Search

Background Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. Methods The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation. Results Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P Conclusion Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines.

Purpose:The molecular events that determine intestinal cell differentiation are poorly understood and it is unclear whether it is primarily a passive event or an active process. It is clinically important to gain a greater understanding of the process, because in colorectal cancer, the degree of differentiation of a tumor is associated with patient survival. SGK1 has previously been identified as a gene that is principally expressed in differentiated intestinal cells. In colorectal cancer, there is marked downregulation of SGK1 compared with normal tissue.Experimental Design: An inducible SGK1 viral overexpression system was utilized to induce reexpression of SGK1 in colorectal cancer cell lines. Transcriptomic and phenotypic analyses of these colorectal cancer lines was performed and validation in mouse and human cohorts was performed.Results:We demonstrate that SGK1 is upregulated in response to, and an important controller of, intestinal cell differentiation. Reexpression of SGK1 in colorectal cancer cell lines results in features of differentiation, decreased migration rates, and inhibition of metastasis in an orthotopic xenograft model. These effects may be mediated, in part, by SGK1-induced PKP3 expression and increased degradation of MYC.Conclusions:Our results suggest that SGK1 is an important mediator of differentiation of colorectal cells and may inhibit colorectal cancer metastasis.

Supplementary Table 1. Differentially expressed genes from colonic crypt tops vs. bottoms of normal individuals (adjusted p

Physical activity brings significant health benefits to middle-aged adults, although the research to date has been focused on late adulthood. This study aims to examine how ageing affects the self-reported and accelerometer-derived measures of physical activity levels in middle-aged adults. We employed the data recorded in the UK Biobank and analysed the physical activity levels of 2,998 participants (1381 men and 1617 women), based on self-completion questionnaire and accelerometry measurement of physical activity. We also assessed the musculoskeletal health of the participants using the dual-energy X-ray absorptiometry (DXA) measurements provided by the UK Biobank. Participants were categorised into three groups according to their age: group I younger middle-aged (40 to 49 years), group II older middle-aged (50 to 59 years), and group III oldest middle-aged (60 to 69 years). Self-reported physical activity level increased with age and was the highest in group III, followed by group II and I (P

People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p lt; 0.001 for both).Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

The desmosome is a type of intercellular junction found in epithelial cells, cardiomyocytes and other specialized cell types. Composed of a network of transmembranous cadherins and intracellular armadillo, plakin and other proteins, desmosomes contribute to cell-cell adhesion, signalling, development and differentiation. Mutations in genes encoding desmosomal proteins result in a spectrum of erosive skin and mucosal phenotypes that also may affect hair or heart. This review summarizes the molecular pathology and phenotypes associated with desmosomal dysfunction with a focus on inherited disorders that involve the skin/hair, as well as associated extracutaneous pathologies. We reviewed the relevant literature to collate studies of pathogenic human mutations in desmosomes that have been reported over the last 25 years. Mutations in 12 different desmosome genes have been documented, with mutations in nine genes affecting the skin/mucous membranes (DSG1, DSG3, DSC2, DSC3, JUP, PKP1, DSP, CDSN, PERP) and eight resulting in hair abnormalities (DSG4, DSC2, DSC3, JUP, PKP1, DSP, CDSN, PERP). Mutations in three genes can result in cardiocutaneous syndromes (DSC2, JUP, DSP), although mutations have been described in five genes in inherited heart disorders that may lack any dermatological manifestations (DSG2, DSC2, JUP, PKP2, DSP). Understanding the diverse nature of these clinical phenotypes, as well as the desmosome gene mutation(s), has clinical value in managing and counselling patients, as well as demonstrating the biological role and activity of specific components of desmosomes in skin and other tissues.

