Evaluation of the parallel coupling constitutive model for biomaterials using a fully coupled network-matrix model.

In this article we discuss the effective properties of composites containing a crosslinked athermal fiber network embedded in a continuum elastic matrix, which are representative for a broad range of biological materials. The goal is to evaluate the accuracy of the widely used biomechanics parallel coupling model in which the tissue response is defined as the additive superposition of the network and matrix contributions, and the interaction of the two components is neglected. To this end, explicit, fully coupled models are used to evaluate the linear and non-linear response of the composite. It is observed that in the small strain, linear regime the parallel model leads to errors when the ratio of the individual stiffnesses of the two components is in the range 0.1-10, and the error increases as the matrix approaches the incompressible limit. The data presented can be used to correct the parallel model to improve the accuracy of the overall stiffness prediction. In the non-linear large deformation regime linear superposition does not apply. The data shows that the matrix reduces the stiffening rate of the network, and the response is softer than that predicted by the parallel model. The correction proposed for the linear regime mitigates to a large extent the error in the non-linear regime as well, provided the matrix Poisson ratio is not close to 0.5. The special case in which the matrix is rendered auxetic is also evaluated and it is seen that the auxeticity of the matrix may compensate the stiffening introduced by the network, leading to a composite with linear elastic response over a broad range of strains.

Cluster analysis demonstrates co-existing sites of fragility fracture and associated comorbidities.

We undertook cluster analysis in 11,003 patients who had sustained ≥ 1 fragility fracture, to find associations between fracture sites and comorbidities. We identified three distinct groups of fracture sites and four clusters of fractures and comorbidities. Knowledge of factors associated with fracture sites will aid prophylaxis in at-risk patients. INTRODUCTION: Fragility fracture (FF) prevalence is increasing. Subsequent fractures lead to greater morbidity and mortality. Few data are available on the association between FF sites and comorbidities. OBJECTIVES: 1. Establish the most common sites of FF and clusters within patients. 2. Identify patterns of co-existing FF and associated comorbidities. METHODS: We retrospectively reviewed clinical records of patients undergoing bone mineral density estimation at a district hospital in North-West England, 2004-2016, identifying those who had sustained ≥ 1 FF. Demographics, FF site(s), comorbidities, and medications were recorded. Cluster analysis was performed on fracture sites alone, and sites and comorbidities, using Jaccard similarity coefficient. Results were plotted on a dendrogram and divided into clusters. RESULTS: Of 28,868 patients, 11,003 had sustained ≥ 1 FF, 84.6% female, with overall mean age 67.5 years and median T-score - 1.12 SD. FF of the forearm was more frequent (n = 5045), most commonly co-existing with tibia/fibula fractures. Three FF site clusters were identified: ankle and elbow; forearm, tibia/fibula, ribs and spine; and pelvis, femur and humerus. When including comorbidities, four clusters were identified: forearm, tibia/fibula, spine, associated with family history of FF, smoking, corticosteroids and bisphosphonates; pelvis associated with hyperparathyroidism, PMR, coeliac disease and HRT; femur and humerus associated with IBD and RA; and ribs associated with alcohol and hyperthyroidism. CONCLUSION: Cluster analysis demonstrated three fracture site clusters, and four subgroups of FF sites and comorbidities. Cluster analysis is a novel method to evaluate comorbidities associated with FF sites. Knowledge of factors associated with FF sites will aid prophylaxis in at-risk patients.

Brain metastases: An update on the multi-disciplinary approach of clinical management.

