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A growing body of evidence has shown that gestational exposure to environmental factors such as imbalanced diet, environmental chemicals, and stress can lead to late-onset health effects in offspring and that some of these effects are heritable by the next generation and subsequent generations. Furthermore, altered epigenetic modifications in DNA methylation, histone modifications and small RNAs in a single sperm genome have been shown to transmit disease phenotypes acquired from the environment to later generations. Recently, our group found that gestational exposure of F0 pregnant dams to an inorganic arsenic, sodium arsenite, increases the incidence of hepatic tumors in male F2 mice, and the effects are paternally transmitted to the F2. Here, we first overview the epigenetic changes involved in paternal intergenerational and transgenerational inheritance caused by exposure to environmental factors. Then, we discuss our recent studies regarding paternal inheritance of the tumor-augmenting effects in F2 mice by gestational arsenite exposure, in which we investigated alterations of DNA methylation status in F2 tumors and causative F1 sperm. We also discuss the possible targets of the F2 effects. Finally, we discuss future perspectives on the studies that are needed to fully understand the health effects of arsenic exposure.
To alert the medical society regarding that hematuria after radical prostatectomy can be caused by pelvic pseudoaneurysm.
Case report of a 61-year-old male underwent extraperitoneal robotic-assisted radical prostatectomy. He was readmitted on the 15th POD due to gross hematuria with resolution after bladder irrigation. It returned on the 21st POD.
The CT angiography evidenced the pseudoaneurysm of the left internal iliac artery. Selective embolization was effectively performed, with no additional bleeding or pelvic ischemia. Endovascular therapy is the preferred method of treatment.
The pelvic pseudoaneurysm is a rare, but serious complication that can cause severe bleeding. In our experience, we had 3 cases of persistent hematuria caused by pelvic pseudoaneurysm after 1810 robotic-assisted radical prostatectomy.
The pelvic pseudoaneurysm is a rare, but serious complication that can cause severe bleeding. In our experience, we had 3 cases of persistent hematuria caused by pelvic pseudoaneurysm after 1810 robotic-assisted radical prostatectomy.In this case, we present imaging findings characteristic of chronic genitourinary schistosomiasis. Schistosoma haematobium, a blood fluke endemic to Africa and the Middle East, is a prominent cause of hematuria and bladder cancer in regions lacking adequate water sanitation. Luminal calcifications of the genitourinary tract, that is, of the bladder and/or ureters, from deposition of fluke eggs are a classic sign of chronic S. haematobium infection and should raise suspicion for the disease even when urine or serological tests are negative. It is important to recognize these findings on CT or, in resource-limited settings, plain film to allow for prompt, effective treatment.Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Increasing evidence highlights the role of age-related chronic inflammation, oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. A combination of these factors impairs the crosstalk between mitochondria and lysosomes, resulting in compromised cell homeostasis. Apolipoprotein D (APOD), an ancient and highly conserved anti-inflammatory and antioxidant lipocalin, and the transcription factor EB (TFEB), a master regulator of mitophagy, autophagy and lysosomal biogenesis, play key roles in these processes. Both APOD and TFEB have attracted attention as therapeutic targets for PD. The aim of this study was to investigate if the selective cyclooxygenase-2 inhibitor celecoxib (CXB) exerts a direct neuroprotective effect in 6-hydroxydopamine (6-OHDA) and paraquat (PQ) PD models. We found that CXB rescued SH-SY5Y cells challenged by 6-OHDA- and PQ-induced toxicity. Furthermore, treatment with CXB led to a marked and sustained upregulation of APOD and the two microphthalmia transcription factors TFEB and MITF. In sum, this study highlights the clinically approved drug CXB as a promising neuroprotective therapeutic tool in PD research that has the potential to increase the survival rate of dopaminergic neurons that are still alive at the time of diagnosis.Significant efforts have been recently made to obtain the three-dimensional (3D) structure of the genome with the goal of understanding how structures may affect gene regulation and expression. Chromosome conformational capture techniques such as Hi-C, have been key in uncovering the quantitative information needed to determine chromatin organization. Complementing these experimental tools, co-polymers theoretical methods are necessary to determine the ensemble of three-dimensional structures associated to the experimental data provided by Hi-C maps. Going beyond just structural information, these theoretical advances also start to provide an understanding of the underlying mechanisms governing genome assembly and function. Recent theoretical work, however, has been focused on single chromosome structures, missing the fact that, in the full nucleus, interactions between chromosomes play a central role in their organization. To overcome this limitation, MiChroM (Minimal Chromatin Model) has been modified to become capable of performing these multi-chromosome simulations. It has been upgraded into a fast and scalable software version, which is able to perform chromosome simulations using GPUs via OpenMM Python API, called Open-MiChroM. To validate the efficiency of this new version, analyses for GM12878 individual autosomes were performed and compared to earlier studies. This validation was followed by multi-chain simulations including the four largest human chromosomes (C1-C4). These simulations demonstrated the full power of this new approach. Comparison to Hi-C data shows that these multiple chromosome interactions are essential for a more accurate agreement with experimental results. Without any changes to the original MiChroM potential, it is now possible to predict experimentally observed inter-chromosome contacts. This scalability of Open-MiChroM allow for more audacious investigations, looking at interactions of multiple chains as well as moving towards higher resolution chromosomes models.
