Search Results (17)

Androgens have long been recognized as oncogenic agents. They can induce both benign and malignant hepatocellular neoplasms, including hepatocellular adenoma (HCA) and hepatocellular carcinoma, though the underlying mechanisms remain unclear. Androgen-induced liver tumors are most often solitary and clinically silent. Herein, we reported an androgen-induced HCA complicated by spontaneous rupture. The patient was a 24-year-old male presenting with fatigue, diminished libido, radiology-diagnosed hepatocellular adenomatosis for 3 years, and sudden-onset, severe, sharp, constant abdominal pain for one day. He used Aveed (testosterone undecanoate injection) from age 17 and completely stopped one year before his presentation. A physical exam showed touch pain and voluntary guarding in the right upper quadrant of the abdomen. An abdominal CT angiogram demonstrated multiple probable HCAs, with active hemorrhage of the largest one (6.6 × 6.2 × 5.1 cm) accompanied by large-volume hemoperitoneum. After being stabilized by a massive transfusion protocol and interventional embolization, he underwent a percutaneous liver core biopsy. The biopsy specimen displayed atypical hepatocytes forming dense cords and pseudoglands. The lesional cells diffusely stained β-catenin in nuclei and glutamine synthetase in cytoplasm. Compared to normal hepatocytes from control tissue, the tumor cells were positive for nuclear AR (androgen receptor) expression but had no increased EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit) protein expression. The case indicated that androgen-induced hepatocellular neoplasms should be included in the differential diagnosis of acute abdomen. Full article

The AIDS and COVID-19 pandemics demonstrated that nations at similar economic development levels varied widely in their capacity to protect the health of their residents. For AIDS, Britain and Australia brought gay representatives into official counsels and adopted harm reduction far more rapidly than the United States or Spain, and East African countries responded more effectively than South Africa or the Democratic Republic of the Congo. National responses to COVID-19 varied widely, with New Zealand, China, and Vietnam more effective than Italy, Brazil, or the United States. Further, as phylogenetic research has demonstrated, these pandemics spread from one country to another, with those that responded poorly acting as sources for mutations and potentially sources of transmission to countries with more effective responses. Many observers expressed surprise at the poor responses of the United States to COVID-19, but in retrospect the cutbacks in public health funding at state and national levels made it clear that this was a predictable weakness even in addition to the political vacillations that crippled the US and Brazilian responses. In a time of global sociopolitical and climate instability, it is important to measure and conduct research into spatial and time variations in 1. public health and medical funding, 2. social influence networks, social cohesion and trust, and stigmatization, 3. income inequality, 4. social conflict, and 5. other factors that affect responsiveness to pandemics. Full article

Explaining individual differences in vocabulary in autism is critical, as understanding and using words to communicate are key predictors of long-term outcomes for autistic individuals. Differences in audiovisual speech processing may explain variability in vocabulary in autism. The efficiency of audiovisual speech processing can be indexed via amplitude suppression, wherein the amplitude of the event-related potential (ERP) is reduced at the P2 component in response to audiovisual speech compared to auditory-only speech. This study used electroencephalography (EEG) to measure P2 amplitudes in response to auditory-only and audiovisual speech and norm-referenced, standardized assessments to measure vocabulary in 25 autistic and 25 nonautistic children to determine whether amplitude suppression (a) differs or (b) explains variability in vocabulary in autistic and nonautistic children. A series of regression analyses evaluated associations between amplitude suppression and vocabulary scores. Both groups demonstrated P2 amplitude suppression, on average, in response to audiovisual speech relative to auditory-only speech. Between-group differences in mean amplitude suppression were nonsignificant. Individual differences in amplitude suppression were positively associated with expressive vocabulary through receptive vocabulary, as evidenced by a significant indirect effect observed across groups. The results suggest that efficiency of audiovisual speech processing may explain variance in vocabulary in autism. Full article

BAG3 is a 575 amino acid protein that is found throughout the animal kingdom and homologs have been identified in plants. The protein is expressed ubiquitously but is most prominent in cardiac muscle, skeletal muscle, the brain and in many cancers. We describe BAG3 as a quintessential multi-functional protein. It supports autophagy of both misfolded proteins and damaged organelles, inhibits apoptosis, maintains the homeostasis of the mitochondria, and facilitates excitation contraction coupling through the L-type calcium channel and the beta-adrenergic receptor. High levels of BAG3 are associated with insensitivity to chemotherapy in malignant cells whereas both loss of function and gain of function variants are associated with cardiomyopathy. Full article

