Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception.
Approaches to hormonal male contraception are based on injectable testosterone esters alone or in combination with gestagens or GnRH analogs but the short half-life of clinically used testosterone esters have long hindered further development. This study was designed to prove the efficacy of the long-acting testosterone undecanoate ester (TU) alone or in combination with oral levonorgestrel (LNG) in a phase II clinical trial. Twenty-eight healthy men were randomized to receive injections of 1000 mg TU every 6 weeks in combination with daily oral LNG (250 microg) or daily oral placebo treatment over a period of 24 weeks, followed by a control period of 28 weeks. During the course of the study semen analysis, reproductive hormone analysis, analysis of clinical chemistry and lipid parameters, well-being and sexual function, sonography of scrotal contents and prostate were performed. Marked suppression of gonadotrophins in both treatment groups resulted in azoospermia in 8/14 and 7/14 volunteers and severe oligozoospermia (< 3 x 1012/l) in 4/14 and 7/14 in the placebo and gestagen treated groups, respectively. Time to induction of azoospermia (mean +/- SEM) was not significantly different between the placebo (week 19.5 +/- 2.2) and LNG groups (week 15.4 +/- 2.2). During the whole treatment period mean testosterone serum concentrations remained within normal limits. Although not significant, it was evident that volunteers who became azoospermic had a better suppression of gonadotrophins and lower SHBG levels during treatment compared to non-azoospermic volunteers. Despite better gonadotrophin suppression in the LNG group no significant differences compared to placebo could be observed in the extent and kinetics of suppression of spermatogenesis, thus not demonstrating a major beneficial effect of LNG in the combination with injectable TU. Treatment led in both groups to a decrease of HDL and Lp(a) which was more pronounced in the LNG group (P > 0.05). Treatment with 1000 mg testosterone undecanoate injected at 6 weekly intervals or in combination with levonorgestrel showed suppression of spermatogenesis comparable to weekly injections of 200 mg testosterone enanthate. Because of its long half-life and in the absence of severe side-effects, testosterone undecanoate can be considered as first choice testosterone ester in further studies of hormonal male contraception.


miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.
miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.


mRNA surveillance mitigates genetic dominance in Caenorhabditis elegans.
Nonsense mutant mRNAs are unstable in all eucaryotes tested, a phenomenon termed nonsense-mediated mRNA decay (NMD) or mRNA surveillance. Functions of the seven smg genes are required for mRNA surveillance in Caenorhabditis elegans. In Smg(+) genetic backgrounds, nonsense-mutant mRNAs are unstable, while in Smg(-) backgrounds such mRNAs are stable. Previous work has demonstrated that the elevated level of nonsense-mutant mRNAs in Smg(-) animals can influence the phenotypic effects of heterozygous nonsense mutations. Certain nonsense alleles of a muscle myosin heavy chain gene are recessive in Smg(+) backgrounds but strongly dominant in Smg(-) backgrounds. Such alleles probably express disruptive myosin polypeptide fragments whose abundance is elevated in smg mutants due to elevation of mRNA levels. We report here that mutations in a variety of C. elegans genes are strongly dominant in Smg(-), but recessive or only weakly dominant in Smg(+) backgrounds. We isolated 32 dominant visible mutations in a Smg(-) genetic background and tested whether their dominance requires a functional NMD system. The dominance of 21 of these mutations is influenced by NMD. We demonstrate, furthermore, that in the case of myosin, the dominant-negative effects of nonsense alleles are likely to be due to expression of N-terminal nonsense-fragment polypeptides, not to mistranslation of the nonsense codons. mRNA surveillance, therefore, may mitigate potentially deleterious effects of many heterozygous germline and somatic nonsense or frame-shift mutations. We also provide evidence that smg-6, a gene previously identified as being required for NMD, performs essential function(s) in addition to its role in NMD.


A comparison of volumetric and circumferential measures of penile erection.
Objective measurements of sexual arousal in men most commonly involve monitoring changes in penile size. Although changes in circumference are most often used, volumetric changes have been reported to be more sensitive and thus more effective. Six men volunteered to observe an erotic videotape while circumferential and volumetric changes of their penises were recorded. The two measures were significantly correlated (r = .68) but the volumetric device was more difficult to use, displayed considerably more artifacts, and was not more sensitive than a mercury-in-rubber strain gauge.


The different faces of the NLRP3 inflammasome in cutaneous Leishmaniasis: A review.
Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by Protozoa of the genus Leishmania. Clinical manifestations of this disease are the result of a complex interplay of diverse factors, including the genetic background and the immune status of the host. Understanding the impact of these factors on the CL pathology may provide new targets to manage the infection and improve clinical outcome. The NLRP3 inflammasome, an innate immune complex of several cell types, seems to be involved in the CL physiopathology. Current studies of its role show contradictory effects of this complex on the evolution of Leishmania infection in mice and humans. In this review, we discuss the data regarding different roles of the NLRP3 inflammasome in murine and human CL.


[Early diagnosis of pancreatic cancer is essential to improving the effect of treatment].
To explore the relation between tumor TNM of pancreatic cancer and treatment, and to summarize the experience in diagnosis and treatment of pancreatic cancer. The data on 321 patients with pancreatic cancer treated at our hospital between January 1990 and December 2000 were reviewed retrospectively. Radical resection and survival for various TNM stages were analyzed. The rates of radical resection for stage I, stage II, stage III, stage IVA, and stage IVB were 100%, 100%, 82.6%, 12.3% and 2.1% respectively. The 1-, 3- and 5-year survivals of stage I, II were 73.3%, 40.0% and 30.0% respectively, and higher than those of other groups. The patients with pancreatic cancer diagnosed early can undergo radical resection. The elevation of early diagnosis rate is significant for the improvement of survival.


Disparities in localized malignant lung cancer surgical treatment: A population-based cancer registry analysis.
Lung cancer (LC) continues to be the leading cause of cancer deaths in the United States. Surgical treatment has proven to offer a favorable prognosis and a better 5-year relative survival for patients with early or localized tumors. This novel study investigates the factors associated with the odds of receiving surgical treatment for localized malignant LC in Tennessee. Population-based data of 9679 localized malignant LC patients from the Tennessee Cancer Registry (2005-2015) were utilized to examine the factors associated with receiving surgical treatment for localized malignant LC. Bivariate and multivariate logistic regression analyses, cross-tabulation, and Chi-Square ( χ 2 ) tests were conducted to assess these factors. Patients with localized malignant LC who initiated treatment after 2.7 weeks were 46% less likely to receive surgery (adjusted odds ratio [AOR] = 0.54; 95% confidence interval [CI] = 0.50-0.59; p < 0.0001). Females had a greater likelihood (AOR = 1.14; CI = 1.03-1.24) of receiving surgical treatment compared to men. Blacks had lower odds (AOR = 0.76; CI = 0.65-0.98) of receiving surgical treatment compared to Whites. All marital groups had higher odds of receiving surgical treatment compared to those who were single/never married. Patients living in Appalachian county had lower odds of receiving surgical treatment (AOR = 0.65; CI = 0.59-0.71) compared with those in the non-Appalachian county. Patients with private (AOR = 2.09; CI = 1.55-2.820) or public (AOR = 1.42; CI = 1.06-1.91) insurance coverage were more likely to receive surgical treatment compared to self-pay/uninsured patients. Overall, the likelihood of patients receiving surgical treatment for localized malignant LC decreases with age. Disparities exist in the receipt of surgical treatment among patients with localized malignant LC in Tennessee. Health policies should target reducing these disparities to improve the survival of these patients.


Parameters optimization using experimental design for headspace solid phase micro-extraction analysis of short-chain chlorinated paraffins in waters under the European water framework directive.
The water framework directives (WFD 2000/60/EC and 2013/39/EU) force European countries to monitor the quality of their aquatic environment. Among the priority hazardous substances targeted by the WFD, short chain chlorinated paraffins C10-C13 (SCCPs), still represent an analytical challenge, because few laboratories are nowadays able to analyze them. Moreover, an annual average quality standards as low as 0.4μgL(-1) was set for SCCPs in surface water. Therefore, to test for compliance, the implementation of sensitive and reliable analysis method of SCCPs in water are required. The aim of this work was to address this issue by evaluating automated solid phase micro-extraction (SPME) combined on line with gas chromatography-electron capture negative ionization mass spectrometry (GC/ECNI-MS). Fiber polymer, extraction mode, ionic strength, extraction temperature and time were the most significant thermodynamic and kinetic parameters studied. To determine the suitable factors working ranges, the study of the extraction conditions was first carried out by using a classical one factor-at-a-time approach. Then a mixed level factorial 3×2(3) design was performed, in order to give rise to the most influent parameters and to estimate potential interactions effects between them. The most influent factors, i.e. extraction temperature and duration, were optimized by using a second experimental design, in order to maximize the chromatographic response. At the close of the study, a method involving headspace SPME (HS-SPME) coupled to GC/ECNI-MS is proposed. The optimum extraction conditions were sample temperature 90°C, extraction time 80min, with the PDMS 100μm fiber and desorption at 250°C during 2min. Linear response from 0.2ngmL(-1) to 10ngmL(-1) with r(2)=0.99 and limits of detection and quantification, respectively of 4pgmL(-1) and 120pgmL(-1) in MilliQ water, were achieved. The method proved to be applicable in different types of waters and show key advantages, such as simplicity, automation and sensitivity, required for the monitoring programs linked to the WFD.


