Are Young Swimmers Short and Middle Distances Energy Cost Sex-Specific?
This study assessed the energy cost in swimming (C) during short and middle distances to analyze the sex-specific responses of C during supramaximal velocity and whether body composition account to the expected differences. Twenty-six swimmers (13 men and 13 women: 16.7 ± 1.9 vs. 15.5 ± 2.8 years old and 70.8 ± 10.6 vs. 55.9 ± 7.0 kg of weight) performed maximal front crawl swimming trials in 50, 100, and 200 m. The oxygen uptake ( V ˙ O2) was analyzed along with the tests (and post-exercise) through a portable gas analyser connected to a respiratory snorkel. Blood samples were collected before and after exercise (at the 1st, 3rd, 5th, and 7th min) to determine blood lactate concentration [La-]. The lean mass of the trunk (LM Trunk ), upper limb (LM UL ), and lower limb (LM LL ) was assessed using dual X-ray energy absorptiometry. Anaerobic energy demand was calculated from the phosphagen and glycolytic components, with the first corresponding to the fast component of the V ˙ O2 bi-exponential recovery phase and the second from the 2.72 ml × kg-1 equivalent for each 1.0 mmol × L-1 [La-] variation above the baseline value. The aerobic demand was obtained from the integral value of the V ˙ O2 vs. swimming time curve. The C was estimated by the rate between total energy releasing (in Joules) and swimming velocity. The sex effect on C for each swimming trial was verified by the two-way ANOVA (Bonferroni post hoc test) and the relationships between LM Trunk , LM UL , and LM LL to C were tested by Pearson coefficient. The C was higher for men than women in 50 (1.8 ± 0.3 vs. 1.3 ± 0.3 kJ × m-1), 100 (1.4 ± 0.1 vs. 1.0 ± 0.2 kJ × m-1), and 200 m (1.0 ± 0.2 vs. 0.8 ± 0.1 kJ × m-1) with p < 0.01 for all comparisons. In addition, C differed between distances for each sex (p < 0.01). The regional LM Trunk (26.5 ± 3.6 vs. 20.1 ± 2.6 kg), LM UL (6.8 ± 1.0 vs. 4.3 ± 0.8 kg), and LM LL (20.4 ± 2.6 vs. 13.6 ± 2.5 kg) for men vs. women were significantly correlated to C in 50 (R 2 adj = 0.73), 100 (R 2 adj = 0.61), and 200 m (R 2 adj = 0.60, p < 0.01). Therefore, the increase in C with distance is higher for men than women and is determined by the lean mass in trunk and upper and lower limbs independent of the differences in body composition between sexes.


Heat shock protein-70 and 4-hydroxy-2-nonenal adducts in human placental villous tissue of normotensive, preeclamptic and intrauterine growth restricted pregnancies.
The purpose of this study was to compare immunohistochemical expression of heat shock protein-70 (hsp70), a marker for oxidative stress, and 4-hydroxy-2-nonenal adducts (HNE), a marker for lipid peroxidation, in placental villous tissue of normotensive, preeclampsia, and intrauterine growth restricted (IUGR) pregnancies. Placentas were collected and flash frozen in liquid nitrogen after delivery from normotensive pregnancies (n=5), and pregnancies complicated by preeclampsia (n=5), IUGR (n=5), and preeclampsia plus IUGR (n=4). Cryosections were cut and immunostained with polyclonal anti-hsp70 and monoclonal anti-HNE antibodies using Vectastain Elite ABC kit. Normal rabbit serum or mouse IgG were used as negative controls. Three independent observers, blinded to identity of tissue, examined each slide to identify cellular localization and intensity of the immunostaining. Western blot analysis and scanning densitometry were used to quantify and compare the amount of hsp70 and HNE adducts present in tissue homogenates. Positive immunostaining for both antibodies was observed in cytoplasm of syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle, and endothelial cells for all groups. Expression of hsp70 and HNE adducts was reported as observers' mean stained intensity. Overall, kappa showed good agreement between observers. Immunostaining intensity was similar in all tissue types for each group with the exception that immunostaining was significantly more intense in the vascular endothelium of the preeclamptic group for HNE adducts (P=.02) and significantly less intense in the IUGR group for hsp70 (P=.013). Scanning densitometric analysis of the Western blots showed no significant difference in total hsp70 and HNE adducts expression in all 4 tissue groups. Immunohistochemistry showed local changes for oxidative stress and lipid peroxidation in the vascular endothelium from placentas of preeclamptic and IUGR pregnancies. However, these changes were masked when studying tissue homogenates.


Left or right carotid endarterectomy in patients with atherosclerotic disease: ipsilateral effects on cognition?
We evaluated hemispheric functions ipsilateral to the side of carotid endarterectomy (CEA) in patients with a severe stenosis in the left or right carotid artery. Assessments took place 1 day before and 3 months after CEA. Only right-handed males were included. Nineteen patients underwent surgery of the left carotid artery and 17 of the right. Valid instruments for hemispheric function were included, such as verbal dichotic listening, finger tapping, and a lateralised test for motor planning. Results showed that, preoperatively, patients had lower scores compared to norms on the laterality tests, and on a visuoconstructive test. There was no evidence of ipsilateral improvement related to side of surgery. Left ear dichotic listening improved, which was seen in both left and right surgery groups. Also in both groups, left- and right-hand movement speed in the motor planning test decreased. Conclusion is that beneficial ipsilateral cognitive change after CEA in patients with severe stenosis in one of the carotid arteries may not be demonstrated, even if valid instruments for hemispheric function are included.


Generation of gene-corrected iPSC line, KIOMi002-A, from Parkinson's disease patient iPSC with LRRK2 G2019S mutation using BAC-based homologous recombination.
Mutations in leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2 G2019S) is a representative autosomal dominant mutation that can cause Parkinson's disease (PD). A bacterial artificial chromosome-based homologous recombination (BAC-based HR) system was utilized for gene therapy of LRRK2 G2019S-mutant induced pluripotent stem cells (iPSCs) produced by reprogramming episomal vectors. The gene-corrected iPSCs retained typical pluripotency required for their spontaneous differentiation into differentiated cells. The iPSCs had a normal karyotype and were confirmed to have no off-target sites by melting curve analysis.


Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts.
Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p=0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p=0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications.


The effect of low-dose conjugated equine estrogens and cyclic MPA on bone density.
to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens on bone mineral density (BMD) in a private practice setting. postmenopausal women interested in hormone replacement therapy were prescribed either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg medroxyprogesterone acetate days 1-12 of the month. All women were given calcium citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies of the spine and hip were performed at baseline and 1 year. there was no significant difference in BMD at the spine, the trochanter or the femoral neck compared with baseline in either the 0.625 or 0.3 mg group. The mean percent increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%, femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. both the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved BMD at the spine and hip over one year in early postmenopausal women who were also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.


[Importance of the study of proliferative processes in the uterus for early diagnosis of ovarian tumors].
Under observation were 1780 females operated upon for ovarian tumors and cysts. Special attention is given to the frequent occurrence in them of hormone-dependent hyperplastic and blastomatous processes in the uterus. These processes in the uterus were observed in 41.7% of all operated patients and in 86.2% of patients, in whom the uterus was studied morphologically.


Endoscopic gastrojejunostomy with survival in a porcine model.
We have previously reported the feasibility and the safety of an endoscopic transgastric approach to the peritoneal cavity in a porcine model. We now report successful performance of endoscopic gastrojejunostomy with survival. All procedures were performed on 50-kg pigs, with the pigs under general anesthesia, in aseptic conditions with sterilized endoscopes and accessories. The stomach was irrigated with antibiotic solution, and a gastric incision was performed with a needle-knife and a sphincterotome. A standard upper endoscope was advanced through a sterile overtube into the peritoneal cavity. A loop of jejunum was identified, was retracted into the stomach, and was secured with sutures while using a prototype endoscopic suturing device. An incision was made into the jejunal loop with a needle-knife, and the filet-opened ends of the jejunal wall were secured to the gastric wall with a second line of sutures, completing the gastrojejunostomy. Two pigs survived for 2 weeks. Endoscopy and a radiographic contrast study performed after gastrojejunostomy revealed a patent anastomosis with normal-appearing gastric and jejunal mucosa. Postmortem examination demonstrated a well-healed anastomosis without infection or adhesions. The endoscopic transgastric approach to create a gastrojejunostomy is technically feasible and can be performed, with survival, in a porcine model.


Comparative study of morbidity and mortality between ileal conduit and ureterosigmoidostomy after radical cystectomy for bladder neoplasm.
Despite the growing trend in the development of orthotopic neobladders, the procedure cannot be performed in many cases, thereby retaining the validity of other techniques. We propose a comparative analysis between patients with radical cystectomy for bladder neoplasm and reconstruction using the ileal conduit (IC) or ureterosigmoidostomy (USG). Observational retrospective study on 255 patients with radical cystectomy between 1985 and 2009, selecting group assignments by the use of IC and USG. Analysis of the demographic and preoperative characteristics, perioperative complications, pathology and medium to long-term complications. Comparison of groups using T-Student, U-Mann-Whitney and chi square tests, with P<.05 indicating statistical significance. Preparation of survival tables according to Kaplan-Meier, establishing comparisons using the log-rank test. There were 41 cases of IC and 55 cases of USG, with a mean patient age of approximately 61 years. USGs were performed on a greater number of females than ICs. There were no differences in the need for transfusion, with similar results as other series. There was a greater trend towards the appearance of intestinal fistulae and greater morbidity and mortality in the postoperative period in USG, although it was not significant. There was a greater long-term presence of eventrations in IC, and of pyelonephritis and the need for taking alkalinizing agents in USG. The appearance of peristomal hernias in IC was less than in previous series. With a mean follow-up greater than 50 months, the overall survival was 40% at 5 years, with no differences according to urinary diversion. IC and USG are two applicable urinary diversions in the event that orthotopic neobladder surgery cannot be performed. They have a similar long-term complication and survival profile in our series, although with a higher morbidity in postoperative complications for USG.


Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata.
The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract.


A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).
At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.


The discovery of biaryl acids and amides exhibiting antibacterial activity against Gram-positive bacteria.
Solid-phase synthetic methods for biaryl-based compounds were developed resulting in the construction of two 1000-member libraries. Numerous compounds were identified by high-throughput screening using whole cell screens to exhibit anti-microbial activity against Gram-positive bacteria. A series of biaryl compounds containing natural and unnatural amino acids were made to explore the SAR of the amino acid functionality.


Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies.
Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg of sildenafil orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant.


Childhood emotional abuse, rejection sensitivity, and depression symptoms in young Chinese gay and bisexual men: Testing a moderated mediation model.
There is a high and increasing prevalence of depression symptoms among gay and bisexual individuals. Studies have found that childhood emotional abuse (CEA) can impact mental-health problems in adulthood; however, limited research on this association among marginalized populations, especially in China. This study aimed to explore the relationship between CEA and depression symptoms in adulthood among gay and bisexual youths in China and to test the mediating role of rejection sensitivity and the moderating role of sexual identity in this relationship. Participants comprised 496 gay and bisexual Chinese men aged 18-29 years. They responded to a questionnaire that assessed history of CEA, rejection sensitivity, and depression symptoms. CEA showed a positive association with depression symptoms among participants. Participants' rejection sensitivity played a partial mediating role in the relationship between CEA and depression symptoms. Sexual identity had a moderating effect on the CEA's influence on depression symptoms, with a stronger impact for gay men than bisexual men. Cross-sectional approach limited casual inferences among variables. Recall bias regarding CEA may have impacted the accuracy of the effect sizes observed. This study contributes to improving understanding of CEA's role as a substantial risk factor for strong depression symptoms in adulthood among gay and bisexual youths and it demonstrates that focusing on educating families and establishing equal policies is important to decrease and eliminate depression symptoms. Theories of sexual minority stress and biphobia are applicable for explaining mental health outcomes among young members of sexual minorities in China.


Serological response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 prime-boost vaccination with a twelve-week interval.
The appropriate interval between heterologous prime adenoviral vectored vaccination and boost mRNA vaccination remains unclear. We recruited 100 adult participants to receive a prime adenoviral vectored vaccine (ChAdOx1, AstraZeneca) and a boost mRNA vaccine (mRNA-1273, Moderna) 12 weeks apart and checked their serum SARS-CoV-2 anti-spike IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on the 28th day after the boost dose. Results were compared with our previous study cohorts who received the same prime-boost vaccinations at 4- and 8-week intervals. Compared to other heterologous vaccination groups, the 12-week interval group had higher neutralizing antibody titers against SARS-CoV-2 variants than the 4-week interval group and was similar to the 8-week interval group at day 28. Adverse reactions after the boost dose were mild and transient. Our results support deploying viral vectored and mRNA vaccines in a flexible schedule with intervals from 8 to 12 weeks.


The snail (Biomphalaria glabrata) genome project.
In 2001, ideas for a snail genome project were discussed at the American Society of Parasitologists meeting (New Mexico) and a snail genome consortium was subsequently established (the first consortium meeting was held in 2005). A proposal for sequencing the snail genome was submitted to the National Human Genome Research Institute, and Biomphalaria glabrata was prioritized as a non-mammalian sequencing target in 2004. The sequencing of the genome of this medically important snail is now underway.


Update on Menopausal Hormone Therapy for Fracture Prevention.
The goal of the review is to assess the appropriateness of menopausal hormone therapy (MHT) for the primary prevention of bone loss in women at elevated risk in the early years after menopause. Estrogen alone or combined with progestin to protect the uterus from cancer significantly reduces the risk of osteoporosis-related fractures. MHT increases type 1 collagen production and osteoblast survival and maintains the equilibrium between bone resorption and bone formation by modulating osteoblast/osteocyte and T cell regulation of osteoclasts. Estrogens have positive effects on muscle and cartilage. Estrogen, but not antiresorptive therapies, can attenuate the inflammatory bone-microenvironment associated with estrogen deficiency. However, already on second year of administration, MHT is associated with excess breast cancer risk, increasing steadily with duration of use. MHT should be considered in women with premature estrogen deficiency and increased risk of bone loss and osteoporotic fractures. However, MHT use for the prevention of bone loss is hindered by increase in breast cancer risk even in women younger than 60 years old or who are within 10 years of menopause onset.


Antioxidative action of the novel calcium channel antagonist mibefradil on low-density lipoproteins.
Mibefradil is a novel calcium channel antagonist that selectively blocks T-channels. It acts to reduce hypertension, is cardioprotective and reduces ischemic episodes. Oxidative modification of low-density lipoproteins (LDL) is well known to contribute to coronary atherosclerosis and we therefore investigated to see whether mibefradil had antioxidative action on LDL. Human LDL were isolated by ultracentrifugation. In vitro oxidation of LDL (0.1 micromol x l(-1) protein) in the presence of various concentrations of mibefradil was initiated by 3.2 micromol x l(-1) copper ions. The kinetics of formation of conjugated dienes was followed photometrically. Malondialdehyde and lipoperoxides were determined at maximum oxidation. LDL (0.3 micromol x l(-1)) were also pre-incubated with mibefradil (120 micromol x l(-1)). Excessive mibefradil was separated by column technique. The resultant LDL were oxidized using copper ions or (AAPH) 2,2'-azobis(2-amidinopropane) hydrochloride. The presence of mibefradil in the concentration range from 10 to 200 micromol x l(-1) had dose-dependent effects. These were protection of LDL against oxidation measured as prolongation of the lagtime up to 250%, and reduction in the formation of malondialdehyde down to 65% and of lipoperoxides to 20%. Pre-incubation of LDL with mibefradil prolonged the lagtime of Cu-mediated oxidation up to 132% and of AAPH-mediated oxidation up to 138%. In addition to the T-channel blocking and antiproliferative effects, our results provide arguments for a protective role of mibefradil (10-200 micromol x l(-1)) on LDL against in vitro oxidation. This was shown with three independent parameters (lagtime, malondialdehyde and lipoperoxides) and in different oxidation models.


Weak and absent peristalsis.
Weak and absent esophageal peristalsis are frequently encountered esophageal motility disorders, which may be associated with dysphagia and which may contribute to gastroesophageal reflux disease. Recently, rapid developments in the diagnostic armamentarium have taken place, in particular, in high-resolution manometry with or without concurrent intraluminal impedance monitoring. This article aims to review the current insights in the terminology, pathology, pathophysiology, clinical manifestations, diagnostic work-up,and management of weak and absent peristalsis.


Bioactive apatite incorporated alginate microspheres with sustained drug-delivery for bone regeneration application.
The strontium-substituted hydroxyapatite microspheres (SrHA) incorporated alginate composite microspheres (SrHA/Alginate) were prepared via adding SrHA/alginate suspension dropwise into calcium chloride solution, in which the gel beads were formed by means of crosslinking reaction. The structure, morphology and in vitro bioactivity of the composite microspheres were studied by using XRD, SEM and EDS methods. The biological behaviors were characterized and analyzed through inductively coupled plasma optical emission spectroscopy (ICP-OES), CCK-8, confocal laser microscope and ALP activity evaluations. The experimental results indicated that the synthetic SrHA/Alginate showed similar morphology to the well-known alginate microspheres (Alginate) and both of them possessed a great in vitro bioactivity. Compared with the control Alginate, the SrHA/Alginate enhanced MC3T3-E1 cell proliferation and ALP activity by releasing osteoinductive and osteogenic Sr ions. Furthermore, vancomycin was used as a model drug to investigate the drug release behaviors of the SrHA/Alginate, Alginate and SrHA. The results suggested that the SrHA/Alginate had a highest drug-loading efficiency and best controlled drug release properties. Additionally, the SrHA/Alginate was demonstrated to be pH-sensitive as well. The increase of the pH value in phosphate buffer solution (PBS) accelerated the vancomycin release. Accordingly, the multifunctional SrHA/Alginate can be applied in the field of bioactive drug carriers and bone filling materials.


Deep-UV excitation fluorescence microscopy for detection of lymph node metastasis using deep neural network.
Deep-UV (DUV) excitation fluorescence microscopy has potential to provide rapid diagnosis with simple technique comparing to conventional histopathology based on hematoxylin and eosin (H&E) staining. We established a fluorescent staining protocol for DUV excitation fluorescence imaging that has enabled clear discrimination of nucleoplasm, nucleolus, and cytoplasm. Fluorescence images of metastasis-positive/-negative lymph nodes of gastric cancer patients were used for patch-based training with a deep neural network (DNN) based on Inception-v3 architecture. The performance on small patches of the fluorescence images was comparable with that of H&E images. Gradient-weighted class activation mapping analysis revealed the areas where the trained model identified metastatic lesions in the images containing cancer cells. We extended the method to large-size image analysis enabling accurate detection of metastatic lesions. We discuss usefulness of DUV excitation fluorescence imaging with the aid of DNN analysis, which is promising for assisting pathologists in assessment of lymph node metastasis.