Endoscopists experience upper extremity musculoskeletal injuries. The primary aim of this study was to compare distal upper extremity biomechanical risk factors during colonoscopy with established risk thresholds. Secondary aims were to determine which subtasks during colonoscopy are associated with the greatest risk and to evaluate an intervention to reduce risks.
Twelve endoscopists performed 2 to 4 colonoscopies while thumb pinch force and forearm muscle loads of extensor carpi radialis (ECR) and flexor digitorum superficialis (FDS) muscles were collected. Peak exertion values were analyzed using amplitude probability distribution functions. An endoscope support device was evaluated during simulated colonoscopy (n= 8).
Mean endoscopist age was 42.3 years; 67% were men. Peak thumb pinch force exceeded risk thresholds for pinch force (10 N) and percent of time spent in forceful pinch for all colonoscopy subtasks. Peak ECR and FDS muscle activity exceeded the action limit (10% maximum voluntary contraction [MVC]) in both forearms. Peak left FDS, left ECR, and right ECR activity exceeded the threshold limit value (>30% MVC). Peak left FDS and ECR activity were significantly greater during insertion than during withdrawal (P< .05). Peak right FDS and ECR activity were significantly greater during right colon insertion compared with withdrawal (P< .05). The endoscope support device reduced left ECR muscle activity (P= .02).
Thumb pinch forces and time spent in forceful pinch indicate high-risk exposures during colonoscopy. Left wrist extensor muscle activity exceeded established thresholds with the greatest risk occurring during insertion. An endoscope support device reduced loads to the left wrist extensors.
Thumb pinch forces and time spent in forceful pinch indicate high-risk exposures during colonoscopy. Left wrist extensor muscle activity exceeded established thresholds with the greatest risk occurring during insertion. An endoscope support device reduced loads to the left wrist extensors.
The American Society for Gastrointestinal Endoscopy (ASGE) 2010 guidelines for suspected choledocholithiasis were recently updated by proposing more specific criteria for selection of high-risk patients to undergo direct ERCP while advocating the use of additional imaging studies for intermediate- and low-risk individuals. We aim to compare the performance and diagnostic accuracy of 2019 versus 2010 ASGE criteria for suspected choledocholithiasis.
We performed a retrospective chart review of a prospectively maintained database (2013-2019) of over 10,000 ERCPs performed by 70 gastroenterologists in our 14-hospital system. We randomly selected 744 ERCPs in which the primary indication was suspected choledocholithiasis. Patients with a history of cholecystectomy or prior sphincterotomy were excluded. The same patient cohort was assigned as low, intermediate, or high risk according to the 2010 and 2019 guideline criteria. Overall accuracy of both guidelines was compared against the presence of stones and/or srmediate risk per 2019 guidelines and will require an additional confirmatory imaging study.
The 2019 ASGE guidelines are more specific for detection of choledocholithiasis during ERCP when compared with the 2010 guidelines. However, a large number of patients are categorized as intermediate risk per 2019 guidelines and will require an additional confirmatory imaging study.The solid-state diversity of active pharmaceutical ingredients can provide theoretical guidance for the production and storage of drugs. In this study, three solid forms of glipizide were obtained through various methods, and the solid-state transformations were extensively investigated. Form I could be prepared using evaporative crystallization, cooling crystallization, anti-solvent crystallization, and solvent-mediated slurry conversion experiments (SSCE). Form II was produced by milling. Form III was obtained by milling and SSCE. The results of solid-state transformations indicated that Form I transformed to II during neat milling at 25 °C. In contrast, solvent inhibited the solid-state transformations of Form I under liquid-assisted milling. Forms II and III remained invariable under neat milling at 25 °C, and solid-state transformation of Form III also did not occur in the liquid-assisted milling. In SSCE, the solvent's nature and its temperature significantly influenced the solid-state conversion of amorphous glipizide. Form II converted to either Form I or III in water above 50 °C, and only transformed into Form I at 25 °C. However, the solid-state transformation did not occur when pure Form I or III was stirred in water. Form II also converted to Form I in the organic solvents SSCE at different temperatures.