Referrals and Treatment Completion for Prescription Opioid Admissions: Five Years of National Data.
This study examines sources of referral for prescription opioid admission to substance use disorder treatment facilities and their relative completion success rates using secondary analysis of an existing data set (treatment episode datasets-discharge). Five years of data from public and private treatment facilities were extracted for client discharges with no prior treatment (N=2,909,884). Healthcare professionals account for very few referrals to treatment (<10%). Prescription opioid clients referred into treatment had lower treatment success compared to other substance clients and when referred by healthcare providers had lower success rates (OR=0.72, 95% CI 0.70-0.75) than clients from other referral sources. Fewer treatment referrals for prescription opioid misuse by healthcare providers and lower success rates are significant and timely findings due to the prevalence of prescription opioid misuse. Healthcare providers are well positioned to refer early for prescription opioid misuse and continue support of their patients during treatment.


Correction of instrument- and reagent-based differences in determination of the International Normalized Ratio (INR) for monitoring anticoagulant therapy.
As recommended by the World Health Organization, standardization of prothrombin time assays involves conversion of prothrombin times into International Normalized Ratios (INR). We investigated the effect of two different methods (Nycomed's Thrombotest, and Instrumentation Laboratory's PT-fibrinogen) and three coagulation instruments (Schnitger & Gross, KC-10, and ACL) on calculations of INR. The INR plots showed considerable scatter of individual values around the regression lines when the two different methods were compared. Systematic differences in the outcome of INR calculation were related to the use of the different coagulation instruments. Prothrombin times obtained with the different instruments were linearly correlated. We used the bias of these lines to correct results for both the patients' samples and the reference samples. This correction yielded INR values from the different instruments that agreed well.


Left atrial appendage ligation with single transthoracic port assistance: a study of survival assessment in a porcine model (with videos).
Left atrial appendage (LAA) exclusion is a well-known procedure for the prevention of stroke in high-risk patients with atrial fibrillation and contraindication to long-term oral anticoagulant therapy. To evaluate a natural orifice transluminal endoscopic surgery (NOTES) approach for LAA ligation. In 4 acute and 6 survival pigs, we performed LAA by using a forward-viewing, single-channel gastroscope and an operative thoracoscope with a 3-mm working channel (introduced through an 8-mm single transthoracic port). Animal laboratory. The gastroscope was introduced in the thoracic cavity through an esophageal submucosal tunnel. An end loop introduced through the gastroscope was used to legate the LAA. In the survival experiments, the esophageal mucosa was closed using hemoclips. The time, safety, and feasibility of the procedure were recorded. In the survival experiments, endoscopy and postmortem examination were performed on postoperative day 14. Creation of a submucosal tunnel and esophagotomy were safely performed in all animals without incidents. The mean time for esophagotomy was 17.0 ± 6.3 minutes. Pericardial dissection and LAA ligation were performed in all animals but 1. The mean time for LAA ligation was 34.4 ± 19.1 minutes. No adverse events occurred during the survival period. Endoscopy showed complete esophageal closure. Postmortem examination revealed pleural adhesions on the site of pericardial dissection, and the LAA was fibrotic with the endoloop in place. Animal study. LAA ligation with single transthoracic trocar assistance is feasible and may be an alternative to anticoagulant therapy or to permanent intracardiac implants in patients with atrial fibrillation.


Cross-Bite and Oral-Health-Related Quality of Life (OHRQoL) in Preadolescents Aged 11 to 14 Years Old: A Pilot Case-Control Study.
Malocclusions have a negative impact on oral-health-related quality of life (OHRQoL). Posterior cross-bite is one of the most prevalent malocclusions in the preadolescent population. This study investigated the influence of posterior cross-bites (unilateral or bilateral) on OHRQoL in an 11- to 14-year-old population. A pilot case-control study was carried out at the Dental Clinic of the University of Salamanca between 2021 and 2023. A consecutive sample of 120 preadolescent patients aged 11 to 14 years old was recruited. Three groups were analyzed: a control group (no posterior cross-bite) (n = 40), a group with unilateral posterior cross-bite (n = 40), and a group with bilateral posterior cross-bite (n = 40). To analyze the OHRQoL, the Spanish version of the Child Perception Questionnaire (CPQ-Esp11-14) was used. The mean age of the sample was 12.2 years old (±0.96 years). The group of patients with a bilateral posterior cross-bite was shown to have higher scores in all dimensions of the CPQ-Esp11-14, as well as a higher total score. Sex only influenced the oral symptom dimension of the CPQ-Esp11-14 questionnaire; in this dimension, the girls described a greater impact. Age did not influence OHRQoL. The presence of a posterior cross-bite had a negative impact on OHRQoL in the preadolescent population that was studied.


A case of laparoscopic partial hepatic S7 resection for postoperative liver metastasis of rectal malignant melanoma.
Anorectal malignant melanoma (ARMM) has an extremely poor prognosis, and there is no report of resection of liver metastases so far. We report herein a rare case of postoperative laparoscopic partial hepatic S7 resection for rectal malignant melanoma. A 51-year-old female patient with a diagnosis of an ARMM underwent a laparoscopic rectal amputation. Eleven months later, computed tomography (CT) revealed a 14-mm nodule in liver segment 7 (S7), which was diagnosed as a hepatic recurrence of the ARMM. Because no other recurrences were found, a laparoscopic partial resection of S7 was performed. Pathological analysis found intracellular melanin deposition, and immunostaining was S-100 (+), HMB-45 (+), and SOX-10 (+). Based on these findings, a liver metastasis of malignant melanoma was diagnosed. The patient is alive 7 months after the second surgery and has so far experienced no recurrences. We reported an extremely rare case of a laparoscopic resection of a liver metastasis following surgery for ARMM.


High Temperature Near-Field NanoThermoMechanical Rectification.
Limited performance and reliability of electronic devices at extreme temperatures, intensive electromagnetic fields, and radiation found in space exploration missions (i.e., Venus &Jupiter planetary exploration, and heliophysics missions) and earth-based applications requires the development of alternative computing technologies. In the pursuit of alternative technologies, research efforts have looked into developing thermal memory and logic devices that use heat instead of electricity to perform computations. However, most of the proposed technologies operate at room or cryogenic temperatures, due to their dependence on material's temperature-dependent properties. Here in this research, we show experimentally-for the first time-the use of near-field thermal radiation (NFTR) to achieve thermal rectification at high temperatures, which can be used to build high-temperature thermal diodes for performing logic operations in harsh environments. We achieved rectification through the coupling between NFTR and the size of a micro/nano gap separating two terminals, engineered to be a function of heat flow direction. We fabricated and tested a proof-of-concept NanoThermoMechanical device that has shown a maximum rectification of 10.9% at terminals' temperatures of 375 and 530 K. Experimentally, we operated the microdevice in temperatures as high as about 600 K, demonstrating this technology's suitability to operate at high temperatures.


RR Myelo POINT: A Retrospective Single-Center Study Assessing the Role of Radiotherapy in the Management of Multiple Myeloma and Possible Interactions with Concurrent Systemic Treatment.
Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.


Postoperative local fractionated radiotherapy for resected single brain metastases.
Evaluation of postoperative fractionated local 3D-conformal radiotherapy (3DRT) of the resection cavity in brain metastases. Between 2011 and 2016, 57 patients underwent resection of a single, previously untreated (37/57, 65%) or recurrent (20/57, 35%) brain metastasis (median maximal diameter 3.5 cm [1.1-6.5 cm]) followed by 3DRT. For definition of the gross tumor volume (GTV), the resection cavity was used and for the clinical target volume (CTV), margins of 1.0-1.5 cm were added. Median dose was 48.0 Gy (30.0-50.4 Gy) in 25 (10-28) fractions; most patients had 36.0-42.0 Gy in 3.0 Gy fractions (n = 16, EQD210Gy 39.0-45.5 Gy) or 40.0-50.4 Gy in 1.8-2.0 Gy fractions (n = 37, EQD210Gy 39.3-50.0 Gy). Median follow-up was 18 months. Local control rates were 83% at 1 year and 78% at 2 years and were significantly influenced by histology (breast cancer 100%, non-small lung cancer 87%, melanoma 80%, colorectal cancer 26% at 2 years, p = 0.006) and resection status (p < 0.0001), but not by EQD210Gy or size of the planning target volume (median 96.7 ml [16.7-282.8 ml]). At 1 and 2 years, 74% and 52% of the patients were free from distant brain metastases. Salvage procedures were applied in 25/27 (93%) of recurrent patients. Survival was 68% at 1 year and 41% at 2 years and was significantly improved in younger patients (p = 0.006) with higher Karnofsky performance score (p < 0.0001) and without prior radiotherapy (54% vs. 9% at 2 years, p = 0.006). No cases of radiographic or symptomatic radionecrosis were observed. Adjuvant fractionated local 3DRT is highly effective in radiosensitive, completely resected metastases and should be considered for treating large resection cavities as an alternative to postoperative stereotactic single dose or hypofractionated radiosurgery.


Mobility is Associated with Higher-risk Sexual Partnerships Among Both Men and Women in Co-resident Couples in Rural Kenya and Uganda: A Longitudinal Cohort Study.
Population mobility is associated with higher-risk sexual behaviors in sub-Saharan Africa and is a key driver of the HIV epidemic. We conducted a longitudinal cohort study to estimate associations between recent mobility (overnight travel away from home in past six months) or migration (changes of residence over defined geopolitical boundaries) and higher-risk sexual behavior among co-resident couples (240 couples aged ≥ 16) from 12 rural communities in Kenya and Uganda. Data on concurrent mobility and sexual risk behaviors were collected every 6-months between 2015 and 2020. We used sex-pooled and sex-stratified multilevel models to estimate associations between couple mobility configurations (neither partner mobile, male mobile/female not mobile, female mobile/male not mobile, both mobile) and the odds of higher-risk (casual, commercial sex worker/client, one night stand, inherited partner, stranger) and concurrent sexual partnerships based on who was mobile. On average across all time points and subjects, mobile women were more likely than non-mobile women to have a higher-risk partner; similarly, mobile men were more likely than non-mobile men to report a higher-risk partnership. Men with work-related mobility versus not had higher odds of higher-risk partnerships. Women with work-related mobility versus not had higher odds of higher-risk partnerships. Couples where both members were mobile versus neither had greater odds of higher-risk partnerships. In analyses using 6-month lagged versions of key predictors, migration events of men, but not women, preceded higher-risk partnerships. Findings demonstrate HIV risks for men and women associated with mobility and the need for prevention approaches attentive to the risk-enhancing contexts of mobility.


