Gastric mucin phenotype defines tumour progression and prognosis of intrahepatic cholangiocarcinoma: gastric foveolar type is associated with aggressive tumour behaviour.
To identify the role of mucus core protein (MUC) in intrahepatic cholangiocarcinoma (ICC). We examined the expression profile of MUC2, MUC5AC and MUC6 by immunohistochemical staining in 100 ICCs and compared the clinicopathological factors and the immunohistochemical results. The expression frequency was: MUC2, 9%; MUC5AC, 40%; and MUC6, 21%. According to the gastric mucin expression profile, ICCs were classified into the following groups: null type (n = 43), gastric foveolar type (n = 36), pyloric gland type (n = 11) and gastric combined type (n = 10). Half of the gastric foveolar type and the gastric combined type were located in the hilar region, but the other types were predominant at the periphery (P = 0.0004). Well-differentiated components were more often detected in the gastric combined type and the pyloric gland type (P = 0.0281). The gastric foveolar type was associated with a higher incidence of lymph node metastasis (P < 0.0001). The pyloric gland type was associated with better survival and the gastric foveolar type was associated with worse survival. The gastric mucin phenotype was an independent prognostic factor by multivariate survival analysis. The gastric foveolar type of ICC was more often associated with aggressive tumour development, whereas the pyloric gland type exhibited less aggressive behaviour.


Quantitative computed tomography perfusion of prostate cancer: correlation with whole-mount pathology.
Microvessel density within the prostate is associated with presence of cancer, disease stage, and disease-specific survival. We evaluated multidetector computed tomography (CT) to estimate prostate perfusion and localize prostate cancer. Ten subjects were evaluated with contrast enhanced CT before radical prostatectomy with the Mx8000IDT 16-slice scanner. Following baseline pelvic scan, 100 cc of Optiray 300 was administered intravenously (4 cc per second). Repeated dynamic scans through the prostate were obtained at 20, 30, 40, 50, and 60 seconds following initiation of contrast injection. Computed tomography perfusion was compared with pathologic findings of Gleason score and tumor volume on whole-mount prostatectomy specimens. Conventional adenocarcinoma (Gleason score, 6-10) was present in all subjects, including one who also demonstrated a mucinous variant of prostate cancer. Visible focal CT enhancement was noted in 1 patient with a high-volume tumor and a Gleason score of 10. A positive correlation between local estimates of CT perfusion and percent of prostate volume occupied by tumor in each sextant was found for half of the subjects (Pearson correlation coefficient, 0.3-0.95; mean, 0.48) but statistically significant correlation (P < 0.05; Pearson coefficient, 0.9-0.95) was present in only the 2 subjects with the highest Gleason scores (8 and 10) and the highest tumor volume (> or = 50% in > or = 1 sextant region). Visible enhancement of prostate cancer during dynamic CT is present in a minority of subjects. Correlation between quantitative CT perfusion and tumor location is statistically significant only in subjects with localized high-volume, poorly differentiated prostate cancer.


A neurodynamic optimization approach for complex-variables programming problem.
A neural network model upon differential inclusion is designed for solving the complex-variables convex programming, and the chain rule for real-valued function with the complex-variables is established in this paper. The model does not need to choose penalty parameters when applied to practical problems, which makes it easier to design. The result is obtained that its state reaches the feasible region in finite time. Furthermore, the convergence for its state to an optimal solution is proved. Some typical examples are shown for the effectiveness of the designed model.


Effect of cigarette smoking on the periodontal health status: A comparative, cross sectional study.
Survey. The objective of the study was to evaluate the periodontal health status among cigarette smokers and non cigarette smokers, and oral hygiene measures. Cross sectional study. The study included 400 male (200 cigarette smokers and 200 non smokers) aged 18-65 years. The subjects were randomly selected from the patients attending dental out-patient department of civil hospital and Himachal Dental College, Sundernagar. Community Periodontal Index (CPI) score was recorded for each patient and a questionnaire was completed by each patient. Chi square and t-test. Periodontal condition as assessed by CPI score showed that there was statistically significant difference in the findings between cigarette smokers and non-smokers. Within the limits of this study, positive association was observed between periodontal disease and cigarette smoking. It was found that cigarette smoking was associated with lesser gingival bleeding and deeper pockets as compared to non-smokers.


Non-suicidal self-injury and life stress: A systematic meta-analysis and theoretical elaboration.
Recent years have seen a considerable growth of interest in the study of life stress and non-suicidal self-injury (NSSI). The current article presents a systematic review of the empirical literature on this association. In addition to providing a comprehensive meta-analysis, the current article includes a qualitative review of the findings for which there were too few cases (i.e., <3) for reliable approximations of effect sizes. Across the studies included in the meta-analysis, a significant but modest relation between life stress and NSSI was found (pooled OR=1.81 [95% CI=1.49-2.21]). After an adjustment was made for publication bias, the estimated effect size was smaller but still significant (pooled OR=1.33 [95% CI=1.08-1.63]). This relation was moderated by sample type, NSSI measure type, and length of period covered by the NSSI measure. The empirical literature is characterized by several methodological limitations, particularly the frequent use of cross-sectional analyses involving temporal overlap between assessments of life stress and NSSI, leaving unclear the precise nature of the relation between these two phenomena (e.g., whether life stress may be a cause, concomitant, or consequence of NSSI). Theoretically informed research utilizing multi-wave designs, assessing life stress and NSSI over relatively brief intervals, and featuring interview-based assessments of these constructs holds promise for advancing our understanding of their relation. The current review concludes with a theoretical elaboration of the association between NSSI and life stress, with the aim of providing a conceptual framework to guide future study in this area.


Increased expression of Na,K-ATPase and a selective increase in phosphorylation at Ser-11 in the cortex of the 2-kidney, 1-clip hypertensive rat.
The mechanism by which blood pressure increases during renovascular hypertension is incompletely understood. We, therefore, tested the hypothesis that in the 2-kidney, 1-clip (2K-1C) rat, in which hypertension develops due to increased angiotensin II (Ang II) levels, there is increased expression and phosphorylation of Na,K-ATPase at Ser-11 and Ser-18 in the kidney cortex. The rationale is Ang II is reported to directly stimulate Na,K-ATPase activity in proximal tubules, which reabsorb 2/3 of filtered sodium, via increased phosphorylation at Ser-11 and Ser-18 and the Na,K-ATPase drives sodium reabsorption. Five-week-old Sprague-Dawley rats underwent unilateral or sham clipping of the right renal artery and placement of telemetry transmitters. Six weeks later blood pressure and plasma Ang II were measured and kidneys harvested. The amount of Na,K-ATPase, phosphorylation at Ser-11 and Ser-18, and the expression of β-actin in each kidney cortex were measured by quantitative immunoblotting. Clipping significantly increased mean arterial pressure from 110 ± 3 to 148 ± 13 mm Hg, plasma Ang II, cortical Na,K-ATPase in the unclipped kidney of 2K-1C compared to sham-clipped rats, the total cortical Na,K-ATPase in both kidneys compared to sham-clipped rats, and the extent to which the Na,K-ATPase was phosphorylated at Ser-11. Clipping did not significantly change phosphorylation at Ser-18, β-actin, or the total protein in the cortexes of both kidneys. Thus, in the kidney cortex of rats with renovascular hypertension there is increased expression of Na,K-ATPase and a selective increase in its phosphorylation at Ser-11 that could increase the capacity to reabsorb sodium and water.


Improving newborn health in countries exposed to political violence: An assessment of the availability, accessibility, and distribution of neonatal health services at Palestinian hospitals.
Geopolitical segregation of Palestine has left a fragile healthcare system with an unequal distribution of services. Data from the Gaza Strip reflect an increase in infant mortality that coincided with a significant increase in neonatal mortality (12.0 to 20.3 per 1,000 live births). A baseline study was carried out to evaluate available resources in neonatal units throughout Palestine. A cross-sectional, hospital-based study was conducted in 2017 using the World Health Organization's "Hospital care for mothers and newborn babies: quality assessment and improvement tool." Data on the main indicators were updated in 2018. There were 38 neonatal units in Palestine: 27 in the West Bank, 3 in East Jerusalem, and 8 in the Gaza Strip. There was an uneven geographic distribution of incubators in relation to population and births that was more marked in the Gaza Strip; 79% of neonatal units and 75% of incubators were in the West Bank. While almost all hospitals with neonatal units accepted very and extremely low birth weight and admitted out-born neonatal cases, there was a shortage in the availability of incubators with humidifiers, high-frequency oscillatory ventilation, mechanical ventilators with humidifiers and isolation wards. There was also a considerable shortage in neonatologists, neonatal nurses, and pediatric subspecialties. Almost all the neonatal units accepted extremely low birth weight neonatal cases despite not being ready to receive these newborns due to considerable shortages in human resources, equipment, drugs, and essential blood tests, as well as frequent disruptions in the availability of based amenities. Together, these factors contribute to the burden of providing quality care to newborns, which is further exacerbated by the lack of referral guidelines and challenges to timely referrals resulting from Israeli measures. Ultimately, this contributes to suboptimal care for neonates and negatively impacts future health outcomes.


Functionalized chitosan for cancer nano drug delivery.
Chitosan is a biotechnological derivative of chitin receiving a widespread pharmaceutical and biomedical applications. It can be used to encapsulate and deliver cancer therapeutics with inherent pH-dependent solubility to confer drug targeting at tumour microenvironment and anti-cancer activity synergizing cancer cytotoxic drug actions. To further reduce the off-target and by-stander adverse effects of drugs, a high targeted drug delivery efficiency at the lowest possible drug doses is clinically required. The chitosan has been functionalized with covalent conjugates or complexes and processed into nanoparticles to encapsulate and control drug release, to avoid premature drug clearance, to deliver drugs passively and actively to cancer site at tissue, cell or subcellular levels, and to promote cancer cell uptake of nanoparticles through membrane permeabilization at higher specificity and scale. Nanomedicine developed using functionalized chitosan translates to significant preclinical improvements. Future challenges related to nanotoxicity, manufacturability, selection precision of conjugates and complexes as a function of cancer omics and their biological responses from administration site to cancer target need critical assessments.