Smoking habit at the time of surgery is associated with higher perioperative complications and mortality across different types of surgeries. In recent years, several studies have attempted to explore the influence of smoking on perioperative outcomes following radical cystectomy (RC) for urothelial bladder cancer (UBC) with contradictory results.
To systematically investigate and meta-analyze the association between smoking habit and perioperative morbidity and mortality in UBC patients treated with RC.
A systematic review of the literature published between January 2000 and January 2020 investigating the impact of smoking habit on perioperative outcomes of patients treated with RC for UBC was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Systematic Reviews of Interventions.
Overall, 27 articles involving 27 854 patients were included in the systematic review, and of these, 11 studies were included in thehe preoperative setting to encourage smoking cessation.
In this study, we reviewed the impact of smoking habit on perioperative outcomes following radical cystectomy (RC). Based on the available data, the impact of smoking on morbidity and mortality after RC is significant and relevant; as such, every effort should be made in the preoperative setting to encourage smoking cessation.
Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures.
Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach.
We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1s (FEV
) (p<0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV
level and to their profile of exposure to a reduced sethe exposures revealed significant association when considered independently.A pneumonia-like disease of unknown origin caused a catastrophe in Wuhan city, China. This disease spread to 215 countries affecting a wide range of people. World health organization (WHO) called it a pandemic and it was officially named as Severe Acute Respiratory Syndrome Corona virus 2 (SARS CoV-2), also known as Corona virus disease (COVID-19). This pandemic compelled countries to enforce a socio-economic lockdown to prevent its widespread. This paper focuses on how the particulate matter pollution was reduced during the lockdown period (23 March to April 15, 2020) as compared to before lockdown. Both ground-based and satellite observations were used to identify the improvement in air quality of Pakistan with primary focus on four major cities of Lahore, Islamabad, Karachi and Peshawar. Both datasets have shown a substantial reduction in PM2.5 pollution levels (ranging from 13% to 33% in case of satellite observations, while 23%-58% in ground-based observations) across Pakistan. Result shows a higher rate of COVID-19 spread in major cities of Pakistan with poor air quality conditions. Yet more research is needed in order to establish linkage between COVID-19 spread and air pollution. However, it can be partially attributed to both higher rate of population density and frequent exposure of population to enhanced levels of PM2.5 concentrations before lockdown period.
The selective reduction of memory T
2 cell responses could be key to affording tolerance and protection from the recurrence of damaging allergic pathology.
We asked whether TNF family costimulatory molecules cooperated to promote accumulation and reactivity of effector memory CD4 T cells to inhaled complex allergen, and whether their neutralization could promote airway tolerance to subsequent reexposure to allergen.
Mice were sensitized intraperitoneally or intranasally with house dust mite and challenged with intranasal allergen after memory had developed. We assessed whether single or combined blockade of OX40L/CD252 and CD30L/CD153 inhibited memory T cells from driving acute asthmatic lung inflammation and protected mice following exposure to allergen at a later time.
OX40- or CD30-deficient animals showed strong or partial protection against allergic airway inflammation; however, neutralizing either molecule alone during the secondary response to allergen had little effect on the frequency of effy reactions following reexposure to allergen.
Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.
We sought to evaluate the role of circulating CXCR5
PD-1
T follicular helper (cT
) and T follicular regulatory (T
) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape.
Phenotype and function of cT
cells were initially evaluated in the grass pollen-allergic (GPA) group (n= 28) and nonatopic healthy controls (NAC, n= 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cT
and T
cells were further enumerated in NAC (n= 12), GPA (n= 14), SCIT- (n= 10), and SLIT- (n= 8) treated groups. Chromatin accessibility in cT
and T
cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups.
cT
cells were shown tunotherapy in cT
and T
cells.
For the first time, we showed dysregulation of cTFH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cTFH and TFR cells.
Whether biologic therapies enhance the risk of coronavirus 2019 (COVID-19) or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained.
We sought to investigate the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population.
This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n= 6501) being treated with biologic therapy and regularly followed up at the divisions of dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates of hospitalization and death per 10,000 person-months with exact mid-p 95% CIs and standardized incidence ratios were estimated in the patients with psoriasis and compared with those in the general population in the same geographic areas.
