Individualization of immediate posttransplant immunosuppression. The value of antilymphocyte globulin in patients with delayed graft function.
In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell greater than or equal to 30% in the first 24 hr (immediate function) were started on CsA and prednisone (P) (group 1, n = 26). The remainder were randomized to P and azathioprine (group 2, n = 32) or P and ALG (group 3, n = 26), and switched to CsA when serum Cr fell greater than 30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P less than .05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3(NS). In patients requiring dialysis, mean day off dialysis was 12 +/- 3 in both groups 2 and 3. Mean hospital stay was 12.5 +/- 1.3 days for group 1, 21.6 +/- 2.1 days for group 2 (P less than .05 vs. 1 & 3), and 14.5 +/- 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P less than .05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P less than .05 vs. 1 and 3) and 35% of group 3 (P less than .05 vs. 1 and 2). Mean serum creatinine at 6-12 months remained higher in patients with DGF (group 1 P less than .05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups.(ABSTRACT TRUNCATED AT 400 WORDS)


Multi-Rater Agreement Using the Adapted Fracture Healing Scale (AFHS) for the Assessment of Tubular Bones on Conventional Radiographs: Preliminary Study.
Better understanding of the timing of fracture healing may help in cases of interpersonal violence but also of personal identification. The intra- and inter-rater agreement for the adapted fracture healing scale (AFHS) assessing the post-traumatic time interval on radiographs were tested. This is a preliminary study, providing essential information on method reliability for upcoming studies using the AFHS. Five raters (two radiologists, a forensic pathologist, an orthopedist, and an anthropologist) were presented with a test in three parts consisting of 85 radiographs (from 30 adults) of fractures of tubular bones in different stages of healing purposefully selected from more than 1500 radiographs. The raters were firstly asked to assess 15 features describing fracture healing as present, absent, or not assessable. Thereafter, the raters were asked to choose from the AFHS a single-stage best representing the observed healing pattern. The intra- and inter-rater agreement were assessed using single-rating, absolute agreement, two-way mixed-effects intra-class correlation (ICC) coefficients. The intra-rater ICC of radiologist 1 ranged from 0.80 to 0.94. The radiologists' inter-rater ICC ranged from 0.68 to 0.74, while it ranged from -0.01 to 0.90 for the other raters. The good to excellent ICC among the radiologists and forensic anthropologist provides good foundation for the use of the AFHS in forensic cases of trauma dating. The poor to good results for the other physicians indicate that using the AFHS requires training in skeletal anatomy and radiology.


Enhancing an oncologist's recommendation to exercise to manage fatigue levels in breast cancer patients: a randomized controlled trial.
Fatigue is a troublesome symptom for breast cancer patients, which might be mitigated with exercise. Cancer patients often prefer their oncologist recommend an exercise program, yet a recommendation alone may not be enough to change behavior. Our study determined whether adding an exercise DVD to an oncologist's recommendation to exercise led to better outcomes than a recommendation alone. Ninety breast cancer patients, at varying phases of treatment and stages of disease, were randomized to receive the following: an oncologist verbal recommendation to exercise (REC; n = 43) or REC plus a cancer-specific yoga DVD (REC + DVD; n = 47). Fatigue, vigor, and depression subscales of the Profile of Mood States, and physical activity levels (MET-min/week), exercise readiness, and self-efficacy were assessed at baseline, 4, and 8 weeks. Analyses controlled for age, time since diagnosis, and metastatic disease. Over 8 weeks, women in REC + DVD used the DVD an average of twice per week. The REC + DVD group had greater reductions in fatigue (- 1.9 ± 5.0 vs. - 1.0 ± 3.5, p = 0.02), maintained exercise readiness (- 0.1 ± 1.1 vs. - 0.3 ± 1.3; p = 0.03), and reported less of a decrease in physical activity (- 420 ± 3075 vs. - 427 ± 5060 MET-min/week, p = 0.06) compared to REC only. A low-cost, easily distributed, and scalable yoga-based DVD could be a simple booster to an oncologist's advice that motivates breast cancer patients, even those with advanced disease and/or in treatment, to engage in self-care, e.g., exercise, to manage fatigue. ClinicalTrials.gov Identifier: NCT03120819.


Increased NAA and reduced choline levels in the anterior cingulum following chronic methylphenidate. A spectroscopic test-retest study in adult ADHD.
The anterior cingulate cortex (ACC) is crucially involved in executive control of attention. Here, seven medication-naïve adult patients suffering from attention deficit/hyperactivity disorder (ADHD) were studied with 2D (1)H-magnetic resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b'-c' and 32'] twice, once before initiation of stimulant treatment and once after 5-6 weeks of methylphenidate. Upon retest, all patients demonstrated marked clinical improvement. Analysis of regional brain spectra revealed a significantly decreased signal of choline containing compounds as well as increased N-acetyl-aspartate (NAA) levels following treatment with methylphenidate whereas total creatine remained unchanged. Our results add to a growing body of evidence implicating the ACC in the pathophysiology of ADHD and suggest that subtle structural changes might be associated with aspects of clinical improvement under stimulant treatment.


Contemporary trends in management of the upper limb in tetraplegia: a multinational perspective.
The 2007 Meeting on Upper Limb in Tetraplegia in Philadelphia provided an opportunity to explore individual and regional differences in surgeons' preferences in tetraplegic upper limb reconstruction. Reports were heard from New Zealand, Canada, Asia, Australia, and Europe. Most presenters attempted to gather data from across their regions. Each reporter made a sincere effort to identify the spectrum of the quality of the data, as well as the opportunities for regional progress. Completeness of reports varied, depending on sophistication of the available data collection agencies. Notwithstanding limitations and omissions, the commonalities and differences revealed in those reports were enlightening and provide opportunities for fruitful study. This article represents a compilation of presentations on regional trends by invited participants.


Limited implementation of measures to reduce nosocomial spread of COVID-19 in hip-fracture patients in the North West of England.
Hip-fracture patients are vulnerable to the outcomes of COVID-19. We performed a cross-sectional survey to determine measures employed to limit nosocomial spread of COVID-19 in 23 orthopaedic trauma departments in the North-West of England. Nineteen (87%) hospitals admitted patients to a ward prior to a negative swab, and only 9 (39%) patients were barrier nursed. Hip-fracture patients were operated in non-COVID-19-free theatres in 21 (91%) hospitals. Regular screening of doctors working in trauma and elective areas for COVID-19 was undertaken in three (13%) and five (22%) hospitals, respectively. Doctors moved freely between trauma and elective areas in 22 (96%) hospitals.


The isolation and characterization of Duck astrovirus type-1 remerging in China.
Since the first report from Cherry Valley ducks on a commercial duck farm in China (2008), duck astrovirus type 1(DAstV-1)-associated duck viral hepatitis (DVH) have been detected in several commercial duck flocks. A highly acute disease characterized by hepatitis broke out in ducklings in Shandong Province in March 2021, all diseased ducks have been immunized against the duck viral hepatitis vaccine. One DAstV-1 strain, designated as DAstV-SDWF, was isolated from a diseased duckling. Here, the isolation, cultivation, and characterization of DAstV-1 isolate are described. The isolated astrovirus grew well in the LMH cell line. To determine the entire genomic of the DAstV-SDWF isolate, the next-generation sequencing (NGS) technique was conducted on the Illumina HiSeq platform. Complete genome sequence analysis revealed that DAstV-SDWF isolate was 91.6%-98.6% homology with others DAstV-1 deposited in Genbank. Similar clinical symptoms were successfully reproduced by an experimental infection study using the DAstV-SDWF isolate. DAstV-SDWF is the first DAstV-1 strain whose experimental infection study has been conducted in China. Results of the above data demonstrated that DAstV-1 could be one of the causative agents of the DVH occurring in China. The present works are likely to provide new insights into the pathogenicity and evolution of DAstV-1 in ducks.


Dendritic cells of the mouse recognized by two monoclonal antibodies.
A new monoclonal antibody, MIDC-8, is described which shows a comparable tissue distribution as the recently described NLDC-145 antibody. It recognizes interdigitating cells, veiled cells and Langerhans cells in lymphoid organs and the skin of the mouse. In contrast to NLDC-145 it recognizes a cytoplasmic component of these cell types. Its distribution is more restricted to the T cell-dependent areas than NLDC-145. Isolation of dendritic cells from lymph nodes, spleen and thymus revealed that both antibodies react with the in vitro isolated dendritic cells. The results show that these antibodies can be used to study dendritic cells in vitro and emphasize the relationship between the in vivo interdigitating cells of the T cell areas and the in vitro isolated dendritic cells.


Impact of biomarker type on periprocedural myocardial infarction in patients undergoing elective PCI.
Periprocedural myocardial infarction (MI) according to the Society for Cardiovascular Angiography and Interventions (SCAI) criteria has prognostic relevance among patients undergoing percutaneous coronary intervention (PCI). However, it is unclear whether the type of cardiac biomarker used for the diagnosis of periprocedural MI plays a role in terms of event frequency and outcomes. To compare the characteristics of SCAI periprocedural MI based on creatine kinase-myocardial band fraction (CK-MB) vs. high-sensitivity cardiac troponin (hs-cTn) in patients undergoing elective PCI. Between 2017 and 2021, periprocedural MI was assessed in a prospective study. The primary clinical outcome of interest was all-cause death at 1-year follow-up. A total of 1010 patients undergoing elective PCI were included. SCAI periprocedural MI based on CK-MB vs. hs-cTnI occurred in 1.8 and 13.5% of patients, respectively. hs-cTnI periprocedural MI in the absence of concomitant CK-MB criteria was associated with lower rates of ancillary criteria, including angiographic, ECG, and cardiac imaging criteria. At 1-year follow-up, periprocedural MI defined by CK-MB (adjusted hazard ratio, HR, 4.27, 95% confidence intervals, CI, 1.23-14.8; P = 0.022) but not hs-cTnI (adjusted HR 2.04, 95% CI 0.94-4.45; P = 0.072) was associated with a higher risk of all-cause death. Hs-cTnI periprocedural MI was not predictive of death unless accompanied by CK-MB criteria (adjusted HR 4.64, 95% CI 1.32-16.31; P = 0.017). In the setting of elective PCI, using hs-cTn instead of CK-MB resulted in a substantial increase in SCAI periprocedural MI events, which were not prognostically relevant in the absence of concurrent CK-MB elevations.


Optical Coherence Tomography Angiography of the Choriocapillaris in Subclinical Toxoplasma Chorioretinitis: A Case Report.
This report describes the optical coherence tomography angiography (OCTA) findings detected at the choriocapillaris slab before the clinical picture of acute toxoplasmosis choroiretinitis (TCR) by following up a patient with serial images of OCT and OCTA from the quiescent to the active stage of the disease. In this case, the increased thickness of the choroid in the OCT B-scan and the prominent flow void at the choriocapillaris slab of the OCTA were detected early in the course of the disease. OCTA is a useful imaging technique in TCR and might help in predicting the TCR lesion at the subclinical stage.


A Sizeable Solitary Pedunculated Peripheral Osteoma of the Hard Palate: A Case Report.
Osteomas are benign, slow growing, usually sessile osteogenic tumors of unknown etiology. They arise from proliferation of either cancellous or compact bone. They can be central, peripheral or extra-skeletal based on their origin from endosteum, periosteum or extra-skeletal soft tissue respectively. They are commonly found in the skull and facial bones, the most common site in the maxillofacial region being paranasal sinuses. Among the jaw bones the most common site is the mandible. The hard palate is a rare site for such osteomas with a very few cases reported in literature. We report a case of large pedunculated peripheral osteoma of the hard palate in a 38 year old male. The tumor was excised with no recurrence after 3 years followup.


Readmission, Complication, and Disposition Calculators in Total Joint Arthroplasty: A Systemic Review.
Predictive tools are useful adjuncts in surgical planning. They help guide patient selection, candidacy for inpatient vs outpatient surgery, and discharge disposition as well as predict the probability of readmissions and complications after total joint arthroplasty (TJA). Surgeons may find it difficult due to significant variation among risk calculators to decide which tool is best suited for a specific patient for optimal decision-based care. Our aim is to perform a systematic review of the literature to determine the existing post-TJA readmission calculators and compare the specific elements that comprise their formula. Second, we intend to evaluate the pros and cons of each calculator. Using a Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols protocol, we conducted a systematic search through 3 major databases for publications addressing TJA risk stratification tools for readmission, discharge disposition, and early complications. We excluded those manuscripts that were not comprehensive for hips and knees, did not list discharge, readmission or complication as the primary outcome, or were published outside the North America. Ten publications met our criteria and were compared on their sourced data, variable types, and overall algorithm quality. Seven of these were generated with single institution data and 3 from large administrative datasets. Three tools determined readmission risk, 5 calculated discharge disposition, and 2 predicted early complications. Only 4 prediction tools were validated by external studies. Seven studies utilized preoperative data points in their risk equations while 3 utilized intraoperative or postsurgical data to delineate risk. The extensive variation among TJA risk calculators underscores the need for tools with more individualized stratification capabilities and verification. The transition to outpatient and same-day discharge TJA may preclude or change the need for many of these calculators. Further studies are needed to develop more streamlined risk calculator tools that predict readmission and surgical complications.


Lasofoxifene (CP-336,156), a novel selective estrogen receptor modulator, in preclinical studies.
Estrogen replacement therapy is reported to reduce the incidence of vertebral fractures in postmenopausal women, however, its compliance is limited because of side effects and safety concerns. Estrogen's side effects on breast and uterine tissues leading to the potential increased risk of uterine and breast cancer limit widespread estrogen usage. Thus, there is a significant medical need for a therapy that protects against postmenopausal bone loss but is free of estrogen's negative effects on reproductive tissues. Selective estrogen receptor modulators (SERMs) have been investigated as an alternative to hormone replacement therapy. One such compound, raloxifene, has been approved for the prevention and treatment of osteoporosis. Lasofoxifene (LAS), a new, nonsteroidal, and potent SERM, is an estrogen antagonist or agonist depending on the target tissue. LAS selectively binds with high affinity to human estrogen receptors. In ovariectomized (OVX) rat studies, LAS prevented the decrease in femoral bone mineral density, tibial and lumbar vertebral trabecular bone mass at an ED100 of about 60 μg/kg/day. LAS inhibited the activation of trabecular and endocortical bone resorption and bone turnover in tibial metaphyses and diaphyses, and lumbar vertebral body in OVX rats. In addition, LAS decreased total serum cholesterol, inhibited body weight gain and increased soleus muscle weight in OVX rats. Similarly, LAS prevented bone loss induced by orchidectomy or aging in male rats by decreasing bone resorption and bone turnover while it had no effect in the prostate. Further, LAS decreased total serum cholesterol in intact aged male rats or in orchidectomized male rats. Synergestic skeletal effects were found with LAS in combination with bone anabolic agents such as prostaglandin E2 (PGE2), parathyroid hormone (PTH) or a growth hormone secretagoue (GHS) in OVX rats. In combination with estrogen, LAS inhibited the uterine stimulating effects of estrogen but did not block the bone protective effects of estrogen. In immature and aged female rats, LAS did not affect the uterine weight and uterine histology. In OVX adult female rats, LAS slightly but significantly increased uterine weight. These results demonstrated that LAS produced effects on the skeleton indistinguishable from estrogen in female and male rats. However, unlike estrogen, LAS had little effect on uterine weight and cellular proliferation of uterus in female rats. In preclinical anti-tumor studies, LAS inhibited human breast cancer growth in mice bearing MCF7 tumors, prevented NMU-induced mammary carcinomas and possessed chemotherapeutic effects in NMU-induced carcinomas in rats. Therefore, we conclude that LAS possesses the antiestrogenic effects in breast tissue and estrogenic effects in bone and serum cholesterol, but lacks estrogen's side effects on uterine tissue. These data support the therapeutic potential of LAS for the prevention and treatment of postmenopausal bone loss and mammary carcinomas in humans.


Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines.
Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. MTT assay was used to determine IC(50) values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.


Physician leadership is a new mandate in surgical training.
Traditionally, development of physician leadership has occurred at random in surgical training. One possible reason is that surgical educators have focused on detailed instruction on critical patient situations, resuscitation, and technical skills, but they have provided little formal training in the essential leadership skills. To determine resident perceptions about the importance of these skills and individual strengths and weaknesses in these areas, a questionnaire was administered to 43 residents in our general surgery program. In part one of the questionnaire, the residents ranked 18 leadership skills on a scale of 1 to 4 in importance ("not important," "minimally important," "somewhat important," and "very important") for career development. The second portion of the questionnaire asked the residents to rate themselves on a similar scale with regard to their personal confidence and competence in these same areas. Twenty-three residents (53%) completed the entire questionnaire. The majority of the residents (92%) rated all 18 leadership skills "somewhat" or "very important" for career development. More than 50% of the residents rated themselves as not competent or minimally competent in 10 of the 18 areas. Ethics was the only area in which >75% of the residents believed themselves to be more than minimally competent. There were no significant differences between postgraduate training levels in any of the parameters calculated. We conclude that although residents see these nontraditional topics as an important part of their professional education, they do not necessarily feel confident or competent in these areas. Establishing a conscious effort to teach these topics and to emphasize their importance during training will enhance residents' self-image, performance, and potential as future leaders.


Guide for collecting and reporting metadata on protocol variables and parameters from slide-based histotechnology assays to enhance reproducibility.
The central tenet of scientific research is the rigorous application of the scientific method to experimental design, analysis, interpretation, and reporting of results. In order to confer validity to a hypothesis, experimental details must be transparent and results must be reproducible. Failure to achieve this minimum indicates a deficiency in rationale, design, and/or execution, necessitating further experimental refinement or hypothesis reformulation. More importantly, rigorous application of the scientific method advances scientific knowledge by enabling others to identify weaknesses or gaps that can be exploited by new ideas or technology that inevitably extend, improve, or refine a hypothesis. Experimental details, described in manuscript materials and methods, are the principal vehicle used to communicate procedures, techniques, and resources necessary for experimental reproducibility. Recent examination of the biomedical literature has shown that many published articles lack sufficiently detailed methodological information to reproduce experiments. There are few broadly established practice guidelines and quality assurance standards in basic biomedical research. The current paper provides a framework of best practices to address the lack of reporting of detailed materials and methods that is pervasive in histological slide-based assays. Our goal is to establish a structured framework that highlights the key factors necessary for thorough collection of metadata and reporting of slide-based assays.


Worm burdens in cows. II. An analysis of the population of nematodes in the abomasa of adult dairy cows.
Over a period of one year, from February 1979-February 1980, the abomasa of four dairy cows were examined each week for the presence of parasitic nematodes. Based on the identification of adult male worms, Ostertagia ostertagi (94%) and Trichostrongylus axei (75%) were the most prevalent species, and Haemonchus contortus was absent. Total worm burdens varied from zero (one cow) to 100,890. The geometric mean total number was 3011. The geometric mean number of arrested larval stages was 685. Of the adult worm burden, more than 85% consisted of O. ostertagi, about 12% of T. axei, the remaining 3% was other species. No relationship could be found between worm burdens and the age of cow, the weight of the abomasum or the milk yield. The adult Ostertagia burden was highest in winter, lowest in summer. Besides those of O. ostertagi, small numbers of arrested larvae of T. axei were observed from September onwards. Cows from farms with a zero-grazing system had significantly fewer worms than cows from other farms independently of the time of the year.


Prenatal diagnosis of partial monosomy 2q (2q37.3→qter) and partial trisomy 10q (10q24.31→qter) of paternal origin associated with increased nuchal translucency and abnormal maternal serum screening results.
We present prenatal diagnosis of terminal 2q deletion and distal 10q duplication of paternal origin in a fetus associated with increased nuchal translucency and abnormal maternal serum screening results. A 26-year-old woman who had experienced spontaneous abortion twice underwent amniocentesis at 16 weeks of gestation because of an increased nuchal translucency thickness of 3.5 mm at 12 weeks of gestation and abnormal maternal serum screening results of 2.573 multiples of the median (MoM) of free β-human chorionic gonadotrophin (β-hCG) and 1.536 MoM of pregnancy-associated plasma protein-A (PAPP-A) resulting in a trisomy 21 risk of 1:64. Amniocentesis revealed a derivative chromosome 2. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr [hg19] 2q37.3 (238,294,223-242,782,258) × 1, 10q24.31q26.3 (102,018,246-135,426,386) × 3. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX in the mother and a karyotype of 46,XY,t(2;10)(q37.3;q24.3) in the father. The fetal karyotype was 46,XX,der(2)t(2;10)(q37.3;q24.3)pat. The pregnancy was terminated at 20 weeks of gestation, and a malformed fetus was delivered with facial dysmorphism. Postnatal analysis of the cord blood confirmed the results of prenatal diagnosis. The fetus had a 4.693-Mb deletion of 2q37.3 encompassing the genes of HDAC4, KIF1A, PASK, HDLBP, FARP2 and D2HGDH, and a 33.34-Mb duplication of 10q24.31-q26.3 encompassing the gene of NFκB2. First-trimester ultrasound and maternal serum biochemistry screening may help to identify an unexpected unbalanced familial translocation at prenatal diagnosis.


Respiratory tract infections in children with tracheostomy.
Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear. We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups. Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children. In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use.


Pneumomediastinum, pneumothorax and subcutaneous emphysema during radiotherapy in primary cavitating bronchogenic carcinoma.
An extremely rare case of cavitating large cell carcinoma lung is reported in a middle aged man who developed pneumomediastinum, pneumothorax and subcutaneous emphysema on thirteenth day of his tele cobalt radiotherapy to chest. Possible mechanisms of such complications during radiotherapy are also discussed.


Costs-benefits of robot-assisted colorectal surgery: a different perspective.
The costs of robot-assisted surgery (RAS) still represent a critical issue. Kulaylat et al. reported a propensity-matched study to compare the outcomes of colorectal surgery between a robotic and a laparoscopic group, concluding that RAS was burdened by higher costs. However, authors did not mention what da Vinci system, Si or Xi, they used and this could be crucial, as recently data published by our group on rectal resections showed that the use of the da Vinci Xi and the surgeon's increased experience could improve the results and significantly reduce the costs of RAS.


Aluminium speciation in natural water by sorption on a complexing resin.
Very stable aluminium complexes may be present in natural waters, which can be detected only using appropriate methods. One of them is the resin titration based on the sorption of aluminium on a strongly sorbing resin, Chelex 100. It was here used to detect strong aluminium complexes, and to characterize them by determining their concentration, and the corresponding stability constant. High and low salinity waters were sampled in different sites in the North of Italy. In all the samples aluminium complexes with high stability constant, up to 10(17.4) M(-1) in the less acidic solution, were detected. The stability constant depends mainly on the solution acidity, increasing with increasing pH up to 7. The concentration of the ligands responsible for the strong complexation is similar to that of aluminium (from 0.5 to 1.5 microM), or somewhat lower in the case of estuarine and sea waters. A small fraction of aluminium (from 0% to 2%) in freshwaters, higher in estuarine and sea waters (14% and 10%, respectively), is present in weakly bound forms which could also be the hydrolysis products. The conditional constants of the strong complexes were determined for the different samples examined. They were found to be slightly lower in the case of the high salinity waters, in which a value of 10(16.1) M(-1) at pH 7.5 was obtained. This is probably due to the higher ionic strength in marine water, which strongly influences the complexation of trivalent metal ions, as seen for example also in the hydrolysis. It could be deduced that similar substances, but at different concentration, would be responsible for the aluminium complexation in the sea and freshwaters here examined. They could be natural organics like fulvic substances, or better some particular complexing sites in this substances with very high affinity for aluminium.


The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer.
Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients.


Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B.
The regulation of interleukin (IL)-2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL-2. However, B cells can also synthesize IL-2. In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus (EBV)-transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin. Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [distal nuclear factor (NF)-AT, proximal NF-AT, AP-1/Octamer (UPS) or NF-chi B (TCEd) sites] were performed. In EBV-transformed B clones, the chi B site exerted the strongest inducible activity; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells. An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells, while it still had activity in Jurkat T cells. In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2, the activity of the IL-2 promoter correlated well with the status of IL-2 secretion. Similarly, a human immunodeficiency virus promoter, whose activity is controlled through chi B factors, was found to be active in the IL-2 producing EBV-B cells, but inactive in the non-IL-2-producing cells. Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes. A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells. These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells, whereas other transcription factors appear to be less important for IL-2 expression in these cells.


Anatomical and histochemical characterization of some highly medicinal plants as a tool for quality control.
Medicinal plants are richest source of chemical compounds that can be used to evolve novel drugs. According to World Health Organization (WHO), in developing countries more than 3.5 billion people relay on herbal drugs for their primary health care. In the present study, an attempt was carried out to authenticate some selected medicinal plants (Fagonia cretica L., Peganum harmala L., Tribulus terrestris L., Chrozophora tinctoria L. Raf. and Ricinus communis L.) from family Zygophyllaceae and Euphorbiaceae using light and scanning electron macroscopic techniques. Macroscopic evaluation and comparative anatomy (Light Microscopy) of the root and fruits revealed great diversity in macro and microscopic features. Scanning electron microscopy (SEM) of root powder showed non-glandular trichomes, stellate trichomes, parenchyma cells and vessels. Fruits SEM exhibited non-glandular trichomes, glandular trichomes, stellate trichomes, peltate trichomes and mesocarp cells. Both macroscopic and microscopic evaluation plays a crucial role in the correct substantiation and validation of novel sources. These findings can serve as an essential source of information to accomplish the authenticity and to appraise the quality and purity of the herbal drugs in accordance to WHO guidelines. These parameters can be used to distinguish the selected plants from their commonly used adulterants. RESEARCH HIGHLIGHTS: In the current work, five plants (Fagonia cretica L., Peganum harmala L., Tribulus terrestris L., Chrozophora tinctoria L. Raf. and Ricinus communis L.) from Zygophyllaceae and Euphorbiaceae were investigated for macroscopy and microscopy (LM & SEM) for the first time. Macroscopic and microscopic evaluation disclosed great diversity in morphology and histology. Microscopy is the backbone of standardization process. Current study helped in correct identification and quality assurance of the plant materials. Their statistical investigation may possess great potency for plant taxonomists to further appraise the vegetative growth and tissue development which is requisite especially for fruit to enhance the yield of herbal drugs and their formulation. Further molecular studies, compounds isolation and characterization are required to deepen the knowledge of these herbal drugs.


Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina.
Complement activation is involved in the pathogenesis of age-related macular degeneration. How complement is activated in the retina is not known. Previously we have shown that complement factor H (CFH) is constitutively expressed by retinal pigment epithelial (RPE) cells and the production of CFH is negatively regulated by inflammatory cytokines and oxidative insults. Here we investigated the production and regulation of complement factor B (CFB) in RPE cells. Immunohistochemistry showed that CFB is expressed at low levels on the apical portion of the RPE cells in normal physiological conditions. With age, CFB expression increases and extends to the basal part of RPE cells. Confocal microscopy and real-time PCR of RPE cultures indicated that the production of CFB by RPE cells is positively regulated by TNF-alpha, IFN-gamma and long-term (30 days) photoreceptor outer segments treatments. Increased CFB expression in RPE cells in vivo is accompanied by the accumulation of complement C3 and C3a deposition at the Bruch's membrane and the basal layer of RPE cells. Our results suggest that RPE cells play important roles in regulating complement activation in the retina. Increased complement activation in the aged retina may be important for retinal homeostasis in the context of accumulating photoreceptor waste products.


Three Novel Heterozygous Mutations of NPHS1 Gene Causing Infants with Congenital Nephrotic Syndrome: Two Chinese (Han) Cases.
Congenital nephrotic syndrome (CNS) of the Finnish type (CNF) is an autosomal recessively disorder. NPHS1 gene mutation is the main gene responsible for CNF. This study aimed to explore the clinical manifestations and the characteristics of genetic variation in Chinese patients with CNS. A 15-minute-old boy and a 34-day-old girl with CNS were included. NPHS1 gene was detected by next-generation high-throughput sequencing. Patient 1 carried two novel heterozygous mutations of NPHS1 gene, one was c.204delG, p. (Leu69fs) in exon 2 of NPHS1 gene, a heterozygote frameshift mutation; the other was c.3558delT, p. (Gly1187fs) in exon 28, a heterozygote frameshift mutation. Patient 2 carried three heterozygous mutations of NPHS1, among them, c.1561-G>A. p.Asp521Asn in exon 12 is a heterozygous missense mutation. It was identified as possible de novo pathogenicity gene. Three novel heterozygous mutations of NPHS1 gene were responsible for the patients with CNS and can enlarge the spectrum of NPHS1 gene mutation.


AF-DX 116 discriminates heart from gland M2-cholinoceptors in man.
The M2-cholinoceptor subtype selective antagonist AF-DX 116 was compared with atropine with respect to effects on heart rate and salivary flow in healthy volunteers. These effects were related with in vitro occupancy of M-cholinoceptor subtypes in radioreceptor assays of plasma samples. Radioreceptor assays comprised M1-cholinoceptors in bovine cerebral cortex and M2-cholinoceptors in pig heart and rat salivary gland membranes. 3H-pirenzepine served as a label in the cerebral cortex 3H-N-methyl-scopolamine in the heart and gland preparations. Oral administration of 240 mg AF-DX 116 led to a time dependent increase in heart rate with a maximum effect comparable to atropine 40 micrograms/kg i.v. The effects of both drugs on heart rate were matched by a greater than 80% occupancy of heart M2-cholinoceptors in the radioreceptor assay of plasma samples. In contrast to the complete inhibition of salivary flow after atropine, AF-DX 116 induced an increase of salivation. The effects on salivary flow coincided with a greater than 80% occupancy of glandular M2-cholinoceptors after atropine but no detectable occupancy after AF-DX 116. Occupancy of the M1-subtype amounted to 61.7% after AF-DX 116 and a blockade of inhibitory, presynaptic M1-autoreceptors at missing postsynaptic blockade of glandular M2-cholinoceptors might explain the hypersalivation induced by AF-DX 116.


Exogenous phospholipid reduces postoperative peritoneal adhesions in rats.
To find out if the previously described ability of phosphatidylcholine to reduce peritoneal adhesions is specific to it, or if other phospholipids such as phosphatidylinositol (PI) or DL-phosphatidylcholine dilauryl (DL-PC) have similar effects. Laboratory experiment. University hospital, Sweden. 160 rats which had had intraperitoneal adhesions induced at laparotomy by peritoneal defects repaired in one of two models. PI was given intraperitoneally either once in a dose of 20 or 40 mg/rat at the end of the operation, or at the end of the operation and repeated on the second and third postoperative days. DL-PC was given once at the end of the operation in a dose of either 20 or 40 mg/rat. Adhesions were assessed a week after operation by an observer who was unaware of the treatment given. PI given on three consecutive days significantly reduced adhesions formed postoperatively in both models (p < 0.05). Neither PI nor DL-PC given in a single dose of 20 mg/rat had any effect, whereas both PI and DL-PC given in single doses of 40 mg/rat significantly reduced adhesions (p < 0.05). Both PI and DL-PC are effective in the prevention and limiting of postoperative adhesions in rats.


Sequence of the mouse Q4 class I gene and characterization of the gene product.
The Q4 class I gene has been shown to participate in gene conversion events within the mouse major histocompatibility complex. Its complete genomic nucleotide sequence has been determined. The 5' half of Q4 resembles H-2 genes more strongly than other Q genes. Its 3' end, in contrast, is Q-like and contains a translational stop signal in exon 5 which predicts a polypeptide with an incomplete membrane spanning segment. The presence of two inverted B1 repeats suggests that part of the Q4 gene may be mobile within the genome. Gene transfer experiments have shown that the Q4 gene encodes a beta 2-microglobulin associated polypeptide of Mr 41,000. A similar protein was found in activated mouse spleen cells. The Q4 polypeptide was found to be secreted both by spleen cells and by transfected fibroblasts and was not detectable on the cell surface. Antibody binding and two-dimensional gel electrophoresis indicate that the Q4 molecule is identical to a mouse class I polypeptide, Qb-1, which has been previously described.


Application of visual evoked potentials for preoperative estimation of visual function in eyes with dense cataract.
To determine whether the temporal frequency characteristics of the visual system as determined by visually evoked potentials (VEP) can be used for a preoperative estimation of the visual function in eyes with cataracts. Light stimuli driven by a pseudorandom binary sequence (PRBS) of 40950 ms duration were presented and EEG recordings were made from 13 control and 20 patients with cataracts preoperatively and 1 week after cataract operation. The first kernel of the PRBS-VEP was obtained as the first-order cross-correlation function between PRBS and PRBS-VEP. The Fourier transform of this function was used as the temporal frequency characteristic (TFC). The mean +/- standard deviation of the latency and amplitude of the VEP in normal controls were 110.8+/-4.3 ms and 2.01+/-0.67 microV, respectively. A high correlation (r>0.7) between the pre-and postoperative VEP waveform was obtained in 13 eyes (65%), and 14 eyes (70%) in the VEP-TFC curves. The sensitivity of the examination was 73%, 27%, and 91% for the latency, amplitude and TFC of the VEP, respectively. The specificity of the examination was 67%, 100%, and 89% for the same measures. Eleven of 12 eyes with abnormal TFC preoperatively showed retinal or optic nerve lesions postoperatively. False-negative results were seen in cases with delayed corneal edema. Postoperative visual function of patients with cataracts can be predicted by preoperative measurement of the TFC obtained by PRBS-VEP.


Liposomalization of SN-38 as active metabolite of CPT-11.
Although many drugs have been developed for the treatment of disease, some drugs have complications such as adverse effects, and antitumor agents should target tumors or cells more selectively. It is therefore necessary to develop drug delivery systems, and liposomes are reportedly useful as an effective drug carrier. An antitumor agent, CPT-11, inhibits DNA synthesis by the inhibition of topoisomerase1 and has a strong antitumor activity. SN-38 is converted from CPT-11 as an active metabolite by carboxylesterase in the liver. As SN-38 is insoluble, it has not been applied at the clinical stage as an injection. It is expected that SN-38 liposomalization may increase its usefulness in cancer chemotherapy. Our purpose is to have a clinical application of SN-38 by a novel method of liposomalization to expand the application for the other insolubility drugs. As SN-38 is hydrophobic, SN-38-trapped liposome preparation was attempted using the Bangham method, which is effective for general preparation. However, a high ratio of SN-38 trapped in liposome was not achieved, and this was not improved by the freezing-thawing method or the freeze-drying method. On the other hand, the ratio of SN-38 trapped in liposome by the modified remote loading method was about 4 times that by the Bangham method, and the ratio by the film loading method, novel method of liposomal preparation, reached 2 times and 8 times that by the modified remote loading method and Bangham method, respectively, showing a remarkable increase. In conclusion, it was suggested that the preparation of SN-38 liposome using the film loading method effectively entraps SN-38. Thus, it is expected that SN-38 liposome can be applied as an injection. This preparation method is useful if application is possible in the other insolubility drugs.


[Acupuncture in the treatment of neuralgic syndromes of the facial region. Methodological studies and evaluation of the clinical results].
The A. present their experiences in the therapy of 274 facial neuralgias treated by acupuncture at the department of Oral Surgery of the University of Turin Medical School, between September 1973 and June 1976. The problems of a precise diagnosis and a research on the methods of treatment and statistical evaluation of the clinical results are presented with particular interest to the relation between acupuncture treatment and drug therapy.


The behavioral treatment of Raynaud's disease: a review.
Raynaud's disease is a peripheral vascular system disorder characterized by episodes of vasoconstriction in the hands and feet resulting in a lowering of skin temperature and pain. Recent studies are reviewed that focus on the behavioral treatment of Raynaud's disease--in particular, biofeedback and autogenic training. Methodological problems and other difficulties include the measurement of skin temperature, schedules of reinforcement/feedback, and characteristics of the experimenter and subject. Studies in this area indicate some promise for certain behavioral interventions, especially finger temperature biofeedback under cold stress conditions. On the other hand, further research is needed to clarify the mechanisms, especially that of vasodilation, and the applications of temperature biofeedback, as well as the role of attitudinal, interpersonal, and cognitive factors.


Schwartz-Jampel syndrome associated with von Willebrand's disease.
We report a very rare case of Schwartz-Jampel syndrome associated with von Willebrand's disease. This association might be coincidental because of the different modes of inheritance of the two disorders. However, we speculate that there might be some link between the two disorders, for example in the locus of the affected gene.


[Usefulness of MLPA technique for rapid prenatal detection of aneuploidy. Results of 409 diagnostic studies].
The study was aimed to determine diagnostic application of MLPA for rapid prenatal identification of chromosome 13, 18, 21 and X and Y aneuploidies. 409 amniotic fluid samples from amniocentesis for fetal karyotyping were studied. DNA was isolated using the QIAmp DNA Blood Midi Kit (348 samples) or through proteinase K treatment (61 samples). SALSA MLPA P095 probes (mrc-Holland) were used to detect aneuploidy In 324 studies (79.2%) diagnostic results were obtained. Chromosomal aberrations were found in 16 cases (4.9%). These results were concordant with standard karyotype. In 3 cases (0.92%) false negative results were found but all abnormalities were undetectable with MLPA. MLPA is a reliable method of rapid prenatal detection of aneuploidy


Childhood sexual abuse in pregnant and parenting adolescents.
To examine childhood sexual abuse in Australian childbearing adolescents and the contribution of abuse variables (sexual and physical abuse) to antenatal and postpartum depression and anxiety in adolescents. Seventy-nine adolescents proceeding with a pregnancy for the first time were surveyed about abuse experiences and were administered the Edinburgh Postnatal Depression Scale (EPDS) and the Hospital Anxiety and Depression Scale (HADS) at the third trimester and at 6 weeks and 6 months postpartum. The prevalence of physical abuse before the age of 16 years was 20.5% and 9% of adolescents met the criteria for sexual abuse. Overall, 20.5% adolescents experienced some kind of abuse (sexual or physical) and 9% experienced both sexual and physical abuse. An experience of sexual and/or physical abuse was related to depression and anxiety in the postpartum, but not during pregnancy. The difficulties associated with the transition to parenting may be exacerbated for adolescent childbearers who have a history of abuse, and in turn, may increase vulnerability to experiencing depression and anxiety. Depression and anxiety may increase perceived stress and compromise their functioning and their ability to parent.


Methadone.
Methadone hydrochloride is an old drug that has been in vogue off and on. It has complex pharmacodynamics and can be potentially fatal in inexperienced settings. Drug switching from an opioid to methadone or vice versa requires knowledge of equianalgesic dosing. It is critical when using the drug to monitor for signs and symptoms of toxicity so that overdosing or toxicity can be identified in a timely manner. This review discusses these important topics so that methadone can be used safely and effectively.


Caught in the act: in vivo molecular imaging of the transcription factor NF-kappaB after myocardial infarction.
Nuclear factor kappaB (NF-kappaB) is a ubiquitous transcription factor activated by various stimuli implicated in heart failure progression. However, its activation in heart failure has not been well defined yet. Therefore, we investigated activation of NF-kappaB after myocardial infarction. For the first time, we performed serial, non-invasive in vivo molecular imaging of transcription factor activation in the heart. We used mice expressing a luciferase reporter whose transcription is dependent upon NF-kappaB activation for up to 8 weeks after myocardial infarction. There was a significant increase of NF-kappaB activity with a maximum at day 3 after myocardial infarction when compared to sham controls. Thus, in vivo measurement of the activation of NF-kappaB is feasible. NF-kappaB activity might play an important role for the remodeling process.


Methionine supplementation spares body protein by regulating the expression of mTORC1 downstream factors in rats fed a soy protein diet with sufficient sulfur amino acids: a pilot study.
Dietary supplementation with methionine and threonine spares body protein in rats fed a low protein diet, but the effect is not observed for other essential amino acids. Although the requirement for sulfur amino acids is relatively high in rodents, the precise mechanisms underlying protein retention are not fully understood. The aim of this study was to explore whether the activation of mammalian target of rapamycin complex 1 (mTORC1) downstream factors in skeletal muscle by supplementation with threonine and/or methionine contributes to protein retention under sufficient cystine requirement. Male Sprague-Dawley rats were freely fed a 0% protein diet for 2 weeks. These experimental rats were then fed a restricted diet (14.5 g/day) containing 12% soy protein supplemented with both cystine and, methionine and threonine (MT), methionine (M), threonine (T), or neither (NA) (n = 8) for an additional 12 days. Two additional groups were freely fed a diet containing 0% protein or 20% casein as controls (n = 6). Body weight and gastrocnemius muscle weight were higher, and blood urea nitrogen and urinary nitrogen excretion were lower, in the M and MT groups than in the T and NA groups, respectively. p70 S6 kinase 1 abundance was higher, and eukaryotic translation initiation factor 4E-binding protein 1 abundance and mRNA levels were lower, in the skeletal muscles of the M and MT groups. These results suggest that methionine regulates mTORC1 downstream factors in skeletal muscle, leading to spare body protein in rats fed a low protein diet meeting cystine requirements.


Radiation induced chromosome aberrations and the Poisson distribution.
Data on the distribution of dicentrics and acentrics observed when human lymphocytes are cultured for 48 h after irradiation by X-rays, gamma-rays, and neutrons are presented. Analysis shows that for dicentrics, the observed distribution for X-rays, gamma-rays, and fission neutrons may be described by Poisson statistics but for higher energy neutrons overdispersion is observed. The phenomenon of overdispersion is also observed for acentrics irrespective of the radiation used. The possibility that overdispersion results from the variations of dose in sensitive sites leads to the conclusion that for dicentrics the site size is considerably larger than the 1--2 micrometer diameter derived by applying the dual action theory to the dose effect relationships. This larger site may well be the cell nucleus.


Cholesteryl ester oxidation products in atherosclerosis.
Lipid oxidation products are formed at sites of increased oxidant stress and have been shown to accumulate in atherosclerotic lesions. Although recent studies have focused on the formation and metabolism of oxidized lipids, very little is known about their biological activities and possible (patho)physiological functions. Oxidation of cholesteryl esters containing unsaturated fatty acids leads to the formation of hydroperoxides that are either reduced to alcohols or degrade into biologically active "core-aldehydes". In this review, the mechanisms of formation and metabolic fate of oxidized cholesteryl esters, their occurrence, as well as possible biological activities are discussed. Based on the current knowledge, cholesteryl ester oxidation leads to the formation of biologically active substances, which could actively contribute to the progression of atherosclerotic lesions and their resulting complications.


Insulin-dependent changes in lysosomal cathepsin D activity in rat liver, kidney, brain and heart.
Streptozotocin-induced diabetes resulted in a decrease in the cathepsin D activity (free and total) in rat liver, kidney, brain and heart with a concomitant increase in tissue protein content and amino acids pool size. Treatment with insulin brought about the restoration of the cathepsin D activity to normal or greater than normal levels; tissue protein content and amino acids pool size also returned to normal values.


Women's access to modern methods of fertility regulation.
Preventing unintended pregnancies through access to modern family planning could avert 20-35% of maternal deaths, saving the lives of more than 100,000 women each year. Obstacles to wider access still exist, but they may be overcome by overt policy commitment to reproductive health services, partnership between stakeholders, community involvement and quality programs.


Magnetic circular dichroism and spin equilibrium of methemoglobin and its subunits.
The intensity of the Soret magnetic circular dichroism (MCD) spectra of various complexes of methemoglobin subunits (alpha + and beta +) as well as methemoglobin (metHb A) was correlated well with the spin states of ferric heme. Upon the subunit association, spin state transition toward higher spin was observed only in high spin derivatives and the changes in spin state were due to mainly those of beta + chains. The effect of an allostric effector, inositol hexaphosphate (IHP), on the MCD spectra of metHb A derivatives was observed much significantly for high spin forms than low spin ones.


COVID-19 and people who use drugs: Impact of the pandemic on general anxiety and depressive disorders among adults in Belgium.
During previous pandemics people who use drugs (PWUD) were categorized among the most vulnerable. In the current study, firstly, we wanted to evaluate the impact of the COVID-19 crisis on the prevalence of anxiety and depressive disorders among PWUD. Furthermore, we wanted to compare the prevalence of these disorders with that of members from the general population who did not use drugs. We used a matched cohort design based on two separate repeated cross-sectional online surveys (April and November 2020) among PWUD and the general population. Results of GAD-7 and PHQ-9 were used as outcome variables. We calculated absolute and relative risks for matched pairs for both affective disorders, and logistic regression to compare affective disorders over both waves for PWUD. In April, the prevalence of affective disorders was similar for PWUD and the general population. In November, the risks for anxiety disorders increased with 64% for PWUD compared to non-PWUD (RR = 1.64, 95%CI 1.42-1.88), whereas the risks for depressive disorders more than doubled (RR = 2.29, 95%CI 1.97-2.67). Having a job and being male were protective factors for PWUD for both anxiety and depressive disorders. As this study used self-reported data, GAD-7 and PHQ-9 give an indication of the presence of anxiety and depression which might differ from a clinician's judgement. PWUD might be disproportionally affected by COVID-19. Health care providers should be attentive to substance use as an indicator for increased risk of mental health problems.


Risk factors for non-alcoholic fatty liver disease are common in patients with non-B non-C hepatocellular carcinoma in India.
The aim of the study was to analyze the prevalence of risk factors for non-alcoholic fatty liver disease (NAFLD) in patients with non-B non-C hepatocellular carcinoma (HCC). Between June 2012 and November 2014, patients with HCC, negative for hepatitis B surface antigen and hepatitis C virus antibody, were included in this study. All patients were assessed for risk factors for NAFLD such as diabetes mellitus (DM), hypertension, dyslipidemia, metabolic syndrome, and obesity. Forty-seven patients with non-B non-C HCC (males, 37; age, 60±10 years; mean±SD) were studied. Model for end-stage liver disease score was 11±4. Twenty-five patients were in Child's class A. History of significant alcohol intake was noted in 11 (23%) patients. Prevalence of risk factors for NAFLD were obesity 24 (51%), DM 22 (47%), metabolic syndrome 21 (45%), hypertension 16 (34%), and dyslipidemia 13 (28%). Forty (85%) patients had at least one risk factor for NAFLD. The mean duration of at least one NAFLD risk factor was 7.5 years, prior to diagnosis of HCC. Thirteen (28%) patients were positive for anti-HBc; however, none of the study patients had detectable HBV DNA in blood. Eighty-five percent of the patients with non-B non-C HCC had at least one risk factor for NAFLD. None of the study patients had occult hepatitis B infection. NAFLD is emerging as the major etiological contributing factor for non-B non-C HCC in India.


Central somatostatinergic regulation of growth hormone secretion in dwarf chickens.
1. Basal circulating growth hormone (GH) concentrations in sex-linked-dwarf (SLD) chickens were unaffected by the intracerebroventricular (icv) injection of 10, 50 or 100 micrograms somatostatin (SRIF). 2. The GH response to systemic thyrotropin-releasing hormone (TRH; 10 micrograms/kg, iv) was, however, 'paradoxically' enhanced 20 min after icv SRIF administration. 3. A lower dose (1.0 micrograms) of SRIF had no effect on basal or TRH-induced GH release. 4. High-titre SRIF antisera (4 microliters) also had no acute effect on basal plasma GH concentrations, but augmented the GH response to TRH challenge. 5. SRIF would appear to act at central sites to modulate stimulated GH secretion in SLD chickens.


Pattern of macular thickness changes measured by ocular coherence tomography in patients with multiple sclerosis.
An analysis of the pattern of retinal thickness changes in macula in patients with multiple sclerosis (MS) was performed. In fifteen patients with MS retinal thickness measurements in the central (fovea plus inner macular ring) and peripheral (outer ring) macula obtained by ocular coherence tomography (OCT-3 device) were compared to those of 15 age-matched healthy controls. Eyes of MS patients had on the average a thinner macula (241.8 +/- 20.6 micrometers) than control eyes (252.0 +/- 16.4, p value 0.038). Significant segmental differences occurred in the central macula (p = 0.013). Eight eyes with a positive history of optic neuritis (ON) had on average a thinner macula (226.8 +/- 14.0) than eyes of MS patients without a history of ON (non-ON eyes: 247.3 +/- 20.1, p value 0.01). The only measure significantly different between non-ON and control eyes was the ratio between the central and peripheral macular thickness (p = 0.017). Average macular thickness in non-ON eyes, unlike control eyes (r = - 0.63, p = 0.0002), did not correlate with age (r = 0.01, p = 0.97), however, it did show a borderline correlation with disease duration (r = - 0.41, p = 0.056). Preferential thinning in the central relative to the peripheral macular region is present in eyes of patients with MS. The macular thickness pattern is likely due to the histological distribution of nerve fibre layer and retinal ganglion cell in the macular area and seems to be particularly informative of neurodegeneration in the eyes of MS patients without a history of optic neuritis.


Dressing on an Incisional Wound Following a Knee Replacement.
This Tuesday, Sophie is carrying out a dressing change on Mrs Savoy's wound. Mrs Savoy is on her third post operative day following her knee replacement. Sophie goes to Mrs Savoy's room to explain what she is intending to do.


TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death.
Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death.


All-trans retinoic acid induced differentiation of rat mammary epithelial cells cultured in serum-free medium.
Retinoids are applied to not only cancer prevention but also cancer chemotherapy by stimulating differentiation of cells. We studied differentiation inducing effect of all-trans retinoic acid (ATRA) by studying proportion of high dense fractions of stem-like cells and the size of S phase fraction in cell cycle. From mammary organoids obtained from 7- to 8-week old F344 female rat mammary gland, we cultured rat mammary epithelial cells (RMEC) and treated physiological doses of 10(-6), 10(-7), and 10(-8) M ATRA from the first day and then cultured for 4, 7, and 14 days. After that, immunostaining was performed using peanut agglutinin (PNA) and anti-Thy-1.1 monoclonal antibody (Thy-1.1) that can be used as markers of differentiation. We separated four different cell subpopulations by flow cytometry: cells negative to both reagents (B-), PNA-positive cells (PNA+), Thy-1.1-positive cells (Thy-1.1+), and cells positive to both reagents (B+). We observed continuous decreases of high dense fractions of stem-like cells (PNA+ subpopulations) for 14 days and as much decreases as high doses of ATRA, which were thought to be proportional to doses of ATRA. We labeled RMEC with bromodeoxyuridine and investigated cell cycle fractions that went through S phase. We observed a tendency of decrease of S phase fraction with time in culture, which is thought to be related to continuous decreases of PNA+ subpopulations and inhibitory role of ATRA on cell cycle. These results suggest that physiological doses of ATRA could stimulate differentiation of RMEC and convert stem-like RMEC to differentiated cells in SFM for a relatively long period of 14 days.


Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study.
Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañón, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments.


Pre-core/basal-core promoter and reverse transcriptase mutations in chronic HBV infected-patients.
Some HBV mutations have been shown to have an association with liver disease. The aim of the study was to investigate the incidence of mutations in hepatitis B virus (HBV) pre-core/basal core promoter (BCP) and reverse transcriptase (RT) regions and their relationship with disease progression in chronic HBV-infected patients. A total of 133 patients were enrolled in this study, comprising the acute-on-chronic hepatitis B liver failure (ACLF-HBV) and chronic hepatitis B (CHB) patients. The pre-core/ BCP and RT gene fragments were amplified by high-fidelity PCR. Mutations of pre-core/BCP and RT regions were examined by direct sequencing. There were no significant differences in age, the average level of ALT and course of disease between the ACLF-HBV and CHB groups. The HBeAg positive rate and average values of HBV-DNA loads of the ACLF-HBV patients were lower than that of CHB patients. In HBV pre-core/ BCP region, the point mutations T1753C (39.06% vs. 21.74%, p<0.01), A1762T (26.56% vs. 13.04%, p<0.05), G1764A (31.25% vs. 18.84%, p<0.01), G1896A (29.69% vs. 15.94%, p<0.05) and G1899 (23.44% vs. 10.14%, p<0.05) were significantly more frequent in the ACLFHBV than CHB patients. For combined mutations, A1762T+G1764A (23.43% vs. 11.59 %, p<0.05) and G1896A+ G1899A (21.88% vs. 13.04%, p<0.05) were significantly more frequent in ACLF-HBV than CHB patients. However, there were no significant differences in RT mutations between two groups. ACLFHBV patients had more frequent mutations in HBV precore/ BCP region than that of CHB patients. Some mutations in HBV pre-core/BCP region might be related to the aggravation of chronic HBV infection.


Efficacy of telavancin (TD-6424), a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action, in a murine model of pneumonia induced by methicillin-resistant Staphylococcus aureus.
The efficacy of telavancin, a bactericidal lipoglycopeptide, was compared to that of vancomycin and linezolid against methicillin-resistant Staphylococcus aureus (MRSA) in a murine pneumonia model. Telavancin produced greater reductions in lung bacterial titer and mortality than did vancomycin and linezolid at human doses equivalent to those described by the area under the concentration-time curve. These results suggest the potential utility of telavancin for treatment of MRSA pneumonia.


The network structure of psychopathic personality traits in a community sample of young adult females.
Despite the growing body of research on the core characteristics of psychopathy, the potential gender differences in the expression and structuration of psychopathic traits have not received adequate attention. Aimed at testing the tacit supposition that the behavioral manifestations and structural architecture of this personality type as it can be observed in men are transposable to women, the present study investigated the network organization of psychopathic traits in a general population sample of young adult women (n=789; 18-20years old) who completed the Youth Psychopathic Traits Inventory - Short Version (YPI-S). We first estimated a network model based on the facets of the YPI-S. We then calculated centrality indices (i.e., strength, expected influence, closeness, and betweenness) in order to identify central and peripheral features of female psychopathy, and finally we performed a bootstrapping procedure to evaluate the accuracy of edge weights as well as the stability of the centrality indices. These last were quite stable and highlighted that unemotionality was the most central trait in the network, followed by manipulation, callousness, and dishonest charm. Our findings therefore corroborate previous results regarding the key contribution of affective characteristics and suggest that the so-called callous-unemotional traits are at the heart of psychopathy regardless of gender. But this research also emphasizes the cardinal role of interpersonal features (and especially manipulation tendencies) in female psychopathy. The centrality of the unemotionality facet-which is not found in male and/or mixed samples - lead us to discuss the links, in women, between psychopathic traits and emotional experience.


The Associations of Electronic Health Record Usability and User Age With Stress and Cognitive Failures Among Finnish Registered Nurses: Cross-Sectional Study.
Electronic health records (EHRs) are expected to provide many clinical and organizational benefits. Simultaneously, the end users may face unintended consequences, such as stress and increased cognitive workload, due to poor EHR usability. However, whether the effects of usability depend on end user characteristics, such as career stage or age, remains poorly understood. The objective of this study was to examine the associations of EHR usability and user age with stress related to information systems and cognitive failures among registered nurses. A cross-sectional survey design was employed in Finland in 2017. A total of 3383 registered nurses responded to the nationwide electronic survey. Multiple linear regression was used to examine the associations of EHR usability (eg, how easily information can be found and a patient's care can be documented) and user age with stress related to information systems and cognitive failures. Interaction effects of EHR usability and age were also tested. Models were adjusted for gender and employment sector. Poor EHR usability was associated with higher levels of stress related to information systems (β=.38; P<.001). The strength of the association did not depend on user age. Poor EHR usability was also associated with higher levels of cognitive failures (β=.28; P<.001). There was a significant interaction effect between age and EHR usability for cognitive failures (β=.04; P<.001). Young nurses who found the EHR difficult to use reported the most cognitive failures. Information system stress due to poor EHR usability afflicts younger and older nurses alike. However, younger nurses starting their careers may be more cognitively burdened if they find EHR systems difficult to use compared to older nurses. Adequate support in using the EHRs may be particularly important to young registered nurses, who have a lot to learn and adopt in their early years of practice.


Psychological determinants of pregnancy-related lumbopelvic pain: a prospective cohort study.
To study whether pregnancy-related lumbopelvic pain outcomes at 36 weeks of gestation can be predicted by psychological determinants earlier in pregnancy. Prospective cohort study. Nine midwifery practices in different regions of the Netherlands. A cohort of 223 low-risk pregnant women in the Netherlands was followed from week 12 of gestation until 36 weeks of gestation. Both psychological determinants and lumbopelvic pain symptoms were investigated with a set of questionnaires at 12, 24 and 36 weeks of gestation. Psychological determinants were measured with the Perceived Stress Scale (PSS), the Symptom Checklist-90-Revised (SCL-90), the Pregnancy-related Anxiety Questionnaire (PRAQ), and the Utrecht Coping List (UCL). Lumbopelvic pain outcomes were measured with the Pregnancy Mobility Index (PMI) and the Overall Complaints Index (OCI). Lumbopelvic pain symptoms and their impact at 36 weeks of gestation. There was a significant increase in scores on both the PMI and OCI across the three sampling occasions in pregnancy. Lumbopelvic pain outcomes showed significant associations with the psychological determinants perceived stress and recently perceived psychological and physical distress at all three times during pregnancy. Pregnancy-related anxiety was not a significant predictor of lumbopelvic pain outcomes, neither was coping. Lumbopelvic pain symptoms and their impact on daily activities at 36 weeks of gestation can be predicted by psychological determinants earlier in pregnancy; the combination of perceived stress and physical disability at 24 weeks of pregnancy seems to be the best predictor of disability in later pregnancy.


Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens.
In order to avoid the risks of non-physiological systemic exposure, serum concentrations of estradiol (E2) and testosterone (as measured by mass spectrometry-based assays) should remain below the 95th centiles measured at 9.3pg/ml and 0.26ng/ml for these respective sex steroids in normal postmenopausal women. To document the possibility of achieving this therapeutic objective, we have measured individual 24h serum E2 and testosterone concentrations in women with vulvovaginal atrophy (VVA) receiving daily intravaginal administration of a clinically effective dose of 6.5mg prasterone (dehydroepiandrosterone, DHEA). Serum E2 and testosterone, as well as DHEA and nine of its other metabolites, were assayed at ten time intervals over 24h on the first and seventh days of daily vaginal administration of 6.5mg prasterone. No significant change from baseline of average 24h serum E2 or testosterone concentrations was observed. Moreover, average 24h serum DHEA remained within the normal postmenopausal range. Estrone sulfate and the androgen metabolites androsterone glucuronide and androstane-3α, 17β-diol glucuronide did not change, thus confirming the absence of any biologically relevant systemic exposure to estrogens and androgens, respectively. Serum concentrations of metabolites of both estrogens and androgens remain within the normal postmenopausal range following daily intravaginal administration of 6.5mg prasterone. As other studies have shown, local formation of sex steroids in peripheral tissues without significant release of E2 or testosterone in the circulation can be achieved with intravaginal prasterone. Thus, prasterone is a promising physiological and attractive solution to treating VVA symptoms.


Assessment of acute scrotum by Doppler color flow imaging: A report of four cases.
We used an Aloka SSD-2000 ultrasound unit with a 5 MHz convex scanner to assess one case of torsion of the spermatic cord, one case of orchitis, and two cases of epididymitis. Color flow imaging showed absence of blood flow signals in the testis in the case of torsion of the spermatic cord, while blood flow signals in the scrotum were significantly increased in the cases of orchitis and epididymitis. Blood flow signals decreased after chemotherapy. Color flow imaging may thus prove useful in the diagnosis and follow-up of patients with acute scrotum.


Independent gene evolution in the potato actin gene family demonstrated by phylogenetic procedures for resolving gene conversions and the phylogeny of angiosperm actin genes.
Nine different actin DNA sequences were isolated from the common potato, Solanum tuberosum, and the nucleotide sequence of five actin loci and of two allelic variants are presented. Unlike the wide variation in intron position among animal actin genes, the potato actin genes have three introns situated in the same positions as reported for all other angiosperm actin genes. Using a novel combination of analytical procedures (G-test and compatibility analysis), we could not find evidence of frequent large or small nonreciprocal exchanges of genetic material between the sequenced loci, although there were a few candidates. Resolution of such gene conversion events and the quantification of independence of gene evolution in multigene families is critical to the inference of phylogenetic relationships. Comparison with actin genes in other angiosperm species suggests that the actin multigene family can be divided into a number of subfamilies, evolved by descent rather than gene conversion, which are of possible functional origin, with one major subfamily diversification occurring before the divergence of monocots and dicots. The silent rate of nucleotide substitution was estimated to be similar to that suggested for a number of other plant nuclear genes, whereas the replacement rate was extremely slow, suggestive of selective constraints.


Implicit learning of symmetry of human movement and gray matter density: Evidence against pure domain general and pure domain specific theories of implicit learning.
Theories of the neural basis of implicit learning postulated that specific regions were responsible for specific structures (e.g., supra-finite state) regardless of domain (e.g., vision, movement); others assumed that implicit learning was the adaptation that occurred within neural regions dealing with each domain. We explored whether people could implicitly learn to detect symmetry in biological motion, and if so, based on voxel-based morphometry (VBM), whether the learning was associated with language-related regions involved with supra-finite state grammars (such as symmetry) or motor-related regions. To explore the relevance of motor-related regions, we investigated brain structural changes in athletes compared with non-athletes and the advantage of athletes in implicit learning of action symmetry. Further, we examined whether motor imagery ability could account for the role of motor-related regions in this learning. Participants passively observed and memorized a number of biological motion sequences instantiating a symmetry rule and then judged new sequences as grammatical or not. Behaviorally, the implicit acquisition of symmetry could extend to process biological motion. Athletes showed superior classification accuracy and kinesthetic imagery ability, and gave more familiarity attributions. VBM results showed that athletes exhibited greater gray matter density in the right cerebellum, as well as the left lingual gyrus, the left precuneus, the left calcarine gyrus, and the right thalamus. Correlation analysis showed that the cerebellar gray matter density was positively associated with classification accuracy, which was mediated by kinesthetic imagery ability. Moreover, gray matter density of the left inferior frontal cortex was also positively associated with classification accuracy, indicating the involvement of regions related to symmetry learning across domains. The study provides initial evidence that implicit learning involves both adaptation within brain regions responsible for the specific domain as well as brain regions processing the same structure across domains, at least in a case of supra-finite state grammars.


Hepatic drug metabolism and haem biosynthesis in lead-poisoned rats.
1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, delta-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment.


The production of 1,3-propanediol from mixtures of glycerol and glucose by a Klebsiella pneumoniae mutant deficient in carbon catabolite repression.
In the present study, mutant strain of Klebsiella pneumoniae with deletion of the crr gene encoding EIIA(Glc) (a component of the glucose-specific phosphoenolpyruvate-dependent transferase system [PTS]) was prepared. This eliminated the ability of the strain to mediate carbon catabolite repression (CCR). Production of 1,3-propanediol (1,3-PD) from glycerol by the crr mutant strain was enhanced (compared to that of the parent) in the presence of glucose. Using molasses as a co-substrate of glycerol, the maximum yield of 1,3-PD was 60.4% greater (81.2g/l) than that obtained when glycerol was used alone, under optimum fermentation conditions.


Prevalence and associated factors of stress, anxiety and depression among prospective medical students.
Many studies have reported that the prevalence of psychological distress among medical students during medical training was high. However, there are very few studies exploring on the psychological health of prospective medical students. This study aimed to determine the prevalence and associated factors for stress, anxiety and depression symptoms among the prospective medical students. A cross-sectional study was done on two cohorts of applicants to a public medical school. A total of 839 applicants were invited to participate in the study. The 21-item Depression Anxiety Stress Scale was administered to the applicants after they completed interviews. A total of 743 (92.2%) applicants took part in the study. The prevalence of moderate to extremely severe level of stress, anxiety and depression were 3.6%, 54.5% and 1.9%, respectively. Stress was significantly associated with extra-curricular activity (p<0.001) and race (p<0.001). Anxiety was associated with extra-curricular activity (p<0.001), race (p<0.001), mother education level (p=0.002) and CGPA group (p=0.034). Depression was associated with academic performance in class (p<0.001) and race (p=0.004). Prevalence of stress and depression among entering medical students was low; however prevalence of anxiety was high which could be due to worry about the interviews to enter medical course. The associated factors of psychological distress among prospective medical students were related to academic, non-academic, parent education and cultural backgrounds.


Gluteal Augmentation with Fat Grafting: Literature Review.
The buttock is the second sex feature of the human body, and the graceful buttock curve gives people confidence. Although the safety of gluteal augmentation with autologous fat grafting is still controversial, the proportion of operations is increasing year by year. To provid a comprehensive and detailed review of the literature on gluteal augmentation with fat grafting. A comprehensive review of the published literature through September of 2020 was performed in PubMed database, with the search terms "gluteal augmentation," "buttock augmentation," "Brazilian buttock lift," "fat grafting," "fat transfer," "gluteal AND aesthetic," "gluteal AND anatomy." A total of 64 articles were included. On the basis of the information obtained, surgical recommendations are proposed to achieve buttocks as close as possible to aesthetic standard and improve surgical safety. With a good grasp of the anatomical structure of the buttocks, complications can be reduced. At the same time, based on the theoretical basis of buttock aesthetics, better postoperative results can be obtained. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling.
Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.


Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.
Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.


USB powered microfluidic paper-based analytical devices.
Microfluidic paper-based analytical devices (μPADs) allow user-friendly and portable chemical determinations, although they provide limited applicability due to insufficient sensitivity. Several approaches have been proposed to address poor sensitivity in μPADs, but they frequently require bulky equipment for power and/or read-outs. Universal serial buses (USB) are an attractive alternative to less portable power sources and are currently available in many common electronic devices. Here, USB-powered μPADs (USB μPADs) are proposed as a fusion of both technologies to improve performance without adding instrumental complexity. Two ITP USB μPADs were developed, both powered by a 5 V potential provided through standard USB ports. The first device was fabricated using the origami approach. Its operation was analyzed experimentally and numerically, yielding a two-order-of-magnitude sample focusing in 15 min. The second ITP USB μPAD is a novel design, which was numerically prototyped with the aim of handling larger sample volumes. The reservoirs were moved away from the ITP channel and capillary action was used to drive the sample and electrolytes to the separation zone, predicting 25-fold sample focusing in 10 min. USB μPADs are expected to be adopted by minimally-trained personnel in sensitive areas like resource-limited settings, the point-of-care and in emergencies.


Metachronous adenoma on ileorectal anastomosis suture line and submucosal deep invasive cancer suspected of rapid growth in rectal remnant following long-term interval after curative surgery for advanced colon cancer.
There is general agreement as to the value of postoperative surveillance and the effectiveness of colonoscopy in the early detection of metachronous colorectal lesions. In the present case, a 56-year-old woman with no family history of colon cancer underwent surveillance colonoscopy in which a metachronous flat adenoma was detected following an interval of 23 years after a colectomy and 20 years subsequent to treatment for uterine cancer. A second metachronous flat lesion histopathologically determined to be a submucosal (sm) deep invasive cancer with lymphovascular involvement was detected 12 months later. This second metachronous lesion was suspected of having developed rapidly in the rectal remnant accounting for its sm deep invasion. The findings of this case suggest colonoscopy surveillance guidelines proposed for individuals at high risk should be evaluated based on cancer history and an analysis of possible mismatch repair gene mutations. In addition, the first metachronous lesion was located directly on the suture line of the anastomosis. Endoscopic submucosal dissection (ESD) was indicated despite severe fibrosis into the sm layer. This case also demonstrates the successful use of improved ESD instruments, sm injection agents and technique refinements in the treatment of a technically difficult lesion with a high risk of complications.


Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016.
Six amino acid positions (145, 155, 156, 158, 159, and 189, referred to as the antigenic motif; H3 numbering) in the globular head region of hemagglutinin (HA1 domain) play an important role in defining the antigenic phenotype of swine Clade IV (C-IV) H3N2 IAV, containing an H3 from a late 1990s human-to-swine introduction. We hypothesized that antigenicity of a swine C-IV H3 virus could be inferred based upon the antigenic motif if it matched a previously characterized antigen with the same motif. An increasing number of C-IV H3 genes encoding antigenic motifs that had not been previously characterized were observed in the U.S. pig population between 2012 and 2016. A broad panel of contemporary H3 viruses with uncharacterized antigenic motifs was selected across multiple clades within C-IV to assess the impact of HA1 genetic diversity on the antigenic phenotype. Hemagglutination inhibition (HI) assays were performed with isolates selected based on antigenic motif, tested against a panel of swine antisera, and visualized by antigenic cartography. A previously uncharacterized motif with low but sustained circulation in the swine population demonstrated a distinct phenotype from those previously characterized. Antigenic variation increased for viruses with similar antigenic motifs, likely due to amino acid substitutions outside the motif. Although antigenic motifs were largely associated with antigenic distances, substantial diversity among co-circulating viruses poses a significant challenge for effective vaccine development. Continued surveillance and antigenic characterization of circulating strains is critical for improving vaccine efforts to control C-IV H3 IAV in U.S. swine.