Tumor Stent for Chronic Ureteral Obstruction: Which Are Predictors of Stent Failure?
Purpose: To identify predictors of UROSOFT® tumor stent failure. According to the manufacturer, this reinforced ureteral stent has a maximal dwell time of 6 months. Nonetheless, stent failure may reduce this maximal dwell time. Methods: All patients undergoing first-time UROSOFT tumor stent insertion in our institution between 2010 and 2018 were considered for this retrospective analysis. Primary endpoint was stent failure and defined as premature stent exchange or percutaneous nephrostomy insertion. The local ethics committee approved the study protocol (study ID: BASEC 2020-00175). Results: In total, 182 patients were available for analysis. Median age was 68 years. Causes for tumor stent placement were extrinsic ureteral obstruction in 144 patients (79%) and intrinsic obstruction in 38 patients (21%). Tumor stent failure-free survival estimates at 1, 2, 3, 4, and 5 months were 89%, 83%, 76%, 65%, and 52%, respectively. Patients with stent failure had significantly higher grade of hydronephrosis, higher urinary culture bacterial growth, higher serum white blood cell count, higher C-reactive protein, and lower estimated glomerular filtration rate at the time of reintervention, compared with patients who underwent regular stent exchange. Of all baseline and perioperative parameters, we found bilateral insertion, intrinsic ureteral obstruction, and urinary tract infection (UTI) at time of tumor stent insertion to be significant and independent predictors of stent failure (all p < 0.05). Conclusion: Despite a theoretical maximal dwell time of 6 months, ∼50% of all cases are subject to premature stent failure. Predictors of stent failure are bilateral insertion, intrinsic ureteral obstruction, and UTI at the time of tumor stent insertion. Preoperative antibiotic therapy may impact on stent failure rate.


The prevalence of binge-eating and bulimia in 1063 college students.
We used a purpose-designed questionnaire to survey the prevalence of binge-eating and bulimia in a sample of 1063 Dublin third-level students aged 17-25 yr. There were 361 males and 701 females. The questionnaire was based on DSM-III, and included a written definition of a binge and cross-check questions. Although 17.7% of males and 37% of females claimed to have had an eating binge, cross-check items reduced this to 1.1% of males and 10.8% of females who met the DSM-III definition. No male and only 7.7% of females also met the behavioural criteria under item B of DSM-III, and only 5% of females reported dysphoric mood. Excluding those experiencing fewer than one episode per week gave a prevalence of 2.8% in females and 0% on males. Previously-reported prevalences using questionnaire may be inflated due to poor respondent understanding of the psychiatric terms being used.


Alternatives to seclusion and restraint in psychiatry and in long-term care facilities for the elderly: perspectives of service users and family members.
There is growing interest in involving patients in decisions regarding healthcare technologies. This research project was conducted in collaboration with decision makers and health technology assessment agents in order to involve healthcare service users (and their loved ones) in the assessment of alternatives to seclusion and restraint in short-term psychiatric wards and long-term care facilities for the elderly. This paper explores the viewpoints and suggestions of service users and service users' families about alternatives to restraint and seclusion, as well as conditions under which they could be used among adults in short-term psychiatric care and residents in long-term care facilities. Using a semi-structured guide, we held eight focus groups: five with mental health service users and three with family members of elderly people in long-term care facilities. Focus group discussions were digitally recorded and transcribed verbatim, and we performed content analysis using NVivo 8 software. In both care environments, participants emphasized the importance of communicating with service users, as well as assessing their needs and their particular situation, for reducing the use of restraint and seclusion. A better welcome and accompaniment of people admitted for short-term psychiatric care emerged also as key approaches to reduce the use of restraint and seclusion. Long-term care facilities could also reduce the need for restraint and seclusion by creating a stimulating home environment and individualized occupational therapy programs. Participants in both groups suggested that caregivers other than healthcare staff could be more involved, especially peer-support workers in the case of psychiatric care and volunteers in the case of long-term care facilities. Participants suggested that changes were needed at a broader and more systemic level than simply replacing current measures of restraint and seclusion with alternative techniques. They favored an approach focused more on the person than on the techniques: they suggested that listening to and communicating with the service user could reduce the use of restraint and seclusion in both healthcare environments.


Direct air capture of CO2 via crystal engineering.
This article presents a perspective view of the topic of direct air capture (DAC) of carbon dioxide and its role in mitigating climate change, focusing on a promising approach to DAC involving crystal engineering of metal-organic and hydrogen-bonded frameworks. The structures of these crystalline materials can be easily elucidated using X-ray and neutron diffraction methods, thereby allowing for systematic structure-property relationships studies, and precise tuning of their DAC performance.


Phase I study of pemetrexed and cisplatin with concurrent high-dose thoracic radiation after induction chemotherapy in patients with unresectable locally advanced non-small cell lung cancer.
This is a phase I, escalating-dose trial targeting exclusively patients with non-small cell lung cancer (NSCLC), investigating pemetrexed and fixed-dose cisplatin concurrently administered with high-dose radiotherapy (RT) after induction chemotherapy (CT). Primary objective was to determine the maximum tolerated dose and recommended phase II dose of pemetrexed. Patients with unresected stage III NSCLC, planned V20 ≤ 35%, and FEV ≥ 1.3 L, were treated every 21 days for 2 cycles (pemetrexed 500 mg/m2; cisplatin 75 mg/m2), followed by 2 cycles of concurrent CT-RT: pemetrexed starting dose was 400 mg/m2, escalated up to 800 mg/m2 per 100mg/m2 dose level (DL), cisplatin at 75 mg/m2 and RT at fixed dose of 66 Gy/33 fractions. Nine of 10 enrolled patients (age range 46-68 years; 6 men; ECOG PS 0 [6 patients], PS 1 [4]; stage IIIA [1], IIIB [9]; 6 adenocarcinomas, 3 squamous cell carcinomas, 1 large cell carcinoma) were entered on 3 DLs. Dose escalation of pemetrexed was conducted up to 600 mg/m2 based on the independent safety monitoring board recommendation. One dose-limiting toxicity occurred at DL3: Grade 4 septic shock. Grade 3 related toxicities: 2 neutropenia at DL3, 2 lymphopenia per DL (3 recurrent), 2 leukopenia (1 recurrent) at DL3, 1 gastric pain (DL3), 1 nausea and 1 recurrent vomiting (DL2). No Grade 3/4 radiation-related toxicities were observed. No toxic death was observed. Disease control rate was 77.7% (1 CR, 4 PR, 2 SD). One-year survival rate was 90%. This phase I report of pemetrexed is dedicated to NSCLC with induction therapy and fixed high-dose RT. Pemetrexed at 500 mg/m2, concurrently given with cisplatin and RT was well tolerated and appears to be the only third-generation agent that can likely be recommended safely at full dose in future trials with concurrent RT.


Gastrointestinal parasites of arctic foxes (Vulpes lagopus) and sibling voles (Microtus levis) in Spitsbergen, Svalbard.
The arctic fox (Vulpes lagopus), an apex predator with an omnipresent distribution in the Arctic, is a potential source of intestinal parasites that may endanger people and pet animals such as dogs, thus posing a health risk. Non-invasive methods, such as coprology, are often the only option when studying wildlife parasitic fauna. However, the detection and identification of parasites are significantly enhanced when used in combination with methods of molecular biology. Using both approaches, we identified unicellular and multicellular parasites in faeces of arctic foxes and carcasses of sibling voles (Microtus levis) in Svalbard, where molecular methods are used for the first time. Six new species were detected in the arctic fox in Svalbard, Eucoleus aerophilus, Uncinaria stenocephala, Toxocara canis, Trichuris vulpis, Eimeria spp., and Enterocytozoon bieneusi, the latter never found in the arctic fox species before. In addition, only one parasite was found in the sibling vole in Svalbard, the Cryptosporidium alticolis, which has never been detected in Svalbard before.


A time-referenced Q-sort technique for evaluating behavioral change.
The behavior of children in residential and day treatment centers alters over time in ways that can be documented objectively. This paper describes a method, field tested with 50 subjects in five agencies, in which observations of behavior are converted into quantitative indices of adjustment to yield a profile of change for each subject.


Does acute primary angle-closure cause an increased choroidal thickness?
We compared the choroidal thickness of the eyes of patients with acute primary angle-closure (APAC) with fellow eyes in the same patients. The analysis included 21 participants with unilateral APAC affected eyes and 21 fellow eyes with a diagnosis of primary angle-closure suspect (PACS). Enhanced depth imaging-optical coherence tomography (EDI-OCT) was used to measure the macular and peripapillary retinal and choroidal thickness in both eyes. The average choroidal thickness of the APAC eyes at each location or segment was compared to that of the fellow eyes. At all macular locations, the choroidal thickness was greatest at the subfovea for both groups. Comparison of the choroidal thickness between the groups showed that the thickness in the APAC eyes was significantly greater than in the PACS eyes at all locations except at 1 mm, 3 mm superior, 3 mm inferior, and 3 mm temporal from the fovea (P < 0.005). The mean subfoveal choroidal thickness was 349.0 ± 78.1 μm in the APAC eyes and 308.1 ± 70.5 μm in the PACS eyes, with a statistically significant difference (P < 0.005). Multivariable linear regression analysis showed that the subfoveal choroidal thickness was significantly greater in association with the APAC diagnosis and diastolic blood pressure and thinner in association with older subjects. APAC eyes have a higher level of macular choroidal thickness than PACS eyes when the IOP is reduced. However, the source of this difference is unclear and must be investigated further.