The incidence rate of hospitalization for COVID-19 was 1an 6 months and not infected with severe acute respiratory syndrome coronavirus 2 to prevent hospitalization and death from COVID-19.
Most studies on the mechanism behind premenstrual syndrome (PMS) have focused on negative emotional overreaction, but little evidence exists regarding the weakening of positive emotions. Given the close relationship between positive emotions and reward processing, the aim of this study is to investigate the dysfunction of reward processing in women with PMS.
Seventeen women with PMS and seventeen healthy women were scanned during a card guessing task in the late luteal phase. By selecting bilateral caudate and orbitofrontal cortex (OFC) as seed regions, region-of-interest (ROI) analysis and functional connectivity (psycho-physiological interaction [PPI]) analysis were conducted to compare the difference between two groups. Exploratory whole brain analysis was also conducted to examine the group differences in other reward-related brain regions.
ROI analysis revealed that healthy women showed stronger activation at the bilateral caudate and OFC when gains were contrasted to losses feedback, whereas womenOur findings provide one of the first evidence that PMS is related to dysfunction in reward processing, which could be associated with the weakening of positive emotions.
The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls.
Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n= 495; n= 387 UC; n= 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted.
ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus dis therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.Extracellular vesicles might be originated from different kinds of cells, mediating cell-cell communication in different normal and pathological contexts. These vesicles contain several biomolecules among them are microRNAs (miRNAs). These small regulatory transcripts can influence cell differentiation, proliferation and migration. Their inclusion in the stem cell-derived microvesicles has provided them the capacity to mediate a number of functional effects of stem cells on normal or malignant cells. In the present manuscript, we explain the results of studies which evaluated the miRNA profile of stem cell-originated extracellular vesicles and their impacts on surrounding cells in normal and tumoral microenvironments. The presented data in the current review shows that exosome-derived miRNAs have practical significance in at least two fields of biology, i.e. regenerative medicine and cancer treatment.Over the past decades, new light has been shed on the efficiency of Mesenchymal Stem Cells (MSCs) in the treatment of autoimmune diseases. The therapeutic functions of MSCs partly stem from their well-recognized ability to efficiently modulate immune responses and it is well substantiated that MSC secretory components, in particular extracellular vesicles (EVs), play a critical role in this immunomodulation. In fact, almost any cell type can generate and release EVs under both pathological and physiological conditions and these nano-sized particles are believed to greatly contribute to homeostasis and cell-cell communication through transportation of a wide variety of biomolecules including nucleic acid, signaling lipids, regulatory proteins, transcription factors, cytokines, and growth factors. Lamentably, despite exhibiting promising results in both animal experiments and clinical trials, MSC therapy is still largely restricted to the experimental stage due to its critical pitfalls and drawbacks such as safety issues, poor cell survival, immune rejection and high cost. On the other hand, MSC-derived EVs, which ideally reflect the exact biophysical features of MSCs, are considered to be much safer and more effective than MSCs themselves. Therefore, introducing alternative approaches based on MSC-derived EVs can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy and thus the extracellular vesicles of MSCs may also provide a far more potent therapeutic strategy for immune-related disorders. In this review, we first focus on the properties of MSC-derived EVs and then we shall provide valuable insight regarding their beneficial therapeutic opportunities to further compare this alternative approach with conventional MSC therapy. Finally, we will attempt to summarize the current findings on the influences of MSC-derived EVs on autoimmune disorders, offering a potential alternative avenue towards treatment of autoimmune diseases.The effects of marijuana's major psychoactive cannabinoid, ∆9-tetrahydrocannibinol (∆9-THC), were examined on memory in female rats by training subjects to respond under a repeated acquisition and delayed-performance procedure. During this task, subjects acquired a different 4-response sequence each session, which was then recalled after a delay. Sequence retention was tested following various delays, and quantified by a percent savings measure. Response rate and percent errors were also recorded. Subsequent to training, subjects underwent an ovariectomy (OVX) or sham surgery (intact). The OVX group then underwent implantation of subcutaneous 17β-estradiol capsules while the intact group received chronic administration of 1 mg/kg of the estrogen receptor modifier, tamoxifen. Increasing delays from 1 min to 24 h produced delay-dependent decreases in percent savings in both OVX and intact rats. Acute administration of ∆9-THC (0.32-3.2 mg/kg) dose-dependently decreased retention, increased percent errors, and decreased response rate in both groups when the delay was 1 h. However, intact rats showed a significantly lower percent savings than OVX rats at the 0.56-mg/kg dose. Delays of 3 h enhanced the disruptive effects of ∆9-THC more in intact than OVX rats; furthermore, implantation of 17β-estradiol attenuated ∆9-THC-induced disruptions in OVX rats and significantly increased estradiol levels and uterine weight as compared to intact rats. Although chronic tamoxifen administration did not alter ∆9-THC's effects on memory in intact rats, it did significantly decrease response rate. These results demonstrate the capacity of chronic 17β-estradiol for attenuating ∆9-THC's acute memory-disrupting effects in OVX female rats.Accumulating evidence indicates that the central orexin (hypocretin) system plays an important role in regulating emotional processes in both humans and rodents. Thus, the orexin system has been repeatedly implicated in the pathophysiology of several neuropsychiatric disorders, such as anxiety disorders. Among others, symptoms like social fear and social withdrawal are frequently observed in these disorders. Based on this, we investigated the role of orexin deficiency in social (fear) behavior. For that, female and male orexin-deficient mice were tested for (1) sociability and social novelty, and (2) acquisition, expression, and extinction of conditioned social fear. We found that female orexin-deficient mice displayed reduced sociability and decreased preference for social novelty compared to their wild-type littermates. These effects of orexin deficiency were not observed in males. Moreover, orexin deficiency facilitated the acquisition and/or expression of conditioned social fear and impaired the extinction of social fear in both sexes. Taken together, our results indicate an important, partly sex-dependent, regulatory role of the orexin system in social (fear) behavior. Our findings support the hypothesis of orexin being an integrator of motivation, affect, and emotion.
To investigate whether curcumin promotes hippocampal neurogenesis in the cerebral ischemia (CI) mice via Wnt/β-catenin signaling pathway.
Male C57BL/6 mice were randomly divided into groups sham operation group (Sham), cerebral ischemic group (CI), curcumin treatment group (50, 100mg/kg/d, i.p.) and curcumin (100mg/kg/d)+DKK1 (a blocker of Wnt receptor, 200ng/d, icv) group. CI was induced by bilateral common carotid arteries occlusion (BCCAO) for 20min. The Morris water maze test was conducted to detect spatial learning and memory. Immunofluorescence staining was used to examine the proliferation and differentiation of immature neurons in the hippocampal dentate gyrus. The proteins involved in neurogenesis and Wnt signaling pathway were examined using Western blot assay.
Curcumin significantly alleviated cognitive deficits induced by CI. Curcumin dose-dependently increased the proliferation of neural stem cells and promoted the differentiation and maturation of newly generated neural cells into neurons. Curcumin also increased the expression of proteins involved in neurogenesis (including Ngn2, Pax6 and NeuroD 1) and the Wnt/β-catenin signaling pathway. Moreover, the forenamed effects of curcumin were abolished by pretreatment with DKK1, a blocker of Wnt receptor.
Curcumin promotes hippocampal neurogenesis by activating Wnt/β-catenin signaling pathway to ameliorate cognitive deficits after acute CI.
Curcumin promotes hippocampal neurogenesis by activating Wnt/β-catenin signaling pathway to ameliorate cognitive deficits after acute CI.The riverine tsetse fly Glossina fuscipes fuscipes is a major vector of trypanosome pathogens causing African trypanosomiasis. This fly species uses a combination of olfactory and visual cues to locate its hosts. Previously, traps and targets baited with visual cues have been used in vector control, but the development of olfactory-based tools has been challenging. Recently, repellents have shown promise as olfactory-based tools in tsetse vector control. Here, we evaluated a three-component blend comprising 6-methyl-5-hepten-2-one, acetophenone and geranyl acetone (blend K), previously identified as a repellent for savannah tsetse flies in zebra skin odor, on G. f. fuscipes populations. Using a series of 6 × 6 randomized Latin square-designed experiments, G. f. fuscipes catches in biconical traps were monitored on four islands of Lake Victoria in western Kenya between July and September 2019, after the long rainy season. Traps were baited with blend K and individual components of this blend. The known tsetse repellent blend WRC (waterbuck repellent compounds) and trap alone were included as controls. Daily catch data in thirty-six replicate trials were analyzed using generalized linear model with negative binomial error structure using the package "MASS" in R. Treatment, day and site were set as predictor variables. Our results showed that, blend K significantly reduced G. f. fuscipes catches by 25.6% (P less then 0.01) compared to the control trap alone but was not significantly different from WRC which reduced catches by 20.7% (P less then 0.05). Of the individual compounds, geranyl acetone solely significantly reduced catches by 29.1% (P less then 0.01) which did not differ from blend K or WRC. We conclude that geranyl acetone accounts for the repellent effect of blend K on the riverine tsetse fly, G. f. fuscipes, demonstrating the ecological importance of animal skin