoc analysis of three randomized, double-blind, placebo insert-controlled clinical trials in subjects with AC. Enrolled subjects were generally healthy adults with ocular allergies and a positive skin test reaction to perennial and/or seasonal allergens. The study used a modified version of the traditional conjunctival allergen challenge (CAC) model, which included multiple, repeated allergen challenges following placement of the intracanalicular insert. Subjects were rechallenged on Days 6, 7 and 8; Days 13, 14 and 15; and Days 26, 27 and 28. RESULTS: The data set included 128 subjects that were administered placebo. Baseline mean (SD) ocular itching and conjunctival redness scores were 3.52 (0.44) and 2.97 (0.39), respectively. On post-insertion Days 7, 14 and 28, mean itching scores were 2.62, 2.26 and 1.91, respectively, representing 26%, 36% and 46% itching reductions, respectively (p < 0.001). On Days 7, 14 and 28, mean conjunctival redness scores were 1.98, 1.90, and 2.08, respectively, representing 33%, 36%, and 30% redness reductions, respectively (p < 0.001). CONCLUSIONS: Based on this post hoc pooled analysis, punctal occlusion with a resorbable hydrogel intracanalicular insert did not worsen ocular itching or conjunctival redness in this patient population.