Strategic silences, eroded trust: The impact of divergent COVID-19 vaccine sentiments on healthcare workers' relations with peers and patients.
Polarized debates about Covid-19 vaccination and vaccine mandates for healthcare workers (HCWs) challenge Belgian HCWs ability to discuss Covid-19 vaccine sentiments with peers and patients.Although studies have identified drivers of HCWs vaccine hesitancy, they do not include effects of workplace interactions and have not addressed consequences beyond vaccine coverage. Interviews and focus group discussions with 74 HCWs practicing in Belgium addressed Covid-19 vaccine sentiments and experiences of discussing vaccination with peers and patients. Most participating HCWs reported difficulties discussing Covid-19 vaccination with peers and patients. Unvaccinated HCWs often feared that expressing their vaccine sentiments might upset patients or peers and that they would be suspended. Consequently, they used social cues to evaluate others' openness to vaccine-skeptical discourses and avoided discussing vaccines. Surprisingly, some vaccine-confident HCWs hid their vaccine sentiments to avoid peer and patient conflicts. Both vaccinated and unvaccinated HCWs observed that unvaccinated patients occasionally received suboptimal care. Suboptimal care was central in unvaccinated HCW unwillingness to express their vaccine sentiments to peers. Both vaccinated and unvaccinated HCWs described loss of trust and ruptured social relations with peers and patients holding divergent vaccine sentiments. Belgian HCW perceived Covid-19 vaccines as a risky discussion topic and engaged in "strategic silences" around vaccination to maintain functional work relationships and employment in health institutions. Loss of trust between HCW and peers or patients, along with suboptimal patient care based on vaccination status, threaten to weaken Belgium's, and by implication, other health systems, and to catalyze preventable disease outbreaks.


Anterior communicating artery aneurysm following radiation therapy for optic glioma: report of a case and review of the literature.
A 42-year-old female presented with subarachnoid hemorrhage (SAH), presumably from a radiation-induced anterior communicating artery aneurysm. Six years earlier, she had undergone radiation treatment for an optic glioma that was diagnosed based on imaging criteria. The aneurysm was successfully clipped, and the optic glioma was biopsied to verify the diagnosis histologically. Radiation-induced cerebral aneurysms often manifest with a fatal SAH. These aneurysms typically develop in the field of radiation and are diagnosed a mean of 8.52 years after radiation. Rarely, the aneurysm sac thromboses spontaneously. Clipping or coiling of the aneurysm can be an effective treatment.


Heterogeneity of the cancer cell line metabolic landscape.
The unravelling of the complexity of cellular metabolism is in its infancy. Cancer-associated genetic alterations may result in changes to cellular metabolism that aid in understanding phenotypic changes, reveal detectable metabolic signatures, or elucidate vulnerabilities to particular drugs. To understand cancer-associated metabolic transformation, we performed untargeted metabolite analysis of 173 different cancer cell lines from 11 different tissues under constant conditions for 1,099 different species using mass spectrometry (MS). We correlate known cancer-associated mutations and gene expression programs with metabolic signatures, generating novel associations of known metabolic pathways with known cancer drivers. We show that metabolic activity correlates with drug sensitivity and use metabolic activity to predict drug response and synergy. Finally, we study the metabolic heterogeneity of cancer mutations across tissues, and find that genes exhibit a range of context specific, and more general metabolic control.


Associations between social COVID-19 exposure and psychological functioning.
The negative consequences of the COVID-19 pandemic on mental health have been widely reported, but less is known about how the impact of COVID-19 on others in one's social circle shapes these high distress levels. This study examines associations between social COVID-19 exposure-knowing someone who had a COVID-19 infection-and psychological functioning, as well as whether socio-demographic factors moderate these relationships. In June 2020, respondents (N = 343) from clinics in Tampa, Florida, U.S.A. reported whether they had social COVID-19 exposure, anxiety, depression, and stress, and other COVID-19-related concerns. Social COVID-19 exposure was associated with increased anxiety, stress, and concerns about a family member getting sick, and concerns about drinking and substance use. Several associations between exposure and psychological functioning were stronger in women, younger people, and people with lower income, implying these groups face elevated psychological risks due to the pandemic, and should be prioritized in mental health recovery efforts.


Larvicidal activity and possible mode of action of four flavonoids and two fatty acids identified in Millettia pinnata seed toward three mosquito species.
Aedes aegypti and Aedes albopictus and Culex pipiens pallens mosquitoes transmit dengue fever and West Nile virus diseases, respectively. This study was conducted to determine the toxicity and mechanism of action of four flavonoids and two fatty acids from Millettia pinnata (Fabaceae) seed as well as six pure fatty acids and four fatty acid esters toward third instar larvae from insecticide-susceptible C. pipiens pallens and A. aegypti as well as wild A. albopictus. Efficacy of 12 experimental liquid formulations containing M. pinnata seed methanol extract and hydrodistillate (0.5-10.0% liquids) was also assessed. The contact toxicities of all compounds and 12 formulations were compared with those of two larvicides, temephos and fenthion and the commercial temephos 200 g/L emulsifiable concentrate (EC). The possible mode of larvicidal action of the constituents was elucidated using biochemical methods. Larval mortality and cAMP level were analyzed by the Bonferroni multiple-comparison method. Potent toxicity was produced by karanjin, oleic acid, karanjachromene, linoleic acid, linolenic acid, pongamol, pongarotene, and elaidic acid toward C. pipiens pallens larvae (24 h LC50, 14.61-28.22 mg/L) and A. aegypti larvae (16.13-37.61 mg/L). Against wild A. albopictus larvae, oleic acid (LC50, 18.79 mg/L) and karanjin (35.26 mg/L) exhibited potent toxicity. All constituents were less toxic than either temephos or fenthion. Structure-activity relationship indicates that the degree of saturation, the side chain length, and the geometric isomerism of fatty acids appear to play a role in determining the fatty acid toxicity. Acetylcholinesterase (AChE) is the main site of action of the flavonoids, oleic acid, and palmitic acid. The mechanism of larvicidal action of elaidic acid, arachidic acid, and behenic acid might be due to interference with the octopaminergic system. Linoleic acid and linolenic acid might act on both AChE and octopaminergic receptor. M. pinnata seed extract or hydrodistillate applied as 10% liquid provided 100% mortality toward the three mosquito species larvae and the efficacy of the liquids was comparable to that of temephos 200 g/L EC. Further studies will warrant possible applications of M. pinnata seed-derived products as potential larvicides for the control of mosquito populations.


Identification and quantification of neuronal ensembles in optical imaging experiments.
Recent technical advances in molecular biology and optical imaging have made it possible to record from up to thousands of densely packed neurons in superficial and deep brain regions in vivo, with cellular subtype specificity and high spatiotemporal fidelity. Such optical neurotechnologies are enabling increasingly fine-scaled studies of neuronal circuits and reliably co-active groups of neurons, so-called ensembles. Neuronal ensembles are thought to constitute the basic functional building blocks of brain systems, potentially exhibiting collective computational properties. While the technical framework of in vivo optical imaging and quantification of neuronal activity follows certain widely held standards, analytical methods for study of neuronal co-activity and ensembles lack consensus and are highly varied across the field. Here we provide a comprehensive step-by-step overview of theoretical, experimental, and analytical considerations for the identification and quantification of neuronal ensemble dynamics in high-resolution in vivo optical imaging studies.


Economic evaluation: what are we looking for and how do we get there?
The interest in economic evaluation of alternative strategies for haemophilia treatment has increased through the years. Few studies have actually been undertaken, however, and most of them have been simple cost-minimization or cost-effectiveness analyses. From the perspective of the binational project 'Treatment strategies for severe haemophilia-prophylaxis vs. on-demand', the present paper discusses the pros and cons of different methods for economic evaluation and their data requirements. Severe haemophilia is a rare disease that requires lifelong treatment. In addition, treatment has both short- and long-term effects which are likely to differ between strategies. Accordingly, regardless of the chosen evaluation method, data requirements are non-trivial. Hence, the various problems connected to the generation of data, as well as how they may be addressed, are also discussed.


Heat shock protein 27 rescues motor neurons following nerve injury and preserves muscle function.
Heat shock proteins (HSPs) are a family of ubiquitously expressed proteins that are up-regulated in response to a range of stresses and play an important role in cellular defence mechanisms. In previous studies, we demonstrated that overexpression of heat shock protein 27 (HSP27) in transgenic mice has significant cytoprotective properties in vivo, reducing caspase-3-mediated cell death in the hippocampus associated with limbic seizures and reducing infarct size in cardiac ischaemia. In motor neurons, HSP27 is also implicated as a survival promoting factor; however, it remains to be established whether HSP27 is able to exert long-term neuroprotective effects following neonatal nerve injury. We now show that, following neonatal nerve crush, HSP27 overexpression in vivo provides a substantial rescue of motor neurons 5-6 months following nerve injury. Furthermore, in vivo isometric tension recordings demonstrate that surviving motor neurons were able to regenerate, resulting in a 90% improvement (P < 0.0005) in motor unit number in HSP27 mice. Moreover, this increase in motor unit number was associated with improved muscle weight, muscle force, contractile speeds, and histochemical markers of muscle activity. These properties of HSP27 therefore have considerable potential for improving long-term muscle function in motor neuron disorders.


Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA).
COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown. We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone. Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing.


Probing the NADH- and Methyl Red-binding site of a FMN-dependent azoreductase (AzoA) from Enterococcus faecalis.
AzoA from Enterococcus faecalis is a member of the polymeric flavin-dependent NADH-preferred azoreductase group. Little is known about the binding and interaction of NADH and azo dye in the azoreductase group. A synergetic strategy based on computational prediction, reverse genetics validation coupled with site-directed mutagenesis, and reconstruction of mutation network was used to investigate the binding and interaction of NADH and a model azo dye, Methyl Red, with AzoA. Methyl Red and NADH interacted in a unique binding mode in which the benzoic acid moiety of Methyl Red and the nicotinamide ring of NADH were not parallel to the flavin isoalloxazine ring, but lay against it at angles of ∼45° and ∼35°, respectively. The adenine ribose moiety of NADH was surrounded by loop ℓ2 on chain B and α3 on chain A in a typical Rossmann fold. There were 12 and 19 amino acid residues that could participate in the binding of Methyl Red and NADH, respectively, especially the residues Tyr-129 and Asp-184. The functional perturbation effects of 13 residues, including Tyr-129 and Asp-184, were mapped to reconstruct the mutation network, which confirmed the proposed binding modes and also provided insights into the interaction among NADH, FMN and Methyl Red.


Novel probabilistic model of core vitreous traction using microsurgical vitrectomy tools.
Traction exerted on the vitreous base during vitrectomy poses a risk for retinal tears. We aimed to quantify core vitreous traction during vitrectomy using spring return and pneumatic cutters. Juvenile porcine vitreous was vacuum held in a vitreous bath while traction was measured using precision force gauge during vitrectomy. The parameters included were aspiration rate, cut-rate, cutter size, and machine types. An empirical probabilistic model was developed. The traction was proportional to the aspiration rate but insignificantly dependent on the cut-rate. The traction probability was inversely proportional to the exponential function of the traction (p < 0.05). The traction was < 0.003 N for 99% of the time using either 23- or 25-gauge cutters. The tractions measured were considered similar to the causative forces of an iatrogenic retinal tear during a pars plana vitrectomy. The results provide a safety reference matrix of instrumental parameters during vitrectomy.


Associations between gastropod shell characteristics and egg production in the hermit crab Pagurus longicarpus.
Two populations (salt marsh and seagrass bed) of the hermit crab Pagurus longicarpus were sampled to examine associations between shell characteristics and egg production. Multivariate statistical analyses controlled for crab size and time of year, variables that otherwise could be confounded with shell effects. Although correlations between shell characteristics and reproduction existed in both populations, generalizations could not be made because associations varied within and between populations. Shell species was not associated with a female's reproductive state (i.e., whether or not she was barren when sampled) in either population. In the seagrass population, medium-large and large females occupying severely damaged or fouled shells were half as likely to be reproductive as females occupying other shell conditions. However, there was no association between shell condition and reproductive state for small and small-medium females in the seagrass population or among all females in the salt marsh population. In the seagrass population, small through medium-large reproductive females occupied shells more similar to their predicted shell size, regardless of whether the occupied shell was relatively small or large, than nonreproductive females. In contrast, relative shell sizes of reproductive and nonreproductive females were similar for large females in the seagrass population and all females in the salt marsh population. Clutch sizes were enhanced for females occupying Polinices duplicatus shells or shells larger than their predicted shell size in the seagrass population. Relative shell size also was associated with clutch size in the salt marsh population, but crabs occupying shells similar to their predicted shell size had the largest clutches.


CT of cerebral venous sinus thrombosis in a child with homocystinuria.
We describe a case of cerebral venous sinus thrombosis in a child with homocystinuria. We present both the classic CT findings of cerebral sinus thrombosis, and also the first report of the CT visualization of transdural venous collateral circulation.


Individual dynamic prediction and prognostic analysis for long-term allograft survival after kidney transplantation.
Predicting allograft survival is vital for efficient transplant success. With dynamic changes in patient conditions, clinical indicators may change longitudinally, and doctors' judgments may be highly variable. It is necessary to establish a dynamic model to precisely predict the individual risk/survival of new allografts. The follow-up data of 407 patients were obtained from a renal allograft failure study. We introduced a landmarking-based dynamic Cox model that incorporated baseline values (age at transplantation, sex, weight) and longitudinal changes (glomerular filtration rate, proteinuria, hematocrit). Model performance was evaluated using Harrell's C-index and the Brier score. Six predictors were included in our analysis. The Kaplan-Meier estimates of survival at baseline showed an overall 5-year survival rate of 87.2%. The dynamic Cox model showed the individual survival prediction with more accuracy at different time points (for the 5-year survival prediction, the C-index = 0.789 and Brier score = 0.065 for the average of all time points) than the static Cox model at baseline (C-index = 0.558, Brier score = 0.095). Longitudinal covariate prognostic analysis (with time-varying effects) was performed. The dynamic Cox model can utilize clinical follow-up data, including longitudinal patient information. Dynamic prediction and prognostic analysis can be used to provide evidence and a reference to better guide clinical decision-making for applying early treatment to patients at high risk.


The effect of chronic nitric oxide synthases inhibition on regulatory proteins in rat hearts.
The aim of the present study was to characterize the effects of chronic nitric oxide synthase (NOS) inhibition on the alterations of regulatory myocardial proteins of intracellular signaling pathways (mitogen-activated protein kinase (MAPK) and Akt kinase cascades) and matrix metalloproteinases (MMP). Chronic NO deficiency (NOD) was induced by NG-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day, 4 weeks). Protein levels and activation of protein kinases were determined using specific antibodies, activities of MMP were analyzed by zymography in gels containing gelatin as a substrate. The development of NOD was associated with decreased activation of endothelial NOS (eNOS) and down-regulation of protein level of inducible NOS (iNOS). Investigation of kinase pathways revealed that the activation of extracellular signal-regulated kinases (ERK) and the levels of upstream activators of ERK (aFGF, H-Ras) were decreased after L-NAME treatment. Western blot analysis revealed that chronic application of L-NAME also decreased the activation of Akt kinase as compared with control hearts. Study of MMPs showed that in L-NAME-treated rat hearts activities of tissue MMP-2 were decreased. It is concluded that development of NOD resulted in inhibition of ERK and Akt kinase pathways and these changes suggest the involvement of these cascades in responses of myocardium to NOD. The results also point to the possible relationship between ERK and Akt kinase pathways and activation of eNOS and/or MMP-2.


Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population.
The angiotensin-converting enzyme (ACE) gene has been implicated in the development of diabetic retinopathy (DR). However, the results have been conflicting. In this study, we performed a meta-analysis to assess the association of insertion/deletion (I/D) polymorphism in the ACE gene with DR in the Chinese population. Published literature from PubMed, CNKI, CBM and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Seventeen studies (1039 cases and 1185 controls) for I/D polymorphism in the ACE gene were identified. The results suggested that I/D polymorphism D allele might increase the risk of DR (DD vs. II: OR = 1.73, 95% CI 1.19-2.51; DD+ID vs. II: OR = 1.41, 95% CI 1.16-1.72; DD vs. ID+II: OR = 1.55, 95% CI 1.13-2.12). Subgroup analyses based on the type of DR showed that the effect size was statistically significant for proliferative DR (PDR) (DD vs. II: OR = 2.67, 95% CI 1.53-4.64; DD+ID vs. II: OR = 1.86, 95% CI 1.18-2.93; DD vs. ID+II: OR = 2.22, 95% CI 1.38-3.55), but not for background DR (BDR) (DD vs. II: OR = 1.38, 95% CI 0.85-2.25; DD+ID vs. II: OR = 1.40, 95% CI 0.98-2.02; DD vs. ID+II: OR = 1.15, 95% CI 0.74-1.79). The results indicated that I/D polymorphism in the ACE gene was associated with PDR, but not with BDR in the Chinese population.


Motion capture changes to induced motion at higher luminance contrasts, smaller eccentricities, and larger inducer sizes.
In the stimulus configuration for "motion capture" phenomenon, we varied luminance contrast of the center disk (target), eccentricity and stimulus size. The subjects had to judge the direction of perceived target motion. We found that motion capture changed to induced motion (the direction of illusory motion was reversed) at smaller eccentricities and larger stimulus sizes. At intermediate eccentricities, motion capture changed to induced motion with increasing luminance contrast of the target. By using magnitude estimation, we also found that even a luminance-defined target was captured ("homochromatic motion capture") and that a moving target was captured by a stationary inducer ("position capture"). Both motion and position capture effects were commonly observed at lower luminance contrasts of the target, larger eccentricities and smaller sizes. From these results, we propose a model of center-surround antagonistic motion contrast detectors in motion processing.


Paradigm shifters, professionals, and community sentinels: immigrant community institutions' roles in shaping places and implications for stigmatized public health initiatives.
Immigrant community institutions are strategically positioned to facilitate or impede public health efforts in their neighborhoods and communities because of their influence over discourse regarding values and tradition. Their authority may be particularly relevant when stigmatized or sensitive issues, such as HIV or reproductive health, are addressed. Using qualitative and quantitative methods to analyze data collected from 22 Chinese and South Asian immigrant institutions in New York City, we examine attitudes about HIV, social change and tradition to delineate the different structural roles that Asian immigrant community institutions play in relation to the preservation of traditional values and culture in their neighborhoods and communities. Implications are explored for working with immigrant community institutions to conduct HIV-related work and other stigmatized public health initiatives in immigrant neighborhoods.


