Stem cell transplantation into the fetal recipient: challenges and prospects.
The interest in therapeutic intervention for those inherited disorders that can be diagnosed early in pregnancy has recently intensified. In-utero transplantation of haematopoietic stem cells (IUT-HSC), a therapy which could be proffered before pathological manifestations of a disorder become apparent, offers considerable potential benefit. However, as reports of IUT-HSC procedures become more prolific, it is necessary to consider the optimum modus operandi for each group of disorders targeted for therapy in order to develop effective procedures that make a real difference to the outcome. This review outlines the current status and prospects of IUT-HSC. It also offers a view of some of the challenges for IUT-HSC to overcome to find wider clinical applications.


Changing social policy: Grassroots to legislation.
Health care in the United States has evolved into a multimillion dollar business. As the health care industry has grown, so too has government regulation and involvement. As both insurers and patients vie to get the most for their health care dollars, federal and state governments attempt to mediate, prevent fraud and abuse, and protect all parties involved. Consumers feel the effects of this "tug of war" in the form of higher copayments, premiums, and out-of-pocket costs, as well as denial of coverage. This denial of coverage sparked a very successful grassroots effort to stop commercial insurers in the state of Connecticut from defining ostomy supplies as cosmetic and thus denying reimbursement. A tremendous amount of collaboration between Connecticut WOC nurses, state legislators, local American Cancer Society advocates, United Ostomy Association chapter members, and health care providers resulted in a powerful mobilization and support for House Bill No. 5120. This bill went beyond defining ostomy supplies as medically necessary but also set a minimum rate for reimbursement. Social policy changed, improving the lives of Connecticut citizens with an ostomy. Although many people fear they do not have the power to make necessary changes in government, this experience proved otherwise. The collaboration that occurred was patient advocacy at its best. This article describes the process that allowed this successful collaboration to take place with the hope that others will be inspired to get involved with patient advocacy through political involvement. It is the intention of this work to capture the essence of dedication of a grassroots campaign involving a small group of well-organized, highly focused participants who were responsible for changing public health care policy in the state of Connecticut.


The illiterate patient: screening and management.
Illiteracy, which affects about 22% of adults in the United States, can hamper patient communication, treatment, compliance, and access to care. Alternative communication methods and active screening for illiteracy are crucial to addressing this problem.


Purification and Some Properties of an Erythrose Reductase from an Aureobasidium sp. Mutant.
An erythrose reductase was obtained from the cells of an Aureobasidium sp. mutant having high erythritol-producing activity. This enzyme was purified 600-fold over the cell-free extract by ammonium sulfate precipitation, ion exchange chromatography, affinity chromatography, and hydrophobic chromatography. It gave a single band on polyacrylamide gel electrophoresis, and had a molecular weight of 37,000 and an isoelectric point of 4.8. This enzyme had maximum reductive activity at 45°C and pH 6.5. The optimum pH of the oxidative reaction was 9.5. It was stable at pH 6.0-8.0 and below 40°C. The enzyme showed the maximum activity to D-erythrose. D-Glyceraldehyde was reduced at a rate 66% of that for D-erythrose. p-Nitrobenzaldehyde, L-erythrulose, dihydroxyacetone, and D-glucuronate were also reduced, although at slower rates. The oxidative activity was less than 0.1% of the reductive one.


Effect of Lactobacillus sakei OK67 in Reducing Body and Visceral Fat in Lifestyle-Modified Overweight Individuals: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Obesity is a global health problem that affects the quality of life. It is a multidimensional chronic risk factor for major medical conditions, such as cardiovascular diseases, diabetes, and cancer. This clinical trial evaluated the efficacy of Lactobacillus sakei OK67 (DW2010), a lactic acid bacterium, in reducing body and visceral fat in overweight individuals (body mass index ≥25 kg/m2 and <30 kg/m2), aged 20-60 years. A total of 100 subjects placed in a lifestyle modification program were randomly assigned to receive either DW2010 (2.0 g/day, 1.0 × 1010 CFU) or a placebo for 12 weeks. The efficacy of DW2010 was evaluated by measuring body fat mass using dual-energy X-ray absorptiometry and visceral fat area using computed tomography. After 12 weeks, the change in body fat in the DW2010 group was not markedly different from that in the placebo group. However, visceral fat area decreased more in the DW2010 group than in the placebo group (p = 0.035). During the clinical trial, no major adverse events were reported. Moreover, no statistical differences were observed in the biochemical parameters of the DW2010 and placebo groups. Overall, we concluded that the intake of DW2010 for 12 weeks is safe and potentially reduces visceral fat in lifestyle-modified overweight subjects.


Bread Wheat Landraces Adaptability to Low-Input Agriculture.
Bread wheat landraces were an important source of biodiversity used in agriculture before the widespread adoption of high-yielding commercial cultivars adapted to high inputs. Could future agriculture exploit these landraces in different cropping systems in organic or lower-input environments? A two-year field trial was conducted to evaluate grain yield, agronomic performance, and grain quality of bread wheat landraces under different cropping systems, including low-input/organic/conventional environments. Significant variability was found for almost all characteristics among landraces, which makes landraces valuable sources of genetic variation for breeding programs aimed at achieving high and consistent production as well as high-quality products in low-input/organic environments. Additionally, landraces play a crucial role in expanding the genetic diversity of cultivated bread wheat and mitigating biodiversity erosion, thereby enabling crops to better withstand the challenges of low-input/organic agriculture. The landrace "Xilokastro Lamias" had the highest yield among the landraces evaluated in the first growing season (2.65 t·ha-1) and one of the highest yields (2.52 t·ha-1) of all genotypes in the second growing season, which shows promising potential as a starting material in breeding programs targeting high and stable yields. GGE biplot analysis identified the landrace "Xilokastro Lamias", along with commercial cultivars "Yecora E" and "Panifor", as suitable candidates for direct use in low-input/organic wheat farming systems to achieve enhanced productivity. In the conventional environment (C2-IPGRB), commercial cultivars showed the highest values (3.09 to 3.41 ton·ha-1). Of the landraces, only the X4 showed a high GY (3.10 ton·ha-1) while the other landraces had ~33-85% lower yield. In the organic environment (O2-IPGRB), the highest productivity was found in the commercial cultivar X5 and the landrace X4. Commercial cultivars X8 and X7 showed ~68% reduction in GY in the organic environment compared to the conventional, while this reduction was half for the landraces. Finally, the reduction in grain yield between conventional and organic environments was observed to be 45% for commercial cultivars, while it was only half for landraces. This finding confirms the adaptability of landraces to organic agriculture.


Surgical Emphysema Following Canalplasty for Aural Exostoses.
To describe the presentation and management of surgical emphysema involving the temporomandibular joint and deep neck following exostoses removal. A 60-year-old male surfer presented with hearing loss and recurrent infections in the right ear. An examination revealed obstructing bony exostoses in the right external auditory canal. He underwent right canalplasty using a postauricular approach. At 5 weeks after surgery, he presented with right otalgia, swelling of the right face and neck, and complaints of a squeaking noise in the right ear with mandibular excursions. An otomicroscopic examination demonstrated a focal area of prolapsing soft tissue along the anterior bony external auditory canal with mandibular movement. The examination also revealed palpable crepitus of the right face and neck. Computed tomography was obtained of the temporal bones and neck confirming a focal anterior canal wall defect allowing communication between the glenoid fossa and external auditory canal with subcutaneous emphysema tracking around the temporomandibular joint into the masticator, parotid, and parapharyngeal spaces. Maxillomandibular fixation for 2 weeks with revision canalplasty using a split tragal cartilage graft. At 6 weeks after revision surgery, the patient reported complete resolution of all symptoms. Repeat imaging demonstrated complete resolution of subcutaneous and deep neck emphysema, and the otomicroscopic examination revealed a fully epithelialized external auditory canal with no further evidence of soft tissue prolapse. Maxillomandibular fixation with autologous cartilage graft is an effective management strategy for complications of canalplasty resulting in exposure of the temporomandibular joint capsule and surgical emphysema.


Object relations in Harry Potter.
Good fiction helps children address their emotional dilemmas by evoking repressed content, and offering strategies and meaningful values that help them work towards resolutions. Because certain fundamental conflicts continue to be revisited and reworked throughout adulthood, it follows that masterful children's literature might enthrall adults as well. Given the extraordinary, worldwide success of the Harry Potter stories with both children and adults, it might be inferred that they, indeed, are among such literature. Common object relations themes, as well as other intrapsychic processes, are presented in such an imaginative and resonant way that the unconscious is readily engaged. The character of Harry Potter, specifically, embodies such universal (repressed) torments as the agony of destroying and losing the mother; the ominous perception of good and bad objects at war within the self; and the earnest reparative efforts offered to save the self from eternal separation from the beloved other.


Considerations for use of blood-based biomarkers in epidemiologic dementia research.
Dementia represents a growing public health burden with large social, racial, and ethnic disparities. The etiology of dementia is poorly understood, and the lack of robust biomarkers in diverse, population-representative samples is a barrier to moving dementia research forward. Existing biomarkers and other pathology measures derived from neuropathology, neuroimaging, and cerebrospinal fluid samples, are commonly collected in predominantly White and highly-educated samples drawn from academic medical centers in urban settings. Blood-based biomarkers are non-invasive and less expensive, offering promise to expand our understanding of the pathophysiology of dementia, including in participants from historically-excluded groups. Although largely not yet FDA-approved or used in clinical settings, blood-based biomarkers are increasingly included in epidemiologic studies on dementia. Blood-based biomarkers in epidemiologic research may allow the field to more accurately understand the multifactorial etiology and sequence of events that characterize dementia-related pathophysiological changes. As blood-based dementia biomarkers continue to be developed and incorporated into research and practice, we outline considerations for using them in dementia epidemiology, and illustrate key concepts with Alzheimer's Disease Neuroimaging Initiative (2003-present) data. We focus on measurement, including both validity and reliability, and on the use of dementia blood-based biomarkers to promote equity in dementia research and cognitive aging.