Background: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort. Methods: A total of 113 AIH patients (i.e., 30 male/83 female, median 57.9 years) were identified. In 81, genotyping of PNPLA3-rs738409, MBOAT7-rs626238, TM6SF2-rs58542926, and HSD17B13-rs72613567:TA, as well as both biochemical and clinical data at baseline and follow-up, were available. Results: The median time of follow-up was 2.8 years; five patients died and one underwent liver transplantation. The PNPLA3-G/G homozygosity was linked to a worse treatment response when compared to wildtype [wt] (ALT 1.7 vs. 0.6 × ULN, p < 0.001). The MBOAT7-C/C homozygosity was linked to non-response vs. wt and heterozygosity (p = 0.022). Male gender was associated with non-response (OR 14.5, p = 0.012) and a higher prevalence of PNPLA3 (G/G vs. C/G vs. wt 41.9/40.0/15.0% males, p = 0.03). The MBOAT7 wt was linked to less histological fibrosis (p = 0.008), while no effects for other SNPs were noted. A polygenic risk score was utilized comprising all the SNPs and correlated with the treatment response (p = 0.04). Conclusions: Our data suggest that genetic risk variants impact the treatment response of AIH in a gene-dosage-dependent manner. Furthermore, MBOAT7 and PNPLA3 mediated most of the observed effects, the latter explaining, in part, the predisposition of male subjects to worse treatment responses. Full article

A protocol for successfully depositing [001] textured, 2–3 µm thick films of Al_0.75Sc_0.25N, is proposed. The procedure relies on the fact that sputtered Ti is [001]-textured $\mathsf{\alpha }$-phase (hcp). Diffusion of nitrogen ions into the α-Ti film during reactive sputtering of Al_0.75,Sc_0.25N likely forms a [111]-oriented TiN intermediate layer. The lattice mismatch of this very thin film with Al_0.75Sc_0.25N is ~3.7%, providing excellent conditions for epitaxial growth. In contrast to earlier reports, the Al_0.75Sc_0.25N films prepared in the current study are Al-terminated. Low growth stress (<100 MPa) allows films up to 3 µm thick to be deposited without loss of orientation or decrease in piezoelectric coefficient. An advantage of the proposed technique is that it is compatible with a variety of substrates commonly used for actuators or MEMS, as demonstrated here for both Si wafers and D263 borosilicate glass. Additionally, thicker films can potentially lead to increased piezoelectric stress/strain by supporting application of higher voltage, but without increase in the magnitude of the electric field. Full article

We compare and contrast three different, but complementary views of “structure” and “pattern” in spatial processes. For definiteness and analytical clarity, we apply all three approaches to the simplest class of spatial processes: one-dimensional Ising spin systems with finite-range interactions. These noncritical systems are well-suited for this study since the change in structure as a function of system parameters is more subtle than that found in critical systems where, at a phase transition, many observables diverge, thereby making the detection of change in structure obvious. This survey demonstrates that the measures of pattern from information theory and computational mechanics differ from known thermodynamic and statistical mechanical functions. Moreover, they capture important structural features that are otherwise missed. In particular, a type of mutual information called the excess entropy—an information theoretic measure of memory—serves to detect ordered, low entropy density patterns. It is superior in several respects to other functions used to probe structure, such as magnetization and structure factors. $ϵ$-Machines—the main objects of computational mechanics—are seen to be the most direct approach to revealing the (group and semigroup) symmetries possessed by the spatial patterns and to estimating the minimum amount of memory required to reproduce the configuration ensemble, a quantity known as the statistical complexity. Finally, we argue that the information theoretic and computational mechanical analyses of spatial patterns capture the intrinsic computational capabilities embedded in spin systems—how they store, transmit, and manipulate configurational information to produce spatial structure. Full article