Reproductive cloning and arguments from potential.
The possibility of human reproductive cloning has led some bioethicists to suggest that potentiality-based arguments for fetal moral status become untenable, as such arguments would be committed to making the implausible claim that any adult somatic cell is itself a potential person. In this article I defend potentiality-based arguments for fetal moral status against such a reductio. Starting from the widely-held claim that the maintenance of numerical identity throughout successive changes places constraints on what a given entity can plausibly be said to have the potential to become, I argue that the cell reprogramming that takes place in reproductive cloning is such that it produces a new individual, and so adult somatic cells cannot be potential persons.


The PHI/GHFP-II Employers' Study: The Hidden Barriers Between Domestic and Global Health Careers and Crucial Competencies for Success.
An ongoing discussion in global health in the United States centers on the future of the US-trained global health workforce and how best to prepare professionals for this career path. The Public Health Institute, through its Global Health Fellows Program (I and II), has been in a unique position to identify the shifting employment dynamic in global health. The purpose of the survey was to gather information on global health employers' hiring practices and insights into the importance of nonclinical skills in contributing to successful professional work; preparedness of graduates with needed nonclinical skills; and the value of domestic work experience for global health careers. The focus was on individuals primarily raised in the United States who studied global health in either graduate or undergraduate settings. A web-based survey and telephone interviews were conducted in early 2015. Overall, 49 project directors from 32 organizations participated. Key findings included: CONCLUSIONS: The process of preparing professionals for global health work has fallen behind emerging realities, including globalization, ever-evolving technologies, and advances in health care. Universities must provide an increased curricular emphasis on nonclinical skills, both interpersonal and business related, as well as the international experience that is valued in the global health workplace.


Induction of hepatic tyrosine aminotransferase in vivo by derivatives of cyclic adenosine 3':5'-monophosphate.
A number of 8- and N6-SUBSTITUTED DERIVATIVES OF CYCLIC ADENOSINE 3':5'-MONOPHOSPHATE-DEPENDENT PROTEIN KINASE, AND AS SUBSTRATES FOR RAT LIVER CYCLIC NUCLEOTIDE PHOSPHODIESTERASE. All of the analogs tested were able to induce the transaminase. The induction by the analogs was shown to be the result of an actual increase in the amount of enzyme, and the mechanism of induction was an increase in the rate of synthesis of the transaminase. The induced enzyme appeared to be immunologically similar to the non-induced enzyme. A good correlation was found to exist between the dose that produced 50% of maximal induction and a combination of the activation constant for cyclic adenosine 3':5'-monophosphate-dependent protein kinase by the analog and its susceptibility to hydrolysis by cyclic nucleotide phosphodiesterase. These data suggest that the phosphorylation of some site is involved in the mechanism by which cyclic adenosine 3':5'-monophosphate affects the rate of synthesis of tyrosine aminotransferase.


Dual-wavelength light radiation for synergistic water disinfection.
Development of the narrow-band mercury-free light sources, such as light emitting diodes (LEDs) and excilamps, has stimulated research on inactivation of pathogenic microorganisms by dual-wavelength light radiation. To date, dual-wavelength light radiation has emerged as an advanced tool for enhancing microbial inactivation in water in view of potential synergistic effect. This is the first review that aims at elucidating its mechanisms under dual-wavelength light exposure and surveying a body of related literature in terms of yes-or-no synergy. We have proposed three key inactivation mechanisms, which function in the estimated spectrum ranges I (190-254 nm), II (250-320 nm) and III (300-405 nm) and provide a synergistic effect when combined. These mechanisms involve proteins damage and DNA repair suppression (I), direct and indirect DNA damage (II) and generation of reactive oxygen species (ROS) by endogenous photosensitizers (III), such as porphyrins and flavins. A synergy under dual-wavelength light irradiation simultaneously or sequentially occurs if coupling two wavelengths of different ranges (I + II, I + III, II + III) in order to trigger different inactivation mechanisms. Recent advances of dual-wavelength light strategy in photodynamic therapy could be applied for water disinfection. They bring opportunities for applying the sources of near-UV and visible radiation and making the disinfection processes more energy- and cost-effective. From this standpoint, the synergistically efficient dual-wavelength combinations II + III and the combinations within the extended to 700 nm range III (near-UV + VIS) appear to be promising for developing novel advanced oxidation processes for disinfection of real turbid waters.


Evaluation of processes occurring in the bottom nepheloid layer (BNL) of an eastern Mediterranean area using 234Th/238U disequilibria.
Particle-reactive radionuclide (234)Th and its ratios with the conservative (238)U were used to trace the marine processes occurring over short timescales in the bottom nepheloid layer (BNL) of seven stations in the Saronikos Gulf and the Elefsis Bay (Greece) during three seasons (summer 2008, autumn 2008 and winter 2009). Summer was considered as a steady season where low physical processes occur and stratification is well established, autumn as a commutative period and winter as period of extensive trawling and physical activities. The obtained ratio profiles showed excess of (234)Th relative to (238)U in the BNL of the sampling area during summer, caused by the dissolved fraction of (234)Th. During autumn, the situation was different with large (234)Th deficit throughout the water column leading to large export fluxes of particles from the water column. Finally, during winter the ratios showed that predominant phenomenon in the area was likely resuspension of bottom sediments. The resuspension signature was additionally evaluated by total suspended matter (TSM) inventories in the BNL. Despite the intense resuspension, small scavenging of dissolved (234)Th was recorded in the BNL resulting in high residence times of dissolved (234)Th. A 1 order of magnitude difference between dissolved and particulate (234)Th residence times was observed indicating that scavenging from dissolved to particulate (234)Th could be highly variable and, as a result, the Saronikos Gulf is a highly dynamic environment, in terms of temporal and spatial particle uptake and removal. Comparing these values to literature ones consistent results were obtained. The possibility of sediment resuspension in the BNL during winter was amplified by the bloom of phytoplankton resulting in even decreased residence times of particulate (234)Th (average values). In contrast, the respective residence times of the dissolved fraction of (234)Th in the BNL were higher showing a maximum in winter at the stations where resuspension concluded. Nevertheless, (234)Th cycling in the area is not controlled by TSM, probably due to the presence of colloids, which could play an essential role in (234)Th scavenging.


Transthoracic electrical bioimpedance: a non-invasive technique for the evaluation of the haemodynamic alterations in patients with liver cirrhosis.
Transthoracic electrical bioimpedance is a non-invasive technique for the evaluation of systemic haemodynamics. Compared to Doppler ultrasound, it has the advantage of being operator-independent, providing continuous monitoring and being less influenced by postural changes. Until now, transthoracic electrical bioimpedance has been applied to a very limited extent in liver cirrhosis. We, therefore, aimed to compare transthoracic electrical bioimpedance and echocardiography in the assessment of haemodynamic status in cirrhotic patients. Thirteen patients with compensated cirrhosis, 10 patients with cirrhosis and ascites and 12 controls were enrolled. Haemodynamic parameters (stroke volume, cardiac output, heart rate, mean arterial pressure and vascular peripheral resistance) were assessed simultaneously by transthoracic electrical bioimpedance monitoring with BioZ.com for at least 10 min and Doppler ultrasound. The absolute mean values of haemodynamic parameters obtained by the two techniques were quite similar in all groups; furthermore, a good agreement between transthoracic electrical bioimpedance and echocardiography measurements was found for all the parameters. Finally, transthoracic electrical bioimpedance proved easy to employ and provided continuous real-time monitoring of cardio-circulatory variations. The present study showed a significant correlation between transthoracic electrical bioimpedance and echocardiography in the assessment of systemic haemodynamics in patients with cirrhosis, supporting the employment of transthoracic electrical bioimpedance in pathophysiological studies requiring real-time continuous monitoring of haemodynamic parameters.


Diagnostic performance of diffusion-weighted magnetic resonance imaging in differentiating human renal lesions (benignity or malignancy): a meta-analysis.
This study aims to quantitatively evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiating malignant and benign human renal lesions. A systematic literature was performed to identify previous research related to the diagnostic performance of DW-MRI for determining whether human renal lesions were benign or malignant. ADC values were extracted from normal renal tissue and different lesion types. Data were extracted to assess the diagnostic performance of DW-MRI for differentiating malignant and benign human renal lesions, as well as running threshold effect and heterogeneity. Nine publications with 11 subsets were eligible for data extraction and diagnostic performance calculation. A total of 988 apparent diffusion coefficient (ADC) measurements were included. The differences in ADC values between benign lesions (2.47 ± 0.81 × 10(-3) mm(2)/s) and malignant lesions (1.81 ± 0.41 × 10(-3) mm(2)/s) were statistically significant (P < 0.001). The diagnostic odds ratio, the overall positive, negative likelihood ratios, pooled weighted sensitivity and specificity with 95% CI were 20.05 (95% CI 12.56-32.02), 3.32 (95% CI 2.13-5.18), 0.20 (95% CI 0.15-0.27), 88% (95% CI 0.84-0.91) and 72% (95% CI 0.67-0.76), respectively. The area under the curve of the summary receiver operating characteristic was 0.90. This meta-analysis indicated that DW-MRI had a relatively good diagnostic accuracy in differentiating malignant and benign human renal lesions. We preliminarily recommend that DW-MRI is performed with a maximum b value ranging from 800 to 1000 s/mm(2) at 3.0 T for imaging protocol, and that DW-MRI should be used with caution when the study population includes children.


Public Opinion on Priorities Toward Fair Allocation of Ventilators During COVID-19 Pandemic: A Nationwide Survey.
Background: The rapidly growing imbalance between supply and demand for ventilators during the COVID-19 pandemic has highlighted the principles for fair allocation of scarce resources. Failing to address public views and concerns on the subject could fuel distrust. The objective of this study was to determine the priorities of the Iranian public toward the fair allocation of ventilators during the COVID-19 pandemic. Methods: This anonymous community-based national study was conducted from May 28 to Aug 20, 2020, in Iran. Data were collected via the Google Forms platform, using an online self-administrative questionnaire. The questionnaire assessed participants' assigned prioritization scores for ventilators based on medical and non-medical criteria. To quantify participants' responses on prioritizing ventilator allocation among sub-groups of patients with COVID-19 who need mechanical ventilation scores ranging from -2, very low priority, to +2, very high priority were assigned to each response. Results: Responses of 2,043 participants, 1,189 women, and 1,012 men, were analyzed. The mean (SD) age was 31.1 (9.5), being 32.1 (9.3) among women, and 29.9 (9.6) among men. Among all participants, 274 (13.4%) were healthcare workers. The median of assigned priority score was zero (equal) for gender, age 41-80, nationality, religion, socioeconomic, high-profile governmental position, high-profile occupation, being celebrities, employment status, smoking status, drug abuse, end-stage status, and obesity. The median assigned priority score was +2 (very high priority) for pregnancy, and having <2 years old children. The median assigned priority score was +1 (high priority) for physicians and nurses of patients with COVID-19, patients with nobel research position, those aged <40 years, those with underlying disease, immunocompromise status, and malignancy. Age>80 was the only factor participants assigned -1 (low priority) to. Conclusions: Participants stated that socioeconomic factors, except for age>80, should not be involved in prioritizing mechanical ventilators at the time of resources scarcity. Front-line physicians and nurses of COVID-19 patients, pregnant mothers, mothers who had children under 2 years old were given high priority.


Effect of synthetic human cholecystokinin-33 on exocrine pancreas.
Synthetic human cholecystokinin-33 was first evaluated with respect to the biological activity on the pancreatic protein secretion. Human cholecystokinin-33 increased pancreatic protein secretion in a dose-related manner. The relative molar potency of this substance compared to that of synthetic cholecystokinin-8 (taken as 1.0) was 0.92. This study supports the concept that longer molecular forms of cholecystokinin are quantitatively important mediators of biological action of cholecystokinin on the pancreas.


Serum glial fibrillary acidic protein and neurofilament light chain in treatment-naïve patients with unipolar depression.
Unipolar depression has been associated with increased levels of glial dysfunction and neurodegeneration biomarkers, such as Glial Fibrillary Acidic Protein (GFAP) and Neurofilament light chain (NfL). However, previous studies were conducted on patients taking psychotropic medication and did not monitor longitudinal associations between disease status and GFAP/NfL. Treatment-naïve patients with unipolar depression (n = 110) and healthy controls (n = 33) were included. GFAP/NfL serum levels were analyzed by Single Molecule Array at baseline and 3-month follow-up. The primary endpoint was GFAP/NfL levels in patients with depression compared with healthy controls. The secondary endpoint was the associations between GFAP/NfL with depression severity and cognitive function. The patients' mean HAM-D17 score was 18.9 (SD 3.9) at baseline and improved by 7.9 (SD 6.8) points during follow-up. GFAP/NfL was quantified in all individuals. At baseline, the adjusted GFAP levels were -16.8 % (95 % CI: -28.8 to -1.9, p = 0.03) lower among patients with depression compared to healthy controls, while NfL levels were comparable between the groups (p = 0.57). In patients with depression, mean NfL levels increased from baseline to follow-up (0.68 pg/ml, p = 0.03), while GFAP levels were unchanged (p = 0.24). We did not find consistent associations between NfL/GFAP with depression scores or cognitive function. This largest study of serum NfL/GFAP levels in patients with depression did not support previous findings of elevated GFAP/NfL in patients with depression or positive associations with depression severity. Although limited by a small control group, our study may support the presence of glial dysfunction but not damage to neurons in depression.


Risk factors for infarct expansion are different between lacunar and giant lacunar infarction.
The precise mechanisms underlying the expansion of lacunar and giant lacunar infarction remain unclear. We aimed to determine risk factors for lacunar and giant lacunar infarction and to clarify differences in pathophysiological mechanisms for these two groups. Patients were selected from a comprehensive stroke center with ≤24 h from onset to initial magnetic resonance imaging with lacunar and giant lacunar infarction. All patients underwent a second magnetic resonance imaging during hospitalization. Infarct size was calculated and compared by the positive region on diffusion-weighted imaging. Factors related to infarct expansion were evaluated separately in the two groups. We screened 1558 consecutive ischemic stroke patients, including 154 patients with small vessel disease (lacunar infarction, 81 patients; giant lacunar infarction, 73 patients). Age (odds ratio (OR), 0.899; 95% confidence interval (CI), 0.824-0.981, p = 0.016), higher cardio-ankle vascular index (OR, 6.011; 95%CI, 2.319-15.581, p < 0.001), higher uric acid (OR, 2.584; 95%CI, 1.091-6.121, p = 0.031), and lower/normal low-density lipoprotein (LDL)-cholesterol (OR, 0.718; 95%CI, 0.557-0.926, p = 0.011) were independently associated with infarct expansion in lacunar infarction patients. Concerning giant lacunar infarction, higher LDL-cholesterol (OR 1.509, 95%CI 1.083-2.103; p = 0.015) and lower/normal body mass index (OR 0.725, 95%CI 0.567-0.926; p = 0.010) were factors independently associated with infarct expansion. Risk factors for infarct expansion differed between lacunar and giant lacunar infarction. The underlying pathophysiological mechanisms for infarct expansion in these two groups should be recognized individually.


Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts.
Immunogenic cell death (ICD) induced by different cancer treatments has been widely evaluated to recruit immune cells and trigger the specific antitumor immunity. However, cancer associated fibroblasts (CAFs) can hinder the invasion of immune cells and polarize the recruited monocytes to M2-type macrophages, which greatly restrict the efficacy of immunotherapy (IT). In this study, an injectable hydrogel induced by copper (Cu) has been designed to contain antibody of PD-L1 and nitric oxide (NO) donor. The therapeutic efficacy of hydrogel was studied in 4T1 cells and CAFs in vitro and 4T1 tumor-bearing mice in vivo. The immune effects on cytotoxic T lymphocytes, dendritic cells (DCs) and macrophages were analyzed by flow cytometry. Enzyme-linked immunosorbent assay, immunofluorescence and transcriptome analyses were also performed to evaluate the underlying mechanism. Due to the absorbance of Cu with the near-infrared laser irradiation, the injectable hydrogel exhibits persistent photothermal effect to kill cancer cells. In addition, the Cu of hydrogel shows the Fenton-like reaction to produce reactive oxygen species as chemodynamic therapy, thereby enhancing cancer treatment and amplifying ICD. More interestingly, we have found that the released NO can significantly increase depletion of CAFs and reduce the proportion of M2-type macrophages in vitro. Furthermore, due to the amplify of ICD, injectable hydrogel can effectively increase the infiltration of immune cells and reverse the immunosuppressive tumor microenvironment (TME) by regulating CAFs to enhance the therapeutic efficacy of anti-PD-L1 in vivo. The ion induced self-assembled hydrogel with NO could enhance immunotherapy via amplifying ICD and regulating CAFs. It provides a novel strategy to provoke a robust antitumor immune response for clinical cancer immunotherapy.


Glioma cell extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in co-cultures with brain-derived fibroblasts.
Extracellular matrix metalloproteinase inducer (EMMPRIN) also called CD147, basigin or M6 in the human is a member of the immunoglobulin superfamily that is enriched on the surface of tumor cells and stimulates adjacent stromal cells to produce several matrix metalloproteinases (MMPs). In this study, we have demonstrated that coculturing of EMMPRIN-expressing human glioblastoma multiforme cells (U251) with brain-derived human fibroblasts not only stimulates production, but also activation of pro-gelatinase A (proMMP-2), an enzyme that is enriched in malignant gliomas and most likely crucial to tumor progression. Production of membrane types 1 and 2-MMPs (MT1-MMP and MT2-MMP), which are activators of proMMP-2, was also stimulated in these cocultures. Stimulation of MMP-2, MT1-MMP and MT2-MMP production was inhibited by anti-EMMPRIN monoclonal antibody in a dose-dependent manner. Thus, we have shown, for the first time, that EMMPRIN causes increased expression of MT1-MMP and MT2-MMP, as well as increased production and activation of MMP-2.


Diagnostic radiography as a risk factor for chronic myeloid and monocytic leukaemia (CML).
This interview study included 136 Los Angeles County residents aged 20-69 with CML diagnosed from 1979 to 1985 (cases) and 136 neighbourhood controls. During the 3-20 years before diagnosis of the case, more cases than controls had radiographic examinations of the back, gastrointestinal (GI) tract and kidneys, and cases more often had GI and back radiography on multiple occasions (odds ratio (OR) for back X-rays on five or more occasions = 12.0; P less than 0.01). Published estimates were used to assign a minimum dose to the active bone marrow for various radiographic procedures. ORs were estimated for cumulative marrow doses for each of four time periods (3-5 years, 6-10 years, 11-20 years and 3-20 years before the diagnosis of the case). The ORs for exposure to 0.99, 100-999, 1000-1999 and greater than or equal to 2000 mrad in the 3-20 years before diagnosis were 1.0, 1.4, 1.6 and 2.4 (P for highest exposure category and P for trend both less than 0.05). The association was strongest for the period 6-10 years before diagnosis, and the effects of radiation exposure during this period remained significant after consideration of other risk factors in a logistic regression analysis.


Phenethyl isothiocyanate induces apoptosis of cholangiocarcinoma cells through interruption of glutathione and mitochondrial pathway.
Phenethyl isothiocyanate (PEITC) is a natural isothiocyanate with anticancer activity against many drug-resistant cancer cells. A body of evidence suggests that PEITC enhances oxidative stress leading to cancer cell death. Cholangiocarcinoma (CCA) is an aggressive bile duct cancer with resistance to chemotherapeutic drugs. PEITC rapidly kills KKU-100 CCA cells with concurrent induction of cellular glutathione depletion, superoxide formation, and loss of mitochondrial transmembrane potential. The loss was associated with increased Bax and decreased Bcl-xl proteins followed by the release of cytochrome c and the activation of caspase-9 and -3. Although TEMPOL could prevent superoxide formation, it did not prevent the disruption of glutathione (GSH) redox, mitochondrial dysfunction, and cell death. On the other hand, N-acetylcysteine could prevent the events and cell death. It was concluded that disruption of GSH redox but not superoxide formation may be an initial step leading to mitochondrial injury. PEITC could be a promising chemopreventive agent for CCA.


Intelligence quotient level and treatment of obsessive-compulsive disorders: Meta-analyses.
Obsessive-compulsive disorder (OCD) is a highly heterogeneous mental disorder that could affect mental capacity and requires different treatment methods. The purpose of this meta-analysis study was to evaluate the OCD subjects' intelligence quotient (IQ) and the effect of different treatments on OCD. Through a systematic literature search up to December-2019, 108-studies were identified, with 8049-subjects with 6719-OCD subjects. The studies identified were 45 reporting IQs in OCD and 38 reporting comparisons between selective-serotonin reuptake-inhibitors (SSRIs) to placebo in the treatment of OCD, 9 reporting comparison between SSRIs to each other, 8 reporting comparison between cognitive-behavioral therapy (CBT) to placebo and 8 reporting comparison between CBT to SSRIs. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated comparison was made according to the study content using a continuous method with a random or fixed-effects model. Subjects with OCD had significantly lower IQ (OR, -3.74; 95% CI, -4.83 to -2.64) than normal subjects. SSRIs (OR, -4.09; 95% CI, -4.87 to -3.30) and CBT (OR, -15.13; 95% CI, -19.27 to -10.99) had better effect than placebo in OCD treatment. No significant difference were found between different types of SSRIs (OR, -0.42; 95% CI, -1.32-0.49) or between CBT and SSRIs (OR, -1.99; 95% CI, -4.20 to 0.22) with non-significant better values favoring CBT. The IQ of the OCD subjects was significantly lower than in normal subjects. The SSRIs and the CBT had a significant effect on treating OCD. Different SSRIs are similar in their effect on OCD. More studies are required to separate between CBT and SSRIs' insignificant differences.


United we stand. Power shifts marginalize physician practices--unless we act and integrate.
How three "seismic events" in Fort Wayne, Ind., pushed a multispecialty group administrator to embrace integration.


Association between gout and abdominal aortic aneurysm.
Previous studies have shown an association between hyperuricemia and microvascular diseases, but the association between uric acid and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to determine the relationship between gout and AAA. A population-based cohort study was conducted to validate the association between gout and AAA formation. The outcome in this study was the cumulative incidence of AAA in patients with or without gout during the 14-year follow-up period. Our analysis included 121,236 patients with gout and 121,236 propensity score-matched controls from the National Health Insurance Research Database in Taiwan. Compared to the controls, patients who had gout exhibited a significantly increased incidence of AAA development [adjusted hazard ratio (HR) = 2.465, p < 0.001]. We also found that patients who were treated with anti-gout medications had a significantly lower risk of being diagnosed with an AAA than patients who were not treated with anti-gout medications (adjusted HR = 0.489, p < 0.001). We have provided clinical evidence that gout is associated with the development of AAA.


Preservation Rhinoplasty: The Endonasal Cottle Push-Down/Let-Down Approach.
Preservation rhinoplasty is a new term for an old technique. The authors have used the endonasal push-down and let-down techniques that are attributed to Dr Maurice Cottle throughout their careers on select patients with excellent success. The endonasal Cottle technique allows the authors to manage the nasal dorsum in a conservative fashion, reducing the need for routine restructuring of the middle third and nasal dorsum. The details of their approach are presented in this publication.


Immunotherapy in fungal allergy.
For decades airborne fungal spores have been implicated as causative factors in respiratory allergy. Exposure to high atmospheric spore counts and sensitization to specific fungal allergens have been associated with severe asthma, mainly in young adults. Although the prevalence of sensitization to commercial fungal extracts is approximately 3% in epidemiologic studies, in selected patients, particularly with asthma, the sensitization rate might increase to 30%. Of the estimated number of more than 1 million of different fungal species, approximately 80 fungi have been connected with respiratory allergy. Currently, diagnosis and specific therapy of fungal allergy is hampered by the poor quality of most of the commercially available extracts. Clinical efficacy of specific immunotherapy with fungal extracts has been shown in 79 actively treated patients in four controlled trials, with only two fungal species, namely Alternaria alternata and Cladosporium herbarum. The use of recombinant fungal allergens might create new prospects in diagnosis and specific immunotherapy for fungal allergy.


Biomechanical Comparison of Two Surgical Repair Techniques of the Distal Biceps Tendon.
This study aimed to characterize the relationship between the distal biceps tendon force and the supination and flexion rotations during the initiation phase and to compare the functional efficiency of anatomic versus nonanatomic repairs. Seven matched pairs of fresh-frozen cadaver arms were dissected to expose the humerus and elbow while preserving the biceps brachii, elbow joint capsule, and distal radioulnar soft tissue complex. For each pair, the distal biceps tendon was severed with a scalpel and then repaired with bone tunnels placed at either the anterior (anatomic) or the posterior (nonanatomic) aspect of the bicipital tuberosity on the proximal radius. A supination test with 90° of elbow flexion and an unconstrained flexion test were conducted on a customized loading frame. The biceps tension was applied incrementally at 200 g per step, whereas the radius rotation was tracked with a 3-dimensional motion analysis system. The tendon force needed to produce a degree of supination or flexion was derived as the regression slope of the tendon force-radial rotation plots. A two-tailed paired t test was performed to compare the difference between the anatomic repair and the nonanatomic repair cadavers. Significantly greater tendon force was required to initiate the first 10° of supination with the elbow in flexion for the nonanatomic group compared with the anatomic group (1.04 ± 0.44 N/degree vs 0.68 ± 0.17 N/degree, P = .02). The average nonanatomic to anatomic ratio was 149% ± 38%. No difference existed between the two groups in the mean tendon force needed to produce the degree of flexion. Our results show that anatomic repair is more efficient in producing supination than nonanatomic repair, but only when the elbow is in 90° of flexion. When the elbow joint is not constrained, the nonanatomic supination efficiency improved, and the difference between the techniques was not significant. The present study added to the body of evidence in comparing anatomic versus nonanatomic repair of the distal biceps tendon and serves as a foundation for future biomechanical and clinical studies in this topic. Given no difference when the elbow joint was not constrained, one could argue that surgeon comfort and preference could guide which technique to use when addressing the distal biceps tendon tears. More studies will be needed to clearly define whether there will be a clinical difference between the two techniques.


Relevance of new drug discovery to reduce NF-κB activation in cardiovascular disease.
The transcription factor nuclear factor-κB (NF-κB) is a main regulator of the expression of several genes involved in the activation of inflammation, cell proliferation, cell immunity and apoptosis. Excess or inappropriate activation of NF-κB has been observed in human inflammatory diseases, including atherosclerosis. Because of the extensive involvement of NF-κB signaling in human diseases, efforts have been made in developing inhibitors of this pathway. Here we will provide an overview of the biology of NF-κB activation pathways. We will here especially focus on current knowledge of the role of the classical ("canonical") NF-κB activation pathway as a potential therapeutic target for anti-atherosclerotic therapies in clinical applications, and discuss classical and novel therapeutic strategies to reduce its prolonged activation.


Atrial Fibrillation Is Associated with Recurrent Ventricular Arrhythmias After LVAD Implant: Incidence and Impact in a Consecutive Series.
This study examined left-ventricular assist device (LVAD) patients with pre-LVAD ventricular arrhythmias (VAs) to determine the rate of recurrent post-LVAD VAs and the impact of pre-LVAD atrial fibrillation (AF) on recurrent post-LVAD VAs. Medical records of 195 consecutive LVAD patients were reviewed. Descriptive statistics were generated and Cox proportional hazard models were used to assess the association of clinical variables with the time to recurrent VA. Forty-seven percent of 195 CHF patients who received LVAD-manifested significant VAs prior to LVAD implant (82% Heartmate II, 14% HVAD, 4% other; median follow-up = 17 months), 41% of whom manifested recurrent post-LVAD VAs. Pre-LVAD AF was associated with recurrent VAs (hazard ratio = 3.73; 95% CI 1.33, 10.48; p = 0.012). Recurrent VAs were associated with increased mortality (hazard ratio = 3.06; 95% CI 1.17, 7.98; p = 0.023). A history of AF is prevalent in over half of LVAD patients with recurrent VAs and is associated with time to recurrence of VA.