Construction of PEGylated chlorin e6@CuS-Pt theranostic nanoplatforms for nanozymes-enhanced photodynamic-photothermal therapy.
Multifunctional nanoagents with photodynamic therapy (PDT) and photothermal therapy (PTT) functions have shown great promise for cancer treatment, while the design and synthesis of efficient nanoagents remain a challenge. To realize nanozyme-enhanced PDT-PTT combined therapy, herein we have synthesized the Ce6@CuS-Pt/PEG nanoplatforms as a model of efficient nanoagents. Hollow CuS nanospheres with an average diameter of ∼ 200 nm are first synthesized through vulcanization using Cu2O as the precursor. Subsequently, CuS nanospheres are surface-decorated with Pt nanoparticles (NPs) as nanozyme via an in-situ reduction route, followed by modifying the DSPE-PEG5000 and loading the photosensitizer Chlorin e6 (Ce6). The obtained Ce6@CuS-Pt/PEG NPs exhibit high photothermal conversion efficiency (43.08%), good singlet oxygen (1O2) generation ability, and good physiological stability. In addition, Ce6@CuS-Pt/PEG NPs show good catalytic performance due to the presence of Pt nanozyme, which can effectively convert H2O2 to O2 and significantly enhance the production of cytotoxic 1O2. When Ce6@CuS-Pt/PEG NPs dispersion is injected into mice, the tumors can be wholly suppressed owing to nanozyme-enhanced PDT-PTT combined therapy, providing better therapeutic effects compared to single-mode phototherapy. Thus, the present Ce6@CuS-Pt/PEG NPs can act as an efficient multifunctional nanoplatform for tumor therapy.


Non-astigmatic children's contrast sensitivities differ from anisotropic patterns of adults.
Monocular contrast thresholds were estimated for horizontal (H), vertical (V) and left and right diagonal 10 c/deg sinusoidal gratings for non-astigmatic children (4:10--11:2 yr) and adults using yes-no signal detection (YN) methods. Some children were also tested with two-interval forced-choice (2IFC). Younger children were less likely to have the typical adult pattern of anisotropic sensitivity, favoring H and V, while 10--11 yr olds had more adult-like anisotropy. Within all age groups patterns of anisotropy varied considerably. Deviation of adults from the typical pattern may be related to small amounts of astigmatism in their untested eyes. 4- and 5-yr olds were confused by 2IFC. For children 6 yr and older, 2IFC and YN threshold estimates were equivalent, but 2IFC required less testing time.


Case report: sudden death following the administration of CAR-NK cells for lung cancer immunotherapy.
Lung cancer is a high degree of malignancy. Although surgery, radiotherapy, and chemotherapy have made significant progress and become general methods of clinical treatment, the overall survival rate is still low. In recent years, targeted therapy and immunotherapy have a rapid development in the clinical treatment of tumors. Among them, natural killer (NK) cells have the advantages of rapid killing of diseased cells and low risk of graft-versus-host reaction. It is considered a great vector for chimeric antigen receptors (CARs), making them have good application prospects in tumor immunotherapy. However, its clinical application in lung cancer needs further research. Herein, we reported a case of a lung cancer patient undergoing CAR-NK cell immunotherapy after resection, which caused a cytokine storm and sudden death after the fourth treatment. This case report provides a reference for the forensic examination of cadavers that died after immunotherapy and challenges the clinical application of cell immunotherapy.


[Food intake during the previous 24h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study].
Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24h (bottle and spoon feeding), as a percentage of usual intake (24h FI), as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea+dyspnea+cough+expiratory sounds). Infants with risk factors (history of prematurity, chronic heart or lung disorders), breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2) was recorded. Hypoxia was noted if SpO2 was below 95% and verified. 24h FI greater or equal to 50% was associated with a 96% likelihood of SpO2 greater or equal to 95% [95% CI, 91-99%]. In univariate analysis, 24h FI less than 50% had the highest odds ratio (13.8) for SpO2 less than 95%, compared to other 24h FI values and other clinical signs, as well as providing one of the best compromises between specificity (90%) and sensitivity (60%) for identifying infants with hypoxia. In multivariate analysis with adjustment for age, SpO2 less than 95% was related to the presence of intercostal retractions (OR=9.1 [95% CI, 2.4-33.8%]) and 24h FI less than 50% (OR=10.9 [95% CI, 3.0-39.1%]). Hospitalization (17 infants) was strongly related to younger age, 24h FI and intercostal retractions. In practice, the measure of 24h FI may be useful in identifying hypoxia and deserves further study.


Cutaneous fungal infections in solid organ transplant recipients.
Although there is an abundance of information on cutaneous malignancies in transplant recipients, information on cutaneous infections in solid organ transplant recipients is underrepresented in dermatologic and transplant literature. Our paper provides a comprehensive review of fungal cutaneous infections within the solid organ transplant population. We compiled literature specific to the solid organ transplant population, reviewing cutaneous manifestations owing to fungal infections. Furthermore, we discuss the diagnosis and treatment of such infections. The following is a list of some of the fungi that we will discuss.


Psychiatric Emergencies.
Psychiatric emergencies are acute disturbances in thought, behavior, mood, or social relationship that require immediate intervention as defined by the patient, family, or social unit to save the patient and/or others from imminent danger. Ensuring the safety of the patient, surrounding persons, and the medical team is the first step of evaluation. Treatment focuses on stabilization of the patient, then on specific symptoms and ultimately the cause of symptoms. There are important legal considerations, particularly regarding involuntary admissions. It is important to debrief with the patient, surrounding family, and the health care team to ensure a continued therapeutic alliance and the emotional health of all involved.


A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and high heterogeneity. The aim of this study was to screen patients for single-nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC. Database-derived SNPs (NextBio, Ensembl, NCBI and MirSNP) located in the 3'-untranslated regions (3'-UTRs) of genes that are differentially expressed in breast cancer were selected. The possible associations between 111 SNPs and progression risk among 323 TNBC patients were investigated using a two-step case-control study with a discovery cohort (n=162) and a validation cohort (n=161). We identified the rs1054135 SNP in the adipocyte fatty acid binding protein 4 (FABP4) gene as a predictor of TNBC recurrence. The G allele of rs1054135 was associated with a reduced risk of disease progression as well as a prolonged disease-free survival time (DFS), with a hazard ratio (HR) for recurrence in the combined sample of 0.269 [95%CI: 0.098-0.735;P=0.001]. Notably, for individuals having the rs1054135 SNP with the AA/AG genotype, the magnitude of increased tumour recurrence risk for overweight patients (BMI≥25kg/m2) was significantly elevated (HR2.53; 95%CI: 1.06-6.03). Immunohistochemical staining of adipocytes adjacent to TNBC tissues showed that the expression level of FABP4 was statistically significantly lower in patients with the rs1054135-GG genotype and those in the disease-free group (P=0.0004 and P=0.0091, respectively). These results suggested that the expression of a lipid metabolism-related gene and an important SNP in the 3'-UTR of FABP4 are associated with TNBC prognosis, which may aid in the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents.


Enabling Indium Channels for Mass Cytometry by Using Reinforced Cyclam-Based Chelating Polylysine.
The synthesis of a polylysine polymer functionalized with the previously reported astonishingly inert [In(cb-te2pa)]+ chelate was performed. A biotin end group allowed the conjugation to biotinylated beads by the intermediary of a fluorescein isothiocyanate/neutravidin receptor. High quality imaging mass cytometry trials, based on 115In detection were performed to highlight the behavior of the material. Anti-CD20 antibody was labeled by the so-obtained In(III)-modified polylysine using the biotin/neutravidin interaction. Ramos (CD20[+]) and HL-60 (CD20[-]) cell lines were costained with the In(III)-modified bioconjugate by finding the best staining conditions. Both immunofluorescence microscopy (IF-M) and mass cytometry analyses confirmed the specific binding of anti-CD20 onto Ramos cells. CyTOF histograms constructed on the 115In detection allowed us to define and to separate, with a good signal-to-noise ratio, two populations (Ramos and HL-60). The inertness of In(III)-MCP-NAv over a three-month storage period was proved by performing new functionality tests involving Jurkat cells (CD20[-]) and multiparametric trials involving the 115In channel. The results ensure a promising future use of the previously announced [In(cb-te2pa)]+ complex-based polymers for mass cytometry.


Individual differences in naturally occurring affect predict conceptual breadth: evidence for the importance of arousal by valence interactions.
Several studies have investigated the effect of induced mood state on conceptual breadth (breadth and flexibility of thought). Early studies concluded that inducing a positive mood state broadened cognition, while inducing a negative mood state narrowed cognition. However, recent reports have suggested that valence and arousal can each influence conceptual breadth. Individual differences in affective dispositions may bias perceptions, thoughts, and behaviors and, in turn, may be biased by them. Here, we examine whether individual differences in valence and arousal dimensions of self-reported, naturally occurring affect relate to conceptual breadth (using the Remote Associates Test, the Object Categorization Task, and the Alternative Uses Task), with no mood manipulations or cues. The three conceptual breadth tasks loaded onto a latent conceptual breadth factor that was predicted significantly by the interaction of valence and arousal. For participants low in arousal, greater positive affect was associated with greater conceptual breadth. For participants high in arousal, greater positive affect was associated with reduced conceptual breadth. In contrast to most existing theories of conceptual breadth that highlight the importance of valence or arousal alone, the present results suggest that the interaction between arousal and valence is key to predicting individual differences in conceptual breadth. We posit that positive mood states predict greater conceptual breadth in the presence of low versus high arousal due to a relaxation of cognitive control under low arousal.