odors in the host-seeking behavior of medically-important tsetse fly vectors.Larval mosquitoes have a more limited home range and lower resistance to adverse environment than adults, thus can be ideal targets for vector control in some cases. Coagulation-flocculation technology, which could be used for water treatment in breeding sites of several vector mosquito species, can significantly change both the distribution of organic particles and surface sediment characteristics in water environment. The aim of this study was to explore the effect, principle and possibility of using coagulation-flocculation technology in immature mosquitoes killing. In this study, dechlorinated water was treated with Poly Aluminum Chloride (PACl, sewage treatment using), and we observed the impacts of PACl treatment on the development and survival of immature Culex pipiens pallens mosquitoes. When exposed to PACl treatment, physical effect is believed to be a main reason of coagulation-flocculation caused high larvae mortality Ⅰ) alum floc layer increases the difficulty of larvae foraging, leads larvae starving to death; (Ⅱ) the little floc particles could attach to the lateral hair of larvae, which impede floatation process and then surface respiration by larval mosquitoes. The alum floc layer had a good killing effect on the mosquito larvae, presented the half lethal time (LT50) of 2d, the 90% lethal time (LT90) of 8.7±7.3 ∼ 14±4.5 d, and the pupation rate of 0 ∼ (6.5±0.5)%, respectively. Our results indicates alum floc, produced by PACl coagulation-flocculation, was shown to be highly active against 1st∼2nd instar larvae, the high mortality rate of immature mosquitoes as a result of physical effect. The observations suggest that coagulation-flocculation technology offers a novel potential approach to a sustainable and low-impact mosquito control method.Recent outbreaks of Cutaneous Leishmaniasis (CL) in Waziristan make the disease a public health concern in Khyber Pakhtunkhwa (KPK) province, Pakistan. The awareness and behavior of local community towards the disease is an important factor towards effective control and management of CL in endemic areas of Pakistan. A cross-sectional community based survey was piloted in new emerging district of North Waziristan Agency (KPK province), Pakistan from August 2019- February 2020. The study aimed to examine the Knowledge, Attitude and Practices (KAP) of the local community members regarding CL. The results revealed that majority of the participants were male. Only 48.2% participants have knowledge about CL and the respondents had a moderate knowledge of CL vector and the disease. Few of the respondents were aware that CL is caused by sand flies, their breeding place, biting time, transmission of CL and control measures. Skin infection and sand-flies were the main disease symptoms and disease vector were known to some of the respondents. Most of the respondents showed positive attitude towards disease seriousness and believed that the disease could be cured and can be treated through modern medicines. Admission to hospitals, cleanliness and use of bed nets were the treatment measures for the disease in suspected patients, whereas some believed that the use of bed nets could be helpful in preventing the leishmaniasis. Moderate knowledge of the CL and its transmission in the study area emphasize the need to initiate health education and awareness campaigns to reduce the disease risk and burden in this highly endemic area in near future.
Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as "fit" by CGA. The interim analysis focusing on safety was reported here as the first part of this trial.
This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m
on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression.
Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects.
Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.
Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.
Depression among older adults with cancer is under recognized and under treated. This study characterizes the burden of depression in older adults with gastrointestinal (GI) malignancies prior to chemotherapy and its relationship with geriatric assessment (GA) domains, health-related quality of life (HRQOL), and self-reported healthcare utilization.
Patients ≥60years in GI oncology clinics at UAB were asked to complete a GA entitled the Cancer & Aging Resilience Evaluation (CARE). We examined depression using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression four-item short form; moderate/severe depression was defined by a t-score≥60. Multivariate analysis was used to examine associations between those with and without moderate/severe depression.
Of 355 included patients, 46 had mild depression (13%) and an additional 46 patients had moderate/severe depression (13%). After adjustment for age, sex, education, cancer type, and cancer stage, those who reported moderate/severe depression had a significantly increased odds of reporting falls (adjusted odds ratio [aOR] 4.01, 95% confidence interval [CI] 1.94-8.26), dependence in IADLs (aOR 7.06,CI 2.91-17.1), dependence in ADLs (aOR 6.23, CI 2.89-13.4), malnutrition (aOR 5.86, CI 2.40-14.3), frailty (aOR 13.7, CI 5.80-32.1), and fatigue (aOR 11.2, CI 3.31-37.6). Moderate/severe depression was also significantly associated with worse physical (aOR 7.58, CI 3.30-17.4) and mental (aOR 26.3, CI 10.1-68.8) HRQOL sub-scores, without significant differences in healthcare utilization.