Sex-based differences in endurance exercise muscle metabolism: impact on exercise and nutritional strategies to optimize health and performance in women.
What is the topic of this review? The topic is how sex influences carbohydrate and fat metabolism during exercise and whether this influences adaptation to nutritional and exercise regimens aiming to improve health and performance. What advances does it highlight? Women respond differently to certain nutritional and training regimens aimed at improving health and performance. Few studies have included women in trials and thus we are unsure how women respond to nutritional and training strategies aimed at improving health and performance. Sex-based differences in substrate metabolism during moderate-intensity endurance exercise (END) have been well established. Specifically, during END of the same relative intensity women have a lower respiratory exchange ratio than men, indicative of a lesser reliance on carbohydrate oxidation to support fuel requirements for exercise. In fact, compared with men, women show a lesser reliance on both liver and muscle glycogen during END. Sex-based differences in intramyocellular lipid (IMCL) utilization during END are controversial. However, women have a larger depot of IMCL available to support END fuel needs and a greater percentage of IMCL in contact with mitochondria after a bout of END compared with men, suggestive of a greater capacity to use IMCL. These sex-based differences in metabolism during END are known to be mediated by oestrogen. Despite the well-recognized sexual dimorphisms in substrate metabolism during END, there is a paucity of research examining the effects of exercise and nutritional regimens aimed to enhance performance and/or health in women. Furthermore, the evidence that does exist is suggestive of discordance in the effectiveness of nutritional and exercise regimens between the sexes. The focus of this review is to provide an overview of the well-established sex-based differences in metabolism during END and how they relate to the physiological responses to nutritional and exercise strategies intended to improve exercise performance and/or health.


A retrospective cohort study of clinical factors, visit patterns, and demographic factors associated with use of remote communications in patients with headache.
To identify the characteristics associated with high utilization of remote communications (RCs) in patients with headache. Patients with headache frequently communicate with their providers using secure portal messaging and telephone calls. However, clinical and demographic factors as well as visit patterns associated with RC utilization remain poorly characterized. We retrospectively analyzed data from patients with headache who were evaluated in the ambulatory neurology faculty practice at the Icahn School of Medicine at Mount Sinai in New York between January 1 and June 30, 2019. We extracted clinical and demographic characteristics, total office visits, secure MyChart portal messages, and telephone encounters from our institutional data warehouse. We defined high RC and MyChart utilization as the top tertile of RC and MyChart message volume, respectively, and assessed the relationship between patient characteristics and high RC (primary outcome), as well as high MyChart utilization (secondary outcome). We characterized the relationship between clinicodemographic characteristics and the ratio of MyChart messages to total RCs (secondary outcome). We identified 1390 patients, of whom 477 (34.3%) were high RC utilizers and 321 (23.1%) were high MyChart utilizers. High RC utilizers generated 3306/3921 (84.3%) RCs. The presence of chronic headache (aOR 2.31, 95% CI 1.75-3.03, p < 0.0001), cluster headache (aOR 18.3, 95% CI 5.0-71.7, p = 0.001), and migraine (aOR 3.82, 95% CI 1.93-9.3, p = 0.011) was associated with high RC utilization. Patients ≥65 years of age were less likely to engage in MyChart messaging as a proportion of RC (191/680, 28.1%) compared with patients 18-30 years of age (243/620, 39.2%, p = 0.049) and 30-64 years of age (1172/2721, 43.1%, p < 0.0001). A minority of patients with headache (477/1390; 34.3%) generated the majority (3306/3921; 84.3%) of RCs. Our findings should be validated in external patient cohorts with the objective of developing strategies to optimize RC utilization.


The Unequal Effects of Social Distancing Policy on Subway Ridership during the COVID-19 Pandemic in Seoul, South Korea.
In the Republic of Korea, social distancing policies relied on voluntary participation by citizens and exhibited short-term changes. In this situation, the effects of such policies varied depending on each community's capacity to comply. Here, we collected subway ridership data for 294 stations on nine Seoul Metro lines and aggregated the data for each station to the 184 smallest administrative areas. We found that the mean percent change in subway ridership was fitted by an additive model of the log-transformed percent ratio of the restaurant industry (estimated degrees of freedom (EDF) = 3.24, P < 0.001), the Deprivation Index (DI) (EDF = 3.66, P = 0.015), and the proportion of essential workers (β = - 0.10 (95% confidence interval - 0.15 to - 0.05, P < 0.001). We found a distinct decrease in subway ridership only in the least deprived areas, suggesting that social distancing is costly.


Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD.
Until recently only two therapeutic options have been available to control symptoms and the esophagitis in chronic gastro-oesophageal reflux disease (GERD), i.e. lifelong proton pump inhibitor (PPI) therapy or anti-reflux surgery. Lately, transoral incisionless fundoplication (TIF) has been developed and found to offer a therapeutic alternative for these patients. To perform a double-blind sham-controlled study in GERD patients who were chronic PPI users. We studied patients with objectively confirmed GERD and persistent moderate to severe GERD symptoms without PPI therapy. Of 121 patients screened, we finally randomised 44 patients with 22 patients in each group. Those allocated to TIF had the TIF2 procedure completed during general anaesthesia by the EsophyX device with SerosaFuse fasteners. The sham procedure consisted of upper GI endoscopy under general anaesthesia. Neither the patient nor the assessor was aware of the patients' group affiliation. The primary effectiveness endpoint was the proportion of patients in clinical remission after 6-month follow-up. Secondary outcomes were: PPI consumption, oesophageal acid exposure, reduction in Quality of Life in Reflux and Dyspepsia and Gastrointestinal Symptom Rating Scale scores and healing of reflux esophagitis. The time (average days) in remission offered by the TIF2 procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P < 0.001. After 6 months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in favour of the TIF2 procedure. No safety issues were raised. Transoral incisionless fundoplication (TIF2) is effective in chronic PPI-dependent GERD patients when followed up for 6 months. Clinicaltrials.gov: CT01110811.


Role of Ca2+ influx in the tert-butyl hydroperoxide-induced apoptosis of HepG2 human hepatoblastoma cells.
Oxidative stress appears to be implicated in the pathogenesis of various diseases including alcoholic liver injury. In this study we investigated the mechanism of apoptosis induced by tert-butyl hydroperoxide (TBHP) in HepG2 human hepatoblastoma cells. Treatment with TBHP significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity, indicating that TBHP induced oxidative stress in the HepG2 cells. TBHP also induced reduction of cell viability and DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. In addition, TBHP induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented by the extracellular Ca2+ chelation with EGTA. TBHP also induced Mn2+ influx. These results indicate that the intracellular Ca2+ increase by TBHP is exclusively due to Ca2+ influx from the extracellular site. Treatment with either an extracellular (EGTA) or an intracellular Ca2+ chelator (BAPTA/AM) significantly suppressed the TBHP-induced apoptosis. Taken together, these results suggest that TBHP induced the apoptotic cell death in the HepG2 cells and that Ca2+ influx may play an important role in the apoptosis induced by TBHP.


Use of paraffin oils in agriculture and beyond: back to the future.
Paraffin (petroleum) oils have been used for many years for their insecticidal properties, but relatively little research had been conducted towards their introduction into the agricultural praxis, due to their potential phytotoxic effects. In the recent years, however, there has been an increased interest in petroleum-based pesticides due to their compatibility with integrated pest management (IPM) programs. Various improvements in the refinement methods have enhanced the manufacture of commercial products with many advantageous features over the original oil formulas. However, literature is still lacking of a general overview about the applicability of newly introduced commercial petroleum oils in agriculture and their compatibility with modern pest management practices. Therefore, the present work aims to depict the current status of petroleum oils in arboriculture and beyond, providing an in-depth analysis of their insecticidal properties with respect to the knowledge gained over the years about the factors responsible for the pesticidal efficacy and the phytotoxic activity of petroleum-derived oil insecticides. Moreover, commercial aspects of petroleum oil formulations and their toxicological profile to non-target organisms have also been addressed through the current legislation in EU and the USA.


Abnormal TNS3 gene methylation in patients with congenital scoliosis.
Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 < 0.01). There was no significant difference in the degree of methylation of SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 < 0.01). Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.


[Prevalence of dementia in several regions of the world: analysis of epidemiologic studies from 1994 to 2000].
To analyse the prevalence studies of dementia from 1994 to 2000. The papers were searched on Medline and Lilacs and the inclusion criteria were: to be an original study, that estimated dementia prevalence and investigated community samples. thirty-eight studies were evaluated from all continents. The mean age-specific prevalence rates of dementia were 1,17% for the 65-69 years group, and 54,83% over 95 years. The results were strongly influenced by age. Dementia prevalence rates were higher on women on 75% of the papers reviewed. The Alzheimer's disease/vascular dementia ratio was higher in South America and lower in Asia. Methodological advances were found, specially regarding the homogeneity of diagnostic criteria. The effect of age on the rates of dementia prevalence was pronounced, up to 90 years of age.