Effect of a novel quaternary ammonium silane cavity disinfectant on durability of resin-dentine bond.
The present study examined the effect of a quaternary ammonium silane (QAS) cavity disinfectant on the viability of human dental pulp cells, dentine bond durability and nanoleakage of simplified etch-and-rinse adhesives. Etched dentine surface of third molars were randomly divided into two adhesive groups, Adper™ Single Bond 2 and Prime & Bond® NT™. For each adhesive, the teeth were randomly assigned to five cavity disinfectant groups (N=6): Group 1: deionised water (control); Group 2: 2% chlorhexidine (CHX); Group 3: 2% QAS; Group 4: 5% QAS and Group 5: 10% QAS. The cavity disinfectants were applied on etched dentine surfaces for 20s, followed by adhesive application. The bonded teeth were sectioned for bond strength testing at 24h, 6 months and 12 months. Viability of human dental pulpal cells was examined using MTT assay. Bond strength data were analysed using 3-way ANOVA and Tukey test. Interfacial nanoleakage was evaluated after 24h and 12 months and analysed using Kruskal-Wallis test. Significant differences in bond strength were observed for the factors disinfectants (p<0.001) and time (p<0.001); while the factor, adhesive, was not significantly different (p=0.203). The 2% QAS cavity disinfectant preserved bond strength of both adhesives and reduced interfacial nanoleakage after 12 months. Cell viability was the lowest for 2% CHX, followed by 2% QAS and the control. The 2% QAS cavity disinfectant demonstrated greater cell viability compared to 2% CHX, with no adverse effect on immediate bond strength and preserved bond stability over time. Incorporation of 2% quaternary ammonium silane cavity disinfectant in the resin-dentine bonding protocol enhances the success rate of bonded restorations.


Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation.
Identification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone. The potential for increased risk for AF in patients with epilepsy is not well appreciated, despite recent evidence from a national survey of 1.4 million hospitalizations indicating that AF is the most common arrhythmia in people with epilepsy. We analyzed inter-lead heterogeneity of P-wave morphology, a marker reflecting arrhythmogenic nonuniformities of activation/conduction in atrial tissue. The study groups consisted of 96 patients with epilepsy and 44 consecutive patients with AF in sinus rhythm before clinically indicated ablation. Individuals without cardiovascular or neurological conditions (n = 77) were also assessed. We calculated P-wave heterogeneity (PWH) by second central moment analysis of simultaneous beats from leads II, III, and aVR ("atrial dedicated leads") from standard 12-lead electrocardiography (ECG) recordings from admission day to the epilepsy monitoring unit (EMU). Female patients composed 62.5%, 59.6%, and 57.1% of the epilepsy, AF, and control subjects, respectively. The AF cohort was older (66 ± 1.1 years) than the epilepsy group (44 ± 1.8 years, p < .001). The level of PWH was greater in the epilepsy group than in the control group (67 ± 2.6 vs. 57 ± 2.5 μV, p = .046) and reached levels observed in AF patients (67 ± 2.6 vs. 68 ± 4.9 μV, p = .99). In multiple linear regression analysis, PWH levels in individuals with epilepsy were mainly correlated with the PR interval and could be related to sympathetic tone. Epilepsy remained associated with PWH after adjustments for cardiac risk factors, age, and sex. Patients with chronic epilepsy have increased PWH comparable to levels observed in patients with AF, while being ~20 years younger, suggesting an acceleration in structural change and/or cardiac electrical instability. These observations are consistent with emerging evidence of an "epileptic heart" condition.


Parent training: implementation strategies for adventures in parenting.
Adventures in Parenting, an informational booklet published by the National Institute of Child Health and Human Development, offers five principles that parents can use to develop a mental model of parenting: Responding, Preventing, Monitoring, Mentoring, and Modeling (RPM3). The current study was designed to assess the differential impact of three intervention conditions utilizing Adventures in Parenting on knowledge of RPM3 principles. Significant intervention effects were found for measures of knowledge of RPM3 principles; the more intensive interventions (i.e., face-to-face groups and web-based sessions) were associated with increased knowledge of RPM3 principles over 3 months. Results are discussed in terms of their contribution to new approaches of parent education, particularly the use of web-based training. Editors' Strategic Implications: Parent educators should review the promising findings regarding the RPM3 model. Preventionists, more broadly, may be interested in the effect of the program's delivery mechanism, with a comparison of participants who were randomly assigned to web-based, group-based, and booklet only conditions.


Endothelial progenitor cells and erectile dysfunction: a brief review on diagnostic significance and summary of our experience.
The article provides a brief review of the literature concerning the diagnostic use of endothelial progenitor cells in patients with erectile dysfunction. In particular, patients with arterial erectile dysfunction could benefit from the use of this diagnostic marker, which in clinical practice can be used together with more conventional methods such as the penile Doppler. It is very important to acquire diagnostic tools for the diagnosis of sub clinical form of endothelial dysfunction in these patients, in particular when the erectile dysfunction is associated with cardiovascular risk factors.


Dermoscopy of inflamed seborrheic keratosis: A great mimic of malignancy.
Clinical and dermoscopic recognition of seborrheic keratoses (SKs) is often straightforward, and biopsy might not be required. However, inflamed SKs (iSKs) can pose a diagnostic challenge. Dermoscopic features of iSKs have not yet been evaluated to date. To assess the diagnostic ability of a group of dermatologists to diagnose iSKs by dermoscopy. To evaluate the dermoscopic findings of a long series of inflamed seborrheic keratoses. Clinical and dermoscopic images of 100 difficult-to-diagnose skin tumours, including 29 iSKs, were presented to 33 clinicians (24 dermatologists and 9 dermatology residents), who were blinded to the diagnosis. The dermoscopic features of a series of 219 iSKs were retrospectively analysed. iSKs were correctly identified in a 37.6% of cases. Classic dermoscopic criteria were present in only 47% of iSKs. The most frequent dermoscopic feature in iSKs was the presence of vascularization (91.3%), but only a 44.5% showed predominance of hairpin vessels. A bluish hue was observed in 18.3% of lesions. Seven dermoscopic patterns were identified, based on the dermoscopic similarity to other tumours: seborrheic keratosis-like (28.8%); squamous cell carcinoma-like (25.6%); melanoma-like (17.8%); keratoacanthoma-like (6.8%); basal cell carcinoma-like (5.9%); verruca vulgaris-like (5.9%); nevus-like (2.3%). The diagnosis of iSKs can be challenging even with dermoscopy. They may behave as authentic mimics of other cutaneous tumours, including squamous cell carcinoma or melanoma. For this reason, histopathological examination should be mandatory in these cases.


Geometry adopted by Manchester radium applicators and Selectron afterloading applicators in intracavitary treatment for carcinoma cervix uteri.
Twenty-eight patients with early-stage carcinoma of the uterine cervix were treated using one standard Manchester radium application and one afterloading Selectron application. In each case, radiographs were analysed to determine differences in geometry of applicators relative to each other, or to the bony pelvis. During the Selectron treatment the applicators lay significantly more anterior in the pelvis, with a reduced angulation between the axes of the uterus and the vagina. The separation between the ovoids was increased. An identical analysis of 25 patients who had received two radium applications showed that the uterine tube lay significantly more anterior in the pelvis during the second application. Reasons for these differences and their possible clinical importance in terms of increased dose rate to critical tissue are discussed.


Serum KL-6 as a novel tumor marker for hepatocellular carcinoma in hepatitis C virus infected patients.
The up-regulation of MUC1 protein is associated with malignant phenotype of cancer. We investigated the significance of KL-6, one of the MUC1 antigens, as a tumor marker in hepatitis C virus positive hepatocellular carcinoma (HCC). Serum KL-6 was determined in 203 patients with chronic hepatitis (CH), 47 patients with liver cirrhosis (LC) and 78 patients with HCC. KL-6 was higher in HCC compared to non-HCC (p=0.0005) and was higher in patients with multiple HCC nodules compared to a single nodule (p=0.02). There was no correlation between KL-6 and existent tumor markers for HCC such as alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein or des-gamma-carboxyprothrombin. In the prospective analysis, the cumulative incidence of HCC was significantly greater in CH and LC patients with high initial KL-6 (above 400U/ml) compared to the others (p=0.02). Moreover, in the prospective observation of 25 patients whose HCC was completely cured by radiofrequency ablation therapy, the cumulative incidence of distant recurrences was significantly greater in patients with high initial KL-6 compared to the others (p=0.005). These results suggest that serum KL-6 could be a novel tumor marker in the diagnosis and the prediction of prognosis of HCC that may have additive value to the existent markers.


An evaluative study of Silver's Cerebral Function Test.
The aim of this study was to evaluate the usefulness of Silver's Cerebral Function Test in predicting the management and placement of patients admitted to a psychogeriatric hospital. Overall, 205 consecutively admitted patients and 54 age-matched controls living in the community were examined, thereby greatly extending the normative data for the test. The results indicated that this brief, easily administered test could distinguish the patients from the controls. Also, the selected cut-off score of 28 significantly differentiated between patients able to benefit from rehabilitation and occupational therapy programs and those who required primarily maintenance care. The test-retest reliability of the test was good (r = 0.91).


What research paradigms have cognitive psychologists used to study "false memory," and what are the implications of these choices?
This research examines the methodologies employed by cognitive psychologists to study "false memory," and assesses if these methodologies are likely to facilitate scientific progress or perhaps constrain the conclusions reached. A PsycINFO search of the empirical publications in cognitive psychology was conducted through January, 2004, using the subject heading, "false memory." The search produced 198 articles. Although there is an apparent false memory research bandwagon in cognitive psychology, with increasing numbers of studies published on this topic over the past decade, few researchers (only 13.1% of the articles) have studied false memory as the term was originally intended--to specifically refer to planting memory for an entirely new event that was never experienced in an individual's lifetime. Cognitive psychologists interested in conducting research relevant to assessing the authenticity of memories for child sexual abuse should consider the generalizability of their research to the planting of entirely new events in memory.