The tripartite influence model of body image and eating disturbance: a replication with a Japanese sample.
To examine the tripartite influence model of body image and eating disturbance as a viable sociocultural explanation for the development of eating and body image problems with young Japanese females. A sample of 289 Japanese female undergraduates completed a variety of measures designed to index family, peer, and media influences, as well as levels of body dissatisfaction, eating disturbances, and self-esteem. The data were evaluated with structural equation modeling to test the tripartite model. Fit indices indicated a moderate fit to the overall tripartite model, replicating previous findings. This study suggests that the sociocultural variables found to influence body image and eating disturbances in Japan are similar to those observed with US samples. The implications for prevention and intervention programs are discussed.


Minimally Invasive Surgical Approaches for Chronic Subdural Hematomas.
Chronic subdural hematomas are one of the most common clinical entities encountered in today's neurosurgical practices owing to an aging population and continued increases in life expectancy. Although there is a role for conservative management, surgical drainage remains the mainstay of current therapy. Regardless of the technique used for hematoma drainage, there is level I evidence to suggest that use of closed-system drainage during the perioperative period significantly decreases the likelihood for hematoma recurrence, length of hospital stay, and mortality.


Role of bioimpedance vectorial analysis in cardio-renal syndromes.
The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS.


Histological aspects of skin reactions to propylene glycol.
In view of the increased use of dermatological preparations containing a high concentration of propylene glycol (PG) for use under occlusive dressings, patch tests were performed with pure PG in a group of 98 out-patients at a skin clinic. No indication of a possible allergic contact dermatitis to PG could be found in the history of any of these patients. In 11 of them, the patch test reactions after a 48-h application were positive. In eight cases the reaction was scored as one plus, in two cases as two plus, and in the remaining case a three plus reaction was observed. In view of the negative history of all patients, the observed reactions were considered to be of a primary irritant nature. Histological examination of the positive patch tests revealed some definite quantitative differences between one and two plus reactions on the one hand and a three plus reaction on the other. The findings suggest that the application of high concentrations of PG under occlusive dressings may give rise to skin reactions of a primary irritant character which may closely simulate an allergic reaction.


Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives.
The aim of the study was to evaluate whether combined oral contraceptives (COCs) can be used as hormone therapy (HT) to preserve bone mineral density (BMD) in women with premature ovarian insufficiency (POI). An observational study of women with POI comparing the use of COC (ethinylestradiol 30 μg + levonorgestrel, continuously) with: low-dose HT (continuous conjugated estrogen 0.625 mg plus medroxyprogesterone or continuous estradiol [E2] 1 mg + norethisterone), high-dose HT (continuous conjugated estrogen 1.25 mg + medroxyprogesterone or continuous E2 2 mg + norethisterone), tibolone 2.5 mg, or no treatment. Bone density scans were performed every 2 ± 1 years. The difference between final and initial (delta) BMD values was calculated for the lumbar spine, total femur, and femoral neck. Generalized estimating equations were used to analyze the effect of treatment over time. Variables without normal distribution were transformed into ranks. Overall, 420 scans (210 deltas) of 119 women were analyzed. The women were 30.3 ± 9.2 years old (mean ± SD). BMD deltas at the lumbar spine and total femur were grater in the COC and high-dose HT groups. At the lumbar spine, the differences between two scans were greater in the COC group when compared to low-dose HT group: -0.043 (95% CI -0.062 to -0.024), untreated: -0.056 (-0.080 to -0.032), and tibolone: -0.050 (-0.094 to -0.006) groups. Total femur BMD decreases and the delta were lower in the low-dose HT group -0.038 (-0.052 to -0.024) when compared to COC. Continuous COC was associated with increased BMD in women with POI compared to low-dose HT, with similar improvement in the COC and high-dose HT groups. : Video Summary:http://links.lww.com/MENO/A620.


["Fit4You"--A Programme for Prevention and Reduction of Overweight in Apprentices in the Workplace Setting].
The effect of health promotion at the worksite for overweight adolescents is not known. This 2-year intervention study examined the effect of a multimodal programme including nutrition counselling, sport, and life-skill training on medical and psychological outcomes. The body mass index increased slightly less in the intervention group. Semistructured interviews at the end showed that participants are highly interested in health promotion at the worksite.


Factorial trial found mixed evidence of effects of pre-notification and pleading on response to Web-based survey.
To evaluate the effectiveness of pre-notification and pleading invitations in Web surveys by embedding a randomized controlled trial (RCT) in a Web-based survey. E-mail addresses of 569 authors of published maternal health research were randomized in a 2×2 factorial trial of a pre-notification vs. no pre-notification e-mail and a pleading vs. a non-pleading invitation e-mail. The primary outcome was completed response rate, and the secondary outcome was submitted response rate (which included complete and partial responses). Pleading invitations resulted in 5.0% more completed questionnaires, although this difference did not reach statistical significance [odds ratio (OR) 1.23; 95% confidence interval (CI): 0.86, 1.74; P=0.25]. Pre-notification did not increase the completion rate (OR 1.04; 95% CI 0.73, 1.48; P=0.83). Response was higher among authors who had published in 2006 or later (OR 2.07; 95% CI: 1.43, 2.98; P=0.001). There was some evidence that pre-notification was more effective in increasing submissions from authors with recent publications (P=0.04). The use of a "pleading" tone to e-mail invitations may increase response to a Web-based survey. Authors of recently published research are more likely to respond to a Web-based survey.


Optical diagnostic imaging and therapy for thyroid cancer.
Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and 131I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging's promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.


Effect of doxazosin GITS on 24-hour blood pressure profile in patients with stage 1 to stage 2 primary hypertension.
To investigate the effect of the doxazosin gastrointestinal therapeutic system (GITS) on the 24 h blood pressure (BP) profile by ambulatory blood pressure measurements (ABPM) in patients with stage 1 to stage 2 primary hypertension. Seventeen hypertensive patients-either untreated or after a two-week run-in/washout period-underwent office and ABPM monitoring before and six weeks after an open-label once-daily morning dose of 4 mg of doxazosin GITS, an alpha(1)-adrenoceptor antagonist. Fourteen patients responded; three did not. Data analyses refers to the responders: linear analysis demonstrated statistically significant reductions from baseline in daytime, night-time, and total 24 h means for systolic BP (SBP) (7-10 mmHg) and diastolic BP (DBP) (5-10 mmHg) after treatment, with no statistically significant change in heart rate (HR). Rhythm analysis demonstrated statistically significant reductions from baseline in mean mesor (8 mmHg), maximum (6 mmHg) and minimum (10 mmHg) values in SBP, and in mean mesor (5 mmHg), maximum (7 mmHg) and minimum (5 mmHg) values in DBP. Circadian rhythm parameters in BP and HR were not significantly altered by treatment. Treatment with doxazosin GITS was well tolerated. A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.


Reduced graphene oxide/carbon nitride composite sponge for interfacial solar water evaporation and wastewater treatment.
Interfacial solar-driven steam generation has been proposed as a cost-effective green sustainable technology to alleviate the freshwater crisis. However, the desire to produce clean water from water sources containing organic contaminants is still remains a challenge due to the limitations of the traditional wastewater treatment methods. Here, we constructed a g-C3N4-based composite sponge solar steam generator (rGCPP) by a simple hydrothermal reaction. Benefiting from its low cost and easy preparation, this evaporator can be expected to be a promising candidate for the alleviation of water shortages and water pollution in practical applications. By combination of the solar steam generation and the photocatalysis into the rGCPP-based interfacial solar-driven steam generation system, the resulted rGCPP-based solar steam generator performs outstanding solar absorption of 90.8%, which achieves high evaporation rate of 1.875 kg m-2 h-1 and solar-to-vapor efficiency of 81.07% under 1 sun irradiation. Meanwhile, organic pollutants in the water source can be completely removed by photocatalytic degradation and the degradation rates were measured to be 99.20% for methylene blue and 91.07% for rhodamine B, respectively. Consequently, the as-prepared composite sponge has promising applications in generating clean water and alleviating water pollution.


Temporary ovarian suspension at laparoscopy for prevention of adhesions.
We performed an innovative technique of temporary ovarian suspension after operative laparoscopy for stage 3 and 4 endometriosis and evaluated the results in a retrospective study. Subjects were 20 women who underwent operative laparoscopy for infertility. Temporary ovarian suspension to the anterior abdominal wall was performed as the last step in the surgical procedure. It was done in an attempt to separate adhesiogenic surfaces during the initial phase of tissue healing (5-7 days). No complications occurred. After excluding patients who had additional infertility factors and/or were of advanced reproductive age, nine women tried to conceive spontaneously. Of these, five conceived (55%): three delivered, one pregnancy continues (80%), and one woman had an ectopic pregnancy (20%). Of the remaining 15 patients who failed to conceive spontaneously, 5 had a second-look laparoscopy. In four patients (80%), we found no evidence of recurrent adhesions. The remaining 20% had minimal adhesions. Temporary ovarian suspension appears to be simple and safe, and may be effective in preventing postoperative adhesions near the ovaries after operative laparoscopy for advanced endometriosis.


