A study of the prevalence of various lower urinary tract symptoms in children with analysis of comorbidities and uroflowmetry

Background: The International Children’s Continence Society (ICCS) in its standardization article in 2006 and subsequent revision in 2014 have provided guidelines for the diagnosis and management of lower urinary tract symptoms (LUTS) in children. However, the terminologies are still not in common parlance and colloquial terms are being heavily used in India. Objective: The objective of the study was to evaluate the clinical spectrum of LUTS and their comorbidities in children. Materials and Methods: This was an observational cross-sectional study conducted in a tertiary care hospital in Northern India. Children, included in the study, aged 5–12 years who presented with LUTS as defined in the ICCS 2014 updated guidelines. A simultaneous analysis of uroflowmetry graphs was also done in these children and the observations presented in this paper. Results: Enuresis was the most common LUTS with which children presented to the OPD (78% cases) followed by increased frequency of micturition (42%). Among comorbidities, constipation was present in one-third patients of LUTS. Uroflowmetry done in LUTS often yields a normal “bell-shaped” graph in majority of the patients (71%). The study shows that many enuretics have underlying other LUTS and comorbidities that we should be aware of and uroflowmetry, if not coupled with urodynamic studies, is not a game changer. Conclusion: There are not many studies post the standardization of the ICCS conducted in India and this study aims at increasing the awareness of the same among physicians and researchers alike

Sociology and postcolonialism: another 'missing' revolution?

Sociology is usually represented as having emerged alongside European modernity. The latter is frequently understood as sociology's special object with sociology itself a distinctively modern form of explanation. The period of sociology's disciplinary formation was also the heyday of European colonialism, yet the colonial relationship did not figure in the development of sociological understandings. While the recent emergence of postcolonialism appears to have initiated a reconsideration of understandings of modernity, with the development of theories of multiple modernities, I suggest that this engagement is more an attempt at recuperating the transformative aspect of postcolonialism than engaging with its critiques. In setting out the challenge of postcolonialism to dominant sociological accounts, I also address `missing feminist/queer revolutions', suggesting that by engaging with postcolonialism there is the potential to transform sociological understandings by opening up a dialogue beyond the simple pluralism of identity claims

Pancytopenia due to proguanil toxicity in a returning traveller with fever

A patient known to have renal insufficiency was admitted to the hospital with fever and pancytopenia after returning from a trip to Mali. Pancytopenia was not caused by a tropical infection but was a side effect of atovaquone/proguanil used as malaria chemoprophylaxis. High and prolonged detectable proguanil serum levels can result in bone marrow suppression in patients with renal insufficiency. This should be taken into account in a returning traveller with fever and pancytopenia

A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. Pancreatic cancer is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer

Using a genetically informative design to examine the relationship between breastfeeding and childhood conduct problems

A number of public health interventions aimed at increasing the uptake of breastfeeding are in place in the United States and other Western countries. While the physical health and nutritional benefits of breastfeeding for the mother and child are relatively well established, the evidence for psychological effects is less clear. This study aimed to examine whether there is an association between breastfeeding and later conduct problems in children. It also considered the extent to which any relationship is attributable to maternally-provided inherited characteristics that influence both likelihood of breastfeeding and child conduct problems. A prenatal cross-fostering design with a sample of 870 families with a child aged 4–11 years was used. Mothers were genetically related or unrelated to their child as a result of assisted reproductive technologies. The relationship between breastfeeding and conduct problems was assessed while controlling for theorised measured confounders by multivariate regression (e.g. maternal smoking, education, and antisocial behaviour), and for unmeasured inherited factors by testing associations separately for related and unrelated mother-child pairs. Breastfeeding was associated with lower levels of conduct disorder symptoms in offspring in middle childhood. Breastfeeding was associated with lower levels of conduct problems even after controlling for observed confounders in the genetically related group, but not in the genetically unrelated group. In contrast, maternal antisocial behaviour showed robust associations with child conduct problems after controlling for measured and inherited confounders. These findings highlight the importance of using genetically sensitive designs in order to test causal environmental influences

The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination

Histone mRNAs are rapidly degraded at the end of S phase, and a 26-nucleotide stem-loop in the 3′ untranslated region is a key determinant of histone mRNA stability. This sequence is the binding site for stem-loop binding protein (SLBP), which helps to recruit components of the RNA degradation machinery to the histone mRNA 3′ end. SLBP is the only protein whose expression is cell cycle regulated during S phase and whose degradation is temporally correlated with histone mRNA degradation. Here we report that chemical inhibition of the prolyl isomerase Pin1 or downregulation of Pin1 by small interfering RNA (siRNA) increases the mRNA stability of all five core histone mRNAs and the stability of SLBP. Pin1 regulates SLBP polyubiquitination via the Ser20/Ser23 phosphodegron in the N terminus. siRNA knockdown of Pin1 results in accumulation of SLBP in the nucleus. We show that Pin1 can act along with protein phosphatase 2A (PP2A) in vitro to dephosphorylate a phosphothreonine in a conserved TPNK sequence in the SLBP RNA binding domain, thereby dissociating SLBP from the histone mRNA hairpin. Our data suggest that Pin1 and PP2A act to coordinate the degradation of SLBP by the ubiquitin proteasome system and the exosome-mediated degradation of the histone mRNA by regulating complex dissociation