Goal achievement in the six months after inpatient rehabilitation for stroke.
The purpose of the project was to identify characteristics associated with successful re-integration into the community post-inpatient rehabilitation after stroke. A key issue was determining re-integration from the person's perspective, taking into account the person's preferred lifestyle choices. A prospective exploratory follow up study. A consecutive sample of 45 participants discharged from IP rehabilitation following stroke and 23 carers associated with the participants. Goal attainment scaling was utilised to determine successful community integration. Factors that may have contributed to goal achievement were measured prior to discharge and at 6 months post-discharge. Scales used include the Functional Independence Measure, Mini Mental test, the CES-D depression scale and a self-efficacy scale, Strategies Used by People to Promote Health. London Handicap Scale scores and Carer Strain Index were collected at 6 months. Twenty percent of participants achieved all their goals. Significant correlations were observed between goal achievement score and concurrent measures of physical function, depression and self efficacy at 6 months post-discharge. Stroke survivors who achieved their goals were less likely to be depressed, showed stronger self efficacy beliefs and more positive perceptions of their participation in everyday and community life.


[Polycystic ovaries in 2001: physiology and treatment].
Clinical characteristics of PCOS Syndrome Two fundamental characteristics: hyperandrogenism and anovulation which lead to hirsutism and oligo-or amenorrhea. Other features include obesity, acanthosis nigricans, and metabolic disruption (insulin resistance with hyperinsulinemia, glucose intolerance, or type II diabetes mellitus). Complementary tests Serum testosterone and DHEA-S levels: to exclude androgen-producing tumors. Serum 17-hydroxyprogesterone level: to exclude congenital adrenal hyperplasia, 21-hydroxylase deficiency. Ultrasound: increased size of the ovaries and central stroma with presence of peripheral follicular cysts (8-10) measuring about 8 mm in diameter. Pathophysiology Therapeutic approaches Therapeutic approaches


Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.
While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.


Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95.
The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2A N-methyl-D-aspartate receptors (NMDAR) subunit and the NMDAR-anchoring protein PSD-95 mediate acute alcohol intoxication and represent putative mechanisms mediating tolerance. We found that chronic intermittent ethanol exposure (CIE) did not produce tolerance [loss of righting reflex (LORR)] or withdrawal-anxiety in C57BL/6J, GluN2A or PSD-95 knockout mice assayed 2-3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C57BL/6J and PSD-95 knockouts, but absent in GluN2A knockouts. These data suggest a role for GluN2A in tolerance, extending evidence that human GluN2A gene variation is involved in alcohol dependence.


Reticulate Evolution in AA-Genome Wild Rice in Australia.
The wild rice gene pool, i.e., AA-genome, in Australia is geographically and genetically distinct from that in Asia. Two distinct taxa are found growing together in northern Australia, Oryza meridionalis (including annual and perennial forms) and an Oryza rufipogon like taxa that have been shown to have a chloroplast genome sequence that is closer to that of O. meridionalis than to O. rufipogon from Asia. Rare plants of intermediate morphology have been observed in the wild despite a reported reproductive barrier between these two species. We now report the resequencing of plants from 26 populations including both taxa and putative hybrids. A comparison of chloroplast and nuclear genome sequences indicated re-combinations that demonstrated hybridisation in both directions. Individuals with intermediate morphology had high nuclear genome heterozygosity consistent with a hybrid origin. An examination of specific genes (e.g., starch biosynthesis genes) revealed the presence of heterozygotes with alleles from both parents suggesting that some wild plants were early generation hybrids. These plants may have low cross-fertility preserving the continuation of the two distinct species. Repeated backcrossing of these rare hybrids to one parent would explain the plants exhibiting chloroplast capture. These observations suggest that reticulate evolution is continuing in wild Oryza populations and may have been a key process in rice evolution and domestication.


Comparison of radical (nasalisation) and functional ethmoidectomy in patients with severe sinonasal polyposis. A retrospective study.
To compare the 5-year outcomes of two endoscopic surgical approaches for diffuse and severe nasal polyposis. A natural experimental situation gave us the opportunity to compare the results 5 years after radical ethmoidectomy (nasalisation) (n= 39), and functional ethmoidectomy (n= 37). The two surgical procedures were performed by two different surgeons on 76 consecutive patients. There was no random assignment for this retrospective study. Five years after surgery, the criteria for comparison were 1) functional results based on a questionnaire using visual analogue scales in patients free of revision surgery; 2) endoscopic and CT-scan assessments of anatomical results. The CT-scans were blinded and randomized, and opacities were measured using a computerized model; 3) the recurrence rate of nasal polyps. Five years after surgery, the overall nasal functional benefit was scored 8.41 +/- 0.40 (mean +/- SEM) after nasalisation, and 5.69 +/- 0.83 after ethmoidectomy P= 0.002) in patients free of revision surgery. The endoscopic appearance of the mucosa was methodically scored according to a pre-defined scale. Results were significantly better in the nasalisation group (6.03 +/- 0.7 versus 3.27 +/- 1.0, P= 0.02). A good correlation was found between the endoscopic and CT-scan scores (r= -0.78, P= 0.0001 for nasalisation, and r= -0.65, P= 0.001 for ethmoidectomy). The total recurrence rate was 22.7% in the nasalisation group, and 58.3% in the ethmoidectomy group (chi2= 10.41, P< 0.01). Our study suggests that in the treatment of nasal polyposis complete ethmoidectomy leads to better long term results than incomplete ethmoidectomy.


[Homes for the aged and health resorts. Reflections on the quality of life in old age homes].
The quality of living in homes for the elderly and health resort institutions must be assessed in accordance with subjective and objective criteria. From the medical point of view, stress factors in the living area should be avoided, and health-promoting factors introduced. In this connection, consideration must be given to the biological, psychological and sociological aspects of ageing. Both in homes for the elderly and in health resort institutions, the particularly features of variability of interior design, compactness, clarity, safety, separation of functional rooms, furnishability and domestic comfort should be taken into account. The question of comfort (homeliness) in the health resort clinics, would appear to be an important factor, since it promotes patient contentment and willingness to cooperate, and thus also patient compliance.


Parental Knowledge about Meningococcal Disease and Vaccination Uptake among 0⁻5 years Old Polish Children.
In Poland, in addition to mandatory, free of charge vaccines, listed in the national immunization schedule, numerous self-paid vaccinations are recommended, including meningococcal vaccination (MV). To assess MV uptake among ≤5-year-old children and to evaluate parental knowledge and attitudes regarding invasive meningococcal disease (IMD). A cross-sectional study was conducted in 2018 among 350 parents (mean age: 32.3 years), attending three randomly selected primary care clinics in Szczecin region, Poland. Anonymous questionnaires were administered to the parents by researchers, present at the time the survey was conducted, to self-complete on a voluntary basis. Chi-square or Fisher's exact for categorical and Mann⁻Whitney U test for continuous variables. Variables significantly (p < 0.05) associated with 'good knowledge' in the bivariate analysis were used to build a logistic regression model. It was found that the response rate was 93.4%, and MV uptake among children was 29.5%. The main knowledge sources were medical staff and media; 72.5% had ever received information about IMD. Only 18.8% of parents self-assessed their knowledge regarding IMD as good; 61.8% scored >50% in the knowledge test 58.9% knew the mode of transmission, 58.7% recognized the severity of meningitis, and 79.7% knew that bacterial meningitis is a vaccine-preventive disease. Knowledge regarding IMD was higher among parents with higher educational level (OR = 3.37; p = 0.01), from urban facilities (OR = 2.20; p = 0.02), who received previous information about IMD (OR = 2.85; p = 0.01) and self-assessed their knowledge as good (OR = 2.59; p = 0.04). Low MV coverage among children up to five years old and knowledge gaps about IMD call for awareness campaigns which may increase the coverage. Although educational interventions should cover all parents, those from provincial facilities, representing lower education level need special attention.


Development of Facial Rejuvenation Procedures: Thirty Years of Clinical Experience with Face Lifts.
Facial rejuvenation procedures can be roughly divided into face lift surgery and nonoperative, less invasive procedures, such as fat grafts, fillers, botulinum toxin injections, thread lifts, or laserbrasion. Face lift surgery or rhytidectomy is the procedure most directly associated with rejuvenation, due to its fundamental ability to restore the anatomical changes caused by aging. Various methods of face lift surgery have been developed over the last hundred years, thanks to advances in the understanding of facial anatomy and the mechanisms of aging, as well as the dedication of innovative surgeons. However, no generally applicable standard method exists, because the condition of each patient is different, and each operative method has advantages and disadvantages. Specific characteristics of the skin of Asians and their skeletal anatomy should be considered when determining the operative method to be used on Asian patients. Plastic surgeons should improve their ability to analyze the original aesthetic properties and problem areas of each patient, drawing on scientific knowledge about the aging process, and they should develop the skills necessary to perform various rejuvenative techniques. In the present article, we reviewed various face lift procedures and the current methods of modified double plane face lift, based on our clinical experience of over 30 years.


Inactivation of the small GTPase Rac1 protects the liver from ischemia/reperfusion injury in the rat.
In ischemia/reperfusion (I/R) injury, a massive generation of reactive oxygen species (ROS) after reperfusion is a critical factor. Rac, a member of the Rho GTPase superfamily, plays important roles in the production of ROS and activation of nuclear factor-kappaB (NF-kappaB) in vitro. However, the exact role of Rac in the ROS production and NF-kappaB activation in vivo after I/R is still obscure. We blocked Rac1 activity in the rat liver using adenovirus encoding a dominant negative rac1 mutant (Ad5N17Rac1) and examined whether inactivation of Rac1 could prevent ROS generation in the hepatic I/R injury. Seventy-two hours after the adenoviral infection, hepatic I/R was induced by Pringle's maneuver for 20 minutes, followed by reperfusion in the rats. Ad5N17Rac1 infection significantly attenuated ROS production after reperfusion and suppressed the hepatic injury. Furthermore, N17Rac1 suppressed NF-kappaB activation and messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthetase (iNOS). Ad5LacZ, a control adenovirus, had no effect on the induced hepatic I/R injury, nor did it affect NF-kappaB activation. Immunohistochemical analysis of NF-kappaB (p65) revealed that translocation of p65 to the nucleus after reperfusion was blocked in many of non-parenchymal cells (NPCs) and in hepatocytes in the Ad5N17Rac1-infected liver. We conclude that Rac1 is required in ROS generation and NF-kappaB activation after hepatic I/R in vivo, and that inactivation of NF-kappaB in NPCs and suppression of ROS generation in NPCs and hepatocytes possibly account for the protective effect of N17Rac1 in this study.


Lichen striatus-like leukoderma.
A particular pigmentary disorder develops on the skin of Chinese children. The lesions are composed of whitish macules and patches arranged in linear bands on the extremities unilaterally. Histologically these lesions are hypopigmented chronic dermatitis. Although the lesions are arranged in a lichen striatus pattern, they differ clinically from lichen striatus by the absence of papules and plaques. These cases may represent a new entity. The differential diagnosis includes lichen striatus, vitiligo, piebaldism, nevus depigmentosus, and hypomelanosis of Ito. The differences between the disorder presented here and those of different diagnosis are discussed.


Direct Synthesis of α-Fluoro-α-Triazol-1-yl Ketones from Sulfoxonium Ylides: A One-Pot Approach.
The work reported herein showcases a new route to access α-fluoro-α-triazol-1-yl ketones from sulfoxonium ylides via α-azido-α-fluoro ketone intermediates. In a one-pot, two-step sequence, the ketosulfoxonium reactant initially undergoes insertion of F+ and N3-, followed by a subsequent CuAAC reaction with arylacetylenes to install a 1,4-triazolo moiety. The approach allows for modification to both the sulfoxonium ylide and arylacetylene reactants. Fifteen examples have been reported, with yields ranging between 22% and 75%.


An examination of the attitudes and practice of general practitioners in the diagnosis and treatment of depression in older people.
Most depression in older people is managed in primary care settings but can be difficult to diagnose and is often under-treated. This study examined the attitudes and practice of general practitioners in the treatment of late-life depression using antidepressant medication. Three hundred and thirty general practitioners in 116 general practices within the Nottingham Health Authority were surveyed. Their responses to a series of attitude statements and clinical vignettes regarding antidepressant prescribing were assessed. Analysis of vignettes showed newer antidepressants to be prescribed much more frequently than older antidepressants, with a substantial increase in the use of SSRIs compared to the results of previous research. Older general practitioners and those who had been in practice for longer were more likely to prescribe tricyclic antidepressants. They were also more likely to identify a need for extra training in treating old age depression, as were those GPs without previous psychiatric training. However, most GPs were confident in treating depression in the elderly although younger GPs were the most confident. Selective Serotonin Re-Uptake Inhibitors are the preferred drugs in treating certain problematic cases of late-life depression. These results suggest there may be a greater propensity for GPs to prescribe SSRIs although further research is needed to clarify whether this finding can be generalised beyond this study. Most general practitioners felt confident in treating late-life depression, but older doctors, those who had been practising for longer and those without previous psychiatric training, may benefit most from further training.


Antibacterial/antifungal activity and synergistic interactions between polyprenols and other lipids isolated from Ginkgo biloba L. leaves.
Polyprenols separated from lipids are promising new components from Ginkgo biloba L. leaves (GBL). In this paper, ginkgo lipids were isolated by extraction with petroleum ether, saponification, and molecular distillation. Eight known compounds: isophytol (1), nerolidol (2), linalool (3), β-sitosterol acetate (4), β-sitosterol (5), stigmasterol (6), ergosterol (7), β-sitosterol-3-O-β-D-glucopyranoside (8) and Ginkgo biloba polyprenols (GBP) were separated from GBL by chromatography and identified mainly by NMR. The separated and identified compounds 1, 2 and 3 are reported here for the first time in GBL. The 3D-DAD-HPLC-chromatogram (190-232 nm) of GBP was recorded. This study provides new evidence as there are no previous reports on antibacterial/antifungal activities and synergistic interactions between GBP and the compounds separated from GBL lipids against Salmonella enterica, Staphylocococus aureus and Aspergillus niger. Nerolidol (2) showed the highest activity among all the tested samples and of all mixture groups tested the GBP with isophytol (1) mixture had the strongest synergistic effect against Salmonella enterica among the three tested strains. A proportion of isophytol and GBP of 38.19%:61.81% (wt/wt) was determined by mixture design as the optimal proportion for the synergistic effect of GBP with isophytol against Salmonella enterica.


Comparison of gonioscopy and anterior segment ocular coherence tomography in detecting angle closure in different quadrants of the anterior chamber angle.
To compare the performance of gonioscopy and anterior segment (AS) optical coherence tomography (OCT) in detecting angle closure in the different quadrants of the anterior chamber angle (ACA). Cross-sectional observational study. Five hundred two consecutive subjects more than 50 years of age with no previous ophthalmic problems recruited from a community clinic in Singapore. All subjects underwent gonioscopy and AS OCT imaging in the dark. Using gonioscopy, the ACA was graded using the Scheie system by a single examiner masked to AS OCT findings. The ACA in a particular quadrant was classified as closed if the posterior trabecular meshwork could not be seen on gonioscopy. A closed ACA on AS OCT imaging was defined by the presence of any contact between the iris and angle wall anterior to the scleral spur. After excluding eyes with poor image quality, a total of 423 right eyes were included in the analysis. A closed angle in at least 1 quadrant was observed in 59% of the eyes by AS OCT and in 33% of the eyes by gonioscopy (P<0.001), with fair agreement between the two methods (kappa = 0.40). The frequency of closed angles by AS OCT and gonioscopy were 48% versus 29% superiorly, 43% versus 22% inferiorly, 18% versus 14% nasally, and 12% versus 20% temporally, respectively. Of the 119 of 1692 quadrants that were closed on gonioscopy but open on AS OCT, a steep iris profile was present in 61 (51%) of 119 quadrants on AS OCT, and of the 276 of 1692 quadrants that were open on gonioscopy but closed on AS OCT, 196 (71%) of 276 quadrants showed short iridoangle contact on AS OCT. The highest rates of closed angles on gonioscopy and AS OCT images were observed in the superior quadrant. Anterior segment OCT tended to detect more closed ACAs than gonioscopy, particularly in the superior and inferior quadrants. Variations in the iris profile and level of iridoangle contact also may explain some of the differences seen between gonioscopy and AS OCT.


Early Phase of Primary Melanoma Growth from the Patient Point of view: A Prospective Cross Sectional Study on Melanoma over 1 mm in Thickness.
A Nodular Pink Lesion with an Uncommon Diagnosis: A QuizMost melanomas are diagnosed by the patients themselves or by their partners or relatives; they alone can describe its history. We designed a prospective cross-sectional study to describe patients' perception of morphology, growth pattern and kinetics of their primary melanoma over 1 mm in thickness before resection. Patients were interviewed with a questionnaire, a grid representing 9 possible scenarios of melanoma growth, and a set of 87 photographs of potential aspects of melanomas and precursors. Most patients were able to describe the growth of their melanoma and select pictures representative of its successive aspects before resection. Among 453 patients, 60% reported a preexisting lesion present for years. Growth pattern scenarios concurred with tumor kinetics but with no statistical difference between nodular and superficial spreading subtypes. These subjective patient-reported indicators about melanoma growth over time could dynamically complement its objective pathological analysis otherwise static at a single time point.


Visual acuity, safe/unsafe practices and self-reported road traffic crash experiences among commuter bus drivers from two motor parks in Lagos, Nigeria.
The sella turcica is an important anatomical landmark and reference point in orthodontics with many studies identifying shape and morphology for different populations. The aim of this study was to evaluate sella turcica shapes in skeletal classes I, II and III orthodontic patients in Benin City, Nigeria. This study was carried out at the Orthodontic Unit of the University of Benin Teaching Hospital, Benin City, Nigeria. Standardized digital pre-treatment lateral cephalometric radiographs of 139 patients (65 male and 74 female; aged 7-30 years) were analyzed according to the skeletal class each of them belonged to. The sella turcica of each radiograph was traced to determine the shape. The chi square and student t-test was used to determine statistical significances between frequencies and association between variables. There was a normal morphology of the sella turcica in the majority (64%) of subjects and a variation of 5 other shapes in the remaining 36% of patients seen. Skeletal class II was the most predominant skeletal class and was seen in 50.4% of the study population. A normal shaped sella turcica was seen in 58.4% of subjects with skeletal class II pattern. Irregular dorsum sella and a pyramidal shape were observed in 57.1% of subjects with skeletal class I pattern. Skeletal Class III was most predominant with an Irregular dorsum sella in 28.6%.The gender distribution in a normal sella turcica shape was seen with females and males demonstrating 53.9% and 46.1% respectively. Sella turcica shapes vary in the three skeletal patterns in orthodontic patients in Benin City, Nigeria.


GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer.
Patients with advanced hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) have a very poor prognosis due to the lack of efficient treatments. As observed in several other tumors, the effectiveness of treatments is mainly hampered by the presence of a highly tumorigenic sub-population of cancer cells called cancer stem cells (CSCs). Indeed, CSCs are resistant to chemotherapy and radiotherapy and can regenerate the tumor bulk. Hence, innovative drugs that are efficient against both bulk tumor cells and CSCs would likely improve cancer treatment. In this study, we demonstrated that GNS561, a new autophagy inhibitor that induces lysosomal cell death, showed significant activity against not only the whole tumor population but also a sub-population displaying CSC features (high ALDH activity and tumorsphere formation ability) in HCC and in liver mCRC cell lines. These results were confirmed in vivo in HCC from a DEN-induced cirrhotic rat model in which GNS561 decreased tumor growth and reduced the frequency of CSCs (CD90+CD45-). Thus, GNS561 offers great promise for cancer therapy by exterminating both the tumor bulk and the CSC sub-population. Accordingly, a global phase 1b clinical trial in liver cancers was recently completed.


Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma.
A mechanism decreasing oxidative metabolism during normal cell division and growth is expected to direct substrates toward biosyntheses rather than toward complete oxidation to CO(2). Hence, any event decreasing oxidative phosphorylations (OXPHOS) could provide a proliferating advantage to a transformed or tumor cell in an oxidative tissue. To test this hypothesis, we studied mitochondrial enzymes, DNA and OXPHOS protein content in three types of renal tumors from 25 patients. Renal cell carcinomas (RCCs) of clear cell type (CCRCCs) originate from the proximal tubule and are most aggressive. Chromophilic RCCs, from similar proximal origin, are less aggressive. The benign renal oncocytomas originate from collecting duct cells. Mitochondrial enzyme and DNA contents in all tumor types or grades differed significantly from normal tissue. Mitochondrial impairment increased from the less aggressive to the most aggressive RCCs, and correlated with a considerably decreased content of OXPHOS complexes (complexes II, III, and IV of the respiratory chain, and ATPase/ATP synthase) rather than to the mitochondrial content (citrate synthase and mitochondrial (mt)DNA). In benign oncocytoma, some mitochondrial parameters (mtDNA, citrate synthase, and complex IV) were increased 4- to 7-fold, and some were slightly increased by a factor of 2 (complex V) or close to normal (complexes II and III). A low content of complex V protein was found in all CCRCC and chromophilic tumors studied. However F(1)-ATPase activity was not consistently decreased and its impairment was associated with increased aggressiveness in CCRCCs. Immunodetection of free F(1)-sector of complex V demonstrated a disturbed assembly/stability of complex V in several CCRCC and chromophilic tumors. All results are in agreement with the hypothesis that a decreased OXPHOS capacity favors faster growth or increased invasiveness.


The origin and kinetics of mononuclear phagocytes.
The origin and turnover of efferent populations of mouse mononuclear phagocytes has been described. Mononuclear phagocytes were defined as mononuclear cells which are able to adhere to glass and phagocytize. In vitro labeling studies with thymidine-(3)H showed that monocytes in the peripheral blood and peritoneal macrophages do not multiply and can be considered end cells in a normal, steady state situation. However, the mononuclear phagocytes of the bone marrow appear to be rapidly dividing cells. This conclusion was supported by in vivo labeling experiments. A peak of labeled mononuclear phagocytes of the bone marrow was found 24 hr after a pulse of thymidine-(3)H. This was followed, 24 hr later, by a peak of labeled monocytes in the peripheral blood. From these experiments it was concluded that the rapidly dividing mononuclear phagocytes of the bone marrow, called promonocytes, are the progenitor cells of the monocytes. Labeling studies after splenectomy and after X-irradiation excluded other organs as a major source of the monocytes. Peak labeling of both the blood monocyte and peritoneal macrophages occurred at the same time. A rapid entry of monocytes from the blood into the peritoneal cavity was observed, after a sterile inflammation was evoked by an injection of newborn calf serum. These data have led to the conclusion that monocytes give rise to peritoneal macrophages. No indications have been obtained that mononuclear phagocytes originate from lymphocytes. In the normal steady state the monocytes leave the circulation by a random process, with a half-time of 22 hr. The average blood transit time of the monocytes has been calculated to be 32 hr. The turnover rate of peritoneal macrophages was low and estimated at about 0.1% per hour. On the basis of these studies the life history of mouse mononuclear phagocytes was formulated to be: promonocytes in the bone marrow, --> monocytes in the peripheral blood, --> macrophages in the tissue.


Fruit and vegetable intake and risk of hip fracture: a cohort study of Swedish men and women.
Dietary guidelines recommend a daily intake of 5 servings of fruits and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n = 75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45 to 83 years). Intake of fruits and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998 to 2010). The mean follow-up time was 14.2 years. One-third of the participants reported an intake of fruits and vegetables of >5 servings/day, one-third reported >3 to ≤5 servings/day, 28% reported >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3644 hip fractures (2266 or 62% in women). The dose-response association was found to be strongly nonlinear (p < 0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR) was 1.88 (95% CI, 1.53 to 2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 versus 5 servings/day was 1.35 (95% CI, 1.21 to 1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 versus 5 servings/day was 0.96; 95% CI, 0.90 to 1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended five servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk.


Properdin factor B (Bf) as an exclusion determinate in parentage testing.
Properdin factor B (Bf) was phenotyped on 519 paternity cases. Gene frequencies of BfF = 0.1870, BfF1 = 0.0105, BfS = 0.7985 and BfSO.7 = 0.0040 were observed in Minnesota Whites. Based on these values the exclusion probability is (p) = 0.1442. Bf accounted for 15% of the 88 observed exclusions. A technique is described for simultaneous electrophoresis of Bf and Gc on the same gel.


[Neonatal neoplasms: a single-centre experience].
Malignant tumors are uncommon in the neonatal period and benign tumors may have malignant potential. To describe the neoplasms diagnosed and treated in newborns (</= 28 days of life) in the Hospital Universitario de Canarias and their association with congenital abnormalities and to evaluate prenatal diagnosis of these tumors. The medical records of patients with neoplasms diagnosed during the neonatal period in the previous 25 years in our hospital were retrospectively reviewed. The variables analyzed were the percentage of neonatal neoplasms among the total number of cancer cases in children aged less than 14 years, their incidence among all the newborns in our hospital, sex, year of diagnosis, age at clinical diagnosis, the presence or absence of prenatal diagnosis, type of tumor (histologic diagnosis), association with syndromes or other congenital anomalies, treatment, and long-term outcome. Of 260 neoplasms diagnosed in our unit from 1980, 16 (6.1 %) were diagnosed in the neonatal period. The incidence of neonatal neoplasms was estimated to be 276.5 per million live births. Males accounted for 43.8 % and females for 56.2 %, with a mean age at diagnosis of 5.5 days (range 1-28 days). Five neonates (31.2 %) had a prenatal diagnosis, 60 % of which were made in the last 7 years of the study period. A further five newborns were diagnosed at the initial neonatal examination. Histologic diagnoses were neuroblastoma (n = 5; 31.2 %), teratoma/ germ cell tumor (n = 4; 25 %), soft tissue sarcoma (one fibrosarcoma of the thigh and two hemangiopericytoma of the back and heart; 18.8 %), and one case each of mesoblastic nephroma, cerebral tumor (ependymoblastoma), melanoma (associated with giant congenital melanocytic nevi), and acute leukemia (associated with Down syndrome). Treatment consisted of surgery alone (n = 10; 62.5 %) and surgery plus chemotherapy (n = 5; 31.2 %); one patient received no treatment. The overall actuarial survival rate was 87.5 %. Sequelae were observed in 33.3 % of survivors. The neoplasms most frequently diagnosed in the neonatal period were solid tumors, mainly neuroblastoma and teratomas/germ cell tumors; 12.5 % were associated with syndromes or congenital anomalies. In the last 7 years, the prenatal diagnosis of these entities has improved. Most of the neoplasms responded to therapy, mainly surgery, and long-term outcome was favorable.


Positron emission tomography for initial staging of esophageal cancer among medicare beneficiaries.
The role of positron emission tomography (PET) in the initial staging of esophageal cancer is to detect occult metastases, but its ability to do so has not been evaluated at the population-level. In 2001, Medicare approved reimbursement of PET for esophageal cancer staging. We hypothesized rapid adoption of PET after 2001 and a coincident increase in the prevalence of stage IV disease. A retrospective cohort study [1997-2009] was conducted of 12,870 Medicare beneficiaries with esophageal cancer using the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. PET use increased from <3% before 2001 to 44% in 2009 (post-PET era) (P trend <0.001). Over the same period, the prevalence of stage IV disease also increased (20% in 1997 and 28% in 2009, P trend <0.001). After adjusting for changing patient characteristics over time, the rate of increase in stage IV disease in the post-PET era [relative risk (RR) =1.06; 95% confidence interval (CI), 1.00-1.13] was no different than the rate of increase in the pre-PET era (RR =1.02; 95% CI, 1.02-1.04). Over the entire study period, the prevalence of unrecorded stage decreased by more than half (43% to 18%, adjusted P trend <0.001) with coincident increases in stage 0-III (37% to 53%, adjusted P trend <0.001) as well as stage IV disease. The increasing frequency of PET use and stage IV disease over time is more likely explained by improved documentation rather than PET's ability to detect occult metastases. The absence of compelling population-level impact compliments previous studies, revealing an opportunity to increase value through selective use of PET.


Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies.
Backgrounds. Outcome of childhood malignancy has been improved mostly due to the advances in diagnostic techniques and treatment strategies. While methotrexate (MTX) related polymorphisms have been under investigation in childhood malignancies, many controversial results have been offered. Objectives. To evaluate associations of polymorphisms related MTX metabolisms and clinical course in childhood lymphoid malignancies. Method. Eighty-two acute lymphoblastic leukemia and 21 non-Hodgkin's lymphoma children were enrolled in this study. Four single nucleotide polymorphisms in 2 genes (MTHFR (rs1801133/c.677C>T/p.Ala222Val and rs1801131/c.1298A>C/p.Glu429Ala) and SLCO1B1 (rs4149056/c.521T>C/p.V174A and rs11045879/c.1865+4846T>C)) were genotyped by Taqman PCR method or direct sequencing. Clinical courses were reviewed retrospectively. Results. No patient who had the AC/CC genotype of rs1801131 (MTHFR) had relapsed or died, in which distribution was statistically different among the AA genotype of rs1801131 (P = 0.004). Polymorphisms of SLCO1B1 (rs11045879 and rs4149056) were not correlated with MTX concentrations, adverse events, or disease outcome. Conclusions. Polymorphisms of MTHFR (rs1801131) could be the plausive candidate for prognostic predictor in childhood lymphoid malignancies.


Eighteen sensations after breast cancer surgery: a comparison of sentinel lymph node biopsy and axillary lymph node dissection.
To evaluate prevalence, severity, and level of distress of 18 sensations at 3-15 days (baseline), 3 months, and 6 months after breast cancer surgery; to compare sentinel lymph node biopsy (SLNB) to SLNB with immediate or delayed axillary lymph node dissection; to evaluate the Breast Sensation Assessment Scale(c) (BSAS(c)) for reliability and validity. Prospective, descriptive. Evelyn H. Lauder Ambulatory Breast Center at Memorial Sloan-Kettering Cancer Center in New York City. 283 women with breast cancer; 187 had SLNB, and 96 had SLNB and axillary lymph node dissection. Patients completed the BSAS(c) at baseline, three months, and six months after surgery. Prevalence, severity, and level of distress of sensations in patients who had breast cancer surgery. Sensations were less prevalent, severe, and distressing following SLNB compared with axillary lymph node dissection at all three time points. Tenderness and soreness remained highly prevalent following SLNB at the three time points. Tenderness, soreness, tightness, and numbness were among the most severe and distressing symptoms in both groups. The BSAS(c) demonstrated good reliability and validity. Overall prevalence, severity, and level of distress were lower following SLNB compared with axillary lymph node dissection at baseline, three months, and six months after surgery. Certain sensations remained prevalent, severe, and distressing in both groups. The BSAS(c) is a reliable and valid instrument. Nurses should be familiar with prevalent sensations patients experience after SLNB and axillary lymph node dissection so they can provide education and support.


Ready for eHealth? Health Professionals' Acceptance and Adoption of eHealth Interventions in Inpatient Routine Care.
eHealth interventions can be effective in treating health problems. However, adoption in inpatient routine care seems limited. The present study therefore aimed to investigate barriers and facilitators to acceptance of eHealth interventions and of online aftercare in particular in health professionals of inpatient treatment. A total of 152 out of 287 health professionals of various professional groups in four inpatient rehabilitation facilities filled out a self-administered web-based questionnaire (response rate: 53%); 128 individuals were eligible for further data analysis. Acceptance and possible predictors were investigated with a complex research model based on the Unified Theory of Acceptance and Use of Technology. Acceptance of eHealth interventions was rather low (M = 2.47, SD = 0.98); however, acceptance of online aftercare was moderate (M = 3.08, SD = 0.96, t(127) = 8.22, p < .001), and eHealth literacy was elevated. Social influence, performance expectancy, and treatment-related internet and mobile use significantly predicted overall acceptance. No differences were found between professional and age groups. Although acceptance of eHealth interventions was limited in health professionals of inpatient treatment, moderate acceptance of online aftercare for work-related stress implies a basis for future implementation. Tailored eHealth education addressing misconceptions about inferiority and incongruity with conventional treatment considering the systemic aspect of acceptance formation are needed.


[Hypofractionated radiation therapy for localized prostate cancer (first experience)].
This paper presents a study of 74 prostate cancer patients divided into 2 groups (study group and comparison group). The comparison group patients (n=50) were treated with radiation therapy in standard fractionated mode, while study group patients (n=24) underwent hypofractionated radiation therapy (STD 7.5 Gy; TTD 37.5 Gy). Early radiation-induced complications occurred only in the comparison group patients. Late radiation-induced complications were observed in 4 and 8 patients in the study group and the comparison group, respectively. Significant statistic differences in quality of life between groups were found in patients with excellent (FET; p=0.0145) and satisfactory (FET; p=0.03) well-being. Hypofractionated radiation therapy is safe given that the necessary technical and clinical conditions are observed. It significantly reduces treatment time and enables quickly bringing a course of radiation therapy to radical doses. This is a noninvasive treatment that significantly reduces risks and cost of procedures.


Molecular insights into the mechanism and the efficiency-structure relationship of phosphorus removal by coagulation.
Types and structures of phosphorus compounds influence the removal of phosphorus by coagulation. Until now, the molecular-level interaction between coagulants and phosphorus (especially organophosphates) and the relationship between removal efficiency and phosphorus structure have not been clear. This work investigated the removal of phosphorus with different structures using conventional coagulants (poly aluminum chloride (PACl) and polymerized ferric sulfate (PFS)) and a novel covalently-bound inorganic-organic hybrid coagulant (CBHyC). CBHyC removed more than 98% of phosphate and most of organophosphates, had more stable performance than PACl and PFS, and was less affected by pH, initial phosphorus concentration, and co-occurring materials. Molecular dynamics simulation demonstrated that CBHyC removed phosphorus mainly through electrostatic attraction and hydrophobic interaction. Furthermore, this work established QSAR (quantitative structure activity relationship) models for removal efficiency and organophosphate structure for the first time. The model showed that atomic charges of phosphorus atoms (QP) and hydrogen atoms (QH+) in the system and the energy gap (ΔEMO) affected electronegativity and hydrophobicity, thus influencing organophosphate removal efficiency. The model had high fitting precision and good predictive ability and has the potential to greatly reduce the cost of optimizing processes and conditions for phosphorus removal.


[Accessory anesthetic breathing systems: verification before use].
Accessory or ancillary anaesthesia breathing systems can be defined as all those connected to the fresh gas outlet of the anaesthetic apparatus and used instead of the circle system associated with the ventilator, which is the main circuit. They include: the Mapleson systems, the systems with a nonrebreathing valve and the disposable systems with a carbon dioxide absorber. They can be a cause of major accidents when not checked before and monitored during use. This technical note describes techniques of preanaesthetic checking and monitoring during anaesthesia.


Pneumonia: the impact of antibiotic resistance on its management.
Pneumonia in the community affects between 1 and 5 per 1000 per year. The microbial aetiology is diverse and influenced by preexisting disease, seasonality, as well as animate and inanimate environmental sources; pneumococci, Legionella spp., Mycoplasma pneumoniae, and more recently Chlamydia pneumoniae are the predominant bacterial pathogens. Gram-negative enteric bacteria although less common are particularly virulent. Antibiotic resistance is well established for Haemophilus influenzae and Gram-negative bacillary infections, but has been a recent phenomenon in the case of Streptococcus pneumoniae, which is numerically the leading pathogen. Despite the concerns raised by this reduced susceptibility to penicillin, evidence that this has been translated into increased clinical failures is currently difficult to establish. Macrolide and tetracycline resistance among pneumococci is more common. beta-Lactamase production by H. influenzae has now reached levels where, in those with severe pneumonia, beta-lactamase stable agents are preferred. Consensus Guidelines on the treatment of community acquired pneumonia have been published by the British Thoracic Society, the American Thoracic Society, and from Expert Panels in Canada and France. These emphasize severity assessment and differentiate management in the community or hospital setting. The recommended regimens are compared and contrasted. In conclusion, mild/moderate pneumonia, when pneumococcal in nature, is likely to still respond to amoxycillin or penicillin G, but in higher dosages where pneumococcal resistance is documented. However, in severe infection where pneumococcal resistance, other beta-lactamase-producing pathogens, or an atypical infection could be operating, it is important that initial empirical therapy be broad spectrum and promptly administered. Treating multiresistant pneumococcal disease in those allergic to beta-lactams presents a particular dilemma. Glycopeptides are currently preferred.


Hospital-related differences in breast cancer management. Analysis of an unselected population-based series of 1353 radically operated patients.
A retrospective review is presented of 1353 consecutive patients with histopathologically confirmed invasive breast carcinoma treated radically with curative intent during the decade 1980-89. None had received adjuvant systemic therapy with hormones or prolonged chemotherapy. The distribution of lymph-node negative (N-) and lymph-node positive (N+) patients was 75% and 25%, respectively. The treatment and outcome were analysed as regards conventional prognostic parameters, in particular considering the axillary lymph-node status and the responsible hospital category (General Municipal Hospitals (MH)) versus Comprehensive Cancer Center (CC)). The most striking difference was detected as regards the number of examined lymph nodes. The median number of nodes described at the MH was 7, as compared to 14 at the CC (p < 0.001). In patients with pT1 tumours the highest rate of lymph-node positivity was observed when 10 or more axillary nodes were removed. Adjuvant radiotherapy reduced the loco-regional recurrence rate in the N-patients, whereas only the regional recurrences were reduced among the N+ patients. The five- and 10-year tumor-related survival rates were 86% and 76%, respectively, with no difference between the MH and the CC. As life-prolonging adjuvant hormone therapy and chemotherapy is now available for patients with axillary lymph node metastases, it is important that patients with breast cancer are operated adequately with the aim to remove at least 10 axillary lymph nodes. A thorough examination of the axillary content should be performed by the pathologist, and the number of resected lymph nodes and metastases should be reported. The establishment of nation-wide standard criteria for the management of breast cancer is recommended.


Antidepressant Treatment of Very Old Patients.
Most studies of the elderly use age 65 as the definition of the onset of old age, and most studies of the pharmacologic treatment of depression in the elderly focus on patients between the ages of 60 and 70. Very few patients over the age of 75 have been specifically studied, and virtually none over the age of 80. Data for this review of treatment of depressed patients over the age of 75 were derived from a larger review prepared for a 1992 NIMH consensus development conference on the diagnosis and treatment of depression in late life. Available studies were divided into three categories: 1) mixed-age studies that include subjects over 75 (n = 18); 2) mixed-age reports of patients having a mean age of 75 or older (n = 13); and 3) reports including only patients with minimum age of 75 years or older (>n = 5). Data are available from only 171 identifiable patients over the age of 75. Consequently, available data for patients in this very old age category are too limited for reliable or valid treatment recommendations to be made; further research is necessary.


Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany.
Resistance against antiretroviral drugs in previously untreated HIV-infected persons is of growing relevance. The aim of the study is to determine the prevalence of resistance-associated mutations in this patient group. In a prospective multicenter-study in Nordrhein-Westfalen, Germany, genotypic resistance testing was performed in untreated HIV-positive patients before administration of first-line highly active antiretroviral therapy (HAART). Between January 2001 and August 2002 resistance testing was performed in 184 therapy-naive individuals. HAART was initiated in 143 patients, who were included into the study. 70.6 % were males, mean age was 39 years, mean duration of diagnosis of HIV-infection was 1.5 years. The proportion of cases at CDC stage C was 45.4%, mean CD4-cell count was 199 /ml, mean viral load was 206,855 copies/ml. Resistance-associated mutations were detected in 20 patients (14.0%). 10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor- (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q), 2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated resistance (V82A, L90M), respectively. Multi-class-resistance was found in 2.1%, mutations indicating revertant variants of resistant strains were found in 4.2% (T215C/E/L/S). 86.7% of the isolates showed secondary mutations in the protease gene. No significant difference in the distribution of the parameters age, sex, duration of HIV diagnosis, CDC stage, CD4-cell count, and viral load, between groups with and without resistance was identified. The prevalence of primary resistant virus strains can be estimated at 14% in chronically infected HAART-naive HIV-patients in Germany. The majority of these cases show NRTI-associated resistance. Resistance against NNRTI or PI as well as multi-class-resistance is of low prevalence. No risk factor of predictive value can be identified for the diagnosis of resistance mutations in the individual. In conclusion, routine genotypic resistance testing in untreated HIV-positive patients should be performed before administration of first-line HAART in this region.


Altered enolase in aged Turbatrix aceti results from conformational changes in the enzyme.
Young- and old-type enolases (2-phospho-D-glycerate hydrolyase, EC 22.214.171.124) from the free-living nematode Turbatrix aceti can be unfolded in 1.25 M guanidine hydrochloride and subsequently refolded with essentially a quantitative recovery. After refolding, both enolases form an identical or near-identical third type of the enzyme as determined by spectral criteria, sensitivity to heat, immunotitration, and rate of inactivation by bacterial protease. By the same criteria, the refolded enolase is closer in conformation to the native old form of the enzyme than to the young form. The results prove that young and old enolases are conformational isomers and that an in vivo transformation from young to old enzyme takes place by conformational changes without covalent modification. The process may be related to the previously demonstrated slowing of enolase turnover in T. aceti. Errors in sequence cannot be involved in the age-related alteration of the enzyme.


Green tea consumption and the risk of pancreatic cancer in Japanese adults.
Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort. At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models. During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women. Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.


[Tolerated and forbidden addictive drugs: various effects on the management of adolescent drug dependent patients].
Of the 168 drug addicts admitted to the Zurich University Psychiatric Clinic between 1973 and 1979, 137 were followed up after an average period of five years, 40 of them dependent on legally tolerated drugs, 97 on prohibited drugs. The two groups were compared in terms of medical and social care, tutelary measures and arrests. Whereas the two groups were comparable as regards emergency inpatient treatment in general hospitals and psychiatric clinics, outpatient care was much more common among illegal-drug addicts. The men in this group were also hospitalized significantly more frequently and for longer periods in special therapeutic clinics. Surprisingly, there was no difference between the groups as regards the percentage of men imprisoned, whereas women dependent on illegal drugs were arrested more often than women dependent on legal drugs. Tutelary measures were significantly more frequent with legal drug addicts. These data suggest that those dependent on legal drugs, particularly young men, still receive insufficient treatment and that social consequences of addiction to legal drugs are underestimated.


Hashimoto's thyroiditis-related myopathy in a patient with SARS-CoV-2 infection: A case report and systematic literature review.
Hashimoto's thyroiditis (HT) is a common autoimmune disease. However, its presentation and management in the context of COVID-19 are unclear, and COVID-19-triggered HT, along with myopathy and persistent creatine kinase (CK) levels, have not been previously reported. Moreover, no literature review is currently available on HT in the context of COVID-19. This study is a case report and systematic review of the literature. A 33-year-old man was admitted with acute-onset myalgia, anosmia, loss of taste, fever, and upper respiratory tract symptoms. He was diagnosed with coronavirus disease (COVID-19) during hospitalization and had abnormal CK levels. The elevated CK level persisted even after the resolution of COVID-19. After excluding myopathies and cardiac factors, HT was diagnosed. CK levels did not decrease appreciably until 14 d after levothyroxine administration. The patient was discharged from the hospital in good health. In the systematic literature review, 7 case reports on COVID-19-associated HT were observed, although no incidence of associated myopathy or persistent elevation of CK was noted. This case report highlights the potential link between COVID-19 and autoimmune thyroid diseases. In particular, this study underscores the significance of recognizing new-onset autoimmune thyroid disease in COVID-19-positive patients with elevated CK levels that cannot be attributed to other factors. This systematic review offers additional perspectives for diagnosing and managing HT in COVID-19 settings. Overall, the findings of this study could have important clinical implications for the care of COVID-19 patients, as early identification and treatment of autoimmune thyroid disease could help prevent long-term complications. Additional research is essential to elucidate the fundamental correlations between COVID-19 and HT and assess the effectiveness of therapeutic approaches for autoimmune thyroid conditions related to COVID-19.


Tree-ring evidence of ecological stress memory.
Plants experiencing stress could develop the ability to reshape their response toward present stress based on past stress experience, called 'ecological stress memory' (ESM), which is important for plant acclimation to repeated stresses. Although ESM has been largely reported, it remains unclear whether ESM could improve tree resistance to recurrent stress in subsequent decades. Here, we explore it from a tree-ring network of 1491 trees from 50 long-living juniper forests on the Tibetan Plateau. Through comparing performances of tree radial growth in past sequential growth stresses, we found that trees could obtain ESM under antecedent stresses and elevate resistance to subsequent stress after several years or even decades. Such positive effects of ESM are associated with post-stress recovery. Trees with slow recovery trajectories after antecedent stress show significantly improved resistance to subsequent stress, while trees with extremely fast post-stress recovery showed decreased resistance to subsequent stress. These results imply that temporary depressive tree radial growth after antecedent stress might be a trigger of long storage of ESM. Incorporating positive effects of ESM and relationship between ESM activation and post-stress recovery into future Earth system models could advance our capacity to predict forest dynamics and forest ecosystem stabilization under future stress conditions.


Fertility and pregnancy outcomes in men and women with cystic fibrosis in the United Kingdom.
The survival of patients with cystic fibrosis (CF) now occurs into the fourth decade of life. Our aim was to evaluate the fertility and pregnancy outcomes of men and women with cystic fibrosis within a large British cohort. A population based cohort study of 4659 males and females registered with the UK Cystic Fibrosis Database in 2001. Poor respiratory health (forced expiratory volume in 1 s FEV1 <50%) and CF-related diabetes increased significantly post-puberty compared with childhood. Few individuals with CF sought fertility treatment (1% men, 0.5% women) or achieved pregnancies (1.3% of partners of men, 5.7% women). However, the majority of pregnancies had a good outcome (67% live term birth among male partners, 74% among women). Women who achieved a pregnancy were less likely to suffer from poor respiratory health (FEV1 <50%), age adjusted Odds Ratio 0.6 (95% CI 0.3-0.9), less likely to be homozygous for the DF508 genotype OR 0.5 (95% CI 0.3-0.9) and had a significantly earlier median age at diagnosis (0 years vs 2 years, P=0.001). Increasing numbers of males and females with cystic fibrosis are reaching reproductive age but currently very few have a child. Optimal adult health should improve the reproductive prognosis for both men and women.


Heat production and respiratory enzymes in normal and runt newborn piglets.
The heat productions of newborn runt and normal piglets were estimated over a range of ambient temperatures. Most runts increased their heat production in the cold, but when expressed as J X kg-0.67 X min-1 it was significantly lower than in normal piglets (201.3 +/- 16.0 and 144.7 +/- 16.2 J X kg-0.67 X min-1 for controls and runts, respectively, at 32 degrees C). Runts consequently had lower deep body temperatures (37.8 +/- 0.2 and 36.8 +/- 0.3 degrees C for controls and runts, respectively, at 32 degrees C). Some runts failed to increase their metabolic rate in the cold and these had the lowest deep body temperature. Activities of respiratory enzymes in heart and diaphragm muscle were similar in all animals, whereas the longissimus dorsi of runts had significantly lower enzyme activities (76.3 +/- 4.2 and 55.5 +/- 6.6 in absorbance units for controls and runts, respectively).


Isolation and characterization of an oligosaccharide- and glycoprotein-specific sialidase from human leucocytes.
A sialidase was solubilized with the aid of Triton X-100 from the insoluble material of a leucocyte homogenate. The enzyme was purified almost to homogeneity by chromatography on Sephadex G-75, equine submandibular gland mucin bound to Sepharose 4B and on Sephacryl S-200. The purification factor was 40 based on an increase of the specific enzyme activity from the Triton X-100 extract (pure enzyme: 40 mU/mg protein). Isolation of the active enzyme required the presence of a proteinase inhibitor. The sialidase is monomeric and has an average molecular mass of 48500 Da, a pH optimum of 4.6, hydrolyses preferably glycoprotein (fetuin) and sialyllactose, is activated by Ca2 and inhibited by N-acetyl-2,3-dehydro-2- deoxyneuraminic acid ( Neu5Ac2en ), Hg2 and N-(4-nitrophenyl) oxamic acid. The relatively stable enzyme shows only low activity with gangliosides and no activity with 4-O-acetylated sialic acid bound glycosidically.


Progression and management of chronic heart failure.
Current heart failure therapeutic guidelines are based on a new classification of the progression of the syndrome of chronic heart failure (CHF) that was proposed by ad hoc committees of the American College of Cardiology (ACC) and the American Heart Association (AHA). The new ACC/AHA classification depicts the progression of CHF in 4 stages that are labeled A to D. The 4 stages range from risk factors for CHF (A) to the presence of structural heart disease (B) and the development of symptoms (C). The last stage (D) is one of low cardiac output state despite optimal medical therapy. The merit of this new classification is to encourage tailoring of CHF therapy according to the stage of the syndrome. However, except for the final stage D that has clear therapeutic implications, the first 3 stages A, B and C do not have clear therapeutic implications. Moreover, these first 3 stages may inadvertently delay the diagnosis of CHF and fail to identify the important therapeutic target at each stage of CHF. A revised classification consisting of only 3 stages is proposed. These 3 stages are: 1) Left ventricular (LV) remodeling; 2) clinical heart failure and 3) low cardiac output state. These 3 stages have the advantage of delineating precise therapeutic targets at each stage thereby facilitating the management of patients with CHF by non-experts in the field.


[Prevention of Perioperative Hypothermia - Guidelines for Daily Clinical Practice].
Inadvertent perioperative hypothermia (body core temperature < 36 °C) is a serious complication leading to increased rates of wound infection, higher blood loss associated with increased transfusion requirements as well as patient dissatisfaction among others. Body core temperature is a vital parameter and needs constant monitoring just like heart rate, blood pressure and arterial oxygen saturation. Patient-, anesthesia-, surgery- and environment-related risk factors were identified for occurring perioperative hypothermia.The avoidance of perioperative hypothermia requires a multidisciplinary approach for both medical and assistant staff. A bundle of procedures has to be arranged in order to improve patient outcome. Steps include general (e.g. staff instruction), pre- (e.g. prewarming), intra- (e.g. active warming) and postoperative (e.g. drug therapy) actions. An effective concept for prevention of perioperative hypothermia has to be adjusted to departments' specific constructional, organizational, process-related and staff characteristics with clearly visible and assigned responsibilities.


Stride Counting in Human Walking and Walking Distance Estimation Using Insole Sensors.
This paper proposes a novel method of estimating walking distance based on a precise counting of walking strides using insole sensors. We use an inertial triaxial accelerometer and eight pressure sensors installed in the insole of a shoe to record walkers' movement data. The data is then transmitted to a smartphone to filter out noise and determine stance and swing phases. Based on phase information, we count the number of strides traveled and estimate the movement distance. To evaluate the accuracy of the proposed method, we created two walking databases on seven healthy participants and tested the proposed method. The first database, which is called the short distance database, consists of collected data from all seven healthy subjects walking on a 16 m distance. The second one, named the long distance database, is constructed from walking data of three healthy subjects who have participated in the short database for an 89 m distance. The experimental results show that the proposed method performs walking distance estimation accurately with the mean error rates of 4.8% and 3.1% for the short and long distance databases, respectively. Moreover, the maximum difference of the swing phase determination with respect to time is 0.08 s and 0.06 s for starting and stopping points of swing phases, respectively. Therefore, the stride counting method provides a highly precise result when subjects walk.


Development and Evaluation of a Mandatory Course in Geriatric Medicine for Fourth Year Medical Students.
As the population ages, older adults will make up an increasing proportion of the practices of most physicians. Because of this, education of medical students in Geriatric Medicine is essential, yet there is considerable variability in the amount, timing within the curriculum, and content of geriatric training in Medical Schools. Our goal was to develop and evaluate an integrated, mandatory 3-week geriatric medicine course for fourth year medical students with emphasis on knowledge acquisition. All fourth year medical students at Dalhousie Medical School underwent 2 ½ days of didactic teaching on core geriatric topics and a 2-week clinical rotation. Pre-rotation knowledge testing occurred on the first day of the rotation. On the final examination, students were retested on the 15 pre-rotation questions, as well as 5 additional questions that they had not encountered previously. There was a statistically significant improvement in examination performance from 46.9% on the pretest to 78.6% on the final examination (t=24.7, p˂.001). It is unlikely that the significant improvement in scores is simply a result of repeat testing, as students tended to score better on the five additional questions that they had not seen before. We developed a geriatric medicine course for fourth year medical students, in one integrated 3-week block, using a combination of didactic teaching and clinical encounters. We used students as their own controls, using the same questions pre- and post-rotation, and demonstrated significant knowledge acquisition on a variety of topics pertaining to geriatric medicine and care of the older patient. Future research should address the issue of translating acquired knowledge in geriatric medicine into demonstrated clinical skills when caring for the elderly.


High-flow priapism leading to the diagnosis of lung cancer.
We report on a patient with spontaneous high-flow priapism. Magnetic resonance imaging showed a sacral tumor. Prior to tumor surgery, signs of lung cancer were found on chest X-ray. The diagnosis was confirmed by bronchoscopy. Priapism in this case can be explained either as a paraneoplastic symptom or as an isolated manifestation of cauda compression. Both are very uncommon reasons for priapism.


Effect of naloxone on circadian rhythms in lung function.
To determine whether the endogenous opioid peptides play a part in the pathogenesis of asthmatic morning dipping, six patients with chronic asthma with a reproducible peak flow pattern of morning dipping were investigated in a double blind, randomised, crossover study of naloxone versus placebo. Naloxone was given as a loading dose of 8 mg followed by a continuous infusion of 5.6 mg/h from midnight until 10 am on two consecutive nights. Naloxone had no significant effect on PEFR, FEV1, or FVC at 6 am. There was, however, an improvement over placebo values in all these indices between the hours of 8 am and 8 pm on the day after the first naloxone infusion in all six patients. This effect was not observed after the second naloxone infusion.


Continuous monitoring of Rabi oscillations in a Josephson flux qubit.
Under resonant irradiation, a quantum system can undergo coherent (Rabi) oscillations in time. We report evidence for such oscillations in a continuously observed three-Josephson-junction flux qubit, coupled to a high-quality tank circuit tuned to the Rabi frequency. In addition to simplicity, this method of Rabi spectroscopy enabled a long coherence time of about 2.5 micros, corresponding to an effective qubit quality factor approximately 7000.


A draining sinus tract of obscure etiology: a case report.
A patient presented with a draining sinus tract on the lingual alveolus of the posterior mandibular ridge. The source of the sinus tract was not readily apparent. Radiographs created the impression that a lesion of unusual and possibly metastatic origin might be involved. Comprehensive diagnostic tests were ordered, but the source of the lesion remained obscure until a surgical exploration was performed.


Selection of housekeeping genes as internal controls for quantitative RT-PCR analysis of the veined rapa whelk (Rapana venosa).
The veined rapa whelk Rapana venosa is an important commercial shellfish in China and quantitative real-time PCR (qRT-PCR) has become the standard method to study gene expression in R. venosa. For accurate and reliable gene expression results, qRT-PCR assays require housekeeping genes as internal controls, which display highly uniform expression in different tissues or stages of development. However, to date no studies have validated housekeeping genes in R. venosa for use as internal controls for qRT-PCR. In this study, we selected the following 13 candidate genes for suitability as internal controls: elongation factor-1α (EF-1α), α-actin (ACT), cytochrome c oxidase subunit 1 (COX1), nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1α subcomplex subunit 7 (NDUFA7), 60S ribosomal protein L5 (RL5), 60S ribosomal protein L28 (RL28), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), β-tubulin (TUBB), 40S ribosomal protein S25 (RS25), 40S ribosomal protein S8 (RS8), ubiquitin-conjugating enzyme E2 (UBE2), histone H3 (HH3), and peptidyl-prolyl cis-trans isomerase A (PPIA). We measured the expression levels of these 13 candidate internal controls in eight different tissues and twelve larvae developmental stages by qRT-PCR. Further analysis of the expression stability of the tested genes was performed using GeNorm and RefFinder algorithms. Of the 13 candidate genes tested, we found that EF-1α was the most stable internal control gene in almost all adult tissue samples investigated with RL5 and RL28 as secondary choices. For the normalization of a single specific tissue, we suggested that EF-1α and NDUFA7 are the best combination in gonad, as well as COX1 and RL28 for intestine, EF-1α and RL5 for kidney, EF-1α and COX1 for gill, EF-1α and RL28 for Leiblein and mantle, EF-1α, RL5, and NDUFA7 for liver, GAPDH, PPIA, and RL28 for hemocyte. From a developmental perspective, we found that RL28 was the most stable gene in all developmental stages measured, and COX1 and RL5 were appropriate secondary choices. For the specific developmental stage, we recommended the following combination for normalization, PPIA, RS25, and RL28 for stage 1, RL5 and RL28 for stage 2 and 5, RL28 and NDUFA7 for stage 3, and PPIA and TUBB for stage 4. Our results are instrumental for the selection of appropriately validated housekeeping genes for use as internal controls for gene expression studies in adult tissues or larval development of R. venosa in the future.


[Complete response in a case of advanced esophageal cancer infiltrating into the main bronchus treated by chemoradiation therapy].
We report a case of advanced esophageal cancer infiltrating into the trachea that was treated by chemoradiation therapy. The patient was a 49-year-old man who complained of dysphagia and dyspnea. Various examinations revealed an esophageal cancer with direct invasion into the trachea( cT4b[ Tr], N2[ 106recR, 106recL, 106pre, 1], M0, cStage IIIc). He underwent radiotherapy. Simultaneously, he was administered morphine to relieve dyspnea and steroid to prevent tracheal edema. From the eight day of radiation therapy, chemotherapy was initiated( DCF; docetaxe[l DTX] +cisplatin[ CDDP] + 5-fluorouracil[ 5-FU]). This chemoradiation therapy considerably reduced the esophageal tumor size. Thereafter, the patient underwent 2 additional courses of chemotherapy( FAP; 5-FU+adriamycin[ ADM] +CDDP). The therapeutic effect was judged as complete response. The patient is still alive without recurrence for 3 years and 6 months after the first treatment. There are some reports about airway stenting and adjuvant therapy for airway obstruction caused by esophageal cancer. However, there are few reports on chemoradiotherapy for esophageal cancer invading into the trachea with administration of steroids to prevent tracheal edema. We believe that this is an effective treatment.


Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC).
Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutations in KCNQ2 and KCNQ3, two genes encoding for potassium channel subunits. A large family with nine members affected by BFNC is described in the present study. All affected members of this family carry a novel deletion/insertion mutation in the KCNQ2 gene (c.761_770del10insA), which determines a premature truncation of the protein. In addition, in the family of the proposita's father, a novel sequence variant (c.2687A>G) in KCNQ3 leading to the p.N821S amino acid change was detected. When heterologously expressed in Chinese hamster ovary cells, KCNQ2 subunits carrying the mutation failed to form functional potassium channels in homomeric configuration and did not affect channels formed by KCNQ2 and/or KCNQ3 subunits. On the other hand, homomeric and heteromeric potassium channels formed by KCNQ3 subunits carrying the p.N821S variant were indistinguishable from those formed by wild-type KCNQ3 subunits. Finally, the current density of the cells mimicking the double heterozygotic condition for both KCNQ2 and KCNQ3 alleles of the proband was decreased by approximately 25% when compared to cells expressing only wild-type alleles. Collectively, these results suggest that, in the family investigated, the KCNQ2 mutation is responsible for the BFNC phenotype, possibly because of haplo-insufficiency, whereas the KCNQ3 variant is functionally silent, a result compatible with its lack of segregation with the BFNC phenotype.


Differences in Stem Cell Processing Lead to Distinct Secretomes Secretion-Implications for Differential Results of Previous Clinical Trials of Stem Cell Therapy for Myocardial Infarction.
Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however, large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study seeks to compare cell processing protocols of clinical trials and investigate effects of differential cell culture conditions on chemokine secretion and functional effects. Different secretomes are compared regarding IL-8, VEGF, MCP-1, and TNF-alpha secretion. Secretome mediated effects are evaluated on endothelial cell (HUVEC) tube formation and migration. Cardioprotective signaling kinases in human cardiomyocytes are determined by Western immunoblotting. Cells processed according to the REPAIR-AMI protocol secrete significantly higher amounts of IL-8 (487.3 ± 1231.1 vs 9.1 ± 8.2 pg mL-1 ; p < 0.05). REAPIR-AMI supernatants lead to significantly pronounced tube formation and migration on HUVEC and enhance the phosphorylation of Akt, ERK, and CREB. Cell processing conditions have a major impact on the composition of the secretome. The REPAIR-AMI secretome significantly enhances proangiogenic chemokine secretion, angiogenesis, cell migration, and cardioprotective signaling pathways. These results might explain differential outcomes between clinical trials. Optimizing cell processing protocols with special regards to paracrine factors, might open a new therapeutic concept for improving patient outcome.


[Growth factors and oncogenes in development and carcinogenesis. Role of the epidermal growth factor system].
The processes of cellular proliferation and progressive acquisition of a specialized phenotype show a remarkable degree of coordination that involves both intracellular programming and intercellular communication. One of the major incentives for studying factors that regulate the processes of cellular proliferation and differentiation is the recognition of their potential contribution to tumorigenesis. In normal cells, stimulatory and inhibitory events are believed to be under the control of growth factors and growth inhibitory factors, which are known to be protooncogene products. Growth regulatory mechanisms usually involve the binding of a growth factor to a specific receptor on the cell surface, which then through an intracellular biochemical cascade leads to cell division. The cell regulation pathways initiated by growth factors may be subverted at several distinct levels in cancer cells. Studies of oncogenes have shown that they may function as abnormal growth factors or abnormal receptors, induce expression of potential signal regulators or encode proteins which modulate gene transcription. The purpose of the present paper is to examine the role of growth factors, growth factor receptors and intracellular proteins involved in signal transduction (with particular regard to the epidermal growth factor receptor system) in the control of normal growth and differentiation, and their contribution to transformation and tumorigenesis. We also review the classical theories of neoplasia and various other models. Chemical carcinogenesis and Vogelstein-Lane model are presented.


Control and Stabilization of bit-wise phase correlation in 160 (4 x 40) Gbit/s OTDM signal and its impact on transmission.
Detail of control technique of bit-wise phase correlation in 160 (4 x 40) Gbit/s optical time division multiplexing (OTDM) signal using a phase-correlation monitor based on 1-bit delay asymmetric interferometers (AIFs) is described. The 1-bit delay AIF transforms a bit-by-bit optical phase discontinuity to an optical power variation, so that it enables to quantify the phase-jump between adjacent bits. By use of this unique technique, we experimentally demonstrated stable generation of bitwisely phase-controlled 160 Gbit/s periodical alternate-phase return-to-Zero (APRZ) signal in addition to other different modulation formats such as conventional RZ, carrier suppressed RZ (CS-RZ), pair-wise alternate-phase CSRZ (PAP-CSRZ) and pi/2-APRZ. And long term stability was observed with CS-RZ signal. Also, we show some experimental results of 120 km un-repeatered transmission using standard single mode fiber (SSMF) and then discuss the impact of bit-wise phase change on 160 Gbit/s OTDM transmission performance.


Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus.
The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.


Hard Physical Work Intensifies the Occupational Consequence of Physician-Diagnosed Back Disorder: Prospective Cohort Study with Register Follow-Up among 10,000 Workers.
While musculoskeletal pain is common in the population, less is known about its labor market consequences in relation to physical activity at work. This study investigates whether hard physical work aggravates the consequences of back disorder. Using Cox regression analyses, we estimated the joint association of physical activity at work and physician-diagnosed back disorder in 2010 with the risk of register-based long-term sickness absence (LTSA) of at least 6 consecutive weeks during 2011-2012 among 9,544 employees from the general working population (Danish Work Environment Cohort Study). Control variables were age, gender, psychosocial work environment, smoking, leisure physical activity, BMI, depression, and mental health. At baseline, 19.4% experienced high low-back pain intensity (≥5, 0-9 scale) and 15.2% had diagnosed back disorder. While high pain intensity was a general predictor for LTSA, physician-diagnosed back disorder was a stronger predictor among those with hard physical work (HR 2.23; 95% CI 1.68-2.96) compared with light work (HR 1.40; 95% CI 1.09-1.80). Similarly, physician-diagnosed back disorder with simultaneous high pain intensity predicted LTSA to a greater extent among those with hard physical work. In conclusion, the occupational consequence of physician-diagnosed back disorder on LTSA is greater among employees with hard physical work.


Establishing an acute care surgery service: lessons learned from the epidemiology of emergent non-trauma patients and increasing utilization of laparoscopy.
Acute care surgery is a fellowship training model created to address the growing crisis in emergency healthcare due to decreased availability of on-call surgeons and reduction in operative procedures for trauma. Our objective was to identify the demographics and spectrum of diseases in patients presenting with non-trauma surgical emergencies and the use of laparoscopy in emergent surgery in light of implementing an acute care surgery model. All non-trauma emergency surgical consultations at a large urban academic medical center from January 2005 to December 2008 were retrospectively reviewed. A clinician-completed registry was used to obtain patient information. Diagnoses were categorized into five broad groups for statistical analysis. Median age was 41 years (range, 6 weeks to 97 years), 50% were men, and the majority (67%) was Hispanic. The most common disease category was infectious followed by hepatobiliary. Prevalence of disease categories differed significantly among various racial groups. Majority (86%) of consult patients required admission. Thirty-eight percent of the consults resulted in an operative procedure, 40% of which were laparoscopic. The percentage of laparoscopic procedures increased during the 4-year study period. Patients with non-trauma surgical emergencies are young with a significantly wide range of diseases based on race. Less than half require emergent surgery. Laparoscopy is prevalent in emergency surgery and growing. Resources should be allocated to maximize the ability to treat infectious and hepatobiliary diseases, and to increase utilization of laparoscopy. The acute care surgeon needs to be proficient in laparoscopy.