More than one out of eight older adults with a GI malignancy reported moderate/severe depression prior to chemotherapy, which was associated with impairments in several GA domains and HRQOL.
More than one out of eight older adults with a GI malignancy reported moderate/severe depression prior to chemotherapy, which was associated with impairments in several GA domains and HRQOL.Asymmetric distribution of lipid molecules in the inner and outer leaflets of the plasma membrane is a common occurrence in the membrane formation. Such asymmetric arrangement is a crucial parameter to manipulate the properties of the cell membrane. It controls signal transduction, endocytosis, exocytosis in the cells. The artificial membrane is often used to study the lateral and transverse arrangement of the lipid molecules in place of the cell membrane. Nano-mechanical characterization of the model membrane helps to understand the mechanical stability of the lipid bilayer. The stability is sensitive to the variations in the lipid composition and their local organization. In this article, we present both topographical and nano-mechanical properties of lipid bilayer characterized by atomic force microscopy (AFM). The results show that the asymmetric lipid bilayer formation is an intrinsic character. We have selected a bi-component fluid-gel phase 1,2-dilauroyl-sn-glycero-3-phosphocholine1,2-disteroyl-sn-glycero-3-phosphocholine (DLPC DSPC) system for our studies. We have observed domain formation and phase separation in the bilayer by increasing the composition of the gel phase DSPC. In force spectroscopy studies, we determine the mechanical strength of the bilayer for unique mixtures of DLPC DSPC by measuring the breakthrough force. These results also show the effect of asymmetry in the lipid bilayer. Besides AFM studies, we have implemented a coarse-grained (CG) molecular dynamics (MD) simulation using the gromacs package at room temperature and 1 bar pressure. The results from the simulation study have been compared with AFM study. It was found that the simulation studies corroborated the findings from AFM such as an increase in the bilayer thickness, change in the phase state, asymmetric and symmetric domain formation in the lipid bilayer.
To evaluate the long-term efficacy of percutaneous ethanol injection treatment (PEIT) as an alternative to thyroid surgery in symptomatic thyroid cysts.
100 subjects (48±12 years; 58% women) with symptomatic thyroid cysts relapsing after drainage were prospectively included. PEIT was conducted using an established procedure, and the initial cyst volume, symptoms and pain perceived by the patient were assessed. The volume of instilled alcohol was ≤2ml without re-extraction in all cases. Patients were followed-up for more than 3 years and final cyst volume and symptom improvement were assessed.
Mean maximum cyst diameter before drainage was 3.1±1.2cm. In 71% of patients ≤2 PEIT sessions were required. Median maximum cyst volume was 12.7 (5.4-21.7)ml before the first drainage and median total volume extracted from the cysts was 13.0 (6.2-37.0)ml. After a mean follow-up period of 52±10 months, 98% of patients reported a complete absence of symptoms. The final median volume for the whole group was 0.8 (0.1-2.0)ml with a median volume reduction of 94 (81-99)%. A final volume reduction greater than 65% was observed in 90% of cases. Reported pain during the procedure was absent or mild in 76.4% of cases.
PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.
PEIT is a safe and well-tolerated first-line treatment for symptomatic thyroid cysts with long-term effectiveness.
Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down.
The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis.
The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI] 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years.
During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.
During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.
The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis.
The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 11 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety agn of the LANDMARK trial.
The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites.
A subgroup analysis of the HEART Pathway Implementation Study was conducted. Adults with chest pain were accrued from November 2013 to January 2016 from 3 Emergency Departments in North Carolina. The primary outcomes were death and myocardial infarction (MI) and hospitalization rates at 30 days. Logistic regression evaluated for interactions of accelerated diagnostic protocol implementation with sex or race and changes in outcomes within subgroups.