Validation of the Chinese Cultural Tightness-Looseness Scale and General Tightness-Looseness Scale.
This study aims to revise the Cultural Tightness-Looseness Scale (CTLS) and General Tightness-Looseness Scale (GTLS), and explore the group heterogeneity of tightness-looseness perception in Chinese populations. Sample 1 (n = 2,388) was used for item analysis and exploratory factor analysis, and sample 2 (n = 2,385) was used for confirmatory factor analysis and latent profile analysis. Sample 3 (n = 512) was used for the reliability test and criterion validity test, among which 162 participants were used for the test-retest reliability examination after a four-week interval. Measurements included the CTLS, GTLS, International Personality Item Pool, Personal Need for Structure Scale, and Campbell Index of Well-Being. The revised CTLS contained four items and retained a single-dimensional structure. The revised GTLS consisted of eight items divided into two dimensions: Compliance with Norms and Social Sanctions. Latent profile analysis extracted two profiles on both CTLS and GTLS scores, indicating that the sample can be divided into two subgroups: high and low perception of tightness. The Chinese versions of the CTLS and GTLS can be used as valid and reliable measures of tightness-looseness perception in a Chinese population.


Epithelioid sarcoma with SYT-SSX1 fusion gene expression: molecular and cytogenetic analysis.
Epithelioid sarcoma is a rare malignant soft tissue tumor of unknown histogenesis, characterized by the epithelioid morphology of tumor cells and co-expression of epithelial and mesenchymal lineage proteins. A common epithelial and mesenchymal immunophenotype is also found in another soft tissue tumor, the biphasic subtype of synovial sarcoma. Furthermore, the presence of a breakpoint at 18q11 in epithelioid sarcoma, similar to that found in synovial sarcoma, has been reported. These facts would support the hypothesis that both tumors may share a common histogenetic background. However, expression of the SYT-SSX fusion genes has been investigated in epithelioid sarcoma with negative results. We report, to our knowledge, the first epithelioid sarcoma in which the presence of SYT-SSX1 fusion gene has been detected by means of conventional RT-PCR analysis and sequencing, real-time RT-PCR and FISH. The SYT-SSX1 gene fusion was identified in a small proportion of tumoral cells. This finding supports a likely common histogenetic background for both epithelioid sarcoma and synovial sarcoma.


Controllable Phase Separation by Boc-Modified Lipophilic Acid as a Multifunctional Extractant.
While phase separation of immiscible liquid-liquid systems has become increasingly significant in diverse areas, the irreversible nature limits their further application in controllable extraction-concentration or capture-release fields. There is a need for the development of simple, efficient and reversible methods for numerous research and industrial extraction and separation applications. We envisioned Boc-modified lipophilic acids as a simple model for such use based on the studies of the multi-phase transitions of Boc-modified supramolecular polymeric systems. Here, we demonstrate that in the presence of Boc-7-aminoheptanoic acid (Boc-7), phase separation occurs in mixtures of miscible organic solvent and water. The separation behavior was confirmed by differential colorimetric development in aqueous and organic phases using methyl orange staining assays. Component substitution experiments verified that the phase separation results from the subtle balance between the aggregation and the solvation forces of Boc-7, and is reversible by adjusting the solution pH. Owing to the intrinsic hydrophobic properties of the organic phase and the hydrogen bonding-forming ability of the carboxyl group of Boc-7, the phase separation system captures and releases Sudan Red, fluorescein, and streptavidin in a controllable manner. Consequently, a reversible and simple phase separation system can be designed as a multifunctional extractant.


The implications of integrated assessment and modelling studies for the future remediation of chromite ore processing residue disposal sites.
Chromite ore processing residue (COPR) waste from a former chromium chemical works (1830-1968) is still contaminating groundwater in Glasgow, Scotland, with carcinogenic hexavalent chromium, Cr(VI). An integrated analytical, experimental and modelling approach has identified and accounted for mineral phases and processes responsible for the retention and release of Cr(VI) under prevailing field conditions. Both the nature of mineral phase retention and the buffered high pH of the sites, however, militate against direct remediative treatment of the source material, for example by the application of generic methods (e.g. FeSO4) that have been successfully employed elsewhere for the reduction of Cr(VI) to Cr(III) in other matrices. The interception and treatment of groundwater to remove Cr(VI) and the capping of sites to reduce human exposure to airborne Cr(VI)-contaminated dust may well be more realistic and effective, at least in the short to medium term.


Pulmonary hypertension secondary to pulmonary fibrosis: clinical data, histopathology and molecular insights.
Pulmonary hypertension (PH) developing secondarily in pulmonary fibrosis (PF) patients (PF-PH) is a frequent co-morbidity. The high prevalence of PH in PF patients is very concerning since the presence of PH is a strong predictor of mortality in PF patients. Until recently, PH was thought to arise solely from fibrotic destruction of the lung parenchyma, leading to hypoxic vasoconstriction and loss of vascular bed density. Thus, potential cellular and molecular dysregulation of vascular remodeling as a driver of PF-PH has been under-investigated. The recent demonstrations that there is no correlation between the severity of the fibrosis and development of PH, along with the finding that significant vascular histological and molecular differences exist between patients with and without PH have shifted the etiological paradigm of PF-PH. This review aims to provide a comprehensive translational overview of PH in PF patients from clinical diagnosis and outcome to the latest understanding of the histology and molecular pathophysiology of PF-PH.


Restrictive bare stent for prevention of stent graft-induced distal redissection after thoracic endovascular aortic repair for type B aortic dissection.
Stent graft-induced distal redissection (SIDR) is one of the major concerns in the durability of endovascular repair for complicated Stanford type B aortic dissection. The characteristics and means of prevention of this complication remain unknown. From April 1997 to March 2010, 674 patients with type B aortic dissections were treated primarily by thoracic endovascular aortic repair (TEVAR) at our center. Criteria for inclusion in this study were treatment primarily with TEVAR and an estimated mismatch rate (ratio of distal diameter of stent graft to long diameter of true lumen) greater than 120%. By this protocol, 465 patients were included in this study and were retrospectively analyzed. Among them, 266 patients were treated in the acute phase, and 199 were treated in the chronic phase. A total of 311 patients were treated with standard TEVAR and 154 patients with TEVAR + restrictive bare stent (RBS). The preoperative mismatch rate (measured as the preoperative long diameter of the true lumen at the level of the intended distal end of the stent graft) of the SIDR was significantly higher than that of the non-SIDR (192.7 ± 54.9% vs 131.9 ± 10.4%; P < .05). The follow-up mismatch rate of the SIDR was significantly higher than that of the non-SIDR (145.4 ± 34.6 vs 120.3 ± 16.1; P < .05). Compared with the standard TEVAR, TEVAR + RBS was associated with a lower incidence of SIDR (0% vs 2.9%; P = .033) and less secondary intervention (3.9% vs 9.3%; P = .040). Placement of the RBS significantly expanded the true lumen at the level of the descending aorta with the narrowest true lumen and at the level of the distal end of the stent graft. The mismatch between the distal diameter of the stent graft and the diameter of the compressed true lumen seems to be the major factor in the occurrence of SIDR. Placement of an RBS, as an adjunctive technique to TEVAR, could reduce the incidence of SIDR. On the basis of early- to midterm observations, RBSs may improve morphological remodeling of the dissected aorta at certain levels.


Specific alignment of nucleosomes on DNA correlates with periodic distribution of purine-pyrimidine and pyrimidine-purine dimers.
Comparison of the X-ray data and results of conformational analysis reveals the sequence-dependent helical anisotrophy of DNA: purine-pyrimidine (RY) and pyrimidine-purine (YR) dimers prefer bending in the opposite directions. On this basis it is suggested that in the optimal nucleosomal DNA sequence the RY and YR dinucleotides alternate at intervals of 5-6 basepairs. Examination of the cases with the known disposition of nucleosomes confirms this concept.


Variations of lipid-protein interactions in erythrocyte ghosts as a function of temperature and pH in physiological and non-physiological ranges. A study using a paramagnetic quenching of protein fluorescence by nitroxide lipid analogues.
1. Incorporation of stearic acid nitroxides into erythrocyte ghosts markedly depresses the fluorescence of membrane protein tryptophan residues. 5-Nitroxide stearate quenches fluorescence more efficiently than 16-nitroxide stearate. Both compounds exhibit dynamic (diffusion-limited) quenching above 0.28 mumol/mg protein and static quenching at lower nitroxide protein ratios. Static quenching can be attributed to high affinity binding of nitroxide stearates by membrane protein. The dynamic phase represents distribution of the stearate analogues into a fluid lipid system. 2. Protein fluorophores accessible to quenching by a cholesterol analogue, androstane nitroxide, are saturated at low nitroxide/protein ratios (less than 0.14 mumol/mg protein), without resolution of a static quenching phase. This suggests that sterols are segregated away from protein, probably in CLusters". 3. Paramagnetic quenching by stearate nitroxides increases abruptly between 35 and 50 degrees C. This discontinuous enhancement of quenching by temperature is reversible up to 41 degrees C but irreversible at higher temperatures. The discontinuity is also diminished by lowering pH from 7.3 through 6.5 to 6.0. Quenching by androstane nitroxide increases linearly with temperature up to approx. 41 degrees C and then rises exponentially. We attribute the reversible quenching thermotropism detected by stearate derivatives to reversible, thermotropic unfolding and/or depolymerisation of membrane proteins. The irreversible phase, detected also by the sterol derivative can be attributed to non-reversible protein denaturation. 4. Paramagnetic quenching of membrane tryptophan fluorescence by stearate derivatives is minimal at approx. pH 7.1 (35 degrees C) and increases sharply at lower and higher pH values, suggesting that two categories of protein residues, titrating between pH 6 and 8, profoundly influence the association of fatty acyl chains and penetrating protein segments. Quenching by androstane nitroxide exhibits no significant variation between pH 6 and 8, consistent with other data indicating that erythrocyte membrane sterols are segregated from membrane proteins, probably in clusters. 5. Our new approach confirms previous suggestions of a boundary layer of lipid in close association with some proteins in erythrocyte membranes, as well as experiments indicating that the lipid status in this boundary layer depends on that state of membrane proteins. However, sterols appear to be largely excluded from this boundary domain. Our data further show that lipid-protein interactions in erythrocyte membranes can vary significantly with fluctuations of temperature and pH in the physiological range.