Adult attachment styles and the psychological response to infant bereavement

Background: Based on Bowlby's attachment theory, Bartholomew proposed a four-category attachment typology by which individuals judged themselves and adult relationships. This explanatory model has since been used to help explain the risk of psychiatric comorbidity. Objective: The current study aimed to identify attachment typologies based on Bartholomew's attachment styles in a sample of bereaved parents on dimensions of closeness/dependency and anxiety. In addition, it sought to assess the relationship between the resultant attachment typology with a range of psychological trauma variables. Method: The current study was based on a sample of 445 bereaved parents who had experienced either peri- or post-natal death of an infant. Adult attachment was assessed using the Revised Adult Attachment Scale (RAAS) while reaction to trauma was assessed using the Trauma Symptom Checklist (TSC). A latent profile analysis was conducted on scores from the RAAS closeness/dependency and anxiety subscales to ascertain if there were underlying homogeneous attachment classes. Emergent classes were used to determine if these were significantly different in terms of mean scores on TSC scales. Results: A four-class solution was considered the optimal based on fit statistics and interpretability of the results. Classes were labelled “Fearful,” “Preoccupied,” “Dismissing,” and “Secure.” Females were almost eight times more likely than males to be members of the fearful attachment class. This class evidenced the highest scores across all TSC scales while the secure class showed the lowest scores. Conclusions: The results are consistent with Bartholomew's four-category attachment styles with classes representing secure, fearful, preoccupied, and dismissing types. While the loss of an infant is a devastating experience for any parent, securely attached individuals showed the lowest levels of psychopathology compared to fearful, preoccupied, or dismissing attachment styles. This may suggest that a secure attachment style is protective against trauma-related psychological distress

A population-based study of anxiety as a precursor for depression in childhood and adolescence

BACKGROUND: Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. METHODS: Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5–17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. RESULTS: Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. CONCLUSIONS: Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression

The effect of birth-weight with genetic susceptibility on depressive symptoms in childhood and adolescence

Low birth-weight has been associated with depression and related outcomes in adults, and with problem behaviours in children. This study aimed to examine the association between low birth-weight for gestation and depressive symptoms in children and adolescents and to examine whether the relationship is moderated by genetic risk for depression. An epidemiological, genetically sensitive design was used including 2,046 twins aged 8–17 years (1,023 families). Data were obtained by parental report and analysed using regression analysis. A small but significant association between birth-weight for gestation and early depressive symptoms was observed. The unit increase in depressive symptoms per unit decrease in birth-weight for gestation was greater for individuals at genetic or familial risk for depression. For low birth-weight children, genetic risk for depression moderated the influence of birth-weight for gestation in predicting early depressive symptoms. Birth-weight for gestation is moderated by genetic and familial risk for depression in influencing early depression symptoms. These observations have clinical implications in that the impact of being small for gestational age on depressive symptoms is greater in children at familial/genetic risk although the association between birth weight and depression does not imply causality

Thyroid Hemiagenesis: Narrative Review and Clinical Implications

Thyroid Hemiagenesis (THA) is an uncommon, congenital anomaly defined by the absence of one thyroid lobe with or without the isthmus. Reports suggest it may be found more often in regions endemic for hypothyroidism. Genetic abnormalities are thought to have a role based on findings in monozygotic twins. Most cases are sporadic, however familiar clusters have also been documented. It is found more frequently in females. A majority of patients report no symptoms and THA is found incidentally during investigations or intraoperatively. THA is usually associated with normal thyroid function, but it can present with thyroid hypofunction. Since a majority of patients are asymptomatic, there are no specific recommendations for management. Ultrasound imaging and thyroid scintigraphy using technetium or iodine are useful in diagnosis. Its clinical importance occurs when the remnant thyroid lobe requires excision leading to the lifelong requirement for thyroxine supplementation. Published English literature (Medline, PubMed, and Embase databases) was searched. Medical subject headings (MeSH) terms used were “thyroid hemiagenesis,” “one thyroid lobe,” and “thyroid aplasia”. Case reports, case series, and original articles were selected to provide a framework for this review. Articles reviewed were published in the past 20 years. The association of THA with thyroid cancer was explored. In this group, the F:M ratio was 3.25:1. Left THA constituted 53% of cases, right THA in 29.4%, and isthmus absence in 17.6% of cases. Also, the authors investigated the link between THA and hyperparathyroidism, both left and right THA are seen in an equal number of cases in the hyperparathyroidism subgroup. In patients with THA and Grave’s disease, left THA was seen in a majority of cases (86.7%), while an equal number of left and right THA was observed in patients with Hashimoto’s thyroiditis. In addition, congenital abnormalities associated with THA were observed, the left THA was seen in 60% and right THA in 40% of cases of this subgroup. The summative review provided a detailed insight into the epidemiology, aetiopathogenesis, genetics, symptomatology, diagnosis, and treatment for THA by combining findings and results from almost a hundred research papers from around the world. THA remains a poorly understood, often incidentally detected, abnormality in euthyroid patients undergoing investigations and treatment for other thyroid disorders