A total of 8,474 patients were accrued, of which 53.6% were female and 34.0% were non-white. The HEART Pathway identified 32.6% of females as low-risk vs 28.5% of males (P = 002) and 35.6% of non-whites as low-risk vs 28.0% of whites (P < .0001). Among low-risk patients, death or MI at 30 days occurred in 0.4% of females vs 0.5% of males (P = .70) and 0.5% of non-whites vs 0.3% of whites (P = .69). Hospitalization at 30 days was reduced by 6.6% in females (aOR 0.74, 95% CI 0.64-0.85), 5.1% in males (aOR 0.87, 95% CI 0.75-1.02), 8.6% in non-whites (aOR 0.72, 95% CI 0.60-0.86), and 4.5% in whites (aOR 0.83, 95% CI 0.73-0.94). Interactions were not significant.
Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race.
Women and non-whites are more likely to be classified as low-risk by the HEART Pathway. HEART Pathway implementation is associated with decreased hospitalizations and a very low death and MI rate among low-risk patients regardless of sex or race.A large and growing body of epidemiologic research spanning roughly 7 decades has demonstrated that individuals who are more physically active have a lower incidence of cardiovascular disease (CVD) and all-cause mortality compared to those who are comparatively sedentary. Despite these well-established benefits of physical activity (PA), most adults and children do not get an adequate amount of PA. This is true not just in the United States but has been increasingly recognized throughout advanced countries. The theme of this Progress in Cardiovascular Diseases Symposium is "moving more", recognizing that any amount of increased physical movement, including occupational, recreational, household tasks, etc., has significant health benefits. Being physically active is associated with better health outcomes independent of cardiorespiratory fitness (CRF), a concept that would have been considered heretical a few decades ago. We now recognize that simply moving from a sedentary to a moderately active group or modest increases in CRF (e.g. moving from the least fit quintile of CRF to the next least fit quintile) has the most noticeable health benefits. In this review, the concept of "moving more" and its implications for CRF are discussed as they relate to the prevention and treatment of CVD.
The Accreditation Council for Graduate Medical Education (ACGME) and The American Board of Orthopaedic Surgery proposed The Orthopaedic Surgery Milestone Project. Training residency and fellowship programs have evolved accordingly adjusting academic curriculums. A new comprehensive Learner-Centered Education Curriculum (LCEC) was designed based on critical reviews and interactive collaboration between faculty, residents, and fellows using structured interviews and iterative feedback. We aim to evaluate the results at 4 years after implementation of a new curriculum.
The new adult arthroplasty LCEC was implemented in 2015; data collected between 2015 and 2019 was retrospectively reviewed and analyzed. Our primary goal was to evaluate educational, research, and quality successes using objective and quantitative academic quality metrics including annual Orthopedic In-Training Examination scores for the Hip & Knee domain to evaluate the medical knowledge competency.
This study was conducted at the Departy and learner attitudes. Significant and consistent improvements in academic, research, and quality metrics were obtained, while maintaining the highest resident evaluation scores in the program.
This LCEC, by enhancing an interactive and active academic learning experience, positively influenced fund of knowledge, conceptual thinking, and interest in the specialty and learner attitudes. Significant and consistent improvements in academic, research, and quality metrics were obtained, while maintaining the highest resident evaluation scores in the program.
Patients are integral to surgical training. Understanding our patients' perceptions of surgical training, resident involvement and autonomy is crucial to optimizing surgical education and thus patient care. In the modern, connected world many factors extrinsic to a patient's experience of healthcare may influence their opinion of our training systems (i.e., social media, television shows, and internet searches). The purpose of this article is to contextualize the literature investigating public perceptions of general surgery training to allow us to effect patient education initiatives to optimize both surgical training and patient safety.
This is a perspective including a literature review summarizing the current knowledge of public perceptions of general surgery training.
Little is published regarding patient and public perceptions of general surgery residency training and the role of residents within this. Current literature demonstrates that the majority of patients are willing to have residents part within this, can guide strategies to improve surgical education.
To describe the successes and challenges associated with developing an otolaryngology-head and neck surgery (OHNS) medical education app and website.
From 2010 to 2018, OHNS faculty across Canada contributed to the development of a smartphone app, LearnENT. LearnENT 1.0, was initially launched in 2012 using the Apple iOS 6 platform. The app utilized a novel user interface and interactive features to help learners develop approaches to OHNS clinical problems, review relevant anatomy, history, and physical examination skills. However, the release of iOS 7 necessitated a redesign and relaunch of LearnENT which occurred from 2015 to 2018 to produce the final version of the app, LearnENT 2.0. Through the relaunching process, the LearnENT team redesigned the app's interface, produced a web version of the app, and created a new content management system.
OHNS departments across Canada.
OHNS faculty members, residents, and medical students.
Through this approach, a sustainable, widely accessible, open access OHNS e-Learning resource was developed.
Here's my website:
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