Antibiotic choices among healthcare professionals for enterococcal bacteremia with patterns of resistance and risk factors of mortality, in settings of poor antibiotic stewardship program - a five-year retrospective cohort study.
Enterococcal bacteremia has become prevalent in the recent decade, especially in hospitalized patients. Moreover, the rise in resistance patterns against antibiotic drugs regarding enterococci infection, such as cephalosporins, ampicillin and vancomycin, is prevailing. The major driving force behind this is the incongruous use of antibiotics with a minor contribution from environmental stressors which calls for vigilant and prudent administration of evidence-based antibiotics. A retrospective study was conducted from January 1 2017 until December 31 2021, at the tertiary care center, Dr Ziauddin Hospital in Karachi, Pakistan. Our research revealed ampicillin resistance in 87 (63.5%), with an estimated 25 (18.8%) mortality. Male gender 19 (76%) and vancomycin resistance 13 (52%) were associated with increased mortality. Furthermore, appropriate antibiotic therapy reduced the risk of death compared with inappropriate and excessive use of antibiotics 10 (40%) vs. 15 (60%) vs. 20 (80%) respectively. Targeted therapy with amoxicillin/clavulanic acid was associated with lower mortality 1 (4%) and higher discharge rates 34 (32.1%). On Kaplan-Meier survival, targeted therapy with amoxicillin/clavulanic acid was associated with shorter hospital stays and prolonged survival. UTI was found as the most common source of enterococcal bacteremia 57 (41.6%), followed by respiratory 21 (15.3%) and intra-abdominal 13 (9.5%). In 26 (19%) patients, no identifiable source of infection was found. Vancomycin resistance and male gender were found independent risk factors for mortality. The use of inappropriate antibiotics significantly increases mortality in these patients. The appropriate antibiotic therapy reduces the risk of death. Furthermore, overuse of antibiotics didn't reduce mortality; instead increased the financial burden and chances of developing multi-drug resistant strains of other organisms by increasing hospital stays of patients.


Refugee women's experiences with contraceptive care after resettlement in high-income countries: A critical interpretive synthesis.
Refugee women often share histories of forced displacement, economic hardship, or gender-based violence and may face common barriers to reproductive health care access after resettlement in high-income countries. This Critical Interpretive Synthesis integrates the available data on contraceptive care for refugee women after resettlement. The review examined shared aspects of the refugee experience that impact women's access to high-quality contraceptive care and transcend the particularities of specific health systems or countries of origin. These include possible shifts in gendered norms and fertility preferences after resettlement, prior experiences with contraception in home countries, refugee camps, and other sites of first-asylum, and negative experiences with health care providers after resettlement (i.e., communication barriers or experiencing discrimination). Our findings demonstrate the need for further methodologically-rigorous research in the field of refugee reproductive health, specifically in relation to evidence-based approaches to training interpreters and providers in contraceptive care for refugees and on male partners and their influence on contraceptive use.


Morbidity after transanal endoscopic microsurgery: risk factors for postoperative complications and the design of a 1-day surgery program.
Transanal endoscopic microsurgery (TEM) is a minimally invasive procedure with low morbidity. The definition of risk factors for postoperative complications would help to identify the patients likely to require more care and surveillance in an ambulatory or 1-day surgery (A-OdS) program. The main endpoints are overall 30-day morbidity and relevant morbidity. The secondary objectives are to detect risk factors for complications, rehospitalization, and the time of occurrence of the postoperative complications, and to describe the adverse effects following hospitalization that the A-OdS program would avoid. This is an observational study of consecutive patients undergoing TEM between June 2004 and December 2016. Overall and relevant morbidity based on the Clavien-Dindo (Cl-D) classification were recorded, as were demographic, preoperative, surgical, and pathology variables. Univariate and multivariate analyses of the risk factors were carried out. Six hundred and ninety patients underwent surgery, of whom 639 were included in the study. Overall morbidity rate was 151/639 patients (23.6%); the clinically relevant morbidity rate was 36/639 (Cl-D > II) (5.6%) and mortality 2/639 (0.3%). The most frequent complication was rectal bleeding, recorded in 16.9% (108/639 patients) and grade I in 86/108 patients (78. 9%). The period with the greatest risk of complications was the first 2 days. The rehospitalization rate after 48 h was 7%. The risk factors for complications were as follows: tumor size > 6 cm (OR 3.2, 95% CI 1.3-7.8), anti-platelet medication (OR 2.3, 95% CI 1.1-5.1), and surgeon's experience < 150 procedures (OR 2.0, 95% CI 1-4.1). TEM is a safe procedure. The low rates of morbidity, re-hospitalization, and postoperative complications in the first 2 days after surgery make the procedure suitable for A-OdS.


Persistent atrial fibrillation in a goat model of chronic left atrial overload.
Atrial dilatation predisposes to atrial fibrillation. Although several animal models focus on the initiating mechanisms of atrial fibrillation in dilated atria, a model of left atrial overload resulting in persistent atrial fibrillation in nonanesthetized animals has not been presented thus far. In 24 goats a vascular shunt was implanted between the aorta and the left atrium through a left thoracotomy. In 6 animals the shunt was ligated immediately (control group). Ultrasonic crystals were implanted to monitor atrial dilatation. Bipolar electrodes were positioned epicardially on the left atrium for measurement of the atrial effective refractory period, conduction times, and atrial fibrillation duration. Four weeks of overload resulted in an increase of left atrial pressure (23.1 +/- 6.8 mm Hg in the open-shunt group vs 7.0 +/- 1.9 mm Hg in the control group, P = .002) and a progressive dilatation of the left atrium (135% +/- 20% in the open-shunt group vs 98% +/- 8.0% in the control group, P = .002). Among the open-shunt group's long-term survivors (n = 12), 9 animals showed prolonged atrial fibrillation (>1 hour), and of these, 6 were in persistent atrial fibrillation (>1 week). The atrial effective refractory period increased during the first week and remained prolonged until death (182 +/- 11 ms in the open-shunt group vs 161 +/- 15 ms, P = .03). The conduction time did not change. An increase in collagen formation was noticed in both groups, without a significant difference between them. A chronic aortic to left atrial shunt is a feasible model in the goat. It induces progressive left atrial dilatation with an increased atrial fibrillation duration up to hours in the majority of animals. Prolonged atrial fibrillation duration could not be explained by a shortening of atrial effective refractory period or increase in fibrosis.


Retinal nerve fibre layer thickness measured with SD-OCT in a population-based study: the Handan Eye Study.
To examine the normative profile of retinal nerve fibre layer (RNFL) thickness and ocular parameters based on spectral-domain optical coherence tomography (SD-OCT) and its associations with related parameters among the Chinese population. This population-based cohort Handan Eye Study (HES) recruited participants aged≥30 years. All subjects underwent a standardised ophthalmic examination. Peripapillary RNFL thickness was obtained using SD-OCT. Mixed linear models were adopted to evaluate the correlation of RNFL thickness with ocular parameters as well as systemic factors. R V.3.6.1 software was used for statistical analysis. 3509 subjects (7024 eyes) with the average age of 55.54±10.37 were collected in this analysis. Overall mean RNFL thickness measured was 113.46±10.90 µm, and the thickest quadrant of parapapillary RNFL was the inferior quadrant, followed by the superior quadrant, the nasal quadrant and the temporal quadrant. In the multivariate linear regression model, thinner RNFL thickness was remarkable association with male (p<0.001), older age (p<0.001), increased body mass index (>30, p=0.018), absence of diabetes (p=0.009), history of cataract surgery (p=0.001), higher intraocular pressure (p=0.007), lower spherical equivalent (p<0.001) and increased axial length (p=0.048). In non-glaucoma individuals, this difference of RNFL thickness in Chinese population should be noted in making disease diagnoses. Meanwhile, multiple ocular and systemic factors are closely related to the thickness of RNFL. Our findings further emphasise the need to demonstrate ethnic differences in RNFL thickness and the specificity of associated ocular and systemic factors, as well as to develop better normative databases worldwide. HES was registered in Chinese Clinical Trial Registry website, and the registry number was ChiCTR-EOC-17013214.


Hypotheses of peripheral and central mechanisms underlying occupational muscle pain and injury.
In an overview of the problem of occupational muscle pain the evidence indicates that injury is more common the greater the load and the worse the posture in which the work is performed. The commonest are backstrains or ligament or joint damage due to overuse. Fatigue is associated with alterations in energy metabolites in muscle while pain is often due to microscopical damage to the cellular architecture. The progress of pathological changes in muscle following occupational injury may be similar to those seen in primary fibromyalgia (fibrositis) because of a final common pathway involving calcium-induced secondary damage. Occupational muscle pain frequently occurs in the muscles supporting the upper limb girdle and head in workers engaged in repetitively performing skilled manipulations or activities requiring high or sustained mental concentration. It is suggested that both occupational myalgia of this kind may be due to an imbalance in the use of muscles for postural activity (holding or supporting fine movements) compared to phasic use in dynamic work. While there are undoubtedly muscular indications of damage these may be secondary to alterations in (unconscious) central motor control mechanisms.