Introduction Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in glucose, which is a ligand-mediated transcription factor. The lipid homeostasis often serves as a pharmacological target for new drug discovery and development. Materials and methods In the research, we synthesized a series of piperine derivatives and then used a fluorescence polarization-based PPARγ ligand screening assay to evaluate the agonistic activity of PPARγ. Then, we cultured human normal hepatocytes, which were treated with 100μM compounds 2a, 2t or 3d. Then, the levels of PPARγ gene were determined so as to show whether the compounds could activate or inhibit the expression of PPARγ. Results A total of 30 piperine derivatives were synthesized and evaluated. Compound 2a was identified as a potential PPARγ agonist with IC50 at 2.43 μM, which is 2 times more potent than the positive control rosiglitazone with IC50 at 5.61μM. The human hepatocytes cells were cultured and treated with compounds 2a, 2t or 3d as described in the "Materials and Methods" section. We found that compounds 2a, 2t and 3d could activate PPARγ by 11.8, 1.9 and 7.0 times compared with the "blank", with compound 2a activation being the most significant. Molecular docking studies indicated that the piperine derivative 2a stably interacts with the amino acid residues of the PPARγ complex active site, which is consistent with the results of the in vitro PPARγ ligand screening assay.

In 2017, 236 rice samples were collected from 42 counties in Jiangsu province, China, and analysed for Fusarium mycotoxins. Mycotoxin analyses showed that deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV), fusarenone X (FUS-X), zearalenone (ZEA), fumonisins (including FB1, FB2, and FB3), and beauvericin (BEA) were present in unhusked rice samples. Regional differences in mycotoxin contamination of unhusked rice were attributed to differences in precipitation during rice anthesis and agricultural practices among the three study regions. Importantly, the mean concentrations of DON, NIV, ZEA, and fumonisins in white rice were significantly lower than those in unhusked rice, and the relative proportion of the toxins in rice by-products exceeded 84%. Fusarium isolates were then obtained from the unhusked rice samples; Fusarium asiaticum was the most common, followed by Fusarium fujikuroi, Fusarium proliferatum, Fusarium verticillioides, and Fusarium commune. Genotype and chemical analyses of mycotoxins showed that most F. asiaticum isolates (71%) were 3-ADON chemotypes; the remainder were NIV producers. All of the F. proliferatum and F. verticillioides isolates, and most of the F. fujikuroi isolates produce fumonisins, and most of the three species coproduced BEA. The present study is the first to evaluate Fusarium mycotoxins and toxigenic Fusarium species from rice freshly harvested in Jiangsu province, China. The results of this study improve our understanding the population dynamics of Fusarium species in rice and the development of effective control measures.

Based on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity.We investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models.The 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and Aβ42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aβ uptake and clearance, as well as pathway changes.We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aβ both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism.Our results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD.It is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD.

Background. We compared the outcomes of laparoscopic-assisted (LA) and robotic-assisted (RA) gastrectomies performed for gastric adenocarcinoma in the National Cancer Database. Methods. The National Cancer Database was queried for patients 18 years old with stages I to III gastric adenocarcinoma who underwent LA or RA gastrectomy. Propensity matching was performed between the 2 groups with regard to clinical staging, adjuvant treatment, demographics, and the extent of surgery. Results. A cohort of 1893 (1262 = LA, 631 = RA) patients was identified in a 2:1 propensity matching. The groups were well matched. The rate of negative margin as well as 30- and 90-day mortality were similar between the 2 cohorts. Long-term survival was similar between the 2 groups (median survival 49.2 months in LA vs 56.2 months for RA, P = .405). However, the average number of lymph nodes (LNs) sampled was significantly higher in the RA group compared with the LA group (19.6 vs 17.4, P < .001). Similarly, the percentage of surgeries in which ≥15 LNs were sampled was also greater in the RA group compared with the LA group (63.9% vs 57.6%, P = .010). On multivariable analysis, having 15 LNs or more examined was associated with better survival (hazard ratio = 0.72, 95% confidence interval = 0.60-0.87, P < .001). Advanced age, nodal positivity, and advanced clinical stages were significantly associated with worse survival. Conclusions. RA gastrectomy may allow a greater harvest of LNs, and thus more accurate staging, without increasing short-term adverse outcomes compared with LA gastrectomy. Short-term and long-term outcomes in this well-matched cohort appear comparable for both approaches.

