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Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of −40.7% (95% confidence interval [CI]: −47.7 to −33.7) in A&E attendances, −25.8% (95% CI: −31.1 to −20.4) in emergency hospital admissions and −60.9% (95% CI: −66.1 to −55.7) in planned hospital admissions, in comparison to the 2018–2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.

This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.

Aims: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). Background: Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. Objectives: Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity and associated functional impairments. Methods: Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. Results: We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology’s within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. Conclusion: Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

• The presentation of urinary tract infections (UTIs) in neonates differs from that seen in older children. • The type and route of infection also differ in neonates, when compared with older children. • An appropriate urine sample for diagnosis is needed, but treatment should not be delayed. • A neonate in whom a UTI is suspected should be evaluated for sepsis, including invasive cultures. • After a documented neonatal UTI, a radiologic work-up is warranted to detect anatomic anomalies. • Vesicoureteral reflux (VUR) is diagnosed in 30%–50% of neonates with proven UTI. • Voiding cystourethrogram is the gold standard for the diagnosis of VUR and should be performed on high-risk neonates. • Treatment of VUR should be tailored to each patient's individual risk of UTI recurrence, with the goals of preventing future UTIs and renal scar formation.

• Papulopustular lesions on the palms and/or soles in the first month of life likely represent a self-limited inflammatory process such as eosinophilic pustular folliculitis or infantile acropustulosis – but scabies should be ruled out. • Neonatal acne (aka cephalic pustulosis) is typically multifactorial and self-limited. Treatment is not necessary but topical agents aimed at reduction of the commensal yeast Malassezia can be beneficial. • Evidence suggests that early use of emollients in infants at risk of developing atopic dermatitis may prevent later disease. • Subcutaneous fat necrosis of the newborn is generally benign and self-limited but when extensive can cause hypercalcemia.

Thrombocytopenia is, after anemia, the most frequent hematological problem among sick neonates. In this population, thrombocytopenia has traditionally been defined as a platelet count 9 /L, and has been classified as mild (100–150 × 10 9 /L), moderate (50–99 × 10 9 /L), and severe ( 9 /L). However, large population-based studies have shown that platelet counts increase with advancing gestational age, and platelet counts between 100 and 150 × 10 9 /L are more frequent among otherwise healthy extremely preterm infants than among full term neonates or older children. This suggests that different definitions of thrombocytopenia and thrombocytosis should be applied to preterm infants. The diagnostic approach to a thrombocytopenic neonate is facilitated if the thrombocytopenia is categorized as “early onset” (within the first 72 hours of life, usually secondary to congenital or intrauterine abnormalities) or “late onset” (after 72 hours, usually due to acquired conditions). Importantly, infection/sepsis should always be considered near the top of the differential diagnosis, as any delay in diagnosis and treatment can have life-threatening consequences. While in vitro studies have clearly shown that neonatal platelets are hyporesponsive to most agonists, this platelet hyporeactivity is well compensated by factors in neonatal blood that increase clotting (i.e. high hematocrit, high VWF concentrations), resulting in adequate primary hemostasis. The risk of bleeding in thrombocytopenic neonates is poorly predicted by the platelet count; gestational age

• An understanding of thyroid embryogenesis and the physiology of the thyroid gland in the perinatal period is important for proper interpretation of abnormal laboratory results and initiation of appropriate treatment. • Appropriate thyroid hormone function is essential for normal neurodevelopment in infancy and childhood. Hypothyroidism in the first year of life can result in significant deleterious effects on growth and neurologic injury. • Delay in treatment of congenital hypothyroidism (CH) is the most common preventable cause of mental retardation. • Neonatal screening can provide early diagnosis and can prevent delays in treatment. Newborn screening methods differ and may possibly miss rare forms of congenital hypothyroidism. • Eighty-five percent of cases of permanent CH are associated with abnormal development of the thyroid gland. • In preterm newborns, thyroid hormone levels may fall because of immaturity of the thyroid gland, but these changes may be exacerbated by complications of prematurity. • Thyroid metabolism can be affected by exogenous sources of iodine, dopamine infusions, blood transfusion, and glucocorticoid treatment. • The clinical manifestations of Graves disease in the newborn include irritability, flushing, diarrhea, vomiting, tachycardia, hypertension, poor weight gain, thyroid enlargement, and exophthalmos. • There is concern for neurologic damage in infants with hemangiomas when hypothyroidism is occult and untreated.