IMPORTANCE: Brain metastasis (BM) is the most common malignant intracranial neoplasm in adults with over 100,000 new cases annually in the United States and outnumbering primary brain tumors 10:1. OBSERVATIONS: The incidence of BM in adult cancer patients ranges from 10-40%, and is increasing with improved surveillance, effective systemic therapy, and an aging population. The overall prognosis of cancer patients is largely dependent on the presence or absence of brain metastasis, and therefore, a timely and accurate diagnosis is crucial for improving long-term outcomes, especially in the current era of significantly improved systemic therapy for many common cancers. BM should be suspected in any cancer patient who develops new neurological deficits or behavioral abnormalities. Gadolinium enhanced MRI is the preferred imaging technique and BM must be distinguished from other pathologies. Large, symptomatic lesion(s) in patients with good functional status are best treated with surgery and stereotactic radiosurgery (SRS). Due to neurocognitive side effects and improved overall survival of cancer patients, whole brain radiotherapy (WBRT) is reserved as salvage therapy for patients with multiple lesions or as palliation. Newer approaches including multi-lesion stereotactic surgery, targeted therapy, and immunotherapy are also being investigated to improve outcomes while preserving quality of life. CONCLUSION: With the significant advancements in the systemic treatment for cancer patients, addressing BM effectively is critical for overall survival. In addition to patient's performance status, therapeutic approach should be based on the type of primary tumor and associated molecular profile as well as the size, number, and location of metastatic lesion(s).

Quality of life of parents of mentally-ill children: a systematic review and meta-analysis.

AIMS: To examine the quality of life (QOL) of parents of children with a specific mental disorder (any age). METHODS: Relevant articles were searched using different databases. Articles were included that compared the QOL of parents with mentally-ill children to parents of healthy controls or norm values or provided the required data for this comparison. A meta-analysis was conducted to obtain an overall mean effect size estimate. Additional analyses were performed to assess publication bias and moderation. RESULTS: Twenty-six out of 10 548 articles met the pre-defined inclusion criteria. Most of these studies focused on attention-deficit/hyperactivity disorder or autism spectrum disorder, used clinical samples that mainly included males and young children and studied the QOL of mothers. The meta-analysis revealed that parents of mentally-ill children are experiencing a clinically relevant reduction in their QOL relative to parents of healthy children and norm values (g = -0.66). CONCLUSIONS: The compromised QOL of parents of mentally-ill children needs to be considered and addressed by health professionals who are in contact with them. The paper provides insights into existing research gaps and suggests improvements for subsequent work.

Predictors of fracture risk in patients with systemic lupus erythematosus.

Objectives Bone loss in systemic lupus erythematosus is multifactorial. Recent studies demonstrate corticosteroids, previous fractures and increasing age decrease bone mineral density. The effect of body mass index and fat mass are less well characterized. We sought to determine fracture risk factors in patients undergoing dual-energy X-ray absorptiometry scanning at a district hospital in 2004-2015. Methods Standard dual-energy X-ray absorptiometry parameters were recorded, plus rheumatoid arthritis diagnosis, smoking status, alcohol consumption, family history of fractures, history of secondary operation and corticosteroid use. Data were analyzed using Fisher's exact test for categorical data and logistic regression for continuous data. Results One hundred and fifty patients (141 women, nine men) with SLE were included; 52 (34.6%) had sustained at least one fracture. Fracture risk increased with increased age, body mass index, fat mass and average tissue thickness, and decreased lean mass (adjusted for steroid use), as well as with smoking and rheumatoid arthritis. Increased femoral and vertebral bone mineral density conversely decreased fracture risk. Conclusion Our study suggests increased age, body mass index, fat mass, smoking and/or rheumatoid arthritis increase fracture risk in SLE patients. To our knowledge, this is the first demonstration of a correlation between increased fat mass, adjusted for steroid use and fracture risk, in adults, potentially indicating a differential effect of fat on bone metabolism and lessening of lean body mass.

Postrenal Transplant Metastatic Colonic Neoplasm: Posttransplant Lymphoproliferative Disorder or Adenocarcinoma?

Transplant recipients are vulnerable to a horde of infections and neoplastic conditions due to immunosuppression. Posttransplant lymphoproliferative disorder (PTLD) is a condition unique to the transplant recipient occurring due to monoclonal lymphocytic proliferation. It may affect any organ system with reportedly highest incidence in the gastrointestinal tract. The incidence of adenocarcinoma of the colon, however, has not been shown to be uniformly higher in transplant recipients. We report here an unusual case of adenocarcinoma of the ascending colon presenting with liver, lymph node and skin metastasis in a transplant recipient, which simulated PTLD both clinically and radiologically. For any gastrointestinal lesion in transplant recipient, the possibility of carcinoma must be considered. However, a high index of suspicion for PTLD facilitates early diagnosis since the treatment of the two conditions is starkly different.