Encapsulation of Nitrilase in Zeolitic Imidazolate Framework-90 to Improve Its Stability and Reusability.
In this study, nitrilase (Nit) was immobilized in zeolite imidazole framework-90 (ZIF-90) by one-pot biomimetic mineralization strategy. The structure, morphology and functional groups of ZIF-90 and immobilized enzyme Nit@ZIF-90 were characterized by scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR). Circular dichroism (CD) proved that the immobilized method of encapsulation in ZIF-90 could effectively maintain the intrinsic conformation of Nit. Meanwhile, the stability and reusability of Nit@ZIF-90 were systematically evaluated. Compared with the free enzyme, the thermal, pH and organic solvents stability of Nit@ZIF-90 were significantly increased. Further, Nit@ZIF-90 exhibited better reusability during the hydrolysis of acrylonitrile and retained 48.34% of the initial activity after 10 cycles. Besides, the Ni@ZIF-90 had preferable storage stability, which showed a high degree of residual activity (more than 64 %) after storage at 4 °C for 7 d. The improved stability and reusability of the Nit@ZIF-90 implied that it could be used as a potential effective biocatalyst for hydrolysis of nitrile compounds in industrial application.


Adrenomedullin - Current perspective on a peptide hormone with significant therapeutic potential.
The peptide hormone adrenomedullin (ADM) consists of 52 amino acids and plays a pivotal role in the regulation of many physiological processes, particularly those of the cardiovascular and lymphatic system. Like calcitonin (CT), calcitonin gene-related peptide (CGRP), intermedin (IMD) and amylin (AMY), it belongs to the CT/CGRP family of peptide hormones, which despite their low little sequence identity share certain characteristic structural features as well as a complex multicomponent receptor system. ADM, IMD and CGRP exert their biological effects by activation of the calcitonin receptor-like receptor (CLR) as a complex with one of three receptor activity-modifying proteins (RAMP), which alter the ligand affinity. Selectivity within the receptor system is largely mediated by the amidated C-terminus of the peptide hormones, which bind to the extracellular domains of the receptors. This enables their N-terminus consisting of a disulfide-bonded ring structure and a helical segment to bind within the transmembrane region and to induce an active receptor confirmation. ADM is expressed in a variety of tissues in the human body and is fundamentally involved in multitude biological processes. Thus, it is of interest as a diagnostic marker and a promising candidate for therapeutic interventions. In order to fully exploit the potential of ADM, it is necessary to improve its pharmacological profile by increasing the metabolic stability and, ideally, creating receptor subtype-selective analogs. While several successful attempts to prolong the half-life of ADM were recently reported, improving or even retaining receptor selectivity remains challenging.


Manual acupuncture for analgesia during electromyography: a pilot study.
To evaluate the analgesic effect of acupuncture for needle electromyography and to validate a sham acupuncture needle. Randomized, double-blinded, controlled study. University-based electrodiagnostics laboratory. Fifty-one subjects referred for electrodiagnostic evaluation. Before the electromyography examination, either real acupuncture needles or telescopic sham needles were applied. Visual analog scale of pain and unpleasantness after 3 muscles were examined with electromyography. Pretest pain was subtracted to give a measurement of pain attributable to the electromyography. Subjects were asked which needle they thought they had received. Twenty-six subjects were randomized to the treatment group and 25 to the sham group. Pain in the treatment group (-.96) was less than in the control group (9.68), but it was not statistically significant (P=.13). Post hoc analysis, excluding 5 subjects known to have been treated by the novice acupuncturist, showed a significant difference of 14.4mm (P=.02). The proportion of subjects who thought they received real needles in the acupuncture group (69%) did not differ from the proportion in the control group (48%) (P=.13). Acupuncture may represent an effective form of analgesia for electromyography. This is the first study to suggest independently the telescopic sham acupuncture needle as an effective control.


Epidemiology of Asbestosis between 2010-2014 and 2015-2019 Periods in Colombia: Descriptive Study.
Asbestosis is a prevalent worldwide problem, but scarce data sourced from developing countries are available. We describe the sociodemographic characteristics and patterns in the occurrence of care provided for asbestosis in Colombia during the periods 2010-2014 and 2015-2019 to establish the behavior, trends, and variables associated with concentrations among people attended by asbestosis. A retrospective descriptive study was carried out with data from the Integrated Social Protection Information System (SISPRO) for two 5-year periods. People attended by asbestosis (ICD-10: J61) were identified; the frequency of patient visits, sociodemographic characteristics, case distribution patterns, and trends in both five-year periods were described, as was the crude frequency (cFr, 95% CI) of asbestosis (1,000,000 people/year) in both five-year periods (cFr ratio, 95% CI). During the period 2010-2019, 765 people attended by asbestosis were identified; there were 308 people attended by asbestosis between 2010-2014 (cFr: 2.20, 1.96-2.47), and ther were 457 people attended by asbestos between 2015-2019 (cFr: 3.14, 2.92-3.50). In both periods, the estimated cFr in men was nine times the estimated cFr in women. The cFr increased in the 2015-2019 period (cFr_ratio: 1.23, 1.06-1.43). Compared with the 2010-2014 period, the cFr of asbestosis increased in women (cFr_ratio: 1.44, 1.03-2.01), in the Andean (cFr_ratio: 1.61, 1.35-1.95) and Caribbean regions (cFr_ratio: 1. 66, 1.21-2.30), in the urban area (cFr_ratio: 1.24, 1.05-1.48), and in the age groups 45-59 years (cFr_ratio: 1.34, 1.001-1.79) and ≥60 years (cFr_ratio: 1.43, 1.13-1.83). During two five-year periods, the cFr of asbestosis was higher in men; between the first and second five-year periods, it increased significantly, especially in urbanized geographic areas and in populations aged ≥45 years. The estimates possibly reflect the effect of disease latency or the expected impact of public health policies to monitor asbestos exposure and complications.


Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation.
Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper (Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4(+) T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4(+) T cells, but augmented CD4(+) T-cell proliferation upon activation with anti-CD3/anti-CD28 antibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4(+) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4(+) T cells under Th2 skewed condition, while decreasing IFN-gamma secretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naïve CD4(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4(+) T-cell activity, as well as the correction of Th1-dominant pathological disorders.


CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes.
Protein phosphatase 2A (PP2A) is a critical human tumor-suppressor complex. A recently characterized PP2A inhibitor protein, namely cancerous inhibitor of PP2A (CIP2A), has been found to be overexpressed at a high frequency in most of the human cancer types. However, our understanding of gene expression programs regulated by CIP2A is almost absent. Moreover, clinical relevance of the CIP2A-regulated transcriptome has not been addressed thus far. Here, we report a high-confidence transcriptional signature regulated by CIP2A. Bioinformatic pathway analysis of the CIP2A signature revealed that CIP2A regulates several MYC-dependent and MYC-independent gene programs. With regard to MYC-independent signaling, JNK2 expression and transwell migration were inhibited by CIP2A depletion, whereas MYC depletion did not affect either of these phenotypes. Instead, depletion of either CIP2A or MYC inhibited cancer cell colony growth with statistically indistinguishable efficiency. Moreover, CIP2A depletion was shown to regulate the expression of several established MYC target genes, out of which most were MYC-repressed genes. CIP2A small-interfering RNA-elicited inhibition of colony growth or activation of MYC-repressed genes was reversed at large by concomitant PP2A inhibition. Finally, the CIP2A signature was shown to cluster with basal-type and human epidermal growth factor receptor (HER)2-positive (HER2+) breast cancer signatures. Accordingly, CIP2A protein expression was significantly associated with basal-like (P=0.0014) and HER2+ (P<0.0001) breast cancers. CIP2A expression also associated with MYC gene amplification (P<0.001). Taken together, identification of CIP2A-driven transcriptional signature, and especially novel MYC-independent signaling programs regulated by CIP2A, provides important resource for understanding CIP2A's role as a clinically relevant human oncoprotein. With regard to MYC, these results both validate CIP2A's role in regulating MYC-mediated gene expression and provide a plausible novel explanation for the high MYC activity in basal-like and HER2+ breast cancers.


Isolation of cDNAs encoding 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase from the mediterranean fruit fly Ceratitis capitata: correlating genetic and physical maps of chromosome 5.
We have isolated and determined the nucleotide sequences for cDNA clones encoding glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) from the medfly Ceratitis capitata. The derived amino acid sequences for G6PD and 6PGD are presented and compared with G6PDs and 6PGDs from other species. The codon usage of the cDNA clones has little bias with the notable exceptions of arginine, glycine and leucine. The chromosomal location of the genes for 6PGD and G6PD were determined by in situ hybridization to salivary gland polytene chromosomes. This localization orients a genetic map of enzymatic loci and illustrates a remarkable similarity in the intra chromosomal order of homologous genes between Drosophila melanogaster and medfly.