• The placenta is the first organ to form in mammals and is required for establishment of a maternal–fetal vascular interface capable of supplying the bioenergetic needs of the developing conceptus. • Multiple placental cell types engage in highly varied functions, from attachment, invasion, and vascular remodeling to cell fusion, hormone production, and nutrient transport. • Multiple mechanisms allow transport of waste and nutrients across the placenta, including diffusion, transporter protein-mediated (facilitated diffusion and active transporters), and receptor-mediated mechanisms. • The placenta is not an inert transport interface. It consumes 40%–60% of the oxygen and glucose delivered to the uterus at term. Thus conditions that alter placental metabolism can indirectly affect nutrient transport to the fetus. • Maternal and fetal health alter placental function, which in turn influences fetal adaptations and contributes to in utero fetal programming. • Abnormal placentation and placental infections can lead to preeclampsia (PE), fetal growth retardation, or preterm birth, which can have lifelong bearing on health. • In the United States, iatrogenic delivery is responsible for almost half the births that occur between 28 and 37 weeks of gestation, primarily caused by placental pathologies such as PE or intrauterine growth restriction. • Efforts to standardize placental examination after delivery are in progress so that connections between specific placental problems and poor outcomes can be better defined. In parallel, new advanced imaging techniques and biomarkers for placental function are being developed.

Chronic diffuse lung diseases involve a spectrum of nonneoplastic inflammatory conditions that affect the lung parenchyma. This chapter reviews the spectrum of disease including idiopathic interstitial pneumonias, pulmonary manifestations of systemic collagen vascular disease, diffuse eosinophilc lung disease, drug-associated lung disease, diffuse granulomatous lung disease, and a variety of miscellaneous diseases that defy classification. Individual entities are reviewed, followed by a section highlighting a practical approach to the four most common patterns of injury encountered in practice.

This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau-an important ACL injury risk factor-causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.

Background Thumb carpometacarpal (CMC) joint arthroplasty is a common procedure in the surgical management of symptomatic thumb basal joint arthritis. Following trapeziectomy, a number of suspensionplasty techniques are often used, but limited comparative evidence exists between these techniques. The central aim of this study was to prospectively compare the outcomes of 2 suspensionplasty techniques following trapeziectomy: suture button (TightRope) versus ligament reconstruction and tendon interposition (LRTI). Methods Prospective data were collected on 112 consecutive patients with Eaton stage III-IV thumb CMC arthritis who underwent open trapeziectomy and suspensionplasty. There were 53 LRTI and 59 TightRope suspensionplasty procedures. Outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand ( QuickDASH) questionnaire, Visual Analogue Scale (VAS) for pain, radiographic analysis, and lateral pinch strength. Patient demographic data and complications were also recorded. Results Patients undergoing TightRope suspensionplasty had significantly higher trapeziometacarpal index and thus less subsidence than the LRTI group at 2 weeks (0.22 vs 0.17 [ P < .0001]) and 3 months (0.17 vs 0.15 [ P < .05]) postoperatively. TightRope suspensionplasty also had a significantly lower QuickDASH score at 2 weeks (64.7 vs 74.6 [ P < .05]), 3 months (20.7 vs 32.5 [ P < .05]), and 1 year postoperatively (7.57 vs 21.5 [ P < .05]) compared with the LRTI group. However, there was no difference in VAS pain, lateral pinch strength, reoperation, or complications at any time point between groups. Conclusions Thumb CMC joint arthroplasty performed with a TightRope suspensionplasty versus LRTI yielded short-term improved resistance to subsidence, long-term greater improvement in clinical outcome by QuickDASH, and no difference in pain or complication rates.

• Current American Urological Association guidelines do not recommend ultrasound for the evaluation of undescended testicles. • Children with an undescended testicle should be referred to a pediatric urologist at approximately 6 months of age. • Infants with bilateral nonpalpable testicles should be evaluated for possible congenital adrenal hyperplasia. • Infants with hypospadias and unilateral or bilateral undescended testicles should be evaluated for disorder of sexual development. • Repair of hypospadias is recommended at between 6 months and 1 year of age. • Bladder exstrophy repairs are currently delayed to 3 months of age. • A voiding cystourethrogram should be performed in infants with high-grade hydronephrosis and bilateral hydronephrosis. • Most hydroceles in infants are noncommunicating, and infants should be referred to a urologist if they fluctuate in size suggesting a communicating hydrocele. • Vesicoureteral reflux is more common in male infants and has a high rate of resolution.