When lean people adopt carbohydrate-restricted diets (CRDs), they may develop a lipid profile consisting of elevated LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) with low triglycerides (TGs). The magnitude of this lipid profile correlates with BMI such that those with lower BMI exhibit larger increases in both LDL-C and HDL-C. The inverse association between BMI and LDL-C and HDL-C change on CRD contributed to the discovery of a subset of individuals—termed Lean Mass Hyper-Responders (LMHR)—who, despite normal pre-diet LDL-C, as compared to non-LMHR (mean levels of 148 and 145 mg/dL, respectively), exhibited a pronounced hyperlipidemic response to a CRD, with mean LDL-C and HDL-C levels increasing to 320 and 99 mg/dL, respectively, in the context of mean TG of 47 mg/dL. In some LMHR, LDL-C levels may be in excess of 500 mg/dL, again, with relatively normal pre-diet LDL-C and absent of genetic findings indicative of familial hypercholesterolemia in those who have been tested. The Lipid Energy Model (LEM) attempts to explain this metabolic phenomenon by positing that, with carbohydrate restriction in lean persons, the increased dependence on fat as a metabolic substrate drives increased hepatic secretion and peripheral uptake of TG contained within very low-density lipoproteins (VLDL) by lipoprotein lipase, resulting in marked elevations of LDL-C and HDL-C, and low TG. Herein, we review the core features of the LEM. We review several existing lines of evidence supporting the model and suggest ways to test the model’s predictions. Full article

The association between malignancy and readmission after Takotsubo syndrome (TTS) hospitalization has not been fully described. We sought to examine the rates, cause, and cost of 30-day readmissions of TTS, with or without malignancy, by utilizing Nationwide Readmissions Databases from 2010 to 2014. We identified 61,588 index hospitalizations for TTS. TTS patients with malignancy tended to be older (70.6 ± 0.2 vs. 66.1 ± 0.1, p < 0.001), and the overall burden of comorbidities was higher than in those without malignancy. TTS patients with malignancy had significantly higher 30-day readmission rates than those without malignancy (15.9% vs. 11.0%; odds ratio (OR), 1.35; 95% confidence interval (CI), 1.18–1.56). Non-cardiac causes were the most common causes of readmission for TTS patients with malignancy versus without malignancy (75.5% vs. 68.1%, p < 0.001). The 30-day readmission rate due to recurrent TTS was very low in both groups (0.4% and 0.5%; p = 0.47). The total costs were higher by 25% (p < 0.001) in TTS patients with vs. without malignancy. In summary, among patients hospitalized with TTS, the presence of malignancy was associated with increased risk of 30-day readmission and increased costs. These findings highlight the importance of optimized management for TTS patients with malignancy. Full article

Arthrogryposis multiplex congenita (AMC) is a rare condition defined as contrac-tures in multiple joints. Surgical interventions for severe knee flexion contractures have included posterior release, distraction and extension with external fixation and distal femoral extension osteotomies. These operations have been able to achieve knee extension, but not increase the range of motion. The purpose of this study was to review our experience with peroneal nerve decompression, posterior knee release and proximal femoral shortening. We retrospectively reviewed the medical charts and radiographs of all patients with a diagnosis of arthrogryposis who underwent aforementioned procedure. There were 39 patients with 73 knees included in the analysis with a mean follow-up of 21 months. The mean preoperative arc of motion was 45° and last followup arc of motion was 79° (p < 0.0001). The mean last followup flexion contracture was 8° (p < 0.0001). Additional subanalyses were performed on those with followup greater than 24 months and those with flexion contractures >60°; there were no differences found in these groups. This study demonstrates that it is possible to achieve a functional range of motion of the knees in patients with AMC while improving ambulatory function. Full article

There are multiple forms of enchondromatosis with Ollier’s and Maffucci’s being the most prevalent types. Limb length discrepancy is a common problem in patients with Ollier’s and Maffucci’s enchondromatosis. There are multiple reports about lengthening bones in patients with enchondromatosis using external fixators. However, there are no case series regarding the use of implantable lengthening technology. The purpose of this paper is to describe our experience with implantable nail lengthening in patients with enchondromatosis. A retrospective chart and radiographic review of patients with enchondromatosis who underwent implantable nail limb lengthening was performed. Seven patients with 14 bony segments were reviewed. A total of 11/14 lengthenings were completed without difficulty. There were no issues in terms of fixation location in patients with Ollier’s disease. One patient with Maffucci’s syndrome experienced migration of the nail during two lengthenings due to a combination of intralesional fixation and preconsolidation. One patient with Ollier’s disease developed a knee extension contracture requiring manipulation under anesthesia. No other complications were recorded. The use of implantable nail lengthening to resolve limb length discrepancies in patients with Ollier’s disease appears to be safe and effective. Full article

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ_1-40, Aβ_1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology. Full article

The number of family caregivers to individuals with dementia is increasing. Family physicians are often the first point of access to the health care system for individuals with dementia and their caregivers. Caregivers are at an increased risk of developing negative physical, cognitive and affective health problems themselves. Caregivers also describe having unmet needs to help them sustain care in the community. Family physicians are in a unique position to help support caregivers and individuals with dementia, but often struggle with keeping up with best practice dementia service knowledge. The Dementia Wellness Questionnaire was designed to serve as a starting point for discussions between caregivers and family physicians by empowering caregivers to communicate their needs and concerns and to enhance family physicians’ access to specific dementia support information. The DWQ aims to alert physicians of caregiver and patient needs. This pilot study aimed to explore the experiences of physicians and caregivers of people using the Questionnaire in two family medicine clinics in Ontario, Canada. Interviews with physicians and caregivers collected data on their experiences using the DWQ following a 10-month data gathering period. Data was analyzed using content analysis. Results indicated that family physicians may have an improved efficacy in managing dementia by having dementia care case specific guidelines integrated within electronic medical records. By having time-efficient access to tailored supports, family physicians can better address the needs of the caregiver–patient dyad and help support family caregivers in their caregiving role. Caregivers expressed that the Questionnaire helped them remember concerns to bring up with physicians, in order to receive help in a more efficient manner. Full article

Single nucleotide polymorphisms (SNPs), including PNPLA3 rs738409 and SERPINA1 rs17580, have been identified as risk modifiers in the progression fatty liver disease (alcoholic (ALD) or non-alcoholic (NAFLD)). While PNPLA3 has been studied in various settings, the value of both SNPs has so far not been addressed in a real-world cohort of subjects referred for a diagnostic work-up of liver disease. Thus, liver disease severity was assessed in 1257 consecutive patients with suspected ALD or NAFLD at the time of referral to a tertiary center. Advanced chronic liver disease (ACLD) was present in 309 (24.6%) patients and clinically significant portal hypertension (CSPH) was present in 185 (14.7%) patients. The PNPLA3 G-allele was independently associated with a higher liver stiffness measurement (LSM; adjusted B: 2.707 (1.435–3.979), p < 0.001), and higher odds of ACLD (adjusted odds ratio (aOR): 1.971 (1.448–2.681), p < 0.001) and CSPH (aOR: 1.685 (1.180–2.406), p = 0.004). While the SERPINA1 Z-allele was not associated with a higher LSM or the presence of ACLD, it was independently associated with higher odds of CSPH (aOR: 2.122 (1.067–4.218), p = 0.032). Associations of the PNPLA3 G-allele and the SERPINA1 Z-allele with CSPH were maintained independently of each other. The presence of both risk variants further increased the likelihood of ACLD and CSPH. Full article

Pluvial flash flooding (PFF) is a growing hazard facing cities around the world as a result of rapid urbanization and more intense precipitation from global warming, particularly for low-resourced settings in developing countries. We present collaborative modeling (CM) as an iterative process to meet diverse decision-making needs related to PFF through the co-production of flood hazard models and maps. CM resulted in a set of flood hazard maps accessible through an online viewer that end-users found useful and useable for understanding PFF threats, including debris blockages and barriers to mobility and evacuation. End-users of information included individuals concerned with general flood awareness and preparedness, and involved in infrastructure and emergency management, planning, and policy. CM also showed that rain-on-grid hydrodynamic modeling is needed to depict PFF threats in ways that are intuitive to end-users. These outcomes evidence the importance and transferability of public health rationale for community-based research and principles used here including recognizing community as a unit of identity, building on strengths of the community, and integrating knowledge for the benefit of all partners. Full article