Help-negation in suicidal youth living in Switzerland

OBJECTIVES: To examine whether help-negation (i.e. not accepting or accessing available helping resources) among suicidal youth could also be found in a Swiss sample. METHODS: Data from 7335 16-20-year olds, who participated in the 2002 Swiss Multicentre Adolescent Survey on Health, were analyzed. Logistic regression analyses were conducted to predict if a person would generally talk with no one when having a mental health problem (e.g. feeling depressed or anxious). Not talking about such problems was interpreted as indicator for help-negation. The main predictor was suicide severity. Additionally, an indicator of depression and socio-demographic variables were included in the statistical models. RESULTS: People with higher levels of suicidality and depression were more likely to report that they would not talk about mental health problems. More non-Swiss (vs. Swiss) participants and apprentices (vs. students) reported high suicidality. Furthermore, these specific sub-groups seemed to be particularly likely to negate help. CONCLUSION: Help-negation can also be found in a Swiss sample of young people and seems to be particularly pronounced in some socio-demographic subgroups. By reducing this reluctance to seek help, premature death due to suicide might be reduced

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Changes in living arrangement, daily smoking, and risky drinking initiation among young Swiss men: a longitudinal cohort study.

OBJECTIVES: The aim of this study was to assess the association between changes in living arrangement and the initiation of daily smoking and monthly risky single-occasion drinking (RSOD) in a cohort of young Swiss men. STUDY DESIGN: Longitudinal cohort study. METHODS: The sample consisted of 4662 young men drawn from the Cohort Study on Substance Use Risk Factors who lived with their family at baseline. Follow-up assessments occurred 15 months later. Multiple regression models were adjusted for individual and family factors (family model), as well as for individual and peer-related factors (peer model). RESULTS: Relative to those still living with their parents at follow-up (n = 3845), those who had moved out (n = 817) were considerably more likely to have taken up smoking or RSOD after adjusting for several individual, family, and peer-related variables: OR (daily smoking) = 1.67 (95% CI 1.15-2.41) (P = 0.007) and OR (monthly RSOD) = 1.42 (95% CI 1.08-1.88) (P = 0.012). The strongest family-related predictors of smoking initiation were family structure and the lack of parental regulation and the strongest peer-related factors alcohol/drug problems in peers. Meanwhile, the strongest peer-related predictors of RSOD initiation were peer pressure (misconduct), perceived social support from friends, and perceived social support from a significant other, whereas family factors were not associated with RSOD initiation. Further subanalyses were conducted to examine the impact of different living arrangement changes on substance use initiation and revealed that living with peers at follow-up was associated with the greatest risk. CONCLUSIONS: We identified a strong association between moving out of one's parents' home and daily smoking and monthly RSOD initiation in young Swiss men. Moving out to live with peers was an especially strong predictor of substance use initiation. Campaigns that aim to prevent heavy smoking and drinking should be intensified at the end of obligatory school.

Adult attention-deficit/hyperactivity disorder and its association with substance use and substance use disorders in young men.