Systematic Video Documentation in Laparoscopic Colon Surgery Using a Checklist: A Feasibility and Compliance Pilot Study.
High-quality images can be readily captured during laparoscopic colon surgery, but there are no guidelines for documentation of these video data or how to best measure surgical quality from an operative video. This study evaluates the feasibility and compliance in documenting key steps during laparoscopic right hemicolectomy and sigmoid colectomy. A retrospective review of previously recorded videos of patients undergoing laparoscopic right hemicolectomy or sigmoid colectomy from September to December 2011 in a single institution was performed. Patients' demographics, intraoperative features, postoperative complications, and variables for video recording and editing were collected. Compliance of key surgical steps was assessed using a checklist by two independent surgeons. Sixteen laparoscopic operations (seven right hemicolectomies and nine sigmoid colectomies) were recorded. Twelve (75%) were laparoscopic-assisted, and four (25%) were hand-assisted laparoscopic operations. Compliance with key surgical steps in laparoscopic right hemicolectomy and sigmoid colectomy was demonstrated in the majority of patients, with steps ranging in compliance from 42.9% to 100% and from 77.8% to 100%, respectively. The edited video had a median duration of 3 minutes 47 seconds (range, 1 minute 44 seconds-5 minutes 38 seconds) with a production time of nearly 1 hour and a resolution of 1440 × 1080 pixels. Key surgical steps during laparoscopic right hemicolectomy and sigmoid colectomy can be documented and edited into a short representative video. Standardization of this process should allow video documentation to improve quality in laparoscopic colon surgery.


Longitudinal Viral Load Monitoring Using Home-Collected Dried Blood Spot Specimens of MSM Living with HIV: Results from a Feasibility Pilot Study.
Novel viral load monitoring strategies are needed to help individuals maintain an undetectable viral load (UVL). In 2018, U.S. MSM living with HIV with a past detectable VL received a dried blood spot (DBS) kit at baseline and 3-month follow-up and returned specimens to a research laboratory. Of 56 consenting participants, 91% returned specimens at baseline and 77% at 3-month follow-up; 74% who returned two specimens had UVL at both time points. At-home DBS collection and longitudinal VL monitoring is feasible among U.S. MSM with fluctuating viral load. This complementary approach to clinical care could improve viral suppression maintenance.


[The origin of lipofuscin granules in a hybridoma cell culture].
The ultrastructure of lipofuscin granules (LG) in hybridoma cells is described. Based on the electron microscopic evidence and literature data the possibility of generation of LG from cell endoplasmic reticulum (ER) is discussed. It is proposed that the production of LG is connected with disturbances in glycosylation of proteins and lipids on the ER membranes.


Theoretical and experimental studies of the stability of drug-drug interact.
Several factors can intervene in the molecular properties and consequently in the stability of drugs. The molecular complexes formation often occur due to favor the formation of hydrogen bonds, leading the system to configuration more energy stable. This work we aim to investigate through theoretical and experimental methods the relation between stability and properties of molecular complexes the molecular complex formed between the drugs, efavirenz (EFV), lamivudine (3TC) and zidovudine (AZT). With this study was possible determining the most stable complex formed between the compounds evaluated. In addition the energy and structural properties of the complex formed in relation to its individual components allowed us to evaluate the stability of the same.


Electroclinical features of seizures in myelin oligodendrocyte glycoprotein antibody-associated cerebral cortical encephalitis: A case report and literature review.
Myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) are associated with various central nervous system demyelinating disorders. Recently, they were detected in cerebral cortical encephalitis (CCE), which often causes seizures. We performed a literature review to elucidate the electroclinical features of CCE. In addition to the published cases, we describe a new, illustrative case of MOG-Ab-associated CCE (MOG-CCE) with multifocal seizures documented by video electroencephalograph (EEG). We searched PubMed with the keywords "[MOG] AND [encephalitis]" and reviewed relevant articles. The articles included reports of patients with CCE (as demonstrated by magnetic resonance imaging) and serum MOG Ab positivity. Cases were excluded if no epileptic seizures were reported or if details of the seizures were unavailable. Our literature review identified 34 patients with MOG-CCE. An analysis of these 34 cases and the new case showed that 20 patients were male (57.1%), and the median age at presentation was 23 years (range, 6 to 46 years). Focal to bilateral tonic-clonic seizure was the most common seizure type, followed by focal motor seizure in the face or an arm or leg. EEG findings were available for 26 patients. Interictal epileptiform discharges (IEDs) and ictal EEG patterns were seen in 10 (38.5%) and 5 (19.2%) patients, respectively. Focal EEG abnormalities, including slow waves and IEDs, were observed in the central, parietal, occipital, or posterior temporal region. MOG-CCE has distinctive electroclinical features that differ from those of other autoimmune encephalitides. Careful electroclinical analysis of seizures can be helpful for diagnosing MOG-CCE.


The partitioning of heavy metals in incineration of sludges and waste in a bubbling fluidized bed 2. Interpretation of results with a conceptual model.
This work addresses the behavior, fate and/or partitioning of six targeted (Cd, Pb, Cr, Cu, Zn and Ni) heavy metals (HMs) in the incineration of sludges and waste in a bubbling fluidized bed (BFB) of 15 cm i.d. and 5.2m high followed by a filter chamber operated at 750-760 degrees C with a commercial ceramic filter. This paper presents three different things: (1) an in depth review of the published work relating to the problem of partitioning of the HMs in BFBs, (2) some more experimental incineration tests regarding the influence of the temperature of the bed of the BFB and the effect of the chlorine content in the feedstock on the partitioning of the HMs, and (3) the modelling of the partitioning of the HMs in the exit flows: bottom ash, coarse fly ashes, fine fly ash and vapour phase. The partitioning of the HMs is governed by fluid dynamic principles together with the kinetics of the diffusion of the HMs inside the ash particles and the kinetics of the reactions between the HMs and the components of the matrix of the ash. Some thermodynamic predictions do not fit the results from the BFB incinerator well enough because equilibria are not reached in at least three exit ash flows: coarse fly ash, fine fly ash and submicron particles. The residence time of these ash particles in these type of incinerators is very short and most of the HMs have no time to diffuse out of the ash particle. Finally, an examination was made on how in the ceramic hot filter the partition coefficients for the HMs increased, mainly for Cd and Pb, when the Cl-content in the feedstock was increased.


Real-time monitoring of the in vivo redox state transition using the ratiometric redox state sensor protein FROG/B.
The intracellular redox state is one of the key factors regulating various physiological phenomena in the cell. Monitoring this state is therefore important for understanding physiological homeostasis in cells. Various fluorescent sensor proteins have already been developed to monitor intracellular redox state. We also developed fluorescent redox sensor proteins named Oba-Q and Re-Q, the emissions of which are quenched under oxidized and reduced conditions, respectively. Although these sensors were useful to visualize the redox changes in the cell over time, they have the weakness that their emission signals are directly influenced by their in situ expression levels. To overcome this problem, we developed a redox sensor protein with a single excitation peak and dual variable emission peaks. This sensor protein shows green emission under oxidized conditions and blue emission under reduced conditions. We therefore named this sensor FROG/B, fluorescent protein with redox-dependent change in green/blue. By using this sensor, we successfully measured the changes in intracellular redox potentials in cyanobacterial cells quantitatively caused by light/dark transition just by calculating the ratio of emission between green and blue signals.


Accuracy of magnetic resonance imaging in the knee.
To determine the accuracy of magnetic resonance imaging (MRI) in the assessment of various knee disorders in comparison with arthroscopic findings and pathologic diagnosis. A retrospective and comparative study. Radiology Department, Aga Khan University Hospital, Karachi, from 01-12-1996 to 30-06-2000. Fifty-six subjects (36 males and 20 females), included in this study, had abnormal findings on MRI, which were correlated with arthroscopic findings in 50 cases and pathological diagnosis in 6 cases. Plain X-rays were available in all cases. The sensitivity, specificity and accuracy for MRI of the menisci and cruciate ligaments were as follows: medial meniscus pathologies 87% sensitivity, 94% specificity and 92% accuracy; lateral meniscus pathologies 92% sensitivity, 89% specificity and 90% accuracy; anterior cruciate ligament injuries 95% sensitivity, 96% specificity and 96% accuracy and posterior cruciate ligament injuries 100% sensitivity, 98% specificity and 98% accuracy. Pathological diagnosis was available in 6 cases. MR imaging suggested the diagnosis of tuberculosis and metastases as well as mapped out the extent of osteogenic sarcoma, fibromatoses and rhabdomyosarcoma. This study confirms that MR imaging of the knee is highly sensitive, specific, and accurate.


Stroke: understanding the differences between males and females.
Stroke is a significant cause of death and long-term disability in the USA. The incidence, mortality, and outcomes of stroke are significantly different between men and women. As with many diseases that affect men and women differently, an understanding on the reasons underlying those differences is critical to effective diagnosis and treatment. This review will examine the sex differences in stroke in both humans and animal models of stroke and review what is known about potential mechanisms underlying these differences. It is clear that there is a complex interaction between hormonal, genetic, and unknown factors at play in generating the sex differences in stroke.


History of the Tfam gene in primates.
Tfam is a single copy nuclear gene mapping on chromosome 10 in human and mouse, 20 in rat and 12 in Presbytis cristata. It encodes for an HMG (high-mobility-group) protein showing a high affinity with the two transcriptional promoters and other mitochondrial DNA regions. It is an activator of mitochondrial transcription acting in the presence of mitochondrial RNA polymerase and of transcription factor B. Other interesting features of Tfam gene in human and rat are reported such as the existence of a smaller isoform, originated by an alternative splicing mechanism of the exon 5 (delta5 isoform) and the presence of different processed pseudogenes in addition to the active copy of the gene. In order to widen knowledge about Tfam gene and the appearance of some of its properties in the evolutionary history of primates, we have studied some aspects of this gene in different species. In particular we have determined its chromosomal localization, suggesting that its locus is highly conserved; we have searched for the presence of the delta5 isoform, demonstrating that it is present only in hominids; we have provided evidence of Tfam processed pseudogenes in the majority of the analysed genomes. Sequence data from this article have been deposited in the EMBL nucleotide database.