Development of pyrimidone D1 dopamine receptor positive allosteric modulators.
MLS1082 is a structurally novel pyrimidone-based D1-like dopamine receptor positive allosteric modulator. Potentiation of D1 dopamine receptor (D1R) signaling is a therapeutic strategy for treating neurocognitive disorders. Here, we investigate the relationship between D1R potentiation and two prominent structural features of MLS1082, namely the pendant N-aryl and C-alkyl groups on the pyrimidone ring. To this end, we synthesized 24 new analogues and characterized their ability to potentiate dopamine signaling at the D1R and the closely related D5R. We identified structure-activity relationship trends for both aryl and alkyl modifications and our efforts afforded several analogues with improvements in activity. The most effective analogues demonstrated an approximately 8-fold amplification of dopamine-mediated D1R signaling. These findings advance the understanding of structural moieties underlying the activity of pyrimidone-based D1R positive allosteric modulators.


Insights into the cellulose degradation mechanism of the thermophilic fungus Chaetomium thermophilum based on integrated functional omics.
Lignocellulose is the most abundant and renewable biomass resource on the planet. Lignocellulose can be converted into biofuels and high-value compounds; however, its recalcitrance makes its breakdown a challenge. Lytic polysaccharide monooxygenases (LPMOs) offer tremendous promise for the degradation of recalcitrant polysaccharides. Chaetomium thermophilum, having many LPMO-coding genes, is a dominant thermophilic fungus in cellulose-rich and self-heating habitats. This study explores the genome, secretomes and transcript levels of specific genes of C. thermophilum. The genome of C. thermophilum encoded a comprehensive set of cellulose- and xylan-degrading enzymes, especially 18 AA9 LPMOs that belonged to different subfamilies. Extracellular secretomes showed that arabinose and microcrystalline cellulose (MCC) could specifically induce the secretion of carbohydrate-active enzymes (CAZymes), especially AA9 LPMOs, by C. thermophilum under different carbon sources. Temporal analyses of secretomes and transcripts revealed that arabinose induced the secretion of xylanases by C. thermophilum, which was obviously different from other common filamentous fungi. MCC could efficiently induce the specific secretion of LPMO2s, possibly because the insert in loop3 on the substrate-binding surface of LPMO2s strengthened its binding capacity to cellulose. LPMO2s, cellobio hydrolases (CBHs) and cellobiose dehydrogenases (CDHs) were cosecreted, forming an efficient cellulose degradation system of oxidases and hydrolases under thermophilic conditions. The specific expression of LPMO2s and cosecretion of hydrolases and oxidases by the thermophilic fungus C. thermophilum play an important role in cellulose degradation. This insight increases our understanding of the cellulose degradation under thermophilic conditions and may inspire the design of the optimal enzyme cocktails for more efficient exploration of biomass resources in industrial applications.


Constructing Robust Covalent Organic Frameworks via Multicomponent Reactions.
Methodology development of robust linkages is fundamentally important for the synthesis and application of covalent organic frameworks (COFs). We report herein a new strategy based on multicomponent reactions (MCRs) to construct ultrastable COFs. With the one-pot formation of five covalent bonds in each cyclic joint, a series of imidazole-linked COFs were robustly constructed through the Debus-Radziszewski MCR from three easily available components. By reaching a higher level of complexity and precision in covalent assembly, this research explores a new direction in integrating sophisticated reversible/irreversible reactions to construct crystalline porous frameworks.


Na(+)/H(+) exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo.
Acute metabolic acidosis and alkalosis cause a series of homeostatic adaptive responses in the kidney and other epithelia. We hypothesized that acid/base disturbances might affect the expression of Na(+)/H(+) exchanger (NHE) isoforms in salivary glands and determined the expression and cellular distribution of NHE3 and NHE4 in rat submandibular glands of controls and after imposed acute or chronic metabolic acidosis or alkalosis in vivo. Reverse transcription/polymerase chain reaction, in situ hybridization, and immunohistochemistry were applied by using specific primers, antisense probes, and antibodies, respectively. The results showed NHE3 and NHE4 transcript expression and protein abundance in rat submandibular gland. NHE3 was apically localized in duct cells, whereas NHE4 was found basolaterally distributed in acinar and duct cells. Acute acidosis and alkalosis and chronic acidosis had no effect on NHE3 and NHE4 expression and localization. In contrast, chronic metabolic alkalosis significantly decreased the number of apically stained NHE3 duct cells but had no effect on NHE3 mRNA expression. The results demonstrate, for the first time, the presence of NHE4 protein in salivary glands. The data also indicate the distinct regulation and adaptive changes of different isoforms of the same transporter in rat submandibular gland as a response to acid/base disturbances.


CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With Rheumatoid Arthritis and Sensitive to Tumor Necrosis Factor Blockade.
Memory stem T (Tscm) cells are long-lived, self-renewing T cells that play a relevant role in immunologic memory. This study was undertaken to investigate whether Tscm cells accumulate in rheumatoid arthritis (RA). The polarization and differentiation profiles of circulating T cells were assessed by flow cytometry. Antigen-specific T cells were characterized by staining with major histocompatibility complex class II tetramers. The T cell receptor (TCR) repertoire was analyzed by high-throughput sequencing using an unbiased RNA-based approach in CD4+ T cell subpopulations sorted by fluorescence-activated cell sorting. We analyzed the dynamics of circulating Tscm cells (identified as CD45RA+CD62L+CD95+ T cells) by flow cytometry in 27 RA patients, 16 of whom were also studied during treatment with the anti-tumor necrosis factor (anti-TNF) agent etanercept. Age-matched healthy donors were used as controls. CD4+ Tscm cells were selectively and significantly expanded in RA patients in terms of frequency and absolute numbers, and significantly contracted upon anti-TNF treatment. Expanded CD4+ Tscm cells displayed a prevalent Th17 phenotype and a skewed TCR repertoire in RA patients, with the 10 most abundant clones representing up to 53.7% of the detected sequences. CD4+ lymphocytes specific for a citrullinated vimentin (Cit-vimentin) epitope were expanded in RA patients with active disease. Tscm cells accounted for a large fraction of Cit-vimentin-specific CD4+ cells. Our results indicate that Tscm cells, including expanded clones specific for relevant autoantigens, accumulate in RA patients not exposed to biologic agents, and might be involved in the natural history of the disease. Further analysis of Tscm cell dynamics in autoimmune disorders may have implications for the design and efficacy assessment of innovative therapies.


Career transitions:planning for alternative futures.
Transition to retirement is a necessary step for all physicians because of the physical and emotional changes that occur with the aging process, the physician's ethical responsibilities to patients, and at times, because there is a desire to pursue different goals. It is important to begin to plan for this transition early in one's career so that some planning for postretirement vocation and avocation can be made and financial concerns can be addressed. A recent ACOG survey of 1000 Fellows ages 40-60 demonstrates that this planning is not occurring universally and the assistance of Fellows in preparation for this transition is now becoming an ACOG initiative.


Dominance and context effects on activation of alternative homophone meanings.
Two eyetracking-during-listening experiments showed frequency and context effects on fixation probability for pictures representing multiple meanings of homophones. Participants heard either an imperative sentence instructing them to look at a homophone referent (Experiment 1) or a declarative sentence that was either neutral or biased toward the homophone's subordinate meaning (Experiment 2). At homophone onset in both experiments, the participants viewed four pictures: (1) a referent of one homophone meaning, (2) a shape competitor for a nonpictured homophone meaning, and (3) two unrelated filler objects. In Experiment 1, meaning dominance affected looks to both the homophone referent and the shape competitor. In Experiment 2, as compared with neutral contexts, subordinate-biased contexts lowered the fixation probability for shape competitors of dominant meanings, but shape competitors still attracted more looks than would be expected by chance. We discuss the consistencies and discrepancies of these findings with the selective access and reordered access theories of lexical ambiguity resolution.


Calculating the Number of Pregnant Women Receiving Standardized Services for PMTCT of HIV in Liangshan Prefecture, Based on the Equivalent Method.
To calculate the number of pregnant women who receive standardized prevention of mother-to-child transmission (PMTCT) services for HIV annually. HIV-positive pregnant women in six counties of Liangshan Prefecture in 2017 were selected as study subjects. The entire process, from when the subjects first received the PMTCT of HIV services to the end, was divided into four stages, which were further divided into 25 phases. The equivalent coefficient was used to indicate the weight of workload in each phase. Seven experts were invited to score the equivalent coefficient; the number of pregnant women who received standardized services to prevent the transmission of HIV was calculated. A total of 663 HIV-positive pregnant women were registered in six Liangshan Prefecture counties in 2017. This figure was converted into 7,780 person-months devoted to HIV-positive pregnant women, with 260 person-months (3.34%) spent on the first antenatal care, 1,510 person-months (19.41%) during pregnancy, 378 person-months (4.86%) on delivery, and 5,632 person-months (72.39%) on post-partum period. The equivalent coefficient calculation showed that 314 HIV-positive pregnant women received standardized PMTCT services. The number of pregnant women receiving standardized services for the PMTCT of HIV can be calculated accurately using the equivalent method to identify the gap between the level of PMTCT of HIV intervention services needed and the actual workload.


