Dietitians' perspectives on key components relevant for successful dietetic treatment of adults with obesity in primary health care: a qualitative study in the Netherlands.

Background: Dietetic treatment of adults with obesity can result in effective weight loss with health improvements. However, it remains unclear which components of dietetic consultation are key for successful treatment of individual patients. Therefore, the aim of this study is to explore dietitians' perceptions of key components relevant for successful dietetic treatment of adults with obesity in primary health care in the Netherlands.

Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRAS Inhibitor.

Oncogenic mutations in the gene account for 30% of all human tumors; more than 60% of which present as KRAS mutations at the hotspot codon 12. After decades of intense pursuit, a covalent inhibition strategy has enabled selective targeting of this previously "undruggable" target. Herein, we disclose our journey toward the discovery of MK-1084, an orally bioavailable and low-dose KRAS covalent inhibitor currently in phase I clinical trials (NCT05067283).

(Dis)continuation of the oral contraceptive pill: A focus group approach in the Netherlands.

Objectives: The oral contraceptive pill (OCP) is the most used contraceptive worldwide; nevertheless, discontinuation rates are relatively high. While advantages of the OCP, like pregnancy prevention and planned parenthood, result in autonomy and independence, side effects and other aspects play a role in the decision to (dis)continue usage. Informed and deliberate decision-making is of importance to prevent adverse effects in health and quality of life.

Multicomponent Synthesis of the SARS-CoV-2 Main Protease Inhibitor Nirmatrelvir.

In the wake of the Covid-19 pandemic, it has become clear that global access to efficacious antiviral drugs will be critical to combat future outbreaks of SARS-CoV-2 or related viruses. The orally available SARS-CoV-2 main protease inhibitor nirmatrelvir has proven an effective treatment option for Covid-19, especially in compromised patients. We report a new synthesis of nirmatrelvir featuring a highly enantioselective biocatalytic desymmetrization (>99% ee) and a highly diastereoselective multicomponent reaction (>25:1 dr) as the key steps.

Prospective Randomized Trial of Biologic Augmentation With Bone Marrow Aspirate Concentrate in Patients Undergoing Arthroscopic Rotator Cuff Repair.

Background: Although initial studies have demonstrated that concentrated bone marrow aspirate (cBMA) injections promote rotator cuff repair (RCR) healing, there are no randomized prospective studies investigating clinical efficacy.

Hypothesis/purpose: To compare outcomes after arthroscopic RCR (aRCR) with and without cBMA augmentation. It was hypothesized that cBMA augmentation would result in statistically significant improvements in clinical outcomes and rotator cuff structural integrity.

Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors.

Mutant isocitrate dehydrogenase 1 (IDH1) has been identified as an attractive oncology target for which >70% of grade II and III gliomas and ∼10% of acute myeloid leukemia (AML) harbor somatic IDH1 mutations. These mutations confer a neomorphic gain of function, leading to the production of the oncometabolite ()-2-hydroxyglutarate (2-HG). We identified and developed a potent, selective, and orally bioavailable brain-penetrant tricyclic diazepine scaffold that inhibits mutant IDH1.

A behavioral approach to annotating sleep in infants: Building on the classic framework.

In infants, monitoring and assessment of sleep can offer valuable insights into sleep problems and neuro-cognitive development. The gold standard for sleep measurements is polysomnography (PSG), but this is rather obtrusive, and unpractical in non-laboratory situations. Behavioral observations constitute a non-obtrusive, infant-friendly alternative.

Affective communication with patients with limited health literacy in the palliative phase of COPD or lung cancer: Analysis of video-recorded consultations in outpatient care.

Objectives: Affective communication in outpatient care is important, especially in the palliative phase. Appropriate responses by healthcare providers to emotional cues or concerns let patients express their feelings and enhance information recall and patient satisfaction. Patients with limited health literacy experience more barriers in health-related communication and information, which makes recognizing their cues and concerns even more relevant.

Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children's Behavioral Measures.

Epigenetic changes are associated with altered behavior and neuropsychiatric disorders and they modify the trajectory of aging. Maternal anxiety during pregnancy is a common environmental challenge for the fetus, causing changes in DNA methylation. Here, we determined the mediating role of DNA methylation and the moderating role of offspring sex on the association between maternal anxiety and children's behavioral measures.

An orally available non-nucleotide STING agonist with antitumor activity.

Pharmacological activation of the STING (stimulator of interferon genes)-controlled innate immune pathway is a promising therapeutic strategy for cancer. Here we report the identification of MSA-2, an orally available non-nucleotide human STING agonist. In syngeneic mouse tumor models, subcutaneous and oral MSA-2 regimens were well tolerated and stimulated interferon-β secretion in tumors, induced tumor regression with durable antitumor immunity, and synergized with anti-PD-1 therapy.

Salvage reverse total shoulder arthroplasty for failed anatomic total shoulder arthroplasty: a cohort analysis.

Background: Reverse total shoulder arthroplasty (RTSA) as a revision procedure for failed anatomic total shoulder arthroplasty (TSA) is increasing in incidence. The purpose of this study was to analyze the results of RTSA as a revision salvage procedure for failed TSA and identify factors that influenced those outcomes.

Methods: All anatomic TSAs that were revised to RTSAs in adult patients, under the care of 2 senior surgeons at a single academic center from 2006 to 2018, were queried and reviewed.

Comparative Clinical Outcomes of Reverse Total Shoulder Arthroplasty for Primary Cuff Tear Arthropathy Versus Severe Glenohumeral Osteoarthritis With Intact Rotator Cuff: A Matched-Cohort Analysis.

Introduction: The purpose of this study was to compare the short- to mid-term outcomes of patients who underwent reverse total shoulder arthroplasty (RTSA) for severe glenohumeral osteoarthritis (GHOA) with an intact rotator cuff (RC) to a matched rotator cuff arthropathy (RCA) cohort.

Methods: Between 2004 and 2014, all patients who underwent RTSA for severe GHOA with a minimum 2-year follow-up were identified. Demographic and baseline variables were extracted from the medical records.

Arthroscopic Rotator Cuff Repair: A General Instructional Course Lecture.

Rotator cuff pathology is one of the most common reasons for patients to seek orthopaedic consultation. Although in many cases these issues can be resolved with proper conservative management, many of these patients benefit from surgical treatment. The goal of this instructional course lecture is to identify factors that can potentially lead to worse outcomes following repair, describe the history and techniques behind transosseous anchorless repairs, discuss subscapularis tears and their management, and to analyze the most current data regarding double-row rotator cuff repairs.

Sometimes the Power of Science is Driven by the Ratio of Love.

An infant with Crouzon syndrome was in need of cranial surgery. The optimum surgical correction was not possible, because at that time she was supported with continuous positive airway pressure attached to her occiput. However, the parents wanted the best craniofacial option and her father designed a respiratory support device with attachment to the forehead.

Tracker-Based Personal Advice to Support the Baby's Healthy Development in a Novel Parenting App: Data-Driven Innovation.

Background: The current generation of millennial parents prefers digital communications and makes use of apps on a daily basis to find information about child-rearing topics. Given this, an increasing amount of parenting apps have become available. These apps also allow parents to track their baby's development with increasing completeness and precision.

Voluntary acromioclavicular joint dislocation: a case report and literature review.

Voluntary glenohumeral dislocations have been reported in academic literature; however, voluntary dislocations of the acromioclavicular joint are rare, with four cases previously reported in published literature. We present a case of an adolescent female with bilateral, atraumatic acromioclavicular joint dislocation who ultimately was treated with arthroscopic reconstruction of the coracoclavicular ligament. The case is discussed in addition to a review of previously reported cases of voluntary acromioclavicular joint dislocations.

Video-Based Actigraphy for Monitoring Wake and Sleep in Healthy Infants: A Laboratory Study.

Prolonged monitoring of infant sleep is paramount for parents and healthcare professionals for interpreting and evaluating infants' sleep quality. Wake-sleep patterns are often studied to assess this. Video cameras have received a lot of attention in infant sleep monitoring because they are unobtrusive and easy to use at home.

Potential benefits of mindfulness during pregnancy on maternal autonomic nervous system function and infant development.

Mindfulness is known to decrease psychological distress. Possible benefits in pregnancy have rarely been explored. Our aim was to examine the prospective association of mindfulness with autonomic nervous system function during pregnancy and with later infant social-emotional development.

Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances.

Altered stress responsiveness is a risk factor for mental and physical illness. In non-pregnant populations, it is well-known that anxiety can alter the physiological regulation of stress reactivity. Characterization of corresponding risks for pregnant women and their offspring requires greater understanding of how stress reactivity and recovery are influenced by pregnancy and women's anxiety feelings.

Differences between human auditory event-related potentials (AERPs) measured at 2 and 4 months after birth.

Infant auditory event-related potentials (AERPs) show a series of marked changes during the first year of life. These AERP changes indicate important advances in early development. The current study examined AERP differences between 2- and 4-month-old infants.

Multimodal processing of emotional information in 9-month-old infants II: prenatal exposure to maternal anxiety.

The ability to read emotional expressions from human face and voice is an important skill in our day-to-day interactions with others. How this ability develops may be influenced by atypical experiences early in life. Here, we investigated multimodal processing of fearful and happy face/voice pairs in 9-month-olds prenatally exposed to maternal anxiety, using event-related potentials (ERPs).

Multimodal processing of emotional information in 9-month-old infants I: emotional faces and voices.

Making sense of emotions manifesting in human voice is an important social skill which is influenced by emotions in other modalities, such as that of the corresponding face. Although processing emotional information from voices and faces simultaneously has been studied in adults, little is known about the neural mechanisms underlying the development of this ability in infancy. Here we investigated multimodal processing of fearful and happy face/voice pairs using event-related potential (ERP) measures in a group of 84 9-month-olds.

Overcoming mutagenicity and ion channel activity: optimization of selective spleen tyrosine kinase inhibitors.

Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors with favorable druglike properties is described. Early leads were discovered through X-ray crystallographic analysis, and a systematic survey of cores within a selected chemical space focused on ligand binding efficiency. Attenuation of hERG ion channel activity inherent within the initial chemotype was guided through modulation of physicochemical properties including log D, PSA, and pKa.

Highly Efficient Conservative Treatment of Pectus Carinatum in Compliant Patients.

Purpose: Pectus carinatum is a thoracic deformity, which causes severe psychological problems for affected patients but almost no physical limitations. Invasive procedures are difficult to justify for this reason. We present a conservative therapy which leads to complete resolution in most cases when performed properly.