Quantitative study of the aerobic and anaerobic faecal flora in neonatal necrotising enterocolitis.
Faeces from 24 neonates with proved necrotising enterocolitis (NEC), from 12 with clinically suspected NEC, and from 41 control infants were quantitatively cultured under aerobic and anaerobic conditions. An important difference in colonisation with Klebsiella was found between the NEC groups and the control group. Although the cause of NEC is unknown, colonisation with Klebsiella seems to increase the risk.


Inpatient Healthcare Resource Utilization, Costs, and Mortality in Adult Patients with Acute Graft-versus-Host Disease, Including Steroid-Refractory or High-Risk Disease, following Allogeneic Hematopoietic Cell Transplantation.
Acute graft-versus-host disease (GVHD) contributes to poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Data are limited regarding the economic burden of acute GVHD, particularly steroid-refractory or high-risk (SR/HR) disease. This retrospective analysis of the Premier Healthcare Database reports inpatient healthcare resource utilization (HCRU), costs, and mortality during initial hospitalization for allogeneic HCT and through 100 days post-HCT among patients who developed acute GVHD, including a subgroup with SR/HR disease, compared with patients without GVHD. The analysis included adults discharged for first HCT between January 1, 2011, and June 30, 2016 (acute GVHD, n = 906; SR/HR acute GVHD, n = 158; no GVHD, n = 1529). During the initial hospitalization for HCT, patients with acute GVHD and SR/HR acute GVHD (n = 455 and 125, respectively) had significantly longer median lengths of stay (31 and 46 days versus 24 days) and higher median total costs ($153,849 and $205,880 versus $97,417) versus patients with no GVHD (n = 1529; P < .0001 for all). During the 100-day post-HCT period, patients with acute GVHD and SR/HR acute GVHD had higher readmission rates (78.3% and 77.2% versus 28.3%; P < .0001) and inpatient mortality rates (20.2% and 35.4% versus 8.9%; P < .0001) versus patients with no GVHD. In summary, acute GVHD, especially SR/HR disease, is associated with longer inpatient stays, higher readmission rates, and higher inpatient mortality compared with no GVHD.


Some new methods for the evaluation of medical school sex education curricula.
This study proposes new ways of evaluating medical school sex education curricula which may be used not only to determine the best educational methods, but also to understand what skills and competence are important for a doctor to have in order to assist patients with their sexual problems. Since present evaluation tools are limited, the theoretical base from which human sexuality programmes are developed is based on unsupported personal judgement. Good research with improved techniques is a requisite for improving this situation.


Anxiety and Depression in Hemodialysis: Sex Differences.
Approach to hemodialysis care from a gender perspective has received a great deal of attention globally since two sexes may have different experiences and manifestations of the same disease. To explore sex differences in anxiety and depression among hemodialysis patients. In the study were enrolled 200 patients (100 men and 100 women) who underwent hemodialysis. Data were collected by the completion of "The Hospital Anxiety and Depression Scale (HADS)" which included patients' self-reported characteristics. The statistical significance level was p < 0.05. In men and women, anxiety was statistically significantly associated with relations with nurses (p = 0.033 and p = 0.001, respectively), concealment of hemodialysis (p = 0.013 and p = 0.001, respectively), and insomnia (p = 0.001 and p = 0.001, respectively). Only in women, anxiety was statistically significantly associated with years under hemodialysis (p = 0.002), relation with doctors (p = 0.001), and their belief that life had changed (p = 0.002), whereas only in men, anxiety was associated with help in daily activities (p = 0.001). In men and women, depression was statistically significantly associated with relations with nurses (p = 0.002 and p = 0.001, respectively) and dependency on health professionals (p = 0.001 and p = 0.002, respectively). Only in women, depression was statistically significantly associated with years under hemodialysis (p = 0.002), level of information (p = 0.022), relations with doctors (p = 0.001), concealment of hemodialysis (p = 0.001), their belief that life had changed (p = 0.001), and insomnia (p = 0.001). The development of an effective treatment that may alleviate anxiety and depression needs to capture how patients perceive and respond to hemodialysis.


Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection.
With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. CRP(P<0.001), D-dimer (P<0.001), ferritin (P=0.039), and hemoglobin (P=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (P<0.001). However, plasmapheresis did not affect the length of hospital stay (P=0.076), which could have significantly increased survival rates (P<0.001). Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.


Evaluation of cell membrane-derived nanoparticles as therapeutic carriers for pancreatic ductal adenocarcinoma using an in vitro tumour stroma model.
Here, we fabricated nanoparticles made solely from the membrane of cells found in the pancreatic tumour's microenvironment (TME), like the human MiaPaCa-2 cells and M2-polarized macrophages. The cell membrane-derived nanoparticles (CMNPs) deriving from the MiaPaCa-2 cells (MPC2-CMNPs) were loaded with the chemotherapeutic drug paclitaxel (PTX), and the CMNPs deriving from M2-polarized macrophages (M2-CMNPs) were loaded with the colony-stimulating factor 1 receptor inhibitor, pexidartinib (PXDB). The CMNPs' thorough morphological and physicochemical characterisation was followed by an in-depth study of their targeting ability and the endocytosis pathway involved during their internalisation. An in vitro model of the desmoplastic stroma comprising cancer-associated fibroblast-mimicking cells and M2-polarized macrophages was also developed. The model was characterised by collagen and α-smooth muscle actin (α-SMA) expression (overexpressed in desmoplasia) and was used to assess the CMNPs' ability to cross the stroma and target the tumour cells. Moreover, we assessed the effect of PXDB-loaded M2-CMNPs on the expression of M1 (CD80/CD86) and M2 (CD206/CD209) polarisation markers on activated macrophages. Finally, we evaluated the PTX and PXDB-loaded CMNPs' effect on the viability of all the used TME cell lines alone or in combination. Overall, this pilot study showed the potential of the CMNPs to cross an in vitro stroma model and act synergistically to treat PDAC.


Opioid pseudoaddiction--an iatrogenic syndrome.
A case is presented of a 17-year-old with leukemia, pneumonia and chest-wall pain. Inadequate treatment of the patient's pain led to behavioral changes similar to those seen with idiopathic opioid psychologic dependence (addiction). The term pseudoaddiction is introduced to describe the iatrogenic syndrome of abnormal behavior developing as a direct consequence of inadequate pain management. The natural history of pseudoaddiction includes progression through 3 characteristic phases including: (1) inadequate prescription of analgesics to meet the primary pain stimulus, (2) escalation of analgesic demands by the patient associated with behavioral changes to convince others of the pain's severity, and (3) a crisis of mistrust between the patient and the health care team. Treatment strategies include establishing trust between the patient and the health care team and providing appropriate and timely analgesics to control the patient's level of pain.


Smart spectrophotometric assessment of tamsulosin hydrochloride and tadalafil in their new pharmaceutical formulation for treatment of benign prostatic hyperplasia and erectile dysfunction.
A novel combination of tamsulosin hydrochloride and tadalafil is recently available for treatment of benign prostatic hyperplasia and erectile dysfunction. For the first time, four simple, accurate, smart and robust spectrophotometric methods have been suggested for their simultaneous quantification. The methods, namely; first derivative, ratio difference, derivative ratio and mean centering of ratio spectra, successfully resolved the spectral overlap of their challenging binary mixture. Calibration curves were linear at 2.0-40.0 and 2.0-55.0 μg/mL for tamsulosin hydrochloride and tadalafil, respectively. The methods were validated according to ICH guidelines and statistically compared with the official ones, revealing no considerable difference with respect to accuracy and precision. Specificity of the developed methods was assessed by evaluating various laboratory prepared mixtures. Furthermore, the methods were successfully applied for the quantification of the two drugs in their combined dosage form.


Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma.
We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations. This conserved IFN-γ transcriptome response in melanoma cells serves to amplify the antitumor immune response. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFN-γ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.


Bluegill growth as modified by plant density: an exploration of underlying mechanisms.
Bluegill (Lepomis macrochira) growth varies inconsistently with plant density. In laboratory and field experiments, we explored mechanisms underlying bluegill growth as a function of plant and invertebrate density. In the laboratory, bluegills captured more chironomids (Chironomus riparius) than damselflies (Enallagma spp. and Ischnura spp.), but energy intake per time spent searching did not differ between damselfly and chironomid treatments. From laboratory data, we described prey encounter rates as functions of plant and invertebrate density. In Clark Lake, Ohio, we created 0.05-ha mesocosms of inshore vegetation to generate macrophyte densities of 125, 270, and 385 stems/m2 of Potamogeton and Ceratophyllum and added 46-mm bluegill (1/m2). In these mesocosms, invertebrate density increased as a function of macrophyte density. Combining this function with encounter rate functions derived from laboratory data, we predicted that bluegill growth should peak at a high macrophyte density, greater than 1000 stems/m2, even though growth should change only slightly beyond 100 stems/m2. Consistent with our predictions, bluegills did not grow differentially, nor did their use of different prey taxa differ, across macrophyte densities in the field. Bluegills preferred chironomid pupae, which were relatively few in numbers but vulnerable to predation, whereas more cryptic, chironomid larvae, which were associated with vegetation but were relatively abundant, were eaten as encountered. Bluegills avoided physid snails, which were abundant. Contrary to previous work, vegetation did not influence growth or diet of bluegill beyond relatively low densities owing to the interaction between capture probabilities and macroinvertebrate densities.


Characterization of left ventricular filling abnormalities and its relation to elevated plasma brain natriuretic peptide level in acute to chronic diastolic heart failure.
Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels. In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 +/-0.4 vs 1.8+/-0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01). A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF.