Prospective analysis of hip arthroscopy with 10-year followup.
Arthroscopic surgery of the hip is a well-established technique with numerous recognized indications. Despite the well-accepted nature of this procedure, there have been no outcomes studies with extended followup. We investigated the response to hip arthroscopy in a consecutive series of patients with 10 years followup. Since 1993, all patients undergoing hip arthroscopy have been assessed prospectively with a modified Harris hip score preoperatively and then postoperatively at 3, 12, 24, 60, and 120 months. A cohort of 50 patients (52 hips) was identified who had achieved 10-year followup and represent the substance of this study. There was 100% followup. The average age of the patients was 38 years (range, 14-84 years), with 27 males and 23 females. The median improvement was 25 points (preoperative, 56 points; postoperative, 81 points). Fourteen patients were converted to THA and two died. Four patients underwent repeat arthroscopy. There were two complications in one patient. The presence of arthritis at the time of the index procedure was an indicator of poor prognosis. This study substantiates the long-term effectiveness of arthroscopy in the hip as treatment for various disorders, including labral pathology, chondral damage, synovitis, and loose bodies. Arthritis is an indicator of poor long-term outcomes with these reported methods. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Anatomy of the lateral circumflex femoral artery: Does the direct anterior approach to the hip jeopardize vascularization of the proximal femur?
Blood supply of the proximal metaphysis of the femur comes mainly from the lateral circumflex femoral artery (LCFA). Essentially, the anterior approach has gained popularity in hip surgery but routinely requires the ligation of the ascending branch of the LCFA. Until now, there is no study analysing the effect of previous hip surgery on the vascularization of the proximal femur. Notably, it might, however, have consequences on osteointegration of uncemented prosthesis as well as in the management of early complications. Therefore we conducted a retrospective study to address the following questions: (1) Is the blood supply of the trochanteric region impaired by previous hip surgery, (2) does the anterior approach alter it more than other ones? We hypothesised that the surgical approach to the hip influences blood supply of the proximal femur, as visualised by retrospective analysis of femoral digital subtraction arteriograms (FDSA). A retrospective review of 1280 FDSA, performed for vascular indications with a standard frame rate, between 07/2014 and 06/2016 in a single institution. Qualitatively sufficient FDSA were divided into 4 groups according to the history of previous hip surgery: hip replacement through an anterior approach (n=10) or through a lateral approach (n=31), cephalomedullary nailing for fractures of the proximal femur (n=5), and a control group of 50 continuous patients without previous hip surgery. The number of frames was counted between contrast injection into the femoral bifurcation and filling of the ipsilateral vessels of the greater trochanter to measure a potential delay/impairment of its arterial perfusion. Anatomic variations of the LCFA were also recorded. The number of frames between contrast injection and visualisation of the blood supply of the greater trochanter was 3.6±0.9 (mean±SD) in the control group (p<0.001 vs. all other groups). In patients with a hip replacement, the delay was 7.0±1.9 frames for the anterior approach and 5.2±1.1 frames for the lateral approach, respectively. In patients after cephalomedullary nailing, a delay of 4.8±1.5 frames was measured. The delay in the anterior approach group was significantly longer (p<0.001) compared to all other investigated groups. The ascending branch of the LCFA could not be detected after the anterior approach. As after lateral approach or as in the control group, the transverse branch was detectable in approximately 2/3 of the patients. Arterial perfusion of the greater trochanter is impaired after hip surgery, particularly after an anterior approach. The clinical relevance of these findings still needs to be investigated. It might, however, explain some early aseptic failures of uncemented stems. Moreover, it should be considered in early revision surgery, because combining different approaches might critically impair femoral blood supply. III, retrospective case control study.


Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN International Studies.
Recovery after stroke occurs on the basis of specific molecular events. Genetic polymorphisms associated with impaired neural repair or plasticity might reduce recovery from stroke and might also account for some of the intersubject variability in stroke recovery. This study hypothesized that the ApoE ε4 polymorphism and the val(66) met polymorphism for brain-derived neurotrophic factor (BDNF) are each associated with poorer outcome after stroke. Associations with mitochondrial genotype were also explored. Genotypes were determined in 255 stroke patients who also received behavioral evaluations in the Glycine Antagonist In Neuroprotection (GAIN) clinical trials. The primary outcome measure was recovery during the first month post-stroke, as this is the time when neural repair is at a maximum and so when genetic influences might have their largest impact. Two secondary outcome measures at 3 months post-stroke were also examined. Genotype groups were similar acutely post-stroke. Presence of the ApoE ε4 polymorphism was associated with significantly poorer recovery over the first month post-stroke (P = 0.023) and with a lower proportion of subjects with minimal or no disability (modified Rankin score 0-1, P = 0.01) at 3 months post-stroke. Indeed, those with this polymorphism were approximately half as likely to achieve minimal or no disability (18.2%) versus those with polymorphism absent (35.5%). Findings were confirmed in multivariate models. Results suggested possible effects from the val(66) met BDNF polymorphism and from the R0 mitochondrial DNA haplotype. Genetic factors, particularly the ApoE ε4 polymorphism, might contribute to variability in outcomes after stroke.


[Effects of Tongnao Huoluo acupuncture therapy on Caspase-3 and Bcl-2 of rats with acute cerebral infarction].
To evaluate effects of Tongnao Huoluo acupuncture therapy (THAT) on Bcl-2 and Caspase-3 rats with acute cerebral infarction (ACI). Totally 264 SD rats were randomly divided into 5 groups, i.e. the THAT group (n =72), the thrombolysis group (n =72), the body acupuncture group (n =72), the ischemia control group (n =24), and the sham-operation group (n =24). Successfully modeled rats were recruited in all groups except the sham-operation group. Rats in the THAT group, the thrombolysis group, and the body acupuncture group were divided into 3 subgroups according to the disease occurrence time, i.e., < or = 1.5 h THAT group, 1.5+ -2 h THAT group, and 2+ -3 h THAT group. The neuroethological scores were assessed at 6, 24, and 72 h after treatment. The expressions of Bcl-2 and Caspase-3 were detected using immunohistochemical staining at 24 and 72 h respectively. In aspect of improving scores of neurological functions: At 6 h after treatment within 2 h after the disease occurrence, the neuroethological scores were lowered more obviously in the thrombolysis group than in the THAT group (P <0.05). There was statistical difference at 24 and 72 h within 2 - 3 h after the,disease occurrence between the THAT group and the thrombolysis group (P <0.05). Compared with before treatment, there was statistical difference at 24 and 72 h within 3 h after the disease occurrence (P <0. 05, P <0.01). In aspect of lowering the expression of Caspase-3 and elevating the expression of Bcl-2: There was statistical difference in lowering the expression of Caspase-3 and elevating the expression of Bcl-2 between the THAT group and the thrombolysis group at 72 h within 2 -3 after the disease occurrence (P <0.05, P < 0.01). THAT showed favorable effects in lowering neuroethological scores, lowering expression of Caspase-3, and elevating the expression of Bcl-2 of ACI rats.


Microglia Activation in the Midbrain of the Human Neonate: The Effect of Perinatal Hypoxic-Ischemic Injury.
Perinatal hypoxia-ischemia (PHI) is a major risk factor for the development of neuropsychiatric deficits later in life. We previously reported that after prolonged PHI, the dopaminergic neurons of the human neonate showed a dramatic reduction of tyrosine hydroxylase (TH) in the substantia nigra, without important signs of neuronal degeneration despite the significant reduction in their cell size. Since microglia activation could precede neuronal death, we now investigated 2 microglia activation markers, ionized calcium-binding adapter molecule 1 (Iba1), and the phagocytosis marker Cd68. The highest Iba1 immunoreactivity was found in neonates with neuropathological lesions of severe/abrupt PHI, while the lowest in subjects with moderate/prolonged or older PHI. Subjects with very severe/prolonged or chronic PHI showed an increased Iba1 expression and very activated microglial morphology. Heavy attachment of microglia on TH neurons and remarkable expression of Cd68 were also observed indicating phagocytosis in this group. Females appear to express more Iba1 than males, suggesting a gender difference in microglia maturation and immune reactivity after PHI insult. PHI-induced microglial "priming" during the sensitive for brain development perinatal/neonatal period, in combination with genetic or other epigenetic factors, could predispose the survivors to neuropsychiatric disorders later in life, possibly through a sexually dimorphic way.