Long-term patency and clinical outcome of the transjugular intrahepatic portosystemic shunt using the expanded polytetrafluoroethylene stent-graft.
Transjugular intrahepatic portosystemic shunt (TIPS) creation is an established treatment option to management the complications of portal hypertension. Recent data on the long-term outcomes of TIPS are scarce. In this single-institution retrospective study, 495 patients underwent TIPS with the Fluency stent-grafts between December 2011 and June 2015 were evaluated. The cumulative rates of TIPS dysfunction, hepatic encephalopathy (HE), survival, and variceal rebleeding were determined using the Kaplan-Meier method. Cox regression analysis was used to assess the parameters on TIPS patency, occurrence of HE and all-cause mortality. Technical success was 98.2%. TIPS-related complications occurred in 67 patients (13.5%) during the index hospital stay. TIPS creation resulted in an immediate decrease in mean portosystemic pressure gradient from 23.4 ± 7.1 mmHg to 7.6 ± 3.5 mmHg. The median follow-up period was 649 days. Primary TIPS patency rates were 93%, and 75.9% at 1 and 3 years, respectively. Previous splenectomy was associated with a higher risk of TPS dysfunction. The cumulative survival rates were 93.4% and 77.2% at 1 and 3 years, respectively. The 1- and 3-year probability of remaining free of variceal bleeding rates were 94.2% and 71.4%, respectively. This retrospective single-center experience with TIPS using the Fluency stent-grafts demonstrates good long-term patency and favorable good clinical results. Previous splenectomy strongly predicts shunt dysfunction.


HSP72 induction by heat stress in human neurons and glial cells in culture.
Expression of 72-kDa heat shock protein (HSP72) induced by heat stress was investigated in cultured neurons and glial cells isolated from fetal human brains using immunoblotting and immunocytochemistry. Under the unstressed condition, a low level of HSP72 expression was observed in astrocytes, microglia, oligodendrocytes, and neurons. Under the heat-stressed condition, an increased expression of HSP72 was observed in all cell types with specific location in the nuclear and cytoplasmic regions. Following heat stress, HSP72 was expressed intensely in more than 50% of astrocytes and microglia during 8-24 h post-recovery, while it was detectable in only 9% of oligodendrocytes and 3% of neurons at 48 h post-recovery. These results indicate that heat stress induces a predominant expression of HSP72 in astrocytes and microglia, and more limited HSP72 expression in oligodendrocytes and neurons in fetal human neural cells in culture. The differential patterns of HSP72 induction in human neural cells by heat stress suggest that cellular mechanisms by which the heat shock response is regulated are different among various cell types in the human central nervous system.


Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells.
In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell-like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4. In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of a neomycin-resistance gene inserted into the endogenous Oct4 (also known as Pou5f1) or Nanog loci. Direct isolation of pluripotent cells from cultured somatic cells is of potential therapeutic interest, but translation to human systems would be hindered by the requirement for transgenic donors in the present iPS isolation protocol. Here we demonstrate that reprogrammed pluripotent cells can be isolated from genetically unmodified somatic donor cells solely based upon morphological criteria.


Influence of Food Intake on 2-D Shear Wave Elastography Assessment of Liver Stiffness in Healthy Subjects.
Transient elastography and Acoustic Radiation Force Impulse imaging are useful non-invasive methods for liver stiffness estimation, although both are influenced by food intake. The aim of the work described here was to identify liver stiffness variation after a standardized meal using 2-D shear wave elastography. Liver stiffness was estimated in 31 apparently healthy subjects, under fasting conditions and after a standardized meal (20, 40, 60, 80, 100 and 120 min after food intake). In most of the cases, liver stiffness values increased between 20 and 40 min after the meal (p < 0.05) and then significantly decreased between 60 and 80 min (p < 0.05). At 120 min after food intake, liver stiffness values were significantly lower compared with liver stiffness values under fasting conditions (p < 0.05). Gender, but not body mass index, had an important role in liver stiffness variation after food intake (p < 0.01). In conclusion, to avoid the influence of food intake on liver stiffness estimation, 2-D shear wave elastography should be performed only under fasting conditions.


[Uterine artery embolization for myomas treatment].
Myoma treatment by uterine artery embolisation (UAE) using non-spherical PVA particles or calibrated tris-acryl microspheres>500μm is effective in more than 90 % of cases in the short-term. In the long-term, menorrhagia, bulk-related symptoms and pelvic pain are significantly improved or eliminated in 75 % of cases at 5 to 7 years. At 6 months, uterine volume reduction and larger myoma volume reduction varies between 30 to 60 % and 50 to 80 % respectively. During hospital stay the complication rate is very low, less than 3 % mostly urinary infection and pain. Secondary hysterectomy for complication is less than 2 % at 3 months. Definitive amenorrhea is reported in less than 5 % of cases in women of more than 45-year of age. No significant impact of embolization on hormonal function has been reported in women less than 45 years with normal baseline function. UAE is not indicated for submucous myomas. Randomized studies comparing embolization to hysterectomy demonstrate that reinterventions are more frequently performed after embolization. Secondary hysterectomy is performed in 13 to 24 % of cases at 2 years and in up to 28 % of cases at 5 years. Hospital stay, duration of recovery and time off work are shorter after embolization compared to hysterectomy. Embolization is cheaper than hysterectomy at 12 and 24 months even taking into consideration the additional costs of imaging and reinterventions. UAE is a good alternative treatment in women with unique myoma of less than 10cm and multiple myomas around 15cm. This treatment should be proposed to women each time possible. Randomized studies comparing embolization to myomectomy demonstrate that in the short and mid-term there is no difference in terms of control of menorrhagia and bulk-related symptoms. Uterine volume reduction and quality of life were not different at 6 months. Periprocedural and 30-day complication rates are not different. At 6 months, the rate of complications is higher after myomectomy. Reinterventions are more frequent after embolization compared to myomectomy. Hospital stay, duration of recovery and time off work are shorter after embolization compared to myomectomy. UAE is less aggressive than myomectomy and should be proposed as a conservative alternative treatment. Embolization should be considered with caution in pregnancy-seeking women since there is still a lack of good quality data available in the specific group of patients. FSH level is more frequently elevated after embolization compared to myomectomy. Pregnancy rate and term pregnancy rate are higher after myomectomy compared to embolization. Spontaneous abortion is more frequent after embolization than after myomectomy. At this time, UAE is not indicated excepted in studies or in specific cases when the woman want a pregnancy. Embolization performed before myomectomy (preoperative or combined procedures) can be discussed for an individual patient but there is not enough data to support its routine use.


Reversibility and irreversibility of adsorption of surfactants and proteins at liquid interfaces.
It is shown experimentally that the desorption of sodium decyl sulphate from the liquid/air interface is purely diffusion controlled, while the desorption of higher surface active surfactants such as the non-ionic surfactants Triton X-100 and tridecyl dimethyl phosphine oxide obeys a mixed mechanism. The desorption kinetics of beta-lactoglobulin (BLG) and beta-casein is, however, determined by a barrier mechanism. From the analysis of the BLG and beta-casein desorption kinetics at different temperatures the activation energy of desorption is calculated. The values obtained are rather close to the free energy of adsorption. The theoretical model of desorption kinetics predicts that these two energetic parameters are similar if the adsorption activation energy is low. This explains why substances with a higher adsorption activity have a lower desorption rate. Adsorption kinetics studies for beta-casein with and without forced convection show the same equilibrium surface tension values. This leads to the conclusion that the protein adsorption at liquid interfaces is thermodynamically reversible, although the slow desorption kinetics would allow to assume it to be an irreversible process.


Elevation of gamma-glutamyltransferase activity in 293 HEK cells constitutively expressing antisense glutaminase mRNA.
Previous studies have shown that the use of dynamic nutrient feeding to maintain glutamine at low levels in fed-batch cultures reduced the overflow of glutamine metabolism. This strategy resulted in the shift of metabolism towards an energetically more efficient state signified by reduced lactate and ammonia production and thus achieving a higher cell density for enhanced productivity. In an effort to mimic the metabolic changes effected by this fed-batch strategy at the molecular level, 293 HEK cells were engineered via stable transfection with an antisense fragment of the rat phosphate-dependent glutaminase (PDG) gene. PDG is localized in the mitochondria and catalyzes the deamination of glutamine to glutamate with the release of ammonia. Stable single cell clones were isolated from the transfected populations. Characterization of these transfectants revealed indications of an altered glutamine metabolism affected by the antisense strategy. Contrary to our expectations, glutamine consumption and ammonia production in the antisense cells did not deviate significantly from that of untransfected cells. Glutamate was also observed to accumulate to high level extracellularly, as opposed to a consumption pattern normally observed in non-transfected cells. Subsequent analyses show that gamma-glutamyltransferase (gamma-GT) may be a significant pathway that resulted in the formation of glutamate and ammonia from glutamine catabolism extracellularly. gamma-GT has been widely investigated in renal glutamine metabolism, but has rarely been implicated in cultured cell metabolism. This study highlights the importance of this alternative glutamine metabolism pathway in cell culture.


Pathogenesis, current treatments and future directions for idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) of unknown origin characterized by epithelial cell dysfunctions, accumulation of fibroblasts and myofibroblasts and relentless deposition of extracellular matrix (ECM). Improved diagnostic accuracy and better trial design have provided important insights from recent clinical trials. Perhaps the most important insight was the realization that 'standard therapy' was actually harmful! This review summarizes the current understanding of the cell types that are altered in IPF and the pathogenic mechanisms that have been identified. It also reviews recent clinical trial results and interpretations. Finally, we highlight attractive biologic targets and therapies in development with recommendations for future therapeutic avenues.


Residual disease detection using targeted parallel sequencing predicts relapse in cytogenetically normal acute myeloid leukemia.
Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty-seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1-5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0-3). The most frequent noncleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non-DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; P = .013) and with a shorter relapse-free survival (333 days vs. not reached; log-rank P = .0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML.


Neural substrates of theory of mind in adults with autism spectrum disorder: An fMRI study of the social animation task.
Although the neural mechanisms of the theory of mind (ToM) in children with autism spectrum disorder (ASD) through fMRI using the social animation task have been investigated, little is known in adults with ASD. Therefore, the present study aimed to explore the neural substrates of ToM in adults with ASD. Moreover, we aimed to elucidate the relationship between brain activation and behavior of social interaction in adults with ASD. Twenty-four healthy controls and 24 adults with the clinical diagnosis of ASD were recruited. Participants were asked to complete the social animation task in functional magnetic resonance imaging. The imaging analyses of within (whole brain analysis) and between (5 regions of interest) group comparisons were conducted to explore the process of ToM. The correlation analyses were further conducted to explore the relationship between neural activations associated with ToM and social interaction abilities assessed by ADI-R. The ASD group showed greater activation in the left precuneus and right superior temporal gyrus (STG) than the control group. For correlation analyses, greater right STG activation was positively correlated with autistic symptoms assessed by the ADI-R in the ASD group. ASD adults might spend a lot of effort on identification processing, thereby influencing social communication skills. Also, the neural deficits of ToM in ASD adults might be associated with their social interaction difficulties.


Clinical Background of Patients with Sperm in Their Urinary Sediment.
The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice. The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples. We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged ≥20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines. In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%). Multivariate analysis demonstrated that younger age (<65) (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.32-2.21), the total number of examinations (≥4) (OR: 1.46, 95%CI: 1.11-1.92), diabetes (OR: 1.72, 95%CI: 1.31-2.25), a history of pelvic surgery for colon cancer (OR: 4.89, 95%CI: 2.38-10.02), alpha-1 blocker use (OR: 1.55, 95%CI: 1.16-2.08), a history of trans-urethral resection of the prostate (OR: 2.77, 95%CI: 1.46-5.13), and selective serotonin reuptake inhibitor use (OR: 2.12, 95%CI: 1.07-4.19) were independent predictors of the presence of at least one sperm in urinary sediment. There is considerable overlap between the factors associated with the presence of at least one sperm in urinary sediment and those that are strongly associated with ejaculatory disorders.


Approaches to the superior calix: renal displacement technique and review of options.
A new percutaneous approach to the superior calix has been implemented with reduced morbidity. To avoid intercostal or retrograde punctures or triangulation methods an Amplatz sheath passed through a central or lower pole calix can be pushed caudally while descent of the kidney is viewed fluoroscopically. An 18-gauge TLA needle passed through the initial skin puncture then is used to form a Y with the original tract. This method has been successful in 21 of 25 cases without complications. The only failures occurred in patients with immobile kidneys secondary to a previous operation.


The activities of alanine aminopeptidase, leucine aminopeptidase, proline dipeptidase and prolyl dipeptidase in the mucosa of the small intestine. Investigations on normal children and patients with the malabsorption syndrome.
Alanine aminopeptidase (EC 220.127.116.11), leucine aminopeptidase (EC 184.108.40.206), proline dipeptidase (EC 184.108.40.206), and prolyl dipeptidase (EC 18.104.22.168) have been investigated in small intestinal mucosa homogenates of normal children and children suffering from different degrees of villous damage. The activities of proline dipeptidase and prolyl dipeptidase could be shown to be significantly decreased in cases of subtotal and total villous atrophy, whereas the activities of alanine aminopeptidase and leucine aminopeptidase were not influenced. The results are discussed in view of the subcellular distribution of these enzymes.


Erratum: Sustained Post-Developmental T-Bet Expression Is Critical for the Maintenance of Type One Innate Lymphoid Cells In Vivo.
[This corrects the article DOI: 10.3389/fimmu.2021.760198.].


Thrombolytic therapy for venous thromboembolism. Complications and contraindications.
There is renewed interest in the treatment of acute deep vein thrombosis and acute pulmonary embolism with thromboembolytic therapy because of the demonstrated mortality reduction in patients with acute myocardial of the demonstrated mortality reduction in patients with acute myocardial infarction and because of the development of newer, fibrin-specific drugs. Bleeding is the major complication of thrombolytic therapy. This article addresses the benefits and risks of using thrombolytic therapy in patients with acute deep vein thrombosis or acute pulmonary embolism.


Aβ potentiates inflammatory activation of glial cells induced by scavenger receptor ligands and inflammatory mediators in culture.
Alzheimer disease (AD) is a neurodegenerative disorder characterized by the accumulation of β amyloid (Aβ) aggregates. Aβ induces the inflammatory activation of glia, inducing secretion of Interleukin 1β (IL1β), nitric oxide (NO) and superoxide radicals. The specific receptor responsible for the induction of inflammatory activation by Aβ, is still an open question. We propose that scavenger receptors (SR) participate in the activation of glia by Aβ. We assessed production of NO, synthesis of IL1β and activation of ERK, JNK and NF-κB signaling pathways by Western blot, in primary rat glial cultures exposed to SR ligands (fucoidan and Poly I), LPS + IFNγ (LI), and Aβ. Poly I but not fucoidan nor fibrillar Aβ increased threefold NO production by astrocytes in a time-dependent manner. Fucoidan and Poly I increased 5.5- and 3.5-fold NO production by microglia, and co-stimulation with Aβ increased an additional 60% NO induced by SR ligands. Potentiation by Aβ was observed later for astrocytes than for microglia. In astrocytes, co-stimulation with Aβ potentiated ERK and JNK activation in response to Fucoidan and Poly I, whereas it reduced induction of JNK activation by LI and left unaffected NF-κB activation induced by LI. Levels of pro-IL1β in astrocytes increased with Aβ, SR ligands and LI, and were potentiated by co-stimulation with Aβ. Our results suggest that SRs play a role on inflammatory activation, inducing production of NO and IL1β, and show potentiation by Aβ. Potentiation of the inflammatory response of Aβ could be meaningful for the activation of glia observed in AD.


Ultrasonic tissue characterization of prostate biopsy tissues by ultrasound speed microscope.
Ultrasound speed microscope was developed for quantitative measurement of ultrasonic parameters of soft tissues. The system can measure the ultrasonic attenuation and sound speed in the tissue using fast Fourier transform of a single pulsed wave instead of burst waves used in conventional acoustic microscopy. Prostate biopsy tissues were formalin-fixed and sectioned approximately 5-6 μm in thickness. They were mounted on glass slides without cover slips. The ultrasonic transducer was mechanically scanned over the specimen. Attenuation was 1.42 ± 0.08 dB/mm and the sound speed was 1584 ± 12 m/s in prostatic cancer while both values were 1.86 ± 0.14 dB/mm and 1614 ± 30 m/s in normal prostate. The basic measurements of ultrasonic properties would help understanding the interpretation of clinical echography in diagnosis of prostate cancer.


[Correlation between gait speed and muscular strength with balance for reducing falls among elderly].
Evidence of the benefit on propioceptive neuromuscular facilitation for reducing falls in older people does not exist. The aim of this study is to evaluate the effects of propioceptive facilitation over falls and biomechanical variables, in comparison to standard treatment and control groups. Series cases comparative for the 24 participants were recruited and randomnly assigned to 3 groups. Group 1, propioceptive neuromuscular facilitation, group 2, standard treatment, and 3 control. Falls and biomechanic variables were measured before and after. Chi(2) was used for falls and multiple regression for biomechanical variables, Participants had similar falls in previous year. Women had higher falls in a relation 7:1 women-men. After intervention, there was no difference between 3 groups. A correlation exista between muscular strength and gait speed with one foot position time r(2) = 0.67, p = 0.02. Improving 1kilogram-force of muscular strength of pelvic limb and 0.1meter/second in gait speed, balance (unipodal position time) increases balance by 11.3%. After 3 months of intervention group 2 got 7.9kg-force and 0.26m/s of profit, while group 1 had 4.1kg-force and 0.15m/s and control group 2.4kg-force and 0.1m/s.


Alpha lipoic acid ameliorates THIM-induced prefrontal cell loss and abnormal enzymatically contents in the developing rat.
Thimerosal (THIM) is a common preservative used in many pharmaceutical drugs, vaccines, cosmetics and many other products. Today, it was somewhat clear that Thimerosal (THIM) is a neurotoxicant preservative. We aimed to use of a suitable agent for preventing of THIM side effects on brain. Therefore, in this research, the protective effects of Alpha Lipoic Acid (ALA), against THIM-induced brain cell loss, changes in neuroimmune cell and enzymatically contents were examined. Male Wistar rats (n = 60) were randomly distributed into five groups: 1- THIM group; this group received THIM at dose of 300 μg /kg on 7, 9, 11, 15 days after birth 2- ALA group; received ALA (20 mg/kg) in the same order. 3- THIM & ALA group; this group received ALA in the same dose, 30 min before THIM administration.4& 5; Saline and ALA vehicle groups were also included. At 56th postnatal day, samples of the prefrontal cortex were collected and prepared for stereological, immune-histochemical, and enzymatic evaluations. The result showed that ALA, prevents the adverse effects of THIM on brain cell loss, abnormal changes in neuroimmune cells (p < 0.05), prefrontal cortex volume (p < 0.05), and the glutathione content of prefrontal cortex (p < 0.05). In conclusion, neonatal exposure to THIM can induce abnormal alterations in neuroimmune cells and brain cell density as well as prefrontal cortex volume & glutathione content, and ALA can ameliorate these abnormalities.


To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma.
Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.


Primary hyperparathyroidism presenting as a "peripheral" giant cell granuloma.
A case of primary hyperparathyroidism is reported in which the initial presentation was an intraoral lesion clinically resembling a peripheral giant cell granuloma. A brief review of hyperparathyroidism is included. Of interest is the fact that most cases of hyperparathyroidism today are found in asymptomatic patients in whom the disease is discovered on routine blood chemistry analysis.


Proximal femoral reconstruction for failed internal fixation of a bisphosphonate-related femur fracture.
We present a case of a bisphosphonate-related femur fracture in an elderly woman, who failed treatment with both cephalomedullary nail and proximal femoral locking plate, leading to successful treatment with total hip arthroplasty. Hardware failure should be included in the differential of patients with previous internal fixation of bisphosphonate-related femur fracture that present with hip or groin pain. Arthroplasty can be an acceptable salvage option in an active elderly patient with a bisphosphonate-related femur fracture.


A medical geology study of an arsenic-contaminated area in Kouhsorkh, NE Iran.
High concentrations of arsenic were determined in sediments from the Kouhsorkh area, Khorasan province, NE Iran. The main rock formations in the area consist of Tertiary volcanic rocks as Tuffaceous sandstone, polymictic conglomerate and andesite. Furthermore, some As-Sb-Au mineralization occurred in this area. Concentrations of arsenic in sediments were determined to range between 4.2 and 268.2 ppm, exceeding US EPA (2004) limits. It seems that young volcanic activity is one of the most important factors for arsenic contamination in this area. The first stage of this medical geology study was done at 2 villages in the Kouhsorkh area in which the arsenic concentration in water is high. People in this residential area suffer from skin diseases including hyperpigmentation, hypopigmentation, keratosis on head, hands, and feet. The 24-h urine specimens were tested for arsenic, the level of total arsenic in urine were determined to range between 13.66 and 75.92 μg/l day, exceeding permissible limits from 5 to 40 μg/day. More systematic studies are needed to determine the link between As exposure and its related diseases.


Color Doppler dynamic tissue perfusion measurement: a novel tool in the assessment of renal parenchymal perfusion in children with vesicoureteral reflux.
Vesicoureteral reflux (VUR) occurs in 20-50% of children suffering from recurrent urinary tract infections (UTIs) and is associated with an increased risk of renal scarring and impaired renal function. Early detection of renal perfusion deterioration would allow for the implementation of more aggressive treatment and potentially prevent further damage to the renal parenchyma. The aim of the study was to assess renal parenchymal perfusions in children with recurrent UTIs with and without coexisting VUR, and compare the findings with the results of healthy patients. Color Doppler sonographic dynamic renal parenchymal perfusion measurements were performed with PixelFlux (Chameleon-Software, Germany) software in 77 children with recurrent UTIs and coexisting VUR and in 30 children with UTIs without VUR. The findings were compared with the results of 53 healthy children. Cortical parenchymal perfusion of children suffering from UTIs and VUR was significantly reduced when compared to the control group. Statistically significant differences (p < 0.05) were found in all perfusion parameters (i.e. mean velocity (v mix ), mean perfused area (A mix ), mean perfusion intensity (I mix ), tissue pulsatility index (TPI), and tissue resistance index (TRI)) between the control group and children suffering from UTIs and VUR, particularly VUR grades III and IV. There were no significant differences between the UTI group and the control group. No differences were found between the controls and VUR grade II. Renal parenchymal perfusion decreases significantly with higher grades of VUR.


Respiratory nursing interventions following tracheostomy in acute traumatic cervical spinal cord injury.
Tracheostomy is frequently performed in severe cervical spinal cord injury (SCI) patients with the pulmonary dysfunction. A series of respiratory nursing interventions are required to plan tracheostomy removal. Tracheostomy was performed in 29 patients after acute traumatic cervical SCI. A series of respiratory nursing interventions were introduced in these patients after closed tracheostomy and decannulation, including closed tracheostomy tube training, manually assisted cough. Chacheostomy was successfully removed in 21 patients after the respiratory nursing interventions. In contrast, eight patients died from associated injuries. The average time from tracheostomy to decannulation was 40 days (14-104 days), the average time from closed tracheostomy to decannulation was 18.80 ± 13.50 days. Second tracheostomy was performed in one patient after 29 days' removal due to pulmonary infection. One patient presented with delayed incision healing for 29 days. Closed tracheostomy tube training and manually assisted cough are key factors for tracheostomy removal, although intensive nursing are also needed. The time from tracheostomy to decannulation and from closed tracheostomy to decannulation is increased in case of "late" (>24 h) tracheostomy and longer mechanical ventilation.


Metastatic epithelioid angiosarcoma to the mandible: report of a case and review of the literature.
Angiosarcoma and its epithelioid variant are vascular malignancies that rarely affect the facial skeleton. Epithelioid angiosarcoma resembles carcinoma and can be difficult to diagnose. A case is presented of metastatic epithelioid angiosarcoma to the mandible from an angiosarcomatoid portion of renal carcinoma. The diagnostic challenge is outlined and the literature is reviewed.


Clinical findings and prognostic factors for mortality in hospitalized dogs with leishmaniosis: aretrospective study.
This retrospective study evaluated factors responsible for mortality of dogs hospitalized for Canine Leishmaniosis. Medical records of 31 dogs with leishmaniosis from a Portuguese Veterinary Teaching Hospital were examined between August 2018 and January 2022. Females (n = 18) and pure breed dogs (n = 27) were overrepresented, with higher frequency of Labrador Retriever (n = 4). Median age was 7 years (interquartile range=7). Most had historical findings of lethargy (n = 26) and the commonest clinicopathological abnormality was hypoalbuminemia (n = 26). Eleven dogs were classified as LeishVet stage II, 10 stage III and 10 stage IV. Fourteen dogs (45.2%) died or were euthanized, with azotemia, leukocytosis, stage IV, absence of diagnosis before hospitalization and lack of leishmaniosis specific treatment during hospitalization contributing to mortality. Absence of hypoalbuminemia and stages II/III increased survival. Mean hospitalization length prior to discharge was 5.41days ( ± 1.84) and diarrhea prolonged hospital stay.


Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent.
Encainide is a newly developed antiarrhythmic agent. With the use of intracardiac electrophysiologic techniques, its effects on the cardiac conduction system were examined in 10 patients with coronary artery disease. Five patients received 0.6 and five received 0.9 mg/kg body weight of encainide intravenously over 15 minutes. Plasma concentration, heart rate, blood pressure and conduction intervals (A-H, H-V, QRS and Q-T) were measured before, during and after encainide infusion. In addition, sinus nodal recovery time, Wenckebach cycle length, and atrial, atrioventricular (A-V) nodal and right ventricular refractory periods were measured before and after encainide infusion. The average peak plasma concentration was 0.49 +/- 0.35 microgram/ml (mean +/- standard error of the mean). Encainide significantly prologned H-V and QRS intervals in all patients by an average of 31 +/- 7 and 18 +/- 9 percent (standard deviation) (P less than 0.001), respectively. A minimal increase in the Q-T interval was also observed after encainide infusion (2 +/- 9 percent, P less than 0.01), but no significant changes were noted in heart rate, blood pressure, A-H interval, corrected sinus noal recovery time, Wenckebach cycle length or refractory periods of the atrium, A-V node or right ventricle. It is concluded that encainide significantly prolongs conduction in the His-Purkinje system without affecting conduction or refractoriness of other parts of the cardiac conduction system in man.


3-(4-Bromo-phenyl-sulfin-yl)-5-chloro-2,7-dimethyl-1-benzo-furan.
In the title compound, C16H12BrClO2S, the 4-bromo-phenyl ring makes a dihedral angle of 88.84 (5)° with the mean plane [r.m.s. deviation = 0.009 (1) Å] of the benzo-furan fragment. In the crystal, mol-ecules are linked by weak C-H⋯O and C-S⋯π [3.386 (2) Å] inter-actions, forming a chain perpendicular to the bc plane.


Reproducibility of a commercially available subgingival plaque sampling strategy and analysis strategy with oligonucleotide probes.
The aim was to evaluate the intra-test agreement of pooled samples from the deepest periodontal pocket of each quadrant with a commercially available test kit based on hybridization of 16S rRNA. Plaque samples of 50 patients with generalized severe chronic periodontitis before therapy were pooled in two separate vials in order to detect and compare counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Cohen's κ and interclass correlation coefficients were calculated to judge intra-test agreement. Cohen's κ for detection and counts of Tannerella forsythia and Treponema denticola showed a perfect agreement. Porphyromonas ginigivalis was identified in both tests with a substantial agreement, whereas detection of Aggregatibacter actinomycetemcomitans varied in eight patients resulting in a good agreement. Possible confounding factors could not be identified statistically. Test results of the commercial 16S rRNA test are perfectly reproducible regarding detection of red complex pathogens. Intra-test agreement concerning detection of Aggregatibacter actinomycetemcomitans was less favorable. Detection of certain periodontal pathogens may alter the treatment and lead to prescription of antibiotics parallel to mechanical debridement. It is quite important not to use antibiotics excessively. Thus, the basis for decision-making in favor of antibiotics should be solid.


Visualizing Mitochondrial Ribosomal RNA and Mitochondrial Protein Synthesis in Human Cell Lines.
Human mitochondria contain their own DNA (mtDNA) that encodes 13 proteins all of which are core subunits of oxidative phosphorylation (OXPHOS) complexes. To form functional complexes, these 13 components need to be correctly assembled with approximately 70 nuclear-encoded subunits that are imported following synthesis in the cytosol. How this complicated coordinated translation and assembly is choreographed is still not clear. Methods are being developed to determine whether all members of a particular complex are translated in close proximity, whether protein synthesis is clustered in submitochondrial factories, whether these align with incoming polypeptides, and if there is evidence for co-translational translation that is regulated and limited by the interaction of the incoming proteins with synthesis of their mtDNA-encoded partners. Two methods are described in this chapter to visualize the distribution of mitochondrial ribosomal RNAs in conjunction with newly synthesized mitochondrial proteins. The first combines RNA Fluorescent In Situ Hybridization (FISH) and super-resolution immunocytochemistry to pinpoint mitochondrial ribosomal RNA. The second localizes nascent translation within the mitochondrial network through non-canonical amino acid labeling, click chemistry and fluorescent microscopy.