A new section on the approach to diagnostic histological interpretation, is the overture to this chapter on inherited and developmental disorders. This initial section is split chronologically into the early neonatal and infantile period and later childhood and adulthood; with the intention of reflecting clinical practice as closely and succinctly as possible. Disorders of the biliary tree, bile formation and secretion, and hepatocyte metabolism are the core of this chapter, a merger of chapters 3 and 4 of the previous edition. Considerations on the pathogenetic and/or clinical overlap between developmental, genetic and metabolic disorders were the rationale behind this change. The complexity of hepatocyte metabolism is reflected into the miriad of related pathological conditions. Recent technological advances, particularly in genomics in the last five years, have resulted in a plethora of new entities and changes in terminology, challenging the authors to balance detail and application to clinical practice. Tables and figures from previous editions have been largely kept due to their quality and contemporary relevance, whilst new ones have been added to accommodate new advances (e.g. classification of mitochondrial disorders), a compromise to bridge between the two editions for the accustomed reader. Liver involvement in immunodeficiency and miscellaneous disorders precede the final section on anatomical anomalies. Vascular anomalies are now included in the chapters on vascular disorders.

Optimal specimen handling is essential for the accurate interpretation of biopsies and cytologic preparations obtained in the course of evaluating the patient with lung disease. Sampling techniques available include bronchoscopy, transthoracic needle core biopsy or aspiration, and surgical wedge biopsy of peripheral lung through a transthoracic approach. In this chapter specimen characteristics and processing steps are presented for each of the common lung samples taken in the course of clinical evaluation for pulmonary disease. Also, for each type of sample the benefits and limitations are reviewed. Such a working knowledge of specimen handling for each procedure ensures the greatest likelihood of success in establishing a specific diagnosis and, in the end, a rational treatment plan. The addition of clinical information dramatically increases the likelihood of a meaningful and accurate pathologic diagnosis, especially in the setting of biopsies for diffuse lung disease (interstitial lung disease).

In the general population, the construct of race is associated with disparities in cognitive aging. There are notable racial group disparities and inequities among people living with schizophrenia (PLWSz). Despite the salience of the construct of race in schizophrenia, there remains a knowledge gap about racial disparities in cognitive impairment among older adults in this vulnerable population. Our study uses mediation analysis to examine racial disparities in cognitive impairment among older adults with schizophrenia.We assess global cognition in PLWSz over age 55 with the Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive test battery in our "all-comer" sample (There was a Black/non-Black group racial disparity in global cognitive score (-2.8, 95% CI: -4.4, -1.3) after adjusting for confounding and interaction. This disparity was significantly mediated by years of education.There are notable racial disparities in cognitive impairment among older adults with schizophrenia; however, differences in cognitive scores between racial groups are mediated by level of education.Social determinants of health, particularly educational attainment, are important risk factors for cognitive impairment in PLWSz and should be considered by clinicians. Early screening and assessment of cognitive symptoms is essential to addressing health disparities/inequalities among older adults living with schizophrenia.Controlled Direct EffectsHIV: Human Immunodeficiency VirusMATRICS: Measurement and Treatment Research to Improve Cognition in SchizophreniaMCCB: MATRICS Consensus Cognitive BatteryMTE: Marginal Total EffectsNDE: Natural Direct EffectsPANSS: Positive and Negative Symptom ScalePLWSz: People with schizophrenia.

• Owing to their cutaneous, immunologic, and renal immaturity, newborns (especially premature neonates) are at increased risk of infection. • As a group of potentially life-threatening but often treatable diseases, infections must always be considered in a newborn with skin lesions. • Prompt diagnosis and initiation of therapy are crucial to prevent devastating long-term sequelae, particularly in instances of disseminated disease. • Staphylococcus aureus, Streptococcus species, Candida albicans, and herpes simplex virus are the most common causes of skin infections in the neonate.

• Infants born with ambiguous genitalia or nonpalpable testes need to be evaluated for congenital adrenal hyperplasia as it can be life threatening. • Adrenal steroid levels vary with gestational age. • Adrenal insufficiency should be treated with hydrocortisone to avoid adrenal crisis. High doses of hydrocortisone contain mineralocorticoid activity.

Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus. Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction characterised by weakness and fatiguability, carrying a high morbidity if treatment is delayed. A clear association with thymoma has led to management with thymectomy as a common practice, but MG presenting post-thymectomy has rarely been reported. We present a case of an 82- year-old woman developing fatigue, ptosis and dysarthria 3 months after thymectomy. After a clinical diagnosis of MG was made, she responded well to prompt treatment with prednisolone and pyridostigmine. Her anti-acetylcholine receptor antibody (anti-AChR) subsequently came back positive. Our systematic review reveals that post-thymectomy MG can be categorised as early-onset or late-onset form with differing aetiology, and demonstrated correlation between preoperative anti-AChR titres and post-thymectomy MG. The postulated mechanisms for post-thymectomy MG centre around long-lasting peripheral autoantibodies. Clinicians should actively look for MG symptoms in thymoma patients and measure anti-AChR preoperatively to aid prognostication.

Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150.000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac-seq and used an integrative data approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as the two critical transcription factors differentially regulating MIBC regulatory landscape. Importantly, we show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these two transcription factors and link this information with their target genes, providing a comprehensive regulatory circuit for the genes implicated in invasive ability of the bladder cancer cells. Finally, for the first time we show that knock-down of FRA1 and FRA1-FLI1 double knock-down results in significant reduction of invasion capacity of MIBC cells towards muscle microenvironment using IC-CHIP assays. Our results collectively highlight the role of these two transcription factors in invasive characteristics of bladder cancer in selection and design of targeted options for treatment of MIBC.

Background: Depression is a concern during pregnancy, but it is especially prevalent for pregnant adolescents. Because prenatal depression is a strong predictor of postpartum depression and other forms of psychopathology in both mothers and children, it is important to understand potential risk and protective factors for prenatal depression.Objectives: The present study examined whether social support buffered the impact of childhood trauma on prenatal depression, and whether social support exerted a stronger buffering effect for adolescents compared to adults.Method: Self-reported levels of childhood trauma, social support, and prenatal depression were collected in a racially and ethnically diverse sample of 682 first-time mothers, 58% were adolescents (n = 396; Mage = 17.38 years) and 42% were adults (n = 286; Mage = 26.29 years).Results: Using multi-group moderation analyses, we found that pregnant adolescents with more social support were buffered from the effects of childhood trauma on prenatal depression symptoms, but pregnant adults with more social support were not.Conclusion: Findings support the stress-buffering model in that those with more stressors may benefit more from social support than those with fewer stressors. These results highlight the importance of social support and inform prenatal depression prevention/intervention strategies particularly with pregnant adolescents.

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

The purpose of the study was to explore the associations of sub-ethnicity to the survivorship experience of Asian American breast cancer survivors and identify the multiple factors that influenced their survivorship experience. This was a secondary analysis of the data among 94 Asian American breast cancer survivors from a larger ongoing study. Instruments included: questions on background characteristics, the perceived isolation scale, the Personal Resource Questionnaire, the Memorial Symptom Assessment Scale-Short Form, and the Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using hierarchical logistic and multiple regression analyses. After controlling for other factors, being a Japanese American (ref. = being a Chinese American) was significantly associated with pain scores (odds ratio [OR] = −0.32, p

Objective Intra-procedural WEB device migration is a scarcely reported complication that necessitates prompt intervention. Case Presentation Endovascular treatment of two broad necked flow-related aneurysms was planned aided by WEB-SL (Woven EndoBridge-single layer) devices in a 71-year-old female with known left temporal arteriovenous malformation. Inadvertent distal migration occurred while performing a control angiogram with an automated iodine injector. Immediate retrieval was successfully performed using a Solitaire stent-retriever. Conclusion To our knowledge, we report for the first time the successful retrieval of a distally migrated WEB using a stent-retriever device.

Leukemia and lymphoma are cancers affecting children, adolescents, and young adults and may affect reproductive outcomes and maternal metabolism. We evaluated for metabolic changes in newborns of mothers with a history of these cancers.A cross-sectional study was conducted on California births from 2007 to 2011 with linked maternal hospital discharge records, birth certificate, and newborn screening metabolites. History of leukemia or lymphoma was determined using ICD-9-CM codes from hospital discharge data and newborn metabolite data from the newborn screening program.A total of 2,068,038 women without cancer history and 906 with history of leukemia or lymphoma were included. After adjusting for differences in maternal age, infant sex, age at metabolite collection, gestational age, and birthweight, among newborns born to women with history of leukemia/lymphoma, several acylcarnitines were significantly (The varied metabolite levels suggest history of leukemia or lymphoma has metabolic impact on newborn offspring, which may have implications for future metabolic consequences such as necrotizing enterocolitis and urea cycle enzyme disorders in children born to mothers with a history of leukemia or lymphoma.

Objective To evaluate pre - to post-season differences in individual subtests of the Visio-Vestibular Examination (VVE) in healthy middle and high school athletes. Methods This prospective cohort study recruited participants from a private suburban United States secondary school. Participants completed a demographic questionnaire prior to the start of their season. A proxy for head impact exposure was estimated by incorporating previously published head impact frequencies by team and sport. The VVE was completed pre - and post-season and consisted of 9 subtests: smooth pursuit, horizontal/vertical saccades and gaze stability, binocular convergence, left/right monocular accommodation, and complex tandem gait. Generalized estimating equations were employed to assess the relative risk of an abnormal VVE outcome based on testing session (pre - vs. post-season). Results Participants included middle and high school athletes (n = 115; female = 59 (51.3%); median age at first assessment = 14.9 years, [IQR = 13.6, 16.0]) during 2017/18 - 2019/20 school years. During pre-season testing, accommodation (10.0%) and complex tandem gait (9.2%) had the largest proportion of abnormal outcomes, while smooth pursuits (10.6%) and convergence (9.5%) had the largest proportion of abnormal outcomes post-season. When assessing the effect of testing session on the relative risk of any abnormal VVE subtest, there were no significant findings (P ≥ 0.25). Additionally, there were no significant effects of testing session when adjusting for estimated head impact exposure for any VVE subtest (P ≥ 0.25). Conclusions Visio-vestibular function as measured by the VVE does not change from pre - to post-season in otherwise healthy adolescent athletes. Our findings suggest that the VVE may be stable and robust to typical neurodevelopment occurring in this dynamic age group and help inform post-injury interpretation of visio-vestibular impairments.

Objectives The study aimed to describe daily sleep characteristics for dementia care dyads in the context of adult day services (ADS) use and examine the associations with sleep quality and daytime functioning (fatigue, affect, and behavior problems). Methods Caregivers (CG; N = 173) reported daily bedtime, wake time, and sleep quality for themselves and the persons living with dementia (PLWD) across 8 consecutive days (N = 1359), where PLWD attended ADS at least 2 days of the week. On each day, caregivers also reported their own fatigue and affect and PLWD's daytime behavior problems and nighttime sleep problems. Considering the context of ADS use, we compared mean differences in bedtime, wake time, and total time in bed on nights before versus after ADS use. We estimated multilevel models to examine daily sleep-well-being associations. Results On nights before an upcoming ADS day, care dyads went to bed and woke up earlier, and spent less time in bed. Further, PLWD had better sleep quality the night before an upcoming ADS day. Using ADS during the day buffered the negative impact of PLWD's sleep problems in the previous night, reducing daytime negative affect for caregivers. For caregivers, using ADS yesterday attenuated the association between shorter than typical time in bed and daytime fatigue; it also attenuated the association between PLWD's nighttime sleep problems and lowered daytime positive affect. Conclusions Regular ADS use may promote earlier sleep timing and protect against the adverse impact of sleep disturbances on daytime functioning for dementia care dyads.

Background Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. Case presentation A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. Conclusion CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

The formation of an intraperitoneal pseudocyst as a complication of ventriculoperitoneal shunts is well known. However, the formation of a pseudocyst at the subcutaneous extraperitoneal abdominal space is unusual and likely secondary to the migration of the peritoneal catheter. We present a 53-year-old male who had placement of a ventriculoperitoneal shunt for hydrocephalus secondary to a vestibular schwannoma. Five months later, he presented with an enormously distended abdomen. Investigations showed the peritoneal catheter in the extraperitoneal space within a large right lower quadrant abdominal wall pseudocyst. The patient was taken to the operating theatre, and the shunt was externalised at the original abdominal incision. Approximately 3 L of cerebrospinal fluid were aspirated from the distal peritoneal catheter. After negative cultures, a new peritoneal catheter was placed intraperitoneally at the contralateral lower abdominal quadrant. The contralateral quadrant was utilised to prevent fluid accumulation into the old extraperitoneal cavity.

Uterine rupture can be associated with severe maternal and neonatal morbidity and mortality. It should be considered as a differential diagnosis in all pregnant women who present with acute abdomen, haemoperitoneum and have specific risk factors, even during the first trimester. This is a case report of a 25-year-old woman who presented to emergency department with abdominal pain and vaginal bleeding at approximately 6–8 weeks gestation. She developed an acute surgical abdomen and required urgent surgical management. Despite intervention, she had massive haemorrhage, disseminate intravascular coagulation, admission to intensive care unit and prolonged hospital stay as complications. Posterior uterine wall rupture while rare, must be considered as a differential diagnosis as early intervention is crucial to prevent bad outcomes.

Introduction: Chronic kidney disease of uncertain etiology (CKDu) has been found at high frequency in several lowland agricultural areas including Meso-America and Sri Lanka. Whether CKDu also occurs in other countries with large agricultural populations remains uncertain, primarily due to lack of systematic data on kidney function. Hemoglobin (Hgb) levels could be an ancillary marker for presence of kidney dysfunction. Our goal is to estimate the causal effect of agricultural work on Hgb level in men. A causal effect may indicate the presence of CKDu. Methods: We use Demographic and Health Surveys (DHS) data from seven African and Asian countries (Ethiopia, Lesotho, Namibia, Senegal, Uganda, Zimbabwe, and India). We use optimal full matching and permutation inference to estimate the causal effect of agricultural work on altitude-adjusted Hgb levels after adjusting for six known confounders. To assess potential bias due to unmeasured socioeconomic differences, we use multiple control groups that differ in non-agricultural occupation. We then conduct sensitivity analyses to assess the robustness of our causal conclusions to unmeasured confounding. Results: Data were available for 41,180 agricultural workers and 55,705 non-agricultural workers in seven countries. On average, Hgb levels were 0.09 g/dL (95% CI [-0.12, -0.07]) lower among agricultural workers compared to matched controls. Significant effects were observed in Ethiopia, India, Lesotho, Senegal, and Uganda, with effects from 0.10 to 0.32 g/dL lower hemoglobin among agricultural workers. The effect was not attenuated in sensitivity analyses involving both better-off and worse-off occupational controls. Discussion: We find evidence that men engaged in agricultural work in five of the seven countries studied have modestly lower Hgb levels compared with other men living in rural areas. Since underlying kidney disease could be a potential explanation for this finding, our data support consideration to integrating kidney function assessments within DHS surveys and other population-based surveys.

Experimental preclinical models have been a cornerstone of lung cancer translational research. Work in these model systems has provided insights into the biology of lung cancer subtypes and their origins, contributed to our understanding of the mechanisms that underlie tumor progression, and revealed new therapeutic vulnerabilities. Initially patient-derived lung cancer cell lines were the main preclinical models available. The landscape is very different now with numerous preclinical models for research each with unique characteristics. These include genetically engineered mouse models (GEMMs), patient-derived xenografts (PDXs) and three-dimensional culture systems ("organoid" cultures). Here we review the development and applications of these models and describe their contributions to lung cancer research.

Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

OBJECTIVE: To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR following trimodality therapy for esophagogastric adenocarcinoma is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (TR) in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P

PURPOSE To determine the predictive value of International Classification of Diseases, 9th Revision (ICD-9) codes for identifying infantile eye diagnoses. METHODS Population-based retrospective cohort study of all residents of Olmsted County, Minnesota diagnosed at ≤1 year of age with an ocular disorder. The medical records of all infants diagnosed with any ocular disorder from January 1, 2005, through December 31, 2014, were identified. To assess ICD-9 code accuracy, the medical records of all diagnoses with ≥20 cases were individually reviewed and compared to their corresponding ICD-9 codes. Main outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-9 codes. RESULTS In a cohort of 5,109 infants with ≥1 eye-related ICD-9 code, 10 ocular diagnoses met study criteria. The most frequent diagnoses were conjunctivitis (N = 1,695) and congenital nasolacrimal duct obstruction (N = 1,250), while the least common was physiologic anisocoria (N = 23). The PPVs ranged from 8.3% to 88.0%, NPVs from 96.3% to 100%, sensitivity from 3.0% to 98.7%, and specificity from 72.6% to 99.9%. ICD-9 codes were most accurate at identifying physiologic anisocoria (PPV: 88.0%) and least accurate at identifying preseptal cellulitis (PPV: 8.3%). In eye specialists versus non-eye specialists, there was a significant difference in PPV of ICD-9 codes for conjunctivitis (26.8% vs. 63.9%, p

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Bruck syndrome is an autosomal recessive disease characterised by the clinical combination of both osteogenesis imperfecta and arthrogryposis multiplex congenita (AMC). It is caused due to collagen miss-folding and cross-linking defect resulting from a deletion in FKBP10 (OMIM #259450) and/or PLOD2

Occurrence of biogenic amines in fresh fish and fishery products constitute a significant safety concern. Ingestion of histamine is identified as the causative agent of several food poisoning incidences on an annual basis. In addition, cadaverine, putrescine and tyramine have been recognized as potentiators of histamine poisoning. Accumulation of biogenic amines in fresh fish and fishery products has been mainly attributed to growth of bacteria possessing amino acid decarboxylase activity, which is facilitated by lack of hygienic conditions and strict temperature control during their storage. To this end, the effectiveness of traditional and modern approaches to control biogenic amine accumulation has been in the epicenter of intensive study. The aim of the present review article is to update and integrate current knowledge regarding the biogenic amine content of fresh fish and fishery products as well as the capacity of traditional and emerging control strategies.

The average values of the seasonal flesh biochemical composition (%) of the pearl oyster Pinctada imbricata radiata originated form 2 sampling sites, the gulfs of Evoikos (E) and Saronikos (S) in the Western Aegean Sea, showed that is rich in proteins (64.00 ± 1.86 -(E), 64.67 ± 2.95-(S)) with low fat content (10.96 ± 1.04-(E), 11.86 ± 1.13-(S)) and carbohydrates (13.29 ± 2.48- (E), 9.94 ± 4.32 (S)). The condition index ranged from 26.16% ± 5.04 in the autumn in (E), to 44.73% ± 7.50 in the summer in (S). The meat yield varied from 20.49% ± 3.20% in the summer in (E) to 30.73% ± 3.47% in the summer in (S). Both results demonstrate the high nutritional profile of the pearl oyster, supporting its suitability as a potential new Mediterranean seafood source for human consumption.

Objective: Relational and emotional vulnerability represent essential problems among patients with personality disorder (PD). Group psychotherapy is a central component of evidence-based PD treatments. Generally, patient and therapist interrelationships predict improvement in therapy. However, although treatment of patients with PD is a more complex process, group processes are poorly elaborated in PD research. Documentation of the psychometric quality of group process measures in PD samples is an important precursor of such research. The Group Questionnaire—GQ is based on concepts of group cohesion and climate, empathy, and alliance and aims to capture the quality of member–member, member–group, and member–leader relationships in group therapy. A three latent factor structure (positive bond, positive work, and negative relationship) has generally been supported. This study aimed to perform a psychometric analysis of GQ administered in a clinical population of patients with PD. Method: The study included 369 patients with PDs attending group psychotherapy in 14 outpatient treatment units on a specialist mental health service level within the Norwegian Network of Personality Disorders in the period 2017–2020. Psychometric analyses included three latent factors and eight subfacets. Results: The three latent factors, positive bond, positive work, and negative relationship, were replicated. Psychometric integrity of the tripartite relationship structure—member–member, member–group, and member–leader, with eight subfacets, was supported. Conclusion: The GQ with three latent factors and eight subfacets can be recommended for future research and clinical practice in patient populations with PD.

Background: Beta blockers, mainly propranalol, are usually administered to control heart rate in patients with thyrotoxicosis, especially when congestive heart failure presents. However, when thyrotoxicosis is not controlled, heart rate may be difficult to control even with maximal doses of propranolol. This presentation alerts physicians to the possibility of using ivabradine, a selective inhibitor of the sinoatrial pacemaker, for the control of heart rate. Case presentation: We present a 37-year-old woman with thyrotoxicosis and congestive heart failure whose heart rate was not controlled with a maximal dose of beta blockers during a thyroid storm. The addition of ivabradine, a selective inhibitor of the sinoatrial pacemaker, controlled her heart rate within 48 hours. Conclusion: Ivabradine should be considered in patients with thyrotoxicosis, including those with heart failure, in whom beta blockers are insufficient to control heart rate