Repetition of educational AIDS advertising affects attitudes.
In educational AIDS campaigns, initiators often use advertisements to warn about the threat of AIDS. The present Internet study (N = 283) tested the assumption of an inverted U-shaped relationship between the number of educational AIDS advertisements in a magazine and the perceived threat of AIDS among different groups (i.e., homosexual men and heterosexual men and women). This expectation was primarily based on signaling theory, which assumes that recipients use repetition frequency as a cue for judgments about the message. Results provided support for the expected inverted U-curve.


The use of povidone-iodine and sugar solution in surgical wound dehiscence in the head and neck following radio-chemotherapy.
Povidone-iodine is known for successfully treating surgical wounds; the combination between povidone-iodine and sugar, also called Knutson's formula, has been proposed to improve wound healing. Currently, no studies have investigated the effects of Knutson's formula to treat defects in wound closure following radio-chemotherapy in the head and neck region. The aim of this study is to evaluate the efficacy of Knutson's formula in improving the wound-healing process in patients who underwent radio-chemotherapy after surgery for head and neck cancer. The study, conducted from August 2013 to January 2017, included a sample of 34 patients (25 males and 9 females; age range: 60-75 years) treated with radio-chemotherapy after head and neck cancer surgery. All patients suffered from defect of wound regeneration. Patients were randomly divided into two groups: patients in the study group (n = 18) were treated with Knutson's formula; patients in the control group (n = 16) were treated with traditional topical drugs. In the study group, 16 of 18 (88.9%) patients reached complete wound closure 1 month after treatment, with no wound infections. In the control group, only three patients (18.7%) showed complete wound closure within a month; in addition, one patient required systemic antibiotic treatment because of supra-bacterial infection of the wound. In our sample, the combination of povidone-iodine and sugar had a higher success rate compared with traditional topical treatment in the treatment of wound defect closure in oncological patients who underwent radio-chemotherapy.


Conditions comorbid with chronic fatigue in a population-based sample.
Chronic fatigue syndrome (CFS) has been found to be comorbid with various medical conditions in clinical samples, but little research has investigated CFS comorbidity in population-based samples. This study investigated conditions concurrent with a CFS-like illness among twins in the population-based Mid-Atlantic Twin Registry (MATR), including chronic widespread pain (CWP), irritable bowel syndrome (IBS), and major depressive disorder (MDD). A survey was mailed to participants in the MATR in 1999. Generalized estimating equations were used to estimate odds ratios to assess associations between CFS-like illness and each comorbid condition. A total of 4590 completed surveys were collected. Most participants were female (86.3%); mean age was 44.7 years. Among participants with a CFS-like illness, lifetime prevalences of CWP, IBS, and MDD were 41%, 16%, and 57% respectively. Participants reporting at least one of the three comorbid conditions were about 14 times more likely to have CFS-like illness than those without CWP, IBS, or MDD (95% confidence interval 8.1%-21.3%). Only MDD showed a temporal pattern of presentation during the same year as diagnosis of CFS-like illness. Age, gender, body mass index, age at illness onset, exercise level, self-reported health status, fatigue symptoms, and personality measures did not differ between those reporting CFS-like illness with and without comorbidity. These results support findings in clinically based samples that CFS-like illness is frequently cormorbid with CWP, IBS, and/or MDD. We found no evidence that CFS-like illnesses with comorbidities are clinically distinct from those without comorbidities.


[Relationship between Surgical Site Infection(SSI)Incidence and Prognosis in Colorectal Cancer Surgery].
We examined the relationship between risk factors for surgical site infections(SSIs)and prognosis in 440 patients who underwent colon cancer surgery. We evaluated factors related to SSIs(GradeB II)and compared survival rates by stage. SSIs were observed in 36 patients. An increased SSI incidence was associated with pulmonary dysfunction, mGPS=2, CONUT≥2, PNI≤40, NLR>4.3, location(rectum), depth of tumor invasion(Bsubserosa, SS), lymph node metastasis, laparotomy, resection of other organs, colostomy, blood loss(large), and operative time(long). Survival rates were lower in Stage II/III patients with SSIs. Preoperative risk judgment is important in colorectal cancer surgery.


Pyrophosphorylases in Solanum tuberosum: II. CATALYTIC PROPERTIES AND REGULATION OF ADP-GLUCOSE AND UDP-GLUCOSE PYