Natural airway as an alternative to intubation for pediatric endoscopic esophageal foreign body removal: A retrospective cohort study of 326 patients.

BACKGROUND: Anesthesia is required for endoscopic removal of esophageal foreign bodies (EFBs) in children. Historically, endotracheal intubation has been the de facto gold standard for airway management in these cases. However, as more elective endoscopic procedures are now performed under propofol sedation with natural airway, there has been a move toward using similar Monitored Anesthesia Care (MAC) for select patients who require endoscopic removal of an EFB. METHODS: In this single-center retrospective cohort study, we compared endoscopic EFB removal with either MAC or endotracheal intubation. Descriptive statistics summarized factors stratified by initial choice of airway technique, including intra- and postanesthesia complications and the frequency of mid-procedure conversion to endotracheal intubation in those initially managed with MAC. To demonstrate the magnitude of associations between these factors and the anesthesiologist's choice of airway technique, univariable Firth logistic and quantile regressions were used to estimate odds ratios (95% CI) and beta coefficients (95% CI). RESULTS: From the initial search, 326 patients were identified. Among them, 23% (n = 75) were planned for intubation and 77% (n = 251) were planned for MAC. Three patients (0.9%) who were initially planned for MAC required conversion to endotracheal intubation after induction. Two (0.6%) of these children were admitted to the hospital after the procedure and treated for ongoing airway reactivity. No patient experienced reflux of gastric contents to the mouth or dislodgement of the foreign body to the airway, and no patient required administration of vasoactive medications or cardiopulmonary resuscitation. Patients had higher odds that the anesthesiologist chose to utilize MAC if the foreign body was a coin (OR, 3.3; CI, 1.9-5.7, p < .001) or if their fasting time was >6 h. Median total operating time was 15 min greater in intubated patients (11 vs. 26 min, p < .001). CONCLUSIONS: This study demonstrates that MAC may be considered for select pediatric patients undergoing endoscopic removal of EFB, especially those who have ingested coins, who do not have reactive airways, who have fasted for >6 h, and in whom the endoscopic procedure is expected to be short and uncomplicated. Prospective multi-site studies are needed to confirm these findings.

Post-Ebola Symptoms 7 Years After Infection: The Natural History of Long Ebola.

BACKGROUND: Lingering symptoms have been reported by survivors of Ebola virus disease (EVD). There are few data describing the persistence and severity of these symptoms over time. METHODS: Symptoms of headache, fatigue, joint pain, muscle pain, hearing loss, visual loss, numbness of hands or feet were longitudinally assessed among participants in the Liberian Ebola Survivors Cohort study. Generalized linear mixed effects models, adjusted for sex and age, were used to calculate the odds of reporting a symptom and it being rated as highly interfering with life. RESULTS: From June 2015 to June 2016, 326 survivors were enrolled a median of 389 days (range 51-614) from acute EVD. At baseline 75.2% reported at least 1 symptom; 85.8% were highly interfering with life. Over a median follow-up of 5.9 years, reporting of any symptom declined (odds ratio for each 90 days of follow-up = 0.96, 95% confidence interval [CI]: .95, .97; P < .0001) with all symptoms declining except for numbness of hands or feet. Rating of any symptom as highly interfering decreased over time. Among 311 with 5 years of follow-up, 52% (n = 161) reported a symptom and 29% (n = 47) of these as highly interfering with their lives. CONCLUSIONS: Major post-EVD symptoms are common early during convalescence and decline over time along with severity. However, even 5 years after acute infection, a majority continue to have symptoms and, for many, these continue to greatly impact their lives. These findings call for investigations to identify the mechanisms of post-EVD sequelae and therapeutic interventions to benefit the thousands of effected EVD survivors.

Comparison of general endotracheal anesthesia versus sedation without endotracheal intubation during initial percutaneous endoscopic gastrostomy insertion for infants: A retrospective cohort study.

BACKGROUND: Critical airway incidents are a major cause of morbidity and mortality during anesthesia. Delayed management of airway obstruction quickly leads to severe complications due to the reduced apnea tolerance in infants and neonates. The decision of whether to intubate the trachea during anesthesia is therefore of great importance, particularly as an increasing number of procedures are performed outside of the operating room. AIM: In this retrospective cohort study, we evaluated airway management for infants below 6 months of age undergoing percutaneous endoscopic gastrostomy insertion. We compared demographic, procedural, and health outcome-related data for infants undergoing percutaneous endoscopic gastrostomy insertion under general endotracheal anesthesia (n = 105) to those receiving monitored anesthesia care (n = 44) without endotracheal intubation. METHODS: A retrospective chart review was completed for all infants <6 months of age who underwent percutaneous endoscopic gastrostomy insertion in our institution's endoscopy suite between January 2002 and January 2017. Descriptive statistics summarized numeric variables using medians and corresponding ranges (minimum-maximum), and categorical variables using frequencies and percentages. Differences in study outcomes between patients undergoing general anesthesia or monitored anesthesia care were evaluated with univariate quantile or Firth logistic regression for numerical and categorical outcomes, respectively. Results are presented as ß [95% confidence interval] or odds ratio [95% confidence interval] along with corresponding p-values. RESULTS: Both groups were similar in distribution of age, race, and gender. However, patients selected for general anesthesia had lower median body weights (3.9 kg [range: 2.0-6.7] vs. 4.4 kg [range: 2.6-6.9]), higher percentages of cardiac (95.2% vs. 84.1%), and/or neurologic comorbidities (74.3% vs. 56.8%) and were more frequently given American Society of Anesthesiologists level IV classifications (41.9% vs. 29.6%) indicating that these infants may have had more severe disease than patients selected for monitored anesthesia care. Three monitored-anesthesia-care patients required intraoperative conversion to general anesthesia. General anesthesia patients experienced greater odds of intraoperative hypoxemia (45.2% vs. 29.0%; odds ratio: 2.0 [0.9-4.3], p-value: .09) and required postoperative airway intervention more frequently than monitored-anesthesia-care patients (13.03% vs. 2.3%; odds ratio: 4.6 [0.8-25.6], p-value: .08). Procedure times were identical in both groups (6 min), but general anesthesia resulted in longer median anesthesia times (44 min [range: 22-292] vs. 12 min [range:19-136]; ß:13 [95% 6.9-19.1], p-value: < .001). CONCLUSION: Study results suggest that providers selected general anesthesia over monitored anesthesia care for infants and neonates with low body weights, cardiac comorbidities, and neurologic comorbidities. Increased rates of airway intervention, and increased length of stay may be at least partially related to more severe patient comorbidity, as indicated by higher American Society of Anesthesiologists classifications. However, due to the exploratory nature of these analyses, further confirmatory studies are needed to evaluate the impact of airway selection during PEG on postoperative patient outcomes.

Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.

BACKGROUND: Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms. METHODS: The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation. RESULTS: At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up. CONCLUSIONS: Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease.

Background: Ebola virus (EBOV) neutralizing antibody in plasma may reduce viral load following administration of plasma to patients with Ebola virus disease (EVD), but measurement of these antibodies is complex. Methods: Anti-EBOV antibody was measured by 2 neutralization and 2 enzyme-linked immunosorbent assays (ELISAs) in convalescent plasma (ECP) from 100 EVD survivor donors in Liberia. Viral load was assessed repetitively in patients with EVD participating in a clinical trial of enhanced standard of care plus ECP. Results: All 4 anti-EBOV assays were highly concordant for detection of EBOV antibody. Antibodies were not detected in plasma specimens obtained from 15 of 100 donors, including 7 with documented EBOV-positive reverse-transcription polymerase chain reaction during EVD. Viral load was reduced following each dose in the 2 clinical trial participants who received ECP with higher antibody levels but not in the 2 who received ECP with lower antibody levels. Conclusions: Recovery from EVD can occur with absence of detectable anti-EBOV antibody several months after disease onset. ELISAs may be useful to select ECP donors or identify ECP units that contain neutralizing antibody. ECP with higher anti-EBOV antibody levels may have greater effect on EBOV load-an observation that requires further investigation. Clinical Trials Registration: NCT02333578.

Ophthalmic Manifestations and Causes of Vision Impairment in Ebola Virus Disease Survivors in Monrovia, Liberia.

PURPOSE: To describe the ocular findings, visual impairment, and association of structural complications of uveitis with visual impairment in a cohort of survivors of Ebola virus disease (EVD) in Monrovia, Liberia. DESIGN: Retrospective, uncontrolled, cross-sectional study. PARTICIPANTS: Survivors of EVD who were evaluated in an ophthalmology clinic at Eternal Love Winning Africa (ELWA) Hospital in Monrovia, Liberia. METHODS: A cohort of EVD survivors who underwent baseline ophthalmic evaluation at ELWA Hospital were retrospectively reviewed for demographic information, length of Ebola treatment unit (ETU) stay, visual acuity (VA), and ophthalmic examination findings. For patients with uveitis, disease activity (active vs. inactive) and grade of inflammation were recorded according to Standardization of Uveitis Nomenclature criteria. The level of VA impairment was categorized according to World Health Organization classification for VA impairment as follows: normal/mild, VA 20/70 or better; moderate, VA 20/70-20/200; severe, VA 20/200-20/400; blindness, VA <20/400. Visual acuity, length of ETU stay, and structural complications were compared between EVD survivors with and without uveitis. Structural complications associated with moderate VA impairment or poorer were analyzed. MAIN OUTCOME MEASURES: Frequency of ocular complications including uveitis and optic neuropathy in EVD survivors, level of VA impairment in EVD survivors with uveitis, and structural complications associated with VA impairment in EVD survivors. RESULTS: A total of 96 survivors of EVD were examined. A total of 21 patients developed an EVD-associated uveitis, and 3 patients developed an EVD-associated optic neuropathy. Visual acuity was blind (VA >20/400) in 38.5% of eyes with uveitis. Anatomic subtypes of uveitis included anterior, posterior, and panuveitis in 2, 13, and 6 patients, respectively. Examination findings associated with at least moderate visual impairment by World Health Organization criteria (VA <20/70) included keratic precipitates (P < 0.002), posterior synechiae (P < 0.002), vitritis (P < 0.005), and chorioretinal scars (P < 0.02). CONCLUSIONS: Survivors of EVD are at risk for uveitis, which may lead to secondary structural complications, visual impairment, and blindness. Eye care resources should be mobilized for EVD survivors in West Africa because of the frequency of this spectrum of disease complication and its potential for severe VA impairment and blindness.

Apheresis for collection of Ebola convalescent plasma in Liberia.

PURPOSE: This report describes initiation of apheresis capability in Liberia, Africa to support a clinical trial of convalescent plasma therapy for Ebola Virus Disease. METHODS: A bloodmobile was outfitted in the United States as a four-bed apheresis unit with capabilities including pathogen reduction, electronic blood establishment computer system, designated areas for donor counseling and laboratory testing, and onboard electrical power generation. After air transport to Liberia, the bloodmobile was positioned at ELWA Hospital, Monrovia, and connected to the hospital's power grid. Liberian staff were trained to conduct donor screening, which included questionnaire and onsite blood typing and transfusion transmitted infection (TTI) testing, and plasma collection and processing. RESULTS: The bloodmobile was operational within 3 weeks after arrival of the advance team. Of 101 donors who passed the pre-screening questionnaire, 32 were deferred. Twenty-eight of ninty-nine tested survivors were deferred for positive transfusion transmitted infection (TTI) tests; twenty-one were positive for hepatitis B, hepatitis C, or human immunodeficiency virus. The majority of donors had type O blood; all but one were Rh positive. Forty-three survivors donated at least once; eighty-nine apheresis attempts resulted in eighty-one successful collections. CONCLUSIONS: Apheresis capability was emergently established in Liberia to support an efficacy trial of Ebola Convalescent Plasma. Extensive cooperation among multinational team members, engineers, logisticians, and blood safety technical personnel at the operational site was required to surmount challenges to execution posed by logistical factors. The high proportion of positive TTI tests supported the use of a pathogen reduction system to enhance product safety. J. Clin. Apheresis 32:175-181, 2017. © 2016 Wiley Periodicals, Inc.

Diabetes Group Visits at the University of South Florida Morsani College of Medicine.

IN BRIEF "Quality Improvement Success Stories" are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a successful project from the Division of General Internal Medicine at the University of South Florida Morsani College of Medicine, Tampa, to improve A1C, systolic blood pressure, and weight in patients with type 2 diabetes.

Striatins contain a noncanonical coiled coil that binds protein phosphatase 2A A subunit to form a 2:2 heterotetrameric core of striatin-interacting phosphatase and kinase (STRIPAK) complex.

The protein phosphatase 2A (PP2A) and kinases such as germinal center kinase III (GCKIII) can interact with striatins to form a supramolecular complex called striatin-interacting phosphatase and kinase (STRIPAK) complex. Despite the fact that the STRIPAK complex regulates multiple cellular events, it remains only partially understood how this complex itself is assembled and regulated for differential biological functions. Our recent work revealed the activation mechanism of GCKIIIs by MO25, as well as how GCKIIIs heterodimerize with CCM3, a molecular bridge between GCKIII and striatins. Here we dissect the structural features of the coiled coil domain of striatin 3, a novel type of PP2A regulatory subunit that functions as a scaffold for the assembly of the STRIPAK complex. We have determined the crystal structure of a selenomethionine-labeled striatin 3 coiled coil domain, which shows it to assume a parallel dimeric but asymmetric conformation containing a large bend. This result combined with a number of biophysical analyses provide evidence that the coiled coil domain of striatin 3 and the PP2A A subunit form a stable core complex with a 2:2 stoichiometry. Structure-based mutational studies reveal that homodimerization of striatin 3 is essential for its interaction with PP2A and therefore assembly of the STRIPAK complex. Wild-type striatin 3 but not the mutants defective in PP2A binding strongly suppresses apoptosis of Jurkat cells induced by the GCKIII kinase MST3, most likely through a mechanism in which striatin recruits PP2A to negatively regulate the activation of MST3. Collectively, our work provides structural insights into the organization of the STRIPAK complex and will facilitate further functional studies.

Cumulative geoecological effects of 62 years of infrastructure and climate change in ice-rich permafrost landscapes, Prudhoe Bay Oilfield, Alaska.

Many areas of the Arctic are simultaneously affected by rapid climate change and rapid industrial development. These areas are likely to increase in number and size as sea ice melts and abundant Arctic natural resources become more accessible. Documenting the changes that have already occurred is essential to inform management approaches to minimize the impacts of future activities. Here, we determine the cumulative geoecological effects of 62 years (1949-2011) of infrastructure- and climate-related changes in the Prudhoe Bay Oilfield, the oldest and most extensive industrial complex in the Arctic, and an area with extensive ice-rich permafrost that is extraordinarily sensitive to climate change. We demonstrate that thermokarst has recently affected broad areas of the entire region, and that a sudden increase in the area affected began shortly after 1990 corresponding to a rapid rise in regional summer air temperatures and related permafrost temperatures. We also present a conceptual model that describes how infrastructure-related factors, including road dust and roadside flooding are contributing to more extensive thermokarst in areas adjacent to roads and gravel pads. We mapped the historical infrastructure changes for the Alaska North Slope oilfields for 10 dates from the initial oil discovery in 1968-2011. By 2010, over 34% of the intensively mapped area was affected by oil development. In addition, between 1990 and 2001, coincident with strong atmospheric warming during the 1990s, 19% of the remaining natural landscapes (excluding areas covered by infrastructure, lakes and river floodplains) exhibited expansion of thermokarst features resulting in more abundant small ponds, greater microrelief, more active lakeshore erosion and increased landscape and habitat heterogeneity. This transition to a new geoecological regime will have impacts to wildlife habitat, local residents and industry.

Test Your Memory-Spanish version (TYM-S): a validation study of a self-administered cognitive screening test.

OBJECTIVES: To develop the Test Your Memory (TYM)-Spanish version (TYM-S), a self-administered cognitive screening test, in a Chilean older sample and to estimate its psychometric properties and diagnostic accuracy. METHODS: The TYM was translated into Spanish and adapted for a Chilean population to develop the TYM-S. Measures of global cognitive impairment and executive dysfunction were administered to 30 controls, 30 dementia patients, and 14 subjects with mild cognitive impairment (MCI). All participants' proxies were interviewed with assessments of dementia severity, functionality in daily living activities, and cognitive change. Convergent validity and internal consistency reliability of the TYM-S were estimated. Cut-off points, sensitivity, and specificity were determined to test its diagnostic capacity for dementia or MCI. RESULTS: Regarding convergent validity, the TYM-S was significantly correlated (p < 0.001) with global cognitive impairment (Mini-Mental State Examination: r = 0.902; Addenbrooke's Cognitive Examination-Revised-Chilean version: r = 0.922; Montreal Cognitive Assessment: r = 0.923), executive dysfunction (Frontal Assessment Battery: r = 0.862), dementia severity (Clinical Dementia Rating: r = -0.757), functional capacity (Technology-Activities of Daily Living Questionnaire: r = -0.864; Pfeffer Functional Activities Questionnaire: r = -0.748; Instrumental Activities of Daily Living: r = 0.769), and cognitive change (Alzheimer's Disease 8-Chilean version: r = -0.700) measures. Regarding reliability, Cronbach's α was 0.776. Optimum cut-off scores of 39 and 44 distinguished dementia cases from controls (93.1% sensitivity, 82.2% specificity) and MCI cases from controls (85.7% sensitivity, 69% specificity), respectively. The extent of assistance required in the TYM-S and cognitive impairment was correlated. CONCLUSIONS: The TYM-S is a valid and reliable instrument to assess cognitive impairment, showing good psychometric properties and diagnostic capacity to identify cases of dementia in a Spanish-speaking older cohort. Although its need for assistance may be limiting, its ability to quickly assess several cognitive domains supports widespread clinical use.

Visualizing key hinges and a potential major source of compliance in the lever arm of myosin.

We have determined the 2.3-Å-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ("smooth") muscle. This structure reveals hinges that may function in the "on" and "off" states of myosin. The molecule adopts two different conformations about the heavy chain "hook" and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 Å. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during the contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.

Concurrent cecal lipoma and Crohn's disease in a pediatric patient: A conservative approach.

We report the case of a 14-year-old patient with a known history of Crohn's disease who was incidentally diagnosed with an asymptomatic cecal lipoma. A routine surveillance colonoscopy as part of the management of the patient's Crohn's Disease revealed a well-defined, submucosal, yellowish mass in the patient's cecum. Histopathological examination of a biopsy specimen revealed submucosal adipose tissue, consistent with the endoscopic images showing the characteristic appearance of the lipoma. A computed tomography examination further confirmed the diagnosis. While colonic lipomas are infrequent and typically manifest later in life, few cases report the coexistence of a cecal lipoma with Crohn's disease, particularly in the pediatric population. In this case, managing this dual condition posed a notable challenge. Here, we present the conservative approach to managing a pediatric patient with cecal lipoma and Crohn's disease. The decision to leave the lipoma in situ was based on the absence of symptoms and potential risks associated with surgical removal.

Managing cow's milk protein allergy during the 2022 formula shortage: decision-making among pediatric healthcare providers.

Introduction: Cow's milk protein allergy (CMPA) affects 2%-7% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding healthcare providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. Methods: This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. Results: 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Discussion: Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care.

Impact of the 2022 national formula shortage on clinical decision-making of healthcare providers in switching amino acid formulas for infants with cow's milk protein allergy: a survey-based study.

Background: In 2022, the United States experienced a national shortage of infant formula due to a global supply chain crisis and a large-scale domestic formula recall. The existing literature on healthcare providers' (HCPs) clinical decision-making during formula shortages is limited. This study aims to analyze the factors influencing pediatric HCP clinical decision-making when switching between amino acid formulas (AAF) for managing cow's milk protein allergy (CMPA) in infants under 24 months of age during an unprecedented national formula shortage. Methods: The study included pediatric HCPs with experience managing CMPA in infants and toddlers under 24 months during the formula shortage from January 2022 to November 2022. A de-identified survey comprising 26 questions examining driving factors used in clinical decision-making was administered to pediatric HCPs using a real-time mobile data collection tool. Results: Among the surveyed pediatric HCPs (n = 75), the factors most frequently considered as "extremely important" when switching to another AAF included safety (85%), tolerability (73%), and efficacy (83%). No statistically significant differences were found in HCP ratings among the listed examined factors of the four AAFs. The availability of specific formulas was the only factor that exhibited a statistically significant difference in perceived performance among pediatric HCPs when comparing the four AAFs (p < 0.05). Discussion: This study elucidates the crucial aspects that influenced pediatric HCPs' selection of AAFs for CMPA management during the 2022 formula shortage. The findings highlight the significance of safety, tolerability, efficacy, and availability in the pediatric HCP decision-making processes.

Corrigendum: Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

[This corrects the article DOI: 10.3389/falgy.2023.1333570.].

Extensively Hydrolyzed Formula and Infant Colic Symptoms: Secondary Analysis of a Prospective Cohort Study.

Cow's milk protein allergy (CMPA) affects 2% to 3% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding health care providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices. This study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages. A total of 104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness. Findings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care.

Deriving how far structural information is transmitted through parallel homodimeric coiled-coils: a correlation analysis of helical staggers.

How local conformation is affected by local sequence is fairly well understood for alpha-helical coiled-coils, but less is known about how local conformation is influenced by distant features. Here, I describe an approach to detect such an effect, based on computing correlation coefficients of local out-of-register alignments, or so-called "staggers" between the helices, as a function of the axial distance between the staggers. This approach requires parallel homodimers, in which each stagger can occur with two "signs," where either one helix or the other is shifted towards the N terminus. The signs of such staggers separated by up to 12 residues are strongly correlated, indicating that the conformations of the ends of coiled-coils are commonly influenced by attached structures. Thus, the structures of coiled-coil residues aberrantly attached to alternative proteins, such as those resulting from leukemogenic chromosomal rearrangements, may be distinguishable from those in normal tissues, and in turn serve as targets of selective drug design. The signs of helical staggers separated by between 13 and 30 residues are moderately yet significantly correlated, indicating that some of the coiled-coils transmit this conformational feature axially for at least 45 Å. A positive, albeit noisy, correlation also exists among tropomyosin coiled-coils for signed staggers separated by the 40-residue actin repeat distance, consistent with the semi-flexible tropomyosin filament binding F-actin and regulating skeletal muscle contraction in a partially cooperative manner. Communication of the signs of axial staggers is explained in part by minimization of main-chain hydrogen bond deformations.