BACKGROUND: Functional and mental health impairments that adults with attention-deficit/hyperactivity disorder (ADHD) experience may be exacerbated by regular substance use and co-morbidity with substance use disorders (SUD). This may be especially true during young adulthood, which represents a critical stage of life associated with increased substance use and associated problems. However, previous studies investigating the association between ADHD and substance use and SUD have demonstrated inconsistent results, probably due to methodological limitations (e.g., small and non-representative samples). Thus, the relationship of ADHD with substance use and related disorders remains unclear. The aim of the present study was to examine the association between ADHD and both the use of licit and illicit substances and the presence of SUD in a large, representative sample of young men. METHOD: The sample included 5677 Swiss men (mean age 20 ± 1.23 years) who participated in the Cohort Study on Substance Use Risk Factors (C-SURF). ADHD was assessed using the adult ADHD Self Report Screener (ASRS). The association between ADHD and substance use and SUD was assessed for alcohol, nicotine, cannabis and other illicit drugs, while controlling for socio-demographic variables and co-morbid psychiatric disorders (i.e., major depression (MD) and anti-social personality disorder (ASPD)). RESULTS: Men with ADHD were more likely to report having used nicotine, cannabis and other illicit drugs at some time in their life, but not alcohol. ADHD was positively associated with early initiation of alcohol, nicotine and cannabis use, the risky use of these substances, and the presence of alcohol use disorders, and nicotine and cannabis dependence. Additionally, our analyses revealed that these patterns are also highly associated with ASPD. After adjusting for this disorder, the association between ADHD and licit and illicit substance use and the presence of SUDs was reduced, but remained significant. CONCLUSIONS: Our findings suggest that adult ADHD is significantly associated with a propensity to experiment with licit and illicit substances, especially at earlier ages, to exhibit risky substance use patterns, and to subsequently develop SUDs. Preventive strategies that include early intervention and addressing co-morbidity with ASPD may be crucial to reducing substance use and the development of pathological substance use patterns in young men affected by ADHD and, thus, helping to prevent further illness burden later in life.

Complete congenital foetal heart block: a case report.

Congenital heart block (CHB) is the most severe manifestation of neonatal lupus which can develop into a lethal atrioventricular (AV) block. Complete congenital foetal heart block related to maternal anti-Ro/SSA autoanti-bodies typically develops between 20 and 24 weeks of gestation. CHB with a structurally normal heart is frequently associated with maternal autoantibodies to Ro/SSA and La/SSB. We are presenting a case of foetal complete CHB with high maternal Ro/SSA and La/SSB titre with favourable outcome.

Psychiatric disorders, suicidality, and personality among young men by sexual orientation.

Personality and its potential role in mediating risk of psychiatric disorders and suicidality are assessed by sexual orientation, using data collected among young Swiss men (n=5875) recruited while presenting for mandatory military conscription. Mental health outcomes were analyzed by sexual attraction using logistic regression, controlling for five-factor model personality traits and socio-demographics. Homo/bisexual men demonstrated the highest scores for neuroticism-anxiety but the lowest for sociability and sensation seeking, with no differences for aggression-hostility. Among homo/bisexual men, 10.2% fulfilled diagnostic criteria for major depression in the past 2weeks, 10.8% for ADHD in the past 12months, 13.8% for lifetime anti-social personality disorder (ASPD), and 6.0% attempted suicide in the past 12months. Upon adjusting (AOR) for personality traits, their odds ratios (OR) for major depression (OR=4.78, 95% CI 2.81-8.14; AOR=1.46, 95% CI 0.80-2.65) and ADHD (OR=2.17, 95% CI=1.31-3.58; AOR=1.00, 95% CI 0.58-1.75) lost statistical significance, and the odds ratio for suicide attempt was halved (OR=5.10, 95% CI 2.57-10.1; AOR=2.42, 95% CI 1.16-5.02). There are noteworthy differences in personality traits by sexual orientation, and much of the increased mental morbidity appears to be accounted for by such underlying differences, with important implications for etiology and treatment.

Conversion of differentiated cancer cells into cancer stem-like cells in a glioblastoma model after primary chemotherapy.