Background Opioids have been prescribed to reduce suffering from pain and to enhance quality of life. Due to the addictive potential and the lack of other effective alternatives to treat severe acute and chronic pains, opioids remain a serious public health issue. While, opioids directly influence the drug-seeking behavior, tolerance and withdrawal processes, through neuroadaptation, the brain's endogenous opioid system also adapts in the presence of chronic pain and could contribute to the difficulty of treatment. Despite the seemingly obvious interaction between the presence of pain and opioid-abuse, little is known about the underlying mechanisms in the brain. Purpose To review the current understanding of the interaction mechanisms of neurotransmitter circuitries in pain modulation and reward in the brain and the effects of L-tetrahydropalmatine (L-THP) and its metabolites in pain management and opioid use disorder and gain a better insight on the pharmacological profile and in vivo effects of L-THP and its metabolites. Method A detailed literature search on available (preclinical and clinical) studies about the effects of L-THP and its metabolites against drug addiction and chronic pain has been performed. The data was collected using various search engines such as PubMed, ScienceDirect, Google scholar and articles in English up to December 2020 were included in this review. Results L-THP and its metabolites demonstrated analgesic and anti-addiction effects. Due to their dual pharmacological properties (D1 partial agonist and D2 antagonist) these compounds could be used as molecular tools to provide a better understanding of the interactions between pain and addiction. Conclusion The available data confirms the potential of L-THP and its metabolites to treat both chronic pain and drug addiction. However, further clinical trials are needed to establish safety and efficacy.

Opioid abuse and misuse have led to an epidemic which is currently spreading worldwide. Since the number of opioid overdoses is still increasing, it is becoming obvious that current rather unsystematic approaches to tackle this health problem are not effective. This review suggests that fighting the opioid epidemic requires a structured public health approach. Therefore, it is important to consider not only scientific and biomedical perspectives, but societal implications and the lived experience of groups at risk as well. Hence, this review evaluates the risk factors associated with opioid overdoses and investigates the rates of chronic opioid misuse, particularly in the context of chronic pain as well as post-surgery treatments, as the entrance of opioids in people’s lives. Linking pharmaceutical biology to narrative analysis is essential to understand the modulations of the usual themes of addiction and abuse present in the opioid crisis. This paper shows that patient narratives can be an important resource in understanding the complexity of opioid abuse and addiction. In particular, the relationship between chronic pain and social inequality must be considered. The main goal of this review is to demonstrate how a deeper transdisciplinary-enriched understanding can lead to more precise strategies of prevention or treatment of opioid abuse.

The use of inertial sensors in fast bowling analysis may offer a cheaper and portable alternative to current methodologies. However, no previous studies have assessed the validity and reliability of such methods. Therefore, this study aimed to assess the validity and reliability of collecting tibial accelerations and spinal kinematics using inertial sensors during in vivo fast bowling. Thirty-five elite male fast bowlers volunteered for this study. An accelerometer attached to the skin over the tibia was used to determine impacts and inertial sensors over the S1, L1 and T1 spinous processes used to derive the relative kinematics. These measurements were compared to optoelectronic and force plate data for validity analysis. Most acceleration and kinematics variables measured report significant correlations > 0.8 with the corresponding gold standard measurement, with intraclass correlation coefficients greater than 0.7. Low standard error of measurement and consequently small minimum detectable change (MDC) values were also observed. This study demonstrates that inertial sensors are as valid and reliable as current methods of fast bowling analysis and may provide some advantages over traditional methods. The novel metrics and methods described in this study may aid coaches and practitioners in the design and monitoring of fast bowling technique. Graphical abstract Graphical abstract illustrating the synopsis of the findings from this paper.

The widespread use of opioids to treat chronic pain led to a nation-wide crisis in the United States. Tens of thousands of deaths annually occur mainly due to respiratory depression, the most dangerous side effect of opioids. Non-opioid drugs and non-pharmacological treatments without addictive potential are urgently required. Traditional Chinese medicine (TCM) is based on a completely different medical theory than academic Western medicine. The scientific basis of acupuncture and herbal treatments as main TCM practices has been considerably improved during the past two decades, and large meta-analyses with thousands of patients provide evidence for their efficacy. Furthermore, opinion leaders in the United States favor non-pharmacological techniques including TCM for pain management to fight the opioid crisis. We advocate TCM as therapeutic option without addictive potential and without life-threatening side effects (e.g., respiratory depression) to treat chronic pain patients suffering from opioid misuse. The evidence suggests that: (1) opioid misuse cannot be satisfactorily managed with standard medication; (2) opinion leaders in the United States favor to consider non-opioid and non-pharmacological treatment strategies including those from TCM to treat acute and chronic pain conditions; (3) large meta-analyses provide scientific evidence for the clinical activity of acupuncture and herbal TCM remedies in the treatment of chronic pain. Future clinical trials should demonstrate the safety of TCM treatments if combined with Western medical practices to exclude negative interactions between both modalities.

