What do patients recall from informed consent given before orthopedic surgery?
We aimed to evaluate the effectiveness of the consent process and the retention of relevant information in patients with orthopedic trauma and those undergoing elective surgery. The study enrolled 142 consecutive patients (79 women, 63 men; mean age 52.02±20.05 years) undergoing either elective or trauma-related surgery. The patients were introduced to the consent process, which involves a verbal and written explanation of the orthopedic condition, surgical procedure, and intraoperative and postoperative risks. At postoperative 1-3 days, patients were asked to recall the orthopedic condition, procedure they underwent, and risks of the surgery. The rate of recall by patients was 131/142 patients (92.3%) for diagnosis, 86/142 patients (60.6%) for surgical procedure, and 32/142 patients (22.5%) for potential complications. Fifty-nine patients (41.5%) could not recall any potential complications. Gender did not influence the ability to describe the operation or potential complications (p>0.05). Advanced age negatively affected recall of information about the surgery and complications (p<0.01), and educational level was correlated with the recall rate (p<0.05). Forty-two patients (29.6%) claimed to have read the consent form before signing it. A greater percentage of patients undergoing elective surgery had read the consent form (p<0.05). Rate of not recalling any potential complications was higher in the trauma group compared with the elective surgery group (p<0.01). Patients had poor retention of information presented during the consent procedure. Further attention should be focused on enhancing patients' understanding of several components of the informed consent process for surgery.


Diversity of the population of Tick-borne encephalitis virus infecting Ixodes ricinus ticks in an endemic area of central Switzerland (Canton Bern).
Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, has a positive-strand RNA genome containing a single open reading frame flanked by non-coding regions (NCRs). Ixodes ricinus ticks (n = 307) were collected from vegetation in a natural TBEV focus in Belp, Switzerland. The presence and identity of the virus were determined by nested RT-PCR followed by sequencing of the 5'-terminal region that comprises the 5' NCR and the capsid-encoding region (C). The presence of the western European TBEV subtype (W-TBEV) genome was detected in 14.3 % of the ticks. Nucleotide sequence analysis revealed a high variability of 55.5 %. In particular, four DNA fragments (CS 'A', CS 'B', the folding-stem structure and the start codon) showed substantial heterogeneity, which has the potential of compromising replication, translation and packaging of the viral genome. This variability may reflect a viral strategy to select the fittest RNA molecule to produce a viral infection in the different vertebrate hosts that may be encountered by the ticks. It may also indicate a possible ancient introduction of TBEV to the Belp site. In addition, it may contribute to explaining the annual low incidence of tick-borne encephalitis in the natural focus of Belp, despite the high prevalence of TBEV genomes in ticks.


Fluid replacement and glucose infusion during exercise prevent cardiovascular drift.
This study examined the influence of both hydration and blood glucose concentration on cardiovascular drift during exercise. We first determined if the prevention of dehydration during exercise by full fluid replacement prevents the decline in stroke volume (SV) and cardiac output (CO) during prolonged exercise. On two occasions, 10 endurance-trained subjects cycled an ergometer in a 22 degrees C room for 2 h, beginning at 70 +/- 1% maximal O2 uptake (VO2max) and in a euhydrated state. During one trial, no fluid (NF) replacement was provided and the subject's body weight declined 2.09 +/- 0.19 kg or 2.9%. During the fluid replacement trial (FR), water was ingested at a rate that prevented body weight from declining after 2 h of exercise (i.e., 2.34 +/- 0.17 1/2 h). SV declined 15% and CO declined 7% during the 20- to 120-min period of the NF trial while heart rate (HR) increased 10% and O2 uptake (VO2) increased 6% (all P less than 0.05). In contrast, SV was maintained during the 20- to 120-min period of FR while HR increased 5% and thus CO actually increased 7% (all P less than 0.05). Rectal temperature, SV, and HR were similar during the 1st h of exercise during NF and FR. However, after 2 h of exercise, rectal temperature was 0.6 degree C higher (P less than 0.05) and SV and CO were 11-16% lower (P less than 0.05) during NF compared with FR.(ABSTRACT TRUNCATED AT 250 WORDS)


Towards the development of a SARS-CoV-2 variant risk assessment tool: expert consultation on the assessment of scientific evidence on emerging variants.
A systematic approach is required for the development of an evidence-based risk assessment tool to robustly estimate the risks and implications of SARS-CoV-2 variants. We conducted a survey among experts involved in technical advisory roles for WHO to capture their assessment of the robustness of different study types that provide evidence for potential changes in transmissibility, antigenicity, virulence, treatability, and detectability of SARS-CoV-2 variants. The views of 62 experts indicated that studies could be grouped on the basis of robustness and reliability for the different risk indicators mentioned. Several study types that experts scored as providing reliable evidence and that can be performed in a timely manner were identified. Although experts from different technical areas had varying responses, there was agreement on the highest and lowest scoring study types. These findings can help to prioritise, harmonise, and optimise study designs for the further development of a systematic, evidence-based, SARS-CoV-2 variant risk assessment tool.


Implementing a birth dose of hepatitis B vaccine for home deliveries in Africa--too soon?
Despite the recommendation of the World Health Organization (WHO) to provide the first hepatitis B vaccine dose at birth (within 24h), there are epidemiological, economic and logistical reasons why this may not be the best approach for home births in Africa. The WHO policy presupposes that the epidemiology of hepatitis B infection in Africa is similar to the rest of the world and that the organizational, infrastructural and financial support is adequate. While babies born in health facilities may be relatively easy to immunize at birth, health systems and infrastructures in many resource-poor countries in Africa would be severely challenged, if required to reach home deliveries within 24h of birth.


Molecular cloning of viral DNA from human genital warts.
The DNA of human papilloma virus type 6 (HPV 6) has been cloned in Escherichia coli K-12 by using pBR322 as vector. The DNA was cloned at the BamHI and EcoRI cleavage sites. This DNA was mapped by employing further restriction endonucleases and by terminal labeling. No major differences were noted as compared to HPV 6 DNA originating directly from a genital wart. The existence of at least two DNA subtypes (HPV 6a and 6b) became apparent.


Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy: open-label pilot study for assessing the efficacy, tolerability and impact on quality of life.
We conducted a prospective, observational study to verify the efficacy, tolerability and impact on quality of life, mood and global neurocognitive performances of oxcarbazepine monotherapy in patients with brain tumor-related epilepsy (BTRE). Patients were followed for 12 months. We recruited 25 patients (11 females 14 males; mean age 49.7) affected with BTRE (17 de novo patients and 7 in monotherapy with other antiepileptics) and introduced oxcarbazepine monotherapy because of uncontrolled seizures and/or side effects. At first visit, patients underwent neurological examination, Qolie 31P V2, EORTC QLQC30, Zung self-depression rating scale (ZSDRS) and adverse events profile. A seizure diary was given to each patient. Follow-up duration was 1-12 months (mean 7.1 months, 5 patients died and 10 dropped out). Totals of 16 patients underwent both chemotherapy and radiotherapy, 4 chemotherapy only, 1 radiotherapy only, and 4 did not undergo any systemic therapy. Mean dosage of oxcarbazepine was 1,230 mg/day (min 600, max 2,100 mg/day). McNemar's test showed a significant difference in seizure freedom rate (P = 0.002) between baseline and final follow-up in the intent-to-treat population. Six patients (24%) had serious side effects and one patient (4%) mild. Logistic regression revealed that, in our study, chemotherapy and radiotherapy did not affect the efficacy of OXC in seizure outcome (P = 0.658). The test evaluation at final follow-up showed a significant improvement in ZSDRS (P = 0.011) and no change over time. Oxcarbazepine seems to be efficacious in controlling seizures and in improving mood in patients with BTRE, but special caution should be taken when it is administered during radiotherapy.


Monitoring Protein Secretion in Streptomyces Using Fluorescent Proteins.
Fluorescent proteins are a major cell biology tool to analyze protein sub-cellular topology. Here we have applied this technology to study protein secretion in the Gram-positive bacterium Streptomyces lividans TK24, a widely used host for heterologous protein secretion biotechnology. Green and monomeric red fluorescent proteins were fused behind Sec (SPSec) or Tat (SPTat) signal peptides to direct them through the respective export pathway. Significant secretion of fluorescent eGFP and mRFP was observed exclusively through the Tat and Sec pathways, respectively. Plasmid over-expression was compared to a chromosomally integrated spSec-mRFP gene to allow monitoring secretion under high and low level synthesis in various media. Fluorimetric detection of SPSec-mRFP recorded folded states, while immuno-staining detected even non-folded topological intermediates. Secretion of SPSec-mRFP is unexpectedly complex, is regulated independently of cell growth phase and is influenced by the growth regime. At low level synthesis, highly efficient secretion occurs until it is turned off and secretory preforms accumulate. At high level synthesis, the secretory pathway overflows and proteins are driven to folding and subsequent degradation. High-level synthesis of heterologous secretory proteins, whether secretion competent or not, has a drastic effect on the endogenous secretome, depending on their secretion efficiency. These findings lay the foundations of dissecting how protein targeting and secretion are regulated by the interplay between the metabolome, secretion factors and stress responses in the S. lividans model.


Primary Cutaneous Histoplasmosis in a HIV-Positive Individual.
A 31-year-old human immunodeficiency virus-positive male who presented to the Dermatology Outpatient Department with complaints of red, raised lesions on the face of 2 weeks duration was, on examination, found to have multiple papulonodular lesions on the face with associated cervical and axillary lymphadenopathy. There was history of local injury on the face 6 months prior to the development of symptoms. Skin biopsy revealed multiple round to oval spores with surrounding halo intracellularly, confirming the diagnosis of cutaneous histoplasmosis. No systemic involvement was detected on further investigations. The patient responded to oral antifungals in a short duration, confirming the local nature of the presentation. This is probably the first time in the literature that a primary cutaneous manifestation of histoplasmosis is being described in an immunocompromised individual.


The longevity of fencing out livestock as a method of decreasing contaminant concentrations in a headwater stream.
Water quality can be improved by fencing off streams from livestock. However, the remedial effect of fencing can fail as livestock trample near stream areas. Water samples were taken every 3-4 wk, and flow was monitored over time in a headwater stream from 2003 to 2019. In November 2005, the stream edge and an area near the stream used for wallowing by farmed red deer was fenced off and planted in native trees, shrubs, and grasses. Contaminant (nitrogen and phosphorus species, sediment, and the fecal indicator bacteria Escherichia coli) concentrations decreased after fencing until at least 2013 (55-84%). However, nitrate concentrations more than doubled owing to the use of a portion of the catchment for a grazed winter forage crop in 2013. Most concentrations remained low after fencing, but sediment concentrations slowing increased (3% yr-1 ), which was attributed to animal tracking near the fence line. The presence of stock in the catchment enriched stormflow losses but prevented losses during baseflow. These data indicate that, when implemented well, fencing and planting could potentially sustain good water quality for decades in farmed red deer systems.


Superiority of 5% NaHCO3 for preoperative hair removal in patients undergoing coronary artery bypass graft surgery with a limb vein: a randomized controlled trial†.
Compared with a dry environment with talcum powder, a wet, alkaline environment with NaHCO3 solution is better for hair removal, as it can soften and expand the hair, decrease the friction and shear forces on the skin, and make hair removal easier and more efficient. The purpose of this study was to compare the effects of a preoperative skin preparation of 5% NaHCO3 with that of talcum powder for softening hair in patients undergoing coronary artery bypass graft (CABG) surgery with the saphenous vein. A prospective randomized, single-blinded, controlled study was established. Between March 2012 and June 2013, 120 patients who met the inclusion and exclusion criteria underwent elective CABG surgery with the saphenous vein in our hospital. The same doctor obtained the saphenous vein of each patient by a uniform method. CABG surgery was performed through an open or endoscopic technique, according to each patient's condition. Patients were divided into two groups of 60 patients each, according to whether the preoperative skin preparation procedure was performed with a 5% solution of NaHCO3 at 45-50°C (experimental group) or with talcum powder (control group). Main outcome measures were the incision inflammation rate, skin preparation time, presence of shaving-induced macroscopic haemorrhagic spots, verbal rating scale (VRS) pain score and satisfaction. Neither group had any evidence of incision inflammation. The average (mean ± standard deviation) skin preparation time of the experimental group was shorter than that of the control group (5.58 ± 1.52 vs 9.74 ± 1.23 min, P < 0.001). Three patients in the experimental group and 17 in the control group had shaving-induced macroscopic haemorrhagic spots after skin preparation (P = 0.001). The VRS pain scores were different between the two groups (P < 0.001). In the control group, 40% of patients and 37% of nurses were satisfied with the skin preparation procedure, compared with 95 and 90%, respectively, in the experimental group (both P < 0.001). Hair softening with a 5% NaHCO3 solution protected the skin integrity, alleviated pain and improved patient satisfaction to a greater extent than talcum powder. Nurses found the 5% NaHCO3 solution to be more convenient and less time-consuming to use.


Hyperoxic attenuation of exercise-induced bronchospasm in asthmatics.
To investigate the mechanism of exercise-induced bronchospasm, we measured specific airway conductance before and after exercise in 7 healthy normals, 12 asthmatics with intact carotid bodies, and 5 asthmatics who had had bilateral carotid body resection. The subjects breathed either air or oxygen (randomly assigned) during cycle ergometer exercise. Post-exercise bronchodilation was the usual pattern in normals, whereas post-exercise bronchospasm occurred in all asthmatics who breathed air during exercise. Oxygen breathing during exercise markedly attenuated the post-exercise bronchospasm in those asthmatics with intact carotid bodies, but had no significant effect in those without effect in those without carotid bodies. The attenuation of the bronchospasm with oxygen occurred with either incremental or constant load exercise of high intensity. The degree of attenuation did not correlate significantly with changes in end-tidal PCO2, maximum work rate, maximum exercise ventilation, or maximum heart rate. These studies indicate that oxygen attenuates exercise-induced bronchospasm in asthmatics through its action on the carotid bodies.


[A comparative study between cefpirome (CPR) and ceftazidime (CAZ) in respiratory tract infections].
Efficacy and safety of a new injectable cephem antibiotic, cefpirome sulfate (hereafter, CPR), against respiratory tract infections were examined and compared with those of a control drug, ceftazidime (hereafter, CAZ). As a rule, CPR 0.5 g twice a day, 1.0 g twice a day, or CAZ 1.0 g twice a day (hereafter CPR 0.5 g group, CPR 1.0 g group, and CAZ group) was administered for 14 days and the following results were obtained. 1. The total number of cases was 470 (155 cases in the CPR 0.5 g group, 160 cases in the CPR 1.0 g group, and 155 cases in the CAZ group). Among them 390 cases were subjected to analyses of clinical efficacy by the efficacy evaluation committee (131 cases in the CPR 0.5 g group, 131 cases in the CPR 1.0 g group and 128 cases in the CAZ group). 2. Efficacy rates determined by the efficacy evaluation committee were 82.4% (108/131) for the CPR 0.5 g group, 81.7% (107/131) for the CPR 1.0 g group, and 83.6% (107/128) for the CAZ group. Efficacy rates determined by the physician in charge were 82.0% (105/128) for the CPR 0.5 g group, 80.5% (99/123) for the CPR 1.0 g group, and 88.5% (108/122) for the CAZ group. No statistically significant difference was observed among the 3 groups. In evaluation of equivalency, clinical efficacy for the CPR 0.5 g group and the CPR 1.0 g group determined by the clinical efficacy evaluation committee was proved to be statistically equivalent to that for the CAZ group. 3. In patients with pneumonia, efficacy rates determined by the efficacy evaluation committee were 87.1% (61/70) for the CPR 0.5 g group, 80.7% (71/88) for the CPR 1.0 g group, and 78.9% (56/71) for the CAZ group. Efficacy rates determined by the physician in charge were 85.3% (58/68) for the CPR 0.5 g group, 80.7% (67/83) for the CPR 1.0 g group, and 86.2% (56/65) for the CAZ group and no statistically significant difference was observed among the 3 groups. In patients with chronic respiratory tract infection, efficacy rates determined by the efficacy evaluation committee were 77.0% (47/61) for the CPR 0.5 g group, 83.7% (36/43) for the CPR 1.0 g group, and 89.5% (51/57) for the CAZ group. Efficacy rates determined by the physician in charge were 78.3% (47/60) for the CPR 0.5 g group, 80.0% (32/40) for the CPR 1.0 g group, and 91.2% (52/57) for the CAZ group. No statistically significant difference was observed among the 3 groups.(ABSTRACT TRUNCATED AT 400 WORDS)


[Team assessment of pain in children].
Using the Smiley analogue scale we investigated the correlation between the self-assessment of defined pain by children and the estimation of this pain by parents, nurses and physicians. In addition, the correlation was studied between the patient's mood and the pain intensity stated by himself and by others. The results of 111 patients, aged from 2(9)/12 to 17(6)/12 years, exhibited a high correlation between the self-assessments of pain intensity and pain duration by all three observing groups. Between patients and parents the best correlation was observed in the estimation of severe pain. All three observing groups inclined mainly to over- than to underestimate the pain intensity. This behavior pattern was mainly observed in parents. The patient's emotion did not influence the self-assessment of pain intensity and pain duration. But a great correlation was observed between the patient's emotion and the pain assessment by all three observing groups. Using a Smiley analogue scale the pain assessment by children or by others is a helpful tool for an individual pain therapy in the daily clinical routine.


Defining Clinical and Microbiological Nonresponse in Ventilator-Associated Pneumonia.
Ventilator-associated pneumonia (VAP) is a severe complication of mechanical ventilation, with mortality reduced most effectively by adequate early antibiotic treatment. The clinical and microbiologic response can be assessed easily from 72 hours after starting antibiotic treatment. Evidence of nonresponse is based on several factors: (1) lack of clinical improvement, (2) radiographic progression, (3) an impaired Sequential Organ Failure Assessment (SOFA) score, (4) no improvement by days 3 to 5 on the Clinical Pulmonary Infection Score (CPIS), (5) no decreased in biomarkers on day 3, and (6) isolation of a new pathogen on day 3. Among the clinical markers of treatment failure, physicians should consider no improvement in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), persistence of fever or hypothermia, persistence of purulent respiratory secretions, and new-onset septic shock or multiple-organ dysfunction syndrome. Microbiological isolation of a new pathogen on day 3 is also associated with higher mortality, but persistence of the original pathogen does not seem to be associated with a worse prognosis. The real impact of changes to treatment after diagnosing nonresponsive VAP is unknown. Physicians must evaluate whether treatments are adequate in terms of sensitivity, dose, and route. Pharmacokinetically and pharmacodynamically optimized doses are recommended in these patients. Clinical stabilization of comorbidities or underlying conditions may be of benefit.


The loss of criteria for mental retardation and regression of symptoms of childhood autism during a five-year follow-up--a case report.
It is usually held that most individuals with childhood autism have poor prognosis. According to our knowledge, a favorable outcome of a child with childhood autism is quite rare and inspires a number of controversies. A 4-year-old boy was diagnosed with childhood autism and mild mental retardation. Interviews and findings reported by other specialists were used in the diagnosis and follow-up that lasted for five years, along with parental counseling and therapy. After three years, regression of the symptoms of childhood autism and loss of the criteria for mental retardation were observed. The difference between the second and first examination was 30 and 24 IQ points. The boy attends regular school with individual approach. Childhood autism and mental retardation should not be viewed as static conditions. Early and intensive therapy is recommended. Some children that make good progress can attend regular school.


Identifying therapeutic targets for Alzheimer's disease with big data.
Nilüfer Ertekin-Taner is a Professor of Neuroscience and Neurology at the Mayo Clinic, Jacksonville, FL, USA. A neurogeneticist and board-certified behavioral neurologist, she received her medical degree from Hacettepe University Medical School in Ankara, Turkey and her doctorate degree in Molecular Neuroscience from Mayo Graduate School. She completed her residency training in the Department of Neurology at Mayo Clinic in Rochester (MN, USA) and fellowship in Behavioral Neurology at Mayo Clinic in Jacksonville. Her laboratory aims to discover and characterize genetic factors underlying the complex genetics of Alzheimer's disease (AD) and related neurodegenerative conditions. Her earlier work contributed to the establishment of the endophenotype approach in genetic studies of AD and pioneered the use of amyloid β peptide levels as an endophenotype in AD genetic research. Her laboratory currently uses biological traits such as gene expression levels and cognitive scores and leverages combined genome, transcriptome and epigenetic data to uncover genetic risk factors for neurodegenerative conditions. She is the principal investigator of numerous NIH and foundation grants. She leads multiple collaborative projects aimed at gene and pathway discoveries in AD and other neurodegenerative diseases, as a part of the NIH initiatives Accelerating Medicines Partnership AD (AMP-AD) and Molecular Mechanisms of the Vascular Etiology of AD (M2OVE-AD) consortia. She is the Principal Investigator of the Florida Consortium for African-American AD Studies (FCA3DS). As a neurologist in the Memory Disorders Clinic at Mayo Clinic in Jacksonville, Florida, she continues to evaluate and manage patients with AD and other dementias and aspires to improve the quality of care that we provide to our patients and their families.


Controlling Morphology and Functions of Cardiac Organoids by Two-Dimensional Geometrical Templates.
Traditionally, tissue-specific organoids are generated as 3D aggregates of stem cells embedded in Matrigel or hydrogels, and the aggregates eventually end up a spherical shape and suspended in the matrix. Lack of geometrical control of organoid formation makes these spherical organoids limited for modeling the tissues with complex shapes. To address this challenge, we developed a new method to generate 3D spatial-organized cardiac organoids from 2D micropatterned human induced pluripotent stem cell (hiPSC) colonies, instead of directly from 3D stem cell aggregates. This new approach opens the possibility to create cardiac organoids that are templated by 2D non-spherical geometries, which potentially provides us a deeper understanding of biophysical controls on developmental organogenesis. Here, we designed 2D geometrical templates with quadrilateral shapes and pentagram shapes that had same total area but different geometrical shapes. Using this templated substrate, we grew cardiac organoids from hiPSCs and collected a series of parameters to characterize morphological and functional properties of the cardiac organoids. In quadrilateral templates, we found that increasing the aspect ratio impaired cardiac tissue 3D self-assembly, but the elongated geometry improved the cardiac contractile functions. However, in pentagram templates, cardiac organoid structure and function were optimized with a specific geometry of an ideal star shape. This study will shed a light on "organogenesis-by-design" by increasing the intricacy of starting templates from external geometrical cues to improve the organoid morphogenesis and functionality.


Anxiety-Related Coping Styles, Social Support, and Internet Use Disorder.
Objective: The Internet can offer a seemingly safe haven for those being disappointed by relationships in the "offline world". Although the Internet can provide lonely people with opportunities to seek for help and support online, complete withdrawal from the offline world comes with costs. It is discussed if people can even become "addicted" to the Internet. Of note, meanwhile, many researchers prefer the term Internet use disorder (IUD) instead of using the term "Internet addiction". To illustrate the importance of one's own social network supporting a person in everyday life, we investigated, for the first time to our knowledge, how social resources in terms of quality and quantity might represent a buffer against the development of IUD. Furthermore, anxiety related coping styles are investigated as a further independent variable likely impacting on the development of an IUD. Method: In the present work, N = 567 participants (n = 164 males and n = 403 females; Mage = 23.236; SDage = 8.334) filled in a personality questionnaire assessing individual differences in cognitive avoidant and vigilant anxiety processing, ergo, traits describing individual differences in everyday coping styles/modes. Moreover, all participants provided information on individual differences in tendencies toward IUD, the perceived quality of social support received, and the size of their social network (hence a quantity measure). Results: Participants with larger social networks and higher scores in the received social support reported the lowest tendencies toward IUD in our data. A vigilant coping style was positively correlated with tendencies toward IUD, whereas no robust associations could be observed between a cognitive avoidant coping style and tendencies toward IUD. Hierarchical linear regression underlined an important predictive role of the interaction term of vigilance in ego-threat scenarios and perceived quality of social support. Conclusion: The current study not only yields support for the hypothesis that the size of one's own social network as well as the perceived quality of social support received in everyday life present putative resilience factors against developing IUD. It also supports the approach that special coping styles are needed to make use of the social support offered.


[The effect of the heptoprotective agent LIV 52 on liver damage].
The action of hepatoprotective drugs is a steady subject of discussions. Despite the equivocal character of action hepatoprotective drugs are used, despite the fact that the effect is partly a placebo effect. In the literature are reports on preparation LIV 52 which is a mixture of substances of plant origin and improves the subjective complaints of patients as well as the objective condition of patients with liver disease. The effect of preparation LIV 52 was investigated in a retrospective study in 19 patients with liver damage. In the majority liver damage caused by alcohol was involved, steatosis and persisting hepatitis without the finding of chronic hepatitis B and C. The authors investigated biochemical parameters (bilirubin, ALT, AST, ALP, TZR, cholesterol). The size of the liver was assessed by ultrasonography and the subjective status of the patients was recorded. Within one year of administration of the preparation subjective improvement occurred, hepatomegaly diminished and the activity of aminotransferases declined. Administration of LIV 52 can improve the subjective condition and clinical parameters in patients with liver damage, in particular in alcoholic liver damage and in steatosis. The effect is certainly due also to better motivation on the patients part, better lifestyle and dietary measures. After one year of treatment no undesirable side-effects were detected.


Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action.
The copper(II) complexes of bis-thiosemicarbazones (Cu(btsc)) such as Cu(atsm) and Cu(gtsm) are neutral, lipophilic compounds that show promise as therapeutics for the treatment of certain neurological diseases and cancers. Although the effects of these compounds have been described at the cellular level, there is almost no information about their biochemical mode of action. In this work, we showed that Cu(atsm) and Cu(gtsm) displayed antimicrobial activities against the human obligate pathogen Neisseria gonorrhoeae that were more than 100 times more potent than Cu(NO3)2 salt alone. Treatment with Cu(btsc) also produced phenotypes that were consistent with copper poisoning, but the levels of intracellular copper were undetectable by ICP MS. We observed that Cu(btsc) interacted with proteins in the cell membrane. Systematic measurements of O2 uptake further demonstrated that treatment with both Cu(atsm) and Cu(gtsm) led to dose-dependent inhibition of respiratory electron transfer processes via succinate and NADH dehydrogenases. These dehydrogenases were not inhibited by a non-btsc source of Cu(II). The results led us to conclude that the biochemical mechanism of Cu(btsc) action is likely more complex than the present, simplistic model of copper release into the cytoplasm.


Incidence and Outcomes of Visceral Ischemia in Acute Aortic Occlusion.
Acute aortic occlusion (AAO) is a morbid diagnosis in which mortality correlates with severity of ischemia on presentation. Visceral ischemia (VI) is challenging to diagnose and its presentation as a consequence of AAO is not well-studied. We aim to identify characteristics associated with VI in AAO to facilitate diagnosis. Patients diagnosed with AAO who underwent revascularization were identified retrospectively from institutional records (2006-2020). The primary outcome was the development of VI (intra-abdominal ischemia). Univariate analysis was used to compare demographic, exam, imaging, and intraoperative variables between patients with and without VI in the setting of AAO. Ninety-one patients were included. The prevalence of VI was 20.9%. Preoperative comorbidities, time to revascularization, and operative approach did not differ between patients with and without VI. Patients with VI more frequently were transferred from outside institutions (100% vs. 53%, P = 0.02), presented with advanced acute limb ischemia (Rutherford III 36.9% vs. 7.5%, P < 0.01), and had elevated preoperative serum lactate (4.31 vs. 2.41 mmol/L, P < 0.01). VI patients had an increased occurrence of bilateral internal iliac artery (IIA) occlusion (47.4% vs. 18.1%, P = 0.01). Unilateral IIA occlusion, level of aortic occlusion, and patency of inferior mesenteric arteries were not associated with VI. Patients with VI had worse postoperative outcomes. In particular, VI conferred significant risk of mortality (odds ratio 5.45, P < 0.01). Visceral ischemia is a common consequence of AAO. Elevated lactate, bilateral IIA occlusion, and advanced acute limb ischemia (ALI) should increase clinical suspicion for concomitant VI with AAO and may facilitate earlier diagnosis to improve outcomes.


Efficacy of Topical Botanical Treatment of Children With Mild to Moderate Atopic Dermatitis
Objective: The study was conducted to determine the efficacy of the botanical combination incorporated in Kamedis Eczema Therapy Cream (the test product) for children with mild to moderate atopic dermatitis. Design: The study was designed as an interventional, multi-center, double-blind, randomized, controlled study. Setting: Children subjects were a sub-population of the 108 combined population of adults and children evenly randomly divided into three treatment groups: test product, vehicle, and comparator. The vehicle used was the identical test product without the botanical combination while the comparator was a leading OTC brand in the US market. All three groups used the same Kamedis body wash followed by one of the three randomized treatment creams for the affected areas. Participants: Thirty-nine (39) children subjects with uncomplicated, stable, mild to moderate atopic dermatitis were recruited and qualified for the study, 24 female and 15 male, ages varying between 3 and 18. Measurements: Investigators assessed the severity of each subject using the Investigator Global Assessment (IGA), affected Body Surface Area (BSA) extent evaluated parameters at each of the visit days 0, 7, 14, and 28. Subjective symptoms of pruritus and insomnia were evaluated by the patient or their legal guardian. The SCORAD and EASI indexes were calculated based on the collected parameters. Results: The test product demonstrated an improvement in all evaluated and calculated clinical parameters over the vehicle at the end of the treatment duration, proving the validation that the test product is much more effective and beneficial than the vehicle. The test product reached 40% of 'clear' IGA subjects out of the enrolled subjects and 60% out of the 'clear' and 'almost clear' IGA subjects comparing to 8% and 38%, respectively, with the vehicle, presenting a clear advantage over the vehicle. The BSA improvement comparison analysis of the test product over the vehicle yielded P value of less than 0.05, which is statistically significant. The SCORAD and EASI indexes also showed an advantage of the test product versus the vehicle at week 4. Conclusion: The study results validate that the botanical combination is the key factor for the efficacy and improvement of the AD symptoms within this population of children. J Drugs Dermatol. 2019;18(10):1038-1045.


Spectral invariance under daylight illumination changes.
We develop a method for calculating invariant spectra of light reflected from surfaces under changing daylight illumination conditions. A necessary part of the method is representing the illuminant in a suitable form. We represent daylight by a function E(lambda, T) = h(lambda)exp[u(lambda)f(T)], where lambda is the wavelength, T is the color temperature, h(lambda) and u(lambda) are any functions of lambda but not T, and f(T) is any function of T but not lambda. We use an eigenvalue decomposition on the logarithm of the CIE daylight standard at various color temperatures to obtain the necessary functions and show that this gives an extremely good fit to CIE daylight over our experimental range. We obtain experimental data over the range 350-830 nm from a range of standard colored surfaces for 50 daylight conditions covering a wide range of illumination spectra. Despite a considerable variation in the spectra of the reflected light, we show only small variations when the transformation is used. We investigate the possible causes of the residual variation and conclude that using the above approximation to daylight is unlikely to be a major cause. Some variation is caused by local daylight conditions being different from the CIE standard and the rest by measurement and modeling errors.


Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization-intracytoplasmic sperm injection and embryo transfer cycles.
To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Retrospective cohort study. University-based reproductive medical center. Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.


Using explanatory crop models to develop simple tools for Advanced Life Support system studies.
System-level analyses for Advanced Life Support require mathematical models for various processes, such as for biomass production and waste management, which would ideally be integrated into overall system models. Explanatory models (also referred to as mechanistic or process models) would provide the basis for a more robust system model, as these would be based on an understanding of specific processes. However, implementing such models at the system level may not always be practicable because of their complexity. For the area of biomass production, explanatory models were used to generate parameters and multivariable polynomial equations for basic models that are suitable for estimating the direction and magnitude of daily changes in canopy gas-exchange, harvest index, and production scheduling for both nominal and off-nominal growing conditions.


Placenta autophagy is closely associated with preeclampsia.
The pathogenesis of preeclampsia (PE) is complex and placental internal homeostasis is regulated by cellular autophagy. However, there are fewer studies related to the role of placental autophagy in the pathogenesis of PE. The GSE75010 and GSE10588 datasets were downloaded from the gene expression omnibus (GEO) database. In the GSE75010 (test cohort), 103 differentially expressed genes (DEGs) were screened using "Limma" package, and 281 PE characteristic genes were screened by weighted gene coexpression network analysis (WGCNA). Combined with the autophagy gene set, a total of 5 autophagy-related hub genes were obtained. Three biomarkers (HK2, PLOD2, and TREM1) were then further screened by random forest(RF) model and least absolute shrinkage and selection operator(LASSO) algorithm as diagnostic of PE. In the unsupervised consensus clustering analysis, HK2, PLOD2, and TREM1 may be synergistically involved in hypoxia-induced autophagy and hypoxia-inducible factor 1(HIF-1) signaling pathway to induce PE. In addition, we constructed and evaluated a nomogram model for PE diagnosis using these three key diagnostic biomarkers, and the results showed that the model had significantly excellent predictive power (AUC values of GSE75010 and GSE10588 datasets were 0.869 and 0.876, respectively). In terms of immune infiltration, a higher proportion of T cells CD8, and a lower proportion of Macrophages M2 were found in PE placentas compared to normal tissue, and high expression of HK2, PLOD2, and TREM1 were accompanied by low levels of Macrophages M2 infiltration. HK2, PLOD2, and TREM1 may be associated with the development of pre-eclampsia, and their mechanisms of action in preeclampsia need to be further investigated.


Living and dying to be counted: What we know about the epidemiology of the global adolescent HIV epidemic.
With increasing survival of vertically HIV-infected children and ongoing new horizontal HIV infections, the population of adolescents (age 10-19 years) living with HIV is increasing. This review aims to describe the epidemiology of the adolescent HIV epidemic and the ability of national monitoring systems to measure outcomes in HIV-infected adolescents through the adolescent transition to adulthood. Differences in global trends between younger (age 10-14 years) and older (age 15-19 years) adolescents in key epidemic indicators are interrogated using 2016 UNAIDS estimates. National population-based survey data in the 15 highest adolescent HIV burden countries are evaluated and examples of national case-based surveillance systems described. Finally, we consider the potential impact of adolescent-specific recommendations in the 2016 WHO Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. UNAIDS estimates indicate the population of adolescents living with HIV is increasing, new HIV infections in older adolescents are declining, and while AIDS-related deaths are beginning to decline in younger adolescents, they are still increasing in older adolescents. National population-based surveys provide valuable estimates of HIV prevalence in older adolescents and recent surveys include data on younger adolescents. Only a few countries have nationwide electronic case-based HIV surveillance, with the ability to provide population-level data on key HIV outcomes in the diagnosed population living with HIV. However, in the 15 highest adolescent HIV burden countries, there are no systems tracking adolescent transition to adulthood or healthcare transition. The strength of the 2016 WHO adolescent-specific recommendations on antiretroviral therapy and provision of HIV services to adolescents was hampered by the lack of evidence specific to this age group. Progress is being made in national surveillance and global monitoring systems to specifically identify trends in adolescents living with HIV. However, HIV programmes responsive to the evolving HIV prevention and treatment needs of adolescents can be facilitated further by: data disaggregation to younger and older adolescents and mode of HIV infection where feasible; implementation of tools to achieve expanded national case-based surveillance; streamlining consent/assent procedures in younger adolescents and consensus on indicators of adolescent healthcare transition and transition to adulthood.


Coaching parents to change: the impact of in vivo feedback on parents' acquisition of skills.
Behavioral parent training (BPT) includes a variety of evidence-based treatments with diverse techniques to alter parent behavior. Parent-Child Interaction Therapy is an innovative BPT with its use of in vivo feedback (i.e., "coaching") during parent-child interactions. An experimental design was used to assess whether coaching without elaborate didactic improves parenting. Sixty mothers with children 2 to 7 years old were recruited from the community and randomly assigned to a coaching or no coaching group. After a baseline assessment, all dyads participated in two play interactions 1 week apart during which parents in the coaching group were provided with in vivo feedback. Coached parents displayed significant improvements in skills, and coaching predicted skill gains beyond the influence of baseline ability. Findings suggest that providing parents with feedback through in vivo coaching is an important mechanism of change.


Use of Hoy's solubility parameters to predict water sorption/solubility of experimental primers and adhesives.
Self-etching primers and adhesives contain very hydrophilic acidic monomers that result in high water sorption/solubilities of their polymers. However, the chemical composition of these products varies widely. The purpose of this work was to vary the chemical composition of experimental self-etching primers and adhesives to determine if the water sorption/solubility of the polymers were affected in a predictable manner. The Hoy's solubility parameters of these mixtures were calculated to permit ranking of the degree of hydrophilicity of the polymers. Water sorption/solubility was measured according to ISO 4049. The results showed highly significant (R(2) = 0.86, P < 0.001) correlations between water sorption and Hoy's solubility parameter for polar forces (delta(p)) of the polymers. Similar correlations were obtained between polymer solubility and delta(p). When these results were compared with previously published results obtained with more hydrophobic resins, excellent correlations were obtained, indicating that Hoy's delta(p) values may be used to predict the water sorption behavior of methylmethacrylate polymers.


Making the transition: the role of helical CT in the evaluation of potentially acute thoracic aortic injuries.
The purpose of this study was to show that helical CT could be used at our center in lieu of routine aortography to examine patients who have had serious blunt chest trauma. We also wanted to assess the potential savings of using CT to avoid unnecessary aortography. The institutional review board approved the parallel imaging-CT immediately followed by aortography-of patients presenting with blunt chest trauma between August 1997 and August 1998. To screen patients for potential aortic injuries, we performed parallel imaging on 142 patients, and these patients comprised our patient population. CT examinations of the patients were reviewed for signs of injury by radiologists who were unaware of each other's interpretations and the aortographic results. Findings of CT examinations were classified as negative, positive, or inconclusive for injury. Aortography was performed immediately after CT. The technical and professional fees for both transcatheter aortography and helical CT were also compared. Our combined kappa value for all CT interpretations was 0.714. The aortographic sensitivity and negative predictive value were both 100%. Likewise, the sensitivity and negative predictive value of CT were 100%. The total costs of performing aortography were estimated at approximately $402,900, whereas those for performing helical CT were estimated at $202,800. Helical CT has a sensitivity and negative predictive value equivalent to that of aortography. Using CT to eliminate the possibility of mediastinal hematoma and to evaluate the cause of an abnormal aortic contour in a trauma patient allows us to use aortography more selectively. Avoiding the performance of unnecessary aortography will expedite patient care and reduce costs. We report the results of our experience with CT and how our center successfully made this transition in the initial examination of patients with serious thoracic trauma.


Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma.
Cholangiocarcinoma (CCA) is a lethal disease, afflicting many thousands the world over. Human CCA develops through a multi-step progression model, preceded by the onset of dysplasia in the cholangiolar ductal epithelium. An animal model of multi-step carcinogenesis in the biliary tree will enable the study of genetic changes in human CCA, and provide an avenue for chemoprevention strategies. We describe an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Male Sprague-Dawley (SD) rats (n = 170), weighing 350 +/- 20 g, were used in this study. Drinking water with TAA 300 mg/l was administered orally, and the liver was harvested and examined histologically at weekly intervals, beginning at 5 weeks after initiation of TAA. Harvested tissues were formalin-fixed and paraffin embedded for morphologic and immunohistochemical studies. Multifocal bile ductular proliferation with intestinal metaplasia (presence of goblet cells) and increasing histologic atypia (biliary dysplasia) was observed by the 9th week of TAA administration. Biliary cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was observed beginning at 20 weeks post-TAA administration. The progression from normal cholangioles to biliary dysplasia to invasive CCA was accompanied by up-regulation of the proto-oncogenes c-met and c-erbB-2, tyrosine kinase receptors over-expressed in human CCAs. The study was terminated at 6 months, at which time no systemic metastases or deaths were observed. Oral administration of TAA in drinking water to male SD rats provides a reproducible animal model for development of CCA with a high yield rate. In particular, the presence of biliary dysplasia beginning at the 9th week, which progresses to invasive CCA, mimics the multi-step model of human CCA. The TAA rat model may serve as a powerful pre-clinical platform for therapeutic and chemoprevention strategies for human CCA.


Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha.
Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARalpha, PPARgamma, and LXRalpha. We show it activates the ligand-binding domain of both PPARalpha and PPARgamma, while inhibiting LXRalpha in GAL4-fusion reporters. Using TR-FRET, we show that naringenin is a partial agonist of LXRalpha, inhibiting its association with Trap220 co-activator in the presence of TO901317. In addition, naringenin induces the expression of PPARalpha co-activator, PGC1alpha. The flavonoid activates PPAR response element (PPRE) while suppressing LXRalpha response element (LXRE) in human hepatocytes, translating into the induction of PPAR-regulated fatty acid oxidation genes such as CYP4A11, ACOX, UCP1 and ApoAI, and inhibition of LXRalpha-regulated lipogenesis genes, such as FAS, ABCA1, ABCG1, and HMGR. This effect results in the induction of a fasted-like state in primary rat hepatocytes in which fatty acid oxidation increases, while cholesterol and bile acid production decreases. Our findings explain the myriad effects of naringenin and support its continued clinical development. Of note, this is the first description of a non-toxic, naturally occurring LXRalpha inhibitor.


[Integral evaluation of optimal microclimate and human thermoregulation].
The article presents integral parameters of heat comfort determined numerically through parameters of microclimate and human heat state. The authors defined human heat state classes that necessitate differentiated evaluation of heat comfort depending on energy expenditure. The materials also cover regression equations to calculate criterial parameters for optimal heat state.


Serum PLR and LMR in Behçet's disease: Can they show the disease activity?
The aim of this study is to determine platelet to lymphocyte ratio (PLR) and lymphocytes to monocytes ratio (LMR) levels in Behçet's disease (BD) and to investigate their relationships with disease activity.Hematological and inflammatory parameters including high-sensitivity C-reactive proteins (hs-CRP), erythrocyte sedimentation rate (ESR), PLR, and LMR were examined in BD and healthy controls.Data from 140 patients with BD (108 with active and 32 with inactive disease) and 107 controls were enrolled. PLR (153.21 ± 65.44, 106.20 ± 28.91, P <.001, respectively) was remarkably higher, whereas LMR (5.37 ± 5.47, 8.95 ± 5.84, P <.001, respectively) was significantly lower in BD than in controls. Active BD patients had significantly higher PLR (159.20 vs 131.14, P = .037), ESR (38.30 vs 24.55, P = .017), and hs-CRP (30.20 vs 17.21, P = .027) than those with inactive BD. However, no significant difference in LMR was found between the groups. Moreover, PLR was positively correlated with BDCAF (r = 0.193, P <.05), hs-CRP (r = 0.402, P <.01), and ESR (r = 0.284, P <.01), whereas LMR was negatively correlated with BDCAF (r = -0.175, P <.05), hs-CPR (r = -0.263, P <.01), and ESR (r = -0.175, P <.05). Additionally, both PLR and LMR were shown to be independent factors for BD by multivariate logistic regression analysis. Furthermore, a PLR level of 124.63 was determined as the best cut-off value by ROC analysis (sensitivity 64.3%, specificity 78.0%, and the area under the ROC curve 0. 753).PLR was elevated in active BD as compared to inactive BD. PLR may be a reliable, cost-effective, and novel potential parameter to help evaluate disease activity in BD.


Oxymatrine Promotes S-Phase Arrest and Inhibits Cell Proliferation of Human Breast Cancer Cells in Vitro through Mitochondria-Mediated Apoptosis.
Breast cancer is one of the most lethal malignancies in the world. Oxymatrine is the major effective and toxic alkaloid component which is derived from the root of Sophora flavescens AIT, a traditional Chinese medicine which is widely distributed in Asia and the Pacific Islands. In the current research study, we investigated the effects and mechanisms of action of oxymatrine on breast cancer cells. We demonstrated that the viability and single cell proliferation capability of MCF-7 and MDA-MB-231, two breast cancer cell lines which are widely used in in vitro study, were significantly suppressed in a time- and concentration-dependent manner. Furthermore, the cell cycle of breast cancer cells treated with oxymatrine was arrested at the S-phase of the cell cycle. Oxymatrine also triggered apoptosis in breast cancer cells by modulating apoptosis-related proteins, such as cleaved Caspase-3, cleaved Caspase-9 and poly(ADP-ribose)polymerase (PARP). The remarkable reduction in the ratio of Bcl-2/Bax was also observed in oxymatrine treated breast cancer cells. In conclusion, our research demonstrated that oxymatrine plays a critical role in suppressing carcinogenesis of breast cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, which suggests a promising application of this drug in breast cancer therapy.


Leukemia reconstitution in vivo is driven by cells in early cell cycle and low metabolic state.
In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations, as defined by surface markers, have shown equal abilities to reconstitute leukemia upon transplantation into immunodeficient mice. Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, we functionally characterized leukemia-initiating cells and found that cells in all stages of the cell cycle are able to reconstitute leukemia in vivo, with early cycling cells (G1blow population) exhibiting the highest leukemia-initiating potential. Interestingly, cells of the G2/M compartment, i.e. dividing cells, were less effective in leukemia reconstitution. Moreover, G1blow cells were more resistant to spontaneous or drug-induced cell death in vitro, were enriched for stem cell signatures and were less metabolically active, as determined by lower levels of reactive oxygen species, compared to G2/M stage cells. Our data provide new information on the biological properties of leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia and underline the concept of a stochastic model of leukemogenesis.


Lineage-specific expression of human immunodeficiency virus (HIV) receptor/coreceptors in differentiating hematopoietic precursors: correlation with susceptibility to T- and M-tropic HIV and chemokine-mediated HIV resistance.
Human immunodeficiency virus (HIV) entry is mediated not only by the CD4 receptor, but also by interaction with closely related molecules that act as membrane coreceptors. We have analyzed mRNA expression and/or cell membrane exposition of the coreceptors most widely used by diverse HIV-1 strains (CXCR4, CCR5, and CCR3) on purified hematopoietic progenitor cells (HPCs) induced in liquid suspension culture to unilineage differentiation/maturation through the erythroid (E), granulocytic (G), megakaryocytic (Mk), and monocytic (Mo) lineages. Reverse transcriptase-polymerase chain reaction (RT-PCR) and cytofluorimetric analysis showed the presence of both CXCR4 and CCR5 in quiescent HPCs, but failed to detect CCR3-specific transcripts. Chemokine expression in HPC progenies showed that CXCR4 receptor is detected on the majority of MKs from early to late stages of maturation, whereas it is moderately decreased in the Mo lineage. In the G pathway, two distinct cell populations, CXCR4(+) and CXCR4(-), were observed: morphological analysis of the sorted populations showed that the CXCR4(+) cells were largely eosinophils and the CXCR4(-) were granulocytes of the neutrophilic series. Furthermore, in the E pathway, CXCR4 was almost completely absent. CCR5 expression is restricted to Mo cultures, ie, approximately 30% to 80% cells throughout all monocytopoietic differentiation/maturation stages. Finally, CCR3 mRNA is always absent in all the unilineage cultures. Evaluation of CD4 expression by flow cytometry on both quiescent HPCs and differentiating unilineage precursors showed that the CD4 receptor is present on approximately 15% of the starting CD34(+) HPC population, highly expressed in the Mo lineage up to 80% at terminal maturation, present on 20% to 30% of maturing Mks, and not detectable in either the E or G lineage. Expression of CD4 receptor together with CXCR4 and/or CCR5 coreceptor in the four lineages correlates with hematopoietic precursor susceptibility to T-lymphotropic and macrophage (M)-tropic HIV strains infection: (1) CD4(-) G and E cells were resistant to both M-tropic and T-lymphotropic strains; (2) HPC-derived Mks were susceptible to T-tropic, but resistant to M-tropic, infection; (3) Mo differentiating cells efficiently replicate both HIV strains. Furthermore, we showed that the CXCR4 and CCR5 ligands (stromal-derived factor 1 and macrophage-inflammatory protein-1alpha [MIP-1alpha], MIP-1beta and RANTES, respectively) inhibit HIV replication in both maturing Mo and Mk cells. Taken together, our data show a lineage-specific modulation of chemokine receptor/coreceptor during hematopoietic cell differentiation and extend previous observations on the relationship between the expression of HIV receptor/coreceptors, susceptibility, and chemokine-mediated resistance to HIV infection.


Mechanisms of call note-type perception in black-capped chickadees (Poecile atricapillus): peak shift in a note-type continuum.
We report on operant conditioning and artificial neural network (ANN) simulations aimed at further elucidating mechanisms of black-capped chickadee chick-a-dee call note category perception. Specifically, we tested for differences in the speed of acquisition among different discrimination tasks and, in two selected discrimination groups, searched for evidence of peak shift. Earlier, unreported ANN data were instrumental in providing the motivation for the current set of studies with chickadees and are provided here. The ANNs revealed differences in the speed of learning among note-type discrimination groups that is related to the degree of perceptual similarity among the three note types tested (i.e., A, B, and C notes). In many respects, bird and network results were in agreement (i.e., in the observation of peak shift in the same group), but they also differed in important ways (i.e., all discrimination groups showed differences in speed of learning in simulations but not in chickadees). We suggest that the start, peak and end frequency of the chick-a portion of chick-a-dee call notes, which form a graded but overlapping continuum, may drive the peak shift observed.


[Measurements of anterior fontanels in Chinese].
Assessment of the size of the anterior fontanel is used as an index of cranial development from birth to the second year of life. From January to May, 1988, measurements of anterior fontanel size were collected for all available newborns and infants from the nursery and well-baby clinics. The size of anterior fontanel was measured as the average value of the length (anterior-posterior dimension) and the width (transverse dimension), as proposed by Popich in 1972. Any fontanel too small to be measured was judged to be closed. Totally 704 subjects, divided into 10 groups by age (3 days, 1, 2, 4, 6, 9, 12, 15, 18, and 24 months) were measured. Results showed that the mean size of anterior fontanel in these 10 groups was 26.7 mm, 25.8 mm, 24.9 mm, 25.7 mm, 20.2 mm, 14.9 mm, 11.5 mm, 10.2 mm, 13.0 mm, and 12.1 mm, respectively. Results also showed a variation of fontanel size in all groups. There was a tendency toward decrease in fontanel size after six months of age. There were no significant differences in size and age of closure of the anterior fontanel between two sexes. Closure of the fontanel was first noted in about 5% of the babies 6 months after term, but in about 8% of the babies at 24 months of age, the fontanel had not closed. The median age of fontanel closure was 14.5 months in males and 14.3 months in females.


Effects of soy consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-releasing hormone in women.
Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.


Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance.
An evidence-based approach is considered the gold standard for health decision-making. Sometimes, a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence is indirect. In such cases, the application of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach for grading the strength of recommendations is inappropriate. Instead, the GRADE Working Group has recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumsances they would be appropriate.Through an evaluation of COVID-1- related recommendations on the eCOVID Recommendation Map (COVID-19.recmap.org), we found that recommendations qualifying a GPS were widespread. However, guideline developers failed to label them as GPS or transparently report justifications for their development. We identified ways to improve and facilitate the operationalisation and implementation of the GRADE guidance for GPS.Herein, we propose a structured process for the development of GPSs that includes applying a sequential order for the GRADE guidance for developing GPS. This operationalisation considers relevant evidence-to-decision criteria when assessing the net consequences of implementing the statement, and reporting information supporting judgments for each criterion. We also propose a standardised table to facilitate the identification of GPS and reporting of their development. This operationalised guidance, if endorsed by guideline developers, may palliate some of the shortcomings identified. Our proposal may also inform future updates of the GRADE guidance for GPS.


Immobilization of bacteriophages on modified silica particles.
Bacteriophages are selective anti-bacterial agents, which are receiving increasing acceptance by regulatory agencies for use both in the food industry and in clinical settings for biocontrol. While immobilized phage could be particularly useful to create antimicrobial surfaces, current immobilization strategies require chemical bioconjugation to surfaces or more difficult processes involving modification of their head proteins to express specific binding moieties, for example, biotin or cellulose binding domains; procedures that are both time and money intensive. We report that morphologically different bacteriophages, active against a variety of food-borne bacteria: Escherichia coli; Salmonella enterica; Listeria monocytogenes; and Shigella boydii, will effectively physisorb to silica particles, prepared by silica surface modification with poly(ethylene glycol), carboxylic acid groups, or amines. The phages remain infective to their host bacteria while adsorbed on the surface of the silica particles. The number of infective phage bound to the silica is enhanced by the presence of ionic surfaces, with greater surface charge - to a maximum - correlating with greater concentration of adsorbed phage. Above the maximum charge concentration, the number of active phage drops.


Herbicide treatment alters the effects of water hyacinth on larval mosquito abundance.
Invasive aquatic weeds are managed with herbicides to reduce their negative impacts on waterways in many areas, including the California Delta Region. Herbicides create a dynamic environment of living and decomposing plant matter that could affect larval mosquitoes and other invertebrates, such as their predators and competitors. Our objective was to compare the number of larval mosquitoes in water or water hyacinth, before and after an herbicide treatment. We created replicated pond mesocosms with water hyacinth, water hyacinth treated with glyphosate and an oil adjuvant, open water, and water with glyphosate plus adjuvant. We sampled for larval mosquitoes and other aquatic invertebrates. Before herbicide addition, there was a trend for more larval mosquitoes in open water tanks than in tanks with water hyacinth. Herbicide application resulted in an immediate decrease of larval mosquitoes. As decay progressed, larval mosquitoes became most abundant in mesocosms with herbicide-treated hyacinth and very few larval mosquitoes were found in other habitat treatments. Although the numbers of predatory and competitor insects had some variation between treatments, no clear pattern emerged. This information on how invasive weed management with herbicides affects larval mosquitoes will allow control practices for larval mosquitoes and invasive weeds to be better integrated.


Does fusion improve the outcome after decompressive surgery for lumbar spinal stenosis?: A two-year follow-up study involving 5390 patients.
Whether to combine spinal decompression with fusion in patients with symptomatic lumbar spinal stenosis remains controversial. We performed a cohort study to determine the effect of the addition of fusion in terms of patient satisfaction after decompressive spinal surgery in patients with and without a degenerative spondylolisthesis. The National Swedish Register for Spine Surgery (Swespine) was used for the study. Data were obtained for all patients in the register who underwent surgery for stenosis on one or two adjacent lumbar levels. A total of 5390 patients fulfilled the inclusion criteria and completed a two-year follow-up. Using multivariable models the results of 4259 patients who underwent decompression alone were compared with those of 1131 who underwent decompression and fusion. The consequence of having an associated spondylolisthesis in the operated segments pre-operatively was also considered. At two years there was no significant difference in patient satisfaction between the two treatment groups for any of the outcome measures, regardless of the presence of a pre-operative spondylolisthesis. Moreover, the proportion of patients who required subsequent further lumbar surgery was also similar in the two groups. In this large cohort the addition of fusion to decompression was not associated with an improved outcome.


Approximal carious lesion depth assessment with insight and ultraspeed films.
This study evaluated the efficiency of a new E/F-speed film, Insight, at the determination of approximal carious lesion depths compared with Ultraspeed. Radiographs of 80 extracted human molars and premolars were taken with both films under standardized conditions. The presence or absence of caries and depth of lesions was determined by three observers using a predetermined scale. The actual status of each surface was determined histologically. Observer responses were assessed with the Gamma measure of association test. Differences between the observers' agreement levels were not significant. The efficiency of Insight and Ultraspeed at true depth diagnosis was found to be 54.9%; 55.8% and Gamma values were found to be 0.883 and 0.922, respectively, at p<0.001. The difference between the two films was not statistically significant (p=0.852). This study suggested that there was no statistically significant difference between the two films at detecting the depths of approximal carious lesions.


Recombination phenotypes of the NCI-60 collection of human cancer cells.
The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60. We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair. Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.


Glutamine and ornithine alpha-ketoglutarate supplementation on malate dehydrogenases expression in hepatectomized rats.
To evaluate the relative gene expression (RGE) of cytosolic (MDH1) and mitochondrial (MDH2) malate dehydrogenases enzymes in partially hepatectomized rats after glutamine (GLN) or ornithine alpha-ketoglutarate (OKG) suplementation. One-hundred and eight male Wistar rats were randomly distributed into six groups (n=18): CCaL, GLNL and OKGL and fed calcium caseinate (CCa), GLN and OKG, 0.5 g/Kg by gavage, 30 minutes before laparotomy. CCaH, GLNH and OKGH groups were likewise fed 30 minutes before 70% partial hepatectomy. Blood and liver samples were collected three, seven and 14 days after laparotomy/hepatectomy for quantification of MDH1/MDH2 enzymes using the real-time polymerase chain reaction (PCR) methodology. Relative enzymes expression was calculated by the 2-(ΔΔC)T method using the threshold cycle (CT) value for normalization. MDH1/MDH2 RGE was not different in hepatectomized rats treated with OKG compared to rats treated with CCa. However, MDH1/MDH2 RGE was greater on days 3 (321:1/26.48:1) and 7 (2.12:1/2.48:1) while MDH2 RGE was greater on day 14 (7.79:1) in hepatectomized rats treated with GLN compared to control animals. Glutamine has beneficial effects in liver regeneration in rats by promoting an up-regulation of the MDH1 and MDH2 relative gene expression.


When Passive Feels Active--Delusion-Proneness Alters Self-Recognition in the Moving Rubber Hand Illusion.
Psychotic patients have problems with bodily self-recognition such as the experience of self-produced actions (sense of agency) and the perception of the body as their own (sense of ownership). While it has been shown that such impairments in psychotic patients can be explained by hypersalient processing of external sensory input it has also been suggested that they lack normal efference copy in voluntary action. However, it is not known how problems with motor predictions like efference copy contribute to impaired sense of agency and ownership in psychosis or psychosis-related states. We used a rubber hand illusion based on finger movements and measured sense of agency and ownership to compute a bodily self-recognition score in delusion-proneness (indexed by Peters' Delusion Inventory - PDI). A group of healthy subjects (n=71) experienced active movements (involving motor predictions) or passive movements (lacking motor predictions). We observed a highly significant correlation between delusion-proneness and self-recognition in the passive conditions, while no such effect was observed in the active conditions. This was seen for both ownership and agency scores. The result suggests that delusion-proneness is associated with hypersalient external input in passive conditions, resulting in an abnormal experience of the illusion. We hypothesize that this effect is not present in the active condition because deficient motor predictions counteract hypersalience in psychosis proneness.


HIV-1 Infection in Persons Homozygous for CCR5-Δ32 Allele: The Next Case and the Review.
CC-chemokine receptor 5 serves as the coreceptor for the HIV-1 R5 strains, which are responsible for the majority of HIV transmissions. A deletion of 32 nucleotides in the gene encoding this receptor (termed CCR5-Δ32) leads to the suppression of CC-chemokine receptor 5 presentation at the cell surface, thus impeding process of HIV entry into the cell. Individuals homozygous for the CCR5-Δ32 allele are resistant to infection with HIV-1 R5 strains, and are extremely rare among HIV-1-infected individuals. We have described a case of person homozygous for CCR5-Δ32, who was infected with subtype B HIV-1. Based on examination of proviral V3 sequences obtained from the first clinical blood sample within less than five months after seroconversion, the CXC-chemokine receptor 4-using strains (X4 or R5/X4) were detected. Data on HIV-1-infected patients homozygous for the CCR5-Δ32 allele, course of HIV-1 infection in these cases, and the infecting viral strains from current and all former reports on HIV-1 infection in CCR5-Δ32 homozygotes were gathered and compared. Identification of HIV-1-infected persons homozygous for CCR5-Δ32 supports the evidence that the lack of functional CC-chemokine receptor 5 at the cell surface does not confer absolute protection against HIV-1 infection, which should be considered when designing future HIV pre-exposure prophylaxis schemes basing on CC-chemokine receptor 5 blocking drugs.


Valganciclovir and bevacizumab for recurrent glioblastoma: A single-institution experience.
Prolonged treatment with adjuvant valganciclovir has been shown in one retrospective study to exert a significant effect on overall survival (OS) in newly diagnosed patients with glioblastoma multiforme (GBM). However, studies evaluating the effectiveness of valganciclovir in the treatment of recurrent GBM have not been performed. We evaluated the effect of valganciclovir in the recurrent setting in combination with bevacizumab therapy. A retrospective analysis was performed on patients treated for recurrent GBM with off-label valganciclovir and bevacizumab at Vanderbilt University. We identified 13 patients who received valganciclovir plus bevacizumab at some point during their treatment, 8 of whom were started on valganciclovir and bevacizumab concurrently upon first recurrence, whereas 5 had valganciclovir added to their bevacizumab regimen prior to a second recurrence. of these patients, 12 were pathologically confirmed to have GBM, and 1 patient was diagnosed with gliosarcoma. We also identified an institutional cohort of 50 patients who had not been exposed to valganciclovir, but were treated with bevacizumab for first recurrence. The progression-free survival (PFS) at 6 months (PF6) and median OS (mOS) in the valganciclovir plus bevacizumab group was 62% and 13.1 months, respectively, for all 13 patients, and 50% and 11.3 months, respectively, for the 8 concurrently treated patients. In the institutional bevacizumab cohort, the PF6 and mOS were 34% and 8.7 months, respectively. In this retrospective analysis, valganciclovir in combination with bevacizumab exhibited a trend toward improved survival in patients with recurrent GBM. However, given the small sample size and the retrospective nature of this study, a larger prospective study is required to confirm these results.


Assessment of physical health status and quality of life among Saudi older adults.
[Purpose] This study investigated physical health status and quality of life among older Saudi adults. [Subjects and Methods] Participants included older adults (N = 55) aged 60-90 years (mean = 67.9± 7.71) from a major hospital in Jeddah. Subjects completed surveys and evaluations including assessments of personal and socio-demographic characteristics, caregiver presence, personal habits, perceived health, primary physical and psychological complaints, physician-diagnosed chronic diseases, and functional capacity (i.e., activities of daily living). [Results] Results showed a significant positive correlation between age and ADL; age and memory problems, anxiety, and loneliness; and sleep disturbance and falls. Main factors contributing to quality of life decline were chronic disease, falls, sedentary lifestyle, sleep disturbances, and financial concerns. Participants with diabetes mellitus (58.18%) and hypertension (29.0%) had a very high fall rate. Participants engaged in minimal physical activity (63%), often due to bone and joint pain (90.0%), and led sedentary lives (69%). Single sensory impairments were significantly and independently linked to high depression risk and decreased self-sufficiency. [Conclusion] Healthy lifestyle and behavioral changes should be promoted through community-based health education programs for older Saudi adults. Chronic disease screening programs for the elderly population (especially diabetes and hypertension) are recommended.


Responsible gambling: general principles and minimal requirements.
Many international jurisdictions have introduced responsible gambling programs. These programs intend to minimize negative consequences of excessive gambling, but vary considerably in their aims, focus, and content. Many responsible gambling programs lack a conceptual framework and, in the absence of empirical data, their components are based only on general considerations and impressions. This paper outlines the consensus viewpoint of an international group of researchers suggesting fundamental responsible gambling principles, roles of key stakeholders, and minimal requirements that stakeholders can use to frame and inform responsible gambling programs across jurisdictions. Such a framework does not purport to offer value statements regarding the legal status of gambling or its expansion. Rather, it proposes gambling-related initiatives aimed at government, industry, and individuals to promote responsible gambling and consumer protection. This paper argues that there is a set of basic principles and minimal requirements that should form the basis for every responsible gambling program.


[Drug use among children between zero and six years old: a population baseline study in the south of Brazil].
The scope of this article was to estimate the prevalence of medication use in children between zero and six years old, analyzing the associated socio-demographic characteristics, and evaluating the adequacy of the medication with respect to pediatric recommendations and restrictions per age group. A cross-sectional study was conducted by means of cluster sampling on a sample comprised of children aged six or under, residents of a city in the south of Brazil. A standardized questionnaire about medication use 15 days prior to the interview was applied. A descriptive analysis was carried out, and the association between medication use and socio-demographic factors was evaluated, as well as the analysis of the pediatric adequacy of the most prevalent medication. Of the 687 children evaluated, 52% used at least one drug in the period. Associations between medication use and socio-demographic characteristics were not found, with the exception of per capita monthly income. The most prevalent medication was paracetamol (17.1%), followed by amoxicillin (9.5%) and dipyrone (8.4%). Among the ten drugs most used in children, six had pediatric restrictions for the age group. The results indicate significant use of medication, including medication with age restrictions, particularly for children under two years of age.


A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction.
Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis. Detection of these contact sites at nanometer scale over time in living cells is challenging. Here, we developed a tool kit for detecting contact sites based on F luorogen- A ctivated B imolecular complementation at CON tact sites, FABCON, using a reversible, low affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic switch.


Racial differences in the prevalence of dementia among patients admitted to nursing homes.
The purpose of this study was to determine the prevalence of dementia among black and white residents on admission to nursing homes and to determine whether demographic and health characteristics known to be associated with dementia were correlated with dementia in this population. Data from medical records and structured interviews with family members, nursing staff, and nursing home residents were gathered for 2,285 persons newly admitted to nursing homes in Maryland from 1992 to 1995. A stratified sample of 59 nursing homes was used. An expert panel of five physicians classified each resident as demented, nondemented, or indeterminate. Associations between dementia status, race, and selected characteristics were examined. Black residents (77 percent) were significantly more likely than white residents (57 percent) to be classified as demented. Older age was associated with dementia in both races. Less education, male gender, and a history of a cerebrovascular accident were associated with an increased prevalence of dementia among white residents only. After demographic and health characteristics associated with dementia were controlled for, black race remained independently associated with a diagnosis of dementia. The rate of dementia on admission to nursing homes was higher among black residents than among white residents, a finding that has implications for the delivery of care. The higher rate may be due to psychosocial factors operating differently in blacks and whites that influence the timing of admission to a nursing home.


Remote Cerebellar Haemorrhage Occurring after Transcranial Pituitary Surgery.
Post supratentorial and spinal surgeries, in rare cases, Remote Cerebellar Haemorrhage (RCH) develops as a complication. Although the exact aetiology of RCH remains uncertain, excessive drainage of the Cerebrospinal Fluid (CSF) is accepted as the most possible cause. It has been suggested that overdrainage of CSF leads to stretching and resultantly tearing of the cerebellar veins. Early diagnosis and appropriate management decrease mortality and morbidity significantly. In this report, we present a case of RCH encountered on the third postoperative day of transcranial pituitary surgery and discuss the possible causative factors. Excessive loss of CSF is considered to be the major cause of RCH. To our knowledge this is the first case of RCH seen after transcranial macroadenoma surgery reported in the literature so far.


Availability of omental flap on prevention against muscular atrophy of a latissimus dorsi cardiomyoplasty.
Dynamic cardiomyoplasty (DCMP) has been performed in more than seven hundreds cases world wide. However, despite symptomatic improvement in the majority of patients surviving the procedure, objective hemodynamic effects have not been consistently demonstrated. Previous studies reported that left ventricular function deteriorated and returned to preoperative level in the chronic phase. We previously reported that atrophy of the latissimus dorsi muscular flap (LDMF) was responsible for the effect of DCMP on improvement of cardiac function in the chronic phase. Ischemia of the muscle flap was proved to induce peripheral muscular atrophy of the flap, and thus preservation of the blood flow is important in preventing muscular atrophy. In the present study, we applied omental flap to LDMF, and postulated that the omentum would improve vascularity and perfusion of latissimus dorsi and prevent peripheral muscle atrophy. In dogs, the right and left latissimus dorsi muscles were dissected free from all attachment except for its thoracodorsal pedicles, and omental flap was wrapped around peripheral part of the left LDMF. Tissue blood flow, maximal muscle isotonic strength, morphologic features, and tissue vascular endothelial growth factor (VEGF) were examined in left LDMF with omental flap (OM group) and in the right LDMF served as the control (Control group). In the distal part of the LDMF, tissue blood flow of OM was significantly preserved than Control (86.4 +/- 6.5% in OM and 33.6 +/- 3.4% in Control, p < 0.05). Maximal isotonic tension was significantly higher in OM as compared to Control. Microscopic findings of H and E stained specimen from distal part of LDMF showed that muscle fibers were preserved in OM. And in the distal part, VEGF expression of OM was 49.6 +/- 7.9 pg/100 micrograms protein and significantly higher than that of Control. Our results indicated that induced endogenous VEGF expression in the LDMF by the omental flap preserved blood perfusion and muscular strength of the LDMF, and suggested that dynamic cardiomyoplasty might not lose its long-term direct cardiac assistance when an omental flap applied for the latissimus dorsi muscle flap.


Defect size determines survival in infants with congenital diaphragmatic hernia.
Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set. This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points. A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair. The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.


Standards for scrotal ultrasonography.
The paper presents a description of essential equipment requirements for scrotal ultrasonography, including current ultrasound techniques, as well as a review of the most common scrotal pathologies. Patient preparation for the examination as well as ultrasound methodology for the assessment of scrotal and inguinal canal structures are discussed. The standard for scrotal ultrasound examination includes a precise B-mode evaluation, including testicular volumetric assessment performed using automatic measurement options based on the formula of a rotating ellipsoid or three measurements perpendicular to one another. Also, criteria for morphological assessment of abnormalities within testicular or epididymal parenchyma, including a precise evaluation of lesion size, delineation, shape and vascular pattern obtained with Doppler US, have been proposed. Standard assessment further includes epididymal evaluation, including epididymal size in the case of enlargement. The paper additionally discusses the method of ultrasonographic examination and describes the most common pathologies occurring within scrotal structures, including a quantitative analysis of hydrocele and other abnormal fluid reservoirs. We have also presented criteria for the assessment of varicocele as well as color and spectral Doppler flows in scrotal pathologies. Furthermore, we have proposed key components of scrotal ultrasound documentation, so that the contained data could be used to establish appropriate diagnosis, allowing for both adequate clinical management and the reproducibility of subsequent US evaluations performed by either the same or a different examiner. The most common causes of diagnostic errors have also been discussed.


When to use mesh in inguinal hernia repair.
With people living longer today, averaging 73 years old, the type of patients with inguinal hernias are different than in the past. At the present time, to avoid the high incidence of recurrence due to the aged and weakened tissue component of the groin area, we reinforce the posterior wall of the inguinal canal with Mersilene (dacron) mesh. Most surgeons agree to use a prosthetic mesh in recurrent inguinal hernia repairs. Moreover, sometimes it is necessary to use mesh in patients with connective tissue disorders like Ehlers syndrome, Marfan syndrome, and acquired absence of the posterior wall fascia transversalis. Currently, polypropylene and dacron mesh are the most satisfactory, since they are readily available and become well incorporated by connective tissue.


Perceived premarital counseling outcomes among recently married army personnel.
Data from 1,285 recently married soldiers who participated in the 1989 Army Family Research Program survey indicated that premarital counseling by itself had little effect on subsequent marital satisfaction. However, those who had premarital counseling were more likely to use marital and family therapy services, at both subclinical and clinical levels of distress, than others who had not had such counseling before marriage.


Roles, quandaries, and remedies: teaching professional boundaries to medical students.
This article conceptualizes a predictable set of tensions that medical students experience in their new roles with patients on clinical clerkships: empathy versus over-identification, objectivity versus avoidance, collaboration versus coercion, and self-confidence versus "special-ness." These tensions are framed in a developmental context for students and are used to highlight potential boundary difficulties. The role of supervision in teaching students and other beginning trainees about possible boundary issues is discussed.


[Usefulness of the oncogenetic molecular counselling in adults whith familial cancer].
More than 200 cancer susceptibility syndromes (CSS) have been recognized through performing classic epidemiologic studies and genetic linkage analysis. In most CSSs clinical conditions of the patients have been identified as well as their hereditary patterns and the predisponent genes to cancer development. Cancer hereditary identification is a useful condition, since cancer family integrants may benefit of efficient strategies in early screening and in tumor prevention strategies; this consultation is performed by oncogenetic molecular medical consultants who must be scientifically competent for Human Genetics and Cancer molecular biology domains. The oncogenetic molecular consult of patients and family relatives of cancer predisposition families is a medical service in health programs of developed and developing countries; in our country this type of medical service needs to be organized and settled to be part of the integral oncology medical service. The oncogenetic molecular consultation is a structural process of assessment and communication of the associated integral problems of the cancer inherited susceptibility in familial cancer.