Glioblastoma multiforme patients have a poor prognosis due to therapeutic resistance and tumor relapse. It has been suggested that gliomas are driven by a rare subset of tumor cells known as glioma stem cells (GSCs). This hypothesis states that only a few GSCs are able to divide, differentiate, and initiate a new tumor. It has also been shown that this subpopulation is more resistant to conventional therapies than its differentiated counterpart. In order to understand glioma recurrence post therapy, we investigated the behavior of GSCs after primary chemotherapy. We first show that exposure of patient-derived as well as established glioma cell lines to therapeutic doses of temozolomide (TMZ), the most commonly used antiglioma chemotherapy, consistently increases the GSC pool over time both in vitro and in vivo. Secondly, lineage-tracing analysis of the expanded GSC pool suggests that such amplification is a result of a phenotypic shift in the non-GSC population to a GSC-like state in the presence of TMZ. The newly converted GSC population expresses markers associated with pluripotency and stemness, such as CD133, SOX2, Oct4, and Nestin. Furthermore, we show that intracranial implantation of the newly converted GSCs in nude mice results in a more efficient grafting and invasive phenotype. Taken together, these findings provide the first evidence that glioma cells exposed to chemotherapeutic agents are able to interconvert between non-GSCs and GSCs, thereby replenishing the original tumor population, leading to a more infiltrative phenotype and enhanced chemoresistance. This may represent a potential mechanism for therapeutic relapse.

A rare case of collodion baby with ophthalmic involvement.

BACKGROUND: Ichthyosis is an infrequent clinical entity worldwide (1:300,000 births). When diagnosed in a newborn, two forms can be identified: collodion baby and its most severe form, harlequin fetus or maligna keratoma. In both cases, clinical manifestations are thick and hard skin with deep splits. The splits are more prominent in the flexion areas. CASE: We report a case of a 4- day-old baby who was referred to JNMC Eye OPD by the Pediatric Department of the JNMC. He was having severe bilateral ectropion of the upper lids and chemosis of conjuntiva, without corneal involvement. There was distortion of the pinna and peeling of the skin, more over the chest around the neck region and over the flexor aspect of limbs. CONCLUSION: Management of collodion baby requires a multi-disciplinary approach.

Presbyopia and its anatomical and physiological variants.

AIM: To study the various ocular anatomical and physiological parameters in presbyopia. MATERIALS AND METHODS: We studied the various ocular anatomical and physiological parameters like corneal curvature (keratometry readings: K1 and K2), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT) and axial length (AL) in 100 presbyopic patients between 35 - 55 years of age. The patients were divided into two age groups: I (35 ± 44 years) and II (45-55 yrs). ACD, AL and LT were measured using an Ascan. CCT was measured with ultrasonic pachymetry. RESULTS: The CCT decreased (BE), LT increased and ACD decreased (RE) significantly with increasing age (p less than 0.05). There was no significant difference in males and females. Nearly 3/4th of the total increase in lens thickness was responsible for the decrease in the anterior chamber depth and the rest, 1/4th , goes posteriorly. Corneal curvature and AL showed no significant change with age. CONCLUSIONS: The mean of CCT decreased significantly with advancing age. As age increased, the mean value of lens thickness increased and anterior chamber depth decreased. Nearly 3/4th of total increase in LT was anteriorly, decreasing the ACD. Corneal curvature and AL has no relation with age.

Accommodation: its relation to refractive errors, amblyopia and biometric parameters.

AIM: To study accommodation in relation to different refractive errors, amblyopia and to measure the anatomical changes in the accommodating eye MATERIALS AND METHODS: We studied the amplitude of accommodation (AA) in 150 patients in the age group 11 ± 30 years which included emmetropes, myopes, hypermetropes and hypermetropic amblyopes using the Royal Air Force (RAF) rule. The anterior chamber depth (ACD), axial length (AxL) and lens thickness (LT) changes during accommodation were measured using an A-scan. Myopes and hypermetropes were further divided based on the amount of refractive error : less than 2D, 2 -4D and greater than 4D. RESULTS: Corrected low myopes had the highest accommodation amplitude (p less than 0.05) followed by emmetropes. Corrected hypermetropes were found to have the lowest amplitude of accommodation (p less than 0.05). The amblyopic eye had a significantly low AA compared to the non-amblyopic eye (p less than 0.05). ACD decreased (p less than 0.05) and LT increased (p less than 0.05) during accommodation. The AxL increase was maximum in myopes (p less than 0.05) followed by hypermetropes but the change was not significant in hypermetropes (p greater than 0.05). CONCLUSION: The amblyopic eye has low amplitudes of accommodation proving the benefit of near adds in amblyopic patients. Prolonged near work might induce myopia in susceptible eyes by increasing the axial length.

Bilateral exudative retinal detachment in a child with orbital pseudotumor.

We describe a 15-year-old girl who presented with bilateral exudative retinal detachment, a previously unreported complication, due to orbital pseudotumor. She initially responded to steroids, but subsequently became steroid dependent. Azathioprine was effective in controlling further relapses during follow-up of 22 months.

Gametogenic responses of the testis in spotted munia (Lonchura punctulata; Aves) to oral administration of lithium chloride.

In the present study, the effects of orally-administered lithium on testicular morphology were examined in the spotted munia (Lonchura punctulata), a seasonally breeding sub-tropical finch. Adult males were procured from natural populations during the month of August, a time when these birds begin to show seasonal reproductive maturity in an annual cycle. Both during the period of acclimation, and throughout the subsequent experimental period, the birds were maintained in an open aviary simulating natural environmental conditions. Lithium was dissolved in distilled water and was administered via the oral route by means of a commercially available stomach-tube. A total of five experimental groups were utilized. The first group (Group A) served as control and received lithium-free distilled water in a similar manner. In the remaining four groups, lithium was administered daily as follows: Group B (2.5 mEq/Kg body weight for 5 days); Group C (2.5 mEq/Kg for 10 days); Group D (5.0 mEq/Kg for 5 days) and Group E (5.0 mEq/Kg for 10 days). All lithium administrations were carried out between 14:00 and 15:00h. Twenty-four hours after the last oral lithium, final body weights were recorded, blood samples were obtained (by brachial vein puncture for the measurement of serum lithium) and the animals were sacrificed, and testes were collected for histological studies. Our results indicated that lithium treatment led to a significant reduction in testicular weight and seminiferous tubular diameter, and a marked degenerative changes in germ cells in that most of the spermatids and mature spermatozoa showed necrotic changes and were sloughed off from the seminiferous tubular epithelium. Complete desquamation and loss of germ cells, and their clump formation were also noted within many seminiferous tubular lumen. Notably these adverse effects were observed when serum lithium levels were within the therapeutic range for human. These results confirm our earlier report on lithium's adverse effects on testicular function, and extend further to show that lithium indeed has a significant adverse effect on the histomorphology, and, thus, the function of the testis in birds.

Isogenic strain of Escherichia coli O157:H7 that has lost both Shiga toxin 1 and 2 genes.

An Escherichia coli O157:H7 strain isolated from a patient with hemorrhagic colitis was found to exhibit two slightly different colony morphology types on differential medium. Each morphological type, designated TT12A and TT12B, was isolated, and serological testing using various assays confirmed that both strains carried the O157 and the H7 antigens. Biochemical testing showed that the strains had identical profiles on AP120E analysis and, like typical O157:H7 strains, did not ferment sorbitol or exhibit beta-glucuronidase activity. Analysis with a multiplex PCR assay showed that TT12B did not carry the gene for either Shiga toxin 1 (Stx1) or Stx2, whereas these genes were present in TT12A and the toxins were produced. Apart from that, both strains carried the +93 gusA mutation, the cluster I ehxA gene for enterohemolysin, and the eae gene for gamma-intimin, which are all characteristics of the O157:H7 serotype. Phenotypic assays confirmed that both strains exhibited enterohemolysin activity and the attachment and effacing lesion on HeLa cells. Multilocus enzyme electrophoresis analysis showed that the strains are closely related genetically and belong in the same clonal group. Pulsed-field gel electrophoresis (PFGE) typing of XbaI-digested genomic DNA revealed that the two strains differed by two bands but shared 90% similarity and clustered in the same clade. All other non-Stx-producing O157:H7 strains examined clustered in a major clade that was distinct from that of Stx-producing O157:H7 strains. The findings that TT12B was identical to TT12A, except for Stx production, and its PFGE profile is also more closely related to that of Stx-producing O157:H7 strains suggest that TT12B was derived from TT12A by the loss of both stx genes.