Pueraria lobata is one of the most important medicinal herbs used traditionally in China. According to Shanghan Lun (Treatise on Exogenous Febrile Disease), it has been used traditionally to relieve body heat, eye soring, dry mouth, headache associated with high blood pressure, and stiff neck problems. Modern studies in the 1970s revealed that isoflavonoids extracted from P. lobata were the bioactive components of an herbal remedy namely Yufeng Ningxin Tablets for the treatment of patients after stroke. This article reviews recent application of P. lobota in the treatment of diabetics and in reducing alcohol drinking. In view of its low toxicity profile, P. lobota stands an excellent chance to be developed as a phytomedicine for treating human diseases.

ObjectivesTo investigate spinal kinematics, tibial and sacral impacts during fast bowling, among bowlers with a history of low back pain (LBP) (retrospective) and bowlers who developed LBP in the follow-up season (prospective).Methods35 elite male fast bowlers; senior (n=14; age=24.1±4.3 years; height=1.89±0.05 m; weight=89.2±4.6 kg) and junior (n=21; age=16.9±0.7; height=1.81±0.05; weight=73.0±9.2 kg) were recruited from professional county cricket clubs. LBP history was gathered by questionnaire and development of LBP was monitored for the follow-up season. Spinal kinematics, tibial and sacral impacts were captured using inertial measurement units placed over S1, L1, T1 and anteromedial tibia. Bonferroni corrected pairwise comparisons and effect sizes were calculated to investigate differences in retrospective and prospective LBP groups.ResultsApproximately 38% of juniors (n=8) and 57% of seniors (n=8) reported a history of LBP. No differences were evident in spinal kinematics or impacts between those with LBP history and those without for seniors and juniors. Large effect sizes suggest greater rotation during wind-up (d=1.3) and faster time-to-peak tibial impacts (d=1.5) in those with no history of LBP. One junior (5%) and four (29%) seniors developed LBP. No differences were evident in spinal kinematics or impacts between those who developed LBP and those who did not for seniors. In seniors, those who developed LBP had lower tibial impacts (d=1.3) and greater lumbar extension (d=1.9) during delivery.ConclusionRetrospective analysis displayed non-significant differences in kinematics and impacts. It is unclear if these are adaptive or impairments. Prospective analysis demonstrated large effect sizes for lumbar extension during bowling suggesting a target for future coaching interventions.

Background Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics’ infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy. Approach We conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19. Results Although bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection. Conclusion There is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.

Dermatofibromas are common benign skin lesions, the etiology of which is poorly understood. We identified two unrelated pedigrees in which there was autosomal dominant transmission of multiple dermatofibromas. Whole exome sequencing revealed a rare shared heterozygous missense variant in the F13A1 gene encoding factor XIII subunit A (FXIII-A), a transglutaminase involved in hemostasis, wound healing, tumor growth, and apoptosis. The variant (p.Lys679Met) has an allele frequency of 0.0002 and is predicted to be a damaging mutation. Recombinant human Lys679Met FXIII-A demonstrated reduced fibrin crosslinking activity in vitro. Of note, the treatment of fibroblasts with media containing Lys679Met FXIII-A led to enhanced adhesion, proliferation, and type I collagen synthesis. Immunostaining revealed co-localization between FXIII-A and α4β1 integrins, more prominently for Lys679Met FXIII-A than the wild type. In addition, both the α4β1 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine-Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may lead to a conformational change in the FXIII-A protein that enhances α4-integrin binding and provides insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma.

This paper presents a numerical study of stratified flow condensation heat transfer in tubes with novel cross-section designs. A design framework of the novel cross-section geometry was developed by first studying and analyzing the condensate film distribution in a circular tube. It was found that the circular arc diameter and orientation have effects on the condensate film thickness. Based on this understanding, four different cross-section designs (models N1, N2, N3 and N4) formed by connecting circular arcs of different curvatures at various orientations were proposed. The heat transfer performances of these models were compared to a circular tube of the same perimeter. Our simulations show that all models possess higher average heat transfer coefficients than a circular tube when no accumulated condensate layer is present. Among all the models proposed, model N4 exhibits the largest heat transfer enhancement ratio of 1.42 at ∊ = 0.96. The design of model N4 utilizes small circular arcs which are arranged in an orientation that increases the effect of the gravitational force, providing significant condensate film thickness reduction over a large area. This study not only demonstrates the possibility of enhancing condensation heat transfer by simply varying the tube curvature but also provided a design guideline which can be employed for the development of novel cross-section tubes that can be fabricated by advanced manufacturing techniques such as selective laser melting.

Deriving from the Greek word λeιχήν for "tree moss" and the Latin word planus for "planar," lichen planus is a relatively uncommon and heterogeneous cutaneous disorder that typically develops in middle-aged adults. Despite the significant clinical burden associated with the disorder, little well-conducted molecular research has been undertaken, possibly because of heterogeneity impeding consistent and confident phenotyping. The multiple variants of lichenoid disease bear overlapping clinical and pathologic features despite manifesting as distinct clinical disorders. The first article in this 2-part continuing medical education series provides a comprehensive overview of the clinical and pathologic characteristics of cutaneous lichenoid dermatoses and links these manifestations to recent advances in our understanding of the underlying pathobiology of such diseases.

Background - Fast bowlers display a high risk of lower back injury and pain. Studies report factors that may increase this risk, however exact mechanisms remain unclear. Objective - To provide a contemporary analysis of literature, up to April 2016, regarding fast bowling, spinal kinematics, ground reaction force (GRF), lower back pain (LBP) and pathology. Method - Key terms including biomechanics, bowling, spine and injury were searched within MEDLINE, Google Scholar, SPORTDiscuss, Science Citation Index, OAIster, CINAHL, Academic Search Complete, Science Direct and Scopus. Following application of inclusion criteria, 56 studies (reduced from 140) were appraised for quality and pooled for further analysis. Results - Twelve times greater risk of lumbar injury was reported in bowlers displaying excessive shoulder counter-rotation (SCR), however SCR is a surrogate measure which may not describe actual spinal movement. Little is known about LBP specifically. Weighted averages of 5.8 ± 1.3 times body weight (BW) vertically and 3.2 ± 1.1 BW horizontally were calculated for peak GRF during fast bowling. No quantitative synthesis of kinematic data was possible due to heterogeneity of reported results. Conclusions - Fast bowling is highly injurious especially with excessive SCR. Studies adopted similar methodologies, constrained to laboratory settings. Future studies should focus on methods to determine biomechanics during live play.

Purpose: This study examined the activation patterns of the cervical and thoracic muscles in people with and without chronic neck pain during functional activities and their associations with pain intensity and functional disability.Methods: Thirty-four adults with chronic neck pain and 34 asymptomatic adults were recruited. They were requested to perform active cervical movements and an upper limb lifting task. Electromyographic activation patterns (EMG) of bilateral upper trapezius, cervical erector spinae, sternocleidomastoid, and thoracic erector spinae were recorded during these tasks. Correlation and multiple regression analysis were used to examine the associations between EMG variables and severity of pain and functional disability.Results: When performing the cervical movements, the neck pain group displayed lower EMG activity levels, especially in the cervical and thoracic extensors. In addition, significantly prolonged activation was observed in seven of the ten muscles during the upper limb lifting task. The changes in EMG amplitude and activation duration were found to be significantly correlated with severity of pain (R2 = 0.716) and functional disability (R2 = 0.623).Conclusions: Significant differences in the activation patterns of multiple cervical and thoracic muscles were found in individuals with neck pain compared with those without neck pain. These were significantly associated with their degree of pain and functional limitation. The findings of this study highlight the importance of assessing and optimising the neuromuscular activation of these muscles in the rehabilitation of those suffering from chronic neck pain.

Background The bioactive alkaloids identified from Cortex Phellodendri (CP) were highly effective in treating rats with benign prostatic hyperplasia (BPH). Specifically, lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) were identified as two primary targets for alleviating inflammation in BPH rats. However, it remains unknown whether the alkaloid components in CP can interact with the two target proteins. Purpose To further identify bioactive alkaloids targeting LOX/COX pathways. Methods An affinity-ultrafiltration mass spectrometry approach was employed to screen dual-target LOX-5/COX-2 ligands from alkaloid extract. The structures of bioactive alkaloids were characterized by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. To understand the molecular mechanisms underlying the effects of bioactive alkaloids, the expression levels of LOX-5 and COX-2 in BPH model rats were investigated at both protein and mRNA levels. The LOX-5/COX-2 enzymes activity experiments and molecular docking analysis were performed to fully evaluate the interactions between bioactive alkaloids and LOX-5/COX-2. Results After comprehensive analysis, the results showed that bioactive alkaloids could suppress the expression of LOX-5 and COX-2 simultaneously to exert an anti-inflammatory effect on the progression of BPH. In addition, the screened protoberberine, demethyleneberberine was found to exhibit prominent inhibitory activities against both LOX-5 and COX-2 enzymes, palmatine and berberine with moderate inhibitory activities. Molecular docking analysis confirmed that demethyleneberberine could interact well with LOX-5/COX-2. Conclusion This study is the first to explore the inhibitory effects of bioactive alkaloids from CP on LOX-5 and COX-2 activities in BPH rats. Our findings demonstrate that the bioactive alkaloids from CP can ameliorate BPH via dual LOX-5/COX-2 pathways, which serves as an efficient approach for the discovery of novel drug leads from natural products with reduced side effects.

This study aims to investigate the dysfunction and recovery of the lumbopelvic movement and motor control of people with chronic nonspecific low back pain after a structured rehabilitation which emphasizes on re-education and training of movement and motor control. The lumbopelvic movement and motor control pattern of 30 adults (15 with chronic low back pain, 15 healthy controls) were assessed using 3D motion and electromyographic analysis during the repeated forward bending test, in additional to the clinical outcome measures. Regional kinematics and muscle recruitment pattern of the symptomatic group was analysed before and after the 6-week rehabilitation, and compared to healthy controls. Significant improvement in back pain, functional capacity and self-efficacy of the symptomatic group was found after the rehabilitation. Patients with chronic nonspecific low back pain were capable to recover to a comparable level of the healthy controls in terms of their lumbopelvic movement and motor control pattern upon completion of a 6-week rehabilitation program, despite their dysfunction displayed at baseline. Phase specific motor control reorganization in which more profound and positive changes shown during the flexion phase. Our findings indicate that the recovery of the movement and motor control pattern in patients with chronic low back pain achieved to a comparable level of the healthy able-bodies. The improvement of both the physical outcome measures suggest that specific rehabilitation program which emphasizes on optimizing motor control during movements would help promoting the functional recovery of this specific low back pain subgroup.

Introduction: Ectodermal dysplasia refers to the abnormal development of two or more embryological elements that give rise to skin, hair, teeth, and sweat glands. Clinically, ectodermal dysplasia c...

Background: fractures occur more commonly in the thoracic than in the lumbar spine. Physical activity complemented with pharmacological interventions has been advocated as a preventive measure for osteoporosis. However, walking has been shown to produce only a small improvement in spinal bone mineral density. The characteristics of vibration transmission during walking at the lumbar and thoracic spines may be different, and this may help explain the relative incidence of fractures in the two spine regions. Objective: to determine how mechanical vibration is transmitted in the lumbar and thoracic spines in older adults with and without osteoporosis. Methods: 16 young healthy adults, 19 older adults without osteoporosis and 41 adults with osteoporosis were recruited. Inertial sensors were attached to the skin over the lumbar and thoracic spines for recording the vibration transmitted during level walking. Vibration characteristics were compared across lumbar and thoracic spines and across groups. Results: the lumbar spine generally amplified the vibration transmitted during walking, whereas the thoracic spine exhibited a much smaller amplification effect, except at the lowest frequency. The magnitude of vibration was generally reduced in the older spines. Osteoporosis had minimal effects on vibration transmission. Conclusions: the larger amplification of vibration in the lumbar spine may explain the lower incidence of vertebral fractures in this region when compared to the thoracic spine. Ageing alters the transmission of vibration in the spine while osteoporosis has minimal effects. Future research should determine the characteristics of vibration transmitted through the thoracic spine during other physical activities.

l-Isocorypalmine is a newly identified metabolite of l-tetrahydropalmatine with a unique dual pharmacological profile as a partial dopamine receptor 1 agonist and dopamine receptor 2 antagonist properties for treating cocaine use disorder. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, and excretion of l-isocorypalmine in Sprague-Dawley rats. A sensitive and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for determination of l-isocorypalmine in biological samples. The biological samples were extracted by liquid-liquid extraction and separated on a Bonshell ASB C18 column (2.1 × 100 mm, 2.7 μm, Agela) with gradient mobile phase at the flow rate of 0.2 mL/min. The detection was performed by positive electrospray ionization with multiple reaction monitoring mode. Satisfactory linearity, precision, accuracy, extraction recovery, and acceptable matrix effect were achieved. The quantitative method was successfully applied to the pharmacokinetics, tissue distribution, and excretion study of l-isocorypalmine. The results showed that l-isocorypalmine was rapidly distributed, and eliminated from rat plasma and manifested linear dynamics in a dose range of 7.5-15 mg/kg. In addition, the results would be helpful for further clinical reference of l-isocorypalmine as a potential candidate drug for the treatment of cocaine addiction.

First described in 1978, Griscelli syndrome (GS) is a rare autosomal recessive disorder featuring pigmentary dilution of hair and skin.1 GS is caused by mutations in any of three genes encoding a tripartite protein complex essential for melanosome transport.2 GS1 (MIM214450) presents as hypomelanosis with primary neurological defects and is caused by mutations in MYO5A,3 and which also may be the same entity as Elejalde syndrome (MIM256710).4 This article is protected by copyright. All rights reserved.

Nowadays, 2D structure of PKG needs to change to 2.5D or 3D structure for high performance of PKG. The standoff property was required to prevent the Si chip damage and electrical short when solder joint is located between substrate and interposer. So, CCSB (Cu Core Solder Ball) is the most popular candidate of interconnection material for 2.5D PKG. However, controlling of plated solder composition has limitation due to difficult deposition over 3 elements by electroplating system. So, SAC305 composition was plated for CCSB product. In this paper, we studied Cu bump formation of new concept. At first, Cu bump was formed with combination with 1st reflowed solder bump and specially controlled Cu ball which is the surface treatment layer to get good wetting property of liquid solder by additional reflow. The applied solder is the Sn-2.5Ag-0.8Cu-0.05Ni-1Bi (MXT02) for high reliability. New concept Cu bump showed higher joint strength than general CCSB product. Therefore, new concept of Cu core ball will show higher reliability, easy application and more fine pitch then general CCSB product.

To accommodate the exceedingly demanding power integrity (PI) requirements for the advanced artificial intelligence (AI) and high performance computing (HPC) components, high-K (HK) based deep trench capacitors (DTC) have been integrated the first time in the silicon interposer with through silicon via (TSV) and fine-pitch interconnects for chip-on-wafer-on-substrate (CoWoS) integration. A specific capacitance density (C s ) of up to 340 nF/mm2 is achieved over a large capacitor array, providing a total capacitance (C t ) of up to 68 μF per interposer die. The HK dielectric has intrinsic time-dependent dielectric breakdown (TDDB) lifetime of > 1,000 years at an operation voltage (V cc ) of 1.35V, and a normalized leakage current (I LK ) density LK & V bd tailing) were observed. The high capacitance, low leakage, large area and reliability-proven Si-interposer integrated DTC, or iCap, provides superior PI performance and therefore greatly enhances the merit of using CoWoS for the next-generation heterogeneous wafer level system integration (WLSI).

Obesity and osteoporotic‐related fractures are two common public health problems, although it is unclear how obesity affects the risk of vertebral fractures. The purpose of this study was to examine the association between different measures of obesity and the risk of vertebral fracture, and to establish the various clinical factors that can predict such risk. We analyzed data obtained from 502,543 participants in the UK Biobank (229,138 men and 273,405 women), aged 40 to 69 years. Imaging information was available in a subset of this cohort (5189 participants: 2473 men and 2716 women). We further examined how BMD and geometry of the vertebrae were related to body fat measures. It was shown that a larger waist circumference (WC), but not BMI, was associated with an increase in fracture risk in men, but in women, neither BMI nor WC affected the risk. Trunk fat mass, visceral adipose tissue (VAT) mass, and limb fat mass were negatively associated with vertebral body BMD and geometry in men and women. BMD and geometry are related to vertebral strength, but may not be directly related to the risk of fractures, which is also influenced by other factors. The binary logistic regression equation established in this study may be useful to clinicians for the prediction of vertebral fracture risks, and may provide further information to supplement the fracture risk assessment tool, which assesses general fracture risks. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Background - Dance has shown to be beneficial for people with Parkinson’s. However, there is a lack of research on ballet for this population. The present study aimed to determine the effect of weekly ballet classes on gait variability and balance confidence for people with Parkinson’s.Methods - The study follows a non-randomized, controlled project evaluation design. A group of 19 people with Parkinson’s who were already involved in weekly ballet classes volunteered for this research. A control group of 13 people with Parkinson’s were asked to not participate in dance classes across the duration of the study. Results - The study did not demonstrate significant effects of weekly ballet classes on gait variability or balance confidence. Conclusions - These findings differ from recent studies that suggest dancing can improve balance and gait for this population. There is a need to examine the optimal ballet class frequency required to elicit any potential positive change.

Mutations in ceramide biosynthesis pathways have been implicated in a few Mendelian disorders of keratinization although ceramides are known to have key roles in several biological processes in skin and other tissues. Using whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identified compound heterozygosity for mutations in KDSR, encoding an enzyme in the de novo synthesis pathway of ceramides. Two individuals had hyperkeratosis confined to palms and soles as well as anogenital skin, whereas the other two had more severe, generalized harlequin ichthyosis-like skin. Of note, thrombocytopenia was present in all cases. The mutations in KDSR were associated with reduced ceramide levels in skin and impaired platelet function. KDSR enzymatic activity was variably reduced in all cases resulting in defective acylceramide synthesis. Mutations in KDSR have recently been reported in inherited recessive forms of progressive symmetric erythrokeratoderma, but our study demonstrates that biallelic mutations in KDSR are implicated in an extended spectrum of disorders of keratinization in which thrombocytopenia is also part of the phenotype. Mutations in KDSR cause defective ceramide biosynthesis, underscoring the importance of ceramide and sphingosine synthesis pathways in skin and platelet biology.

Background Previous study has found that people with chronic neck pain moved with a consistently compromised acceleration/deceleration at their cervical and thoracic spines. This study examined the strength of the association between the electromyographic activities and the acceleration/deceleration of the cervical and thoracic spine, and its correlation with the functional disabilities in individuals with neck pain. Methods Time history of the cervical and thoracic acceleration/deceleration and EMG activity was acquired in thirty-four subjects with chronic neck pain and thirty-four age- and gender-matched asymptomatic subjects during active neck movements. The strength of the association between the electromyographic activity of spinal muscles and the cervical and thoracic acceleration/deceleration was determined using cross-correlation method. Relationship between the strength of this association and the severity of the functional disabilities in neck pain group was examined using correlation analysis. Findings The strength of the association between cervical and thoracic acceleration/deceleration and electromyographic activities was significantly lower in neck pain group. Significant negative correlations were found between the functional disability level and the strength of this defined association in the symptomatic group. Interpretation The compromised capability of the spinal muscles to produce acceleration/deceleration in the neck pain group may imply an impaired electromechanical coupling of these spinal muscles when performing neck movements. Significant negative correlation of the degree of functional disabilities suggests that the present approach can be used as an objective and specific evaluation of the dynamic performance of the spinal muscles and its relationship with the functional disabilities in neck pain subjects.

A fast, sensitive, and reliable ultra-high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation and pharmacokinetic study of five phthalides (senkyunolide A, ligustilide, butylidenephthalide, 3-butylphthalide, and levistilide A) in rat plasma after oral administration of Huo Luo Xiao Ling Dan (HLXLD) or Angelica sinensis--Ligusticum chuanxiong herb pair (DG-CX) between normal and arthritis rats. After extraction from blood, the analytes and internal standard were subjected to ultra-high performance liquid chromatography with a Shim-pack XR-ODS column (75 × 3.0 mm(2) , 2.2 μm particles) and mobile phase was composed of methanol and water (containing 0.05% formic acid) under gradient elution conditions, with an electrospray ionization source in the positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.192-0.800 ng/mL for all the analytes. Satisfactory linearity, precision, accuracy, mean extraction recovery, and acceptable matrix effect have been achieved. The validated method was successfully applied to a comparative pharmacokinetic study of five bioactive components in rat plasma after oral administration of HLXLD or DG-CX alone, respectively, between normal and arthritic rats. The results showed that there were unlike characters of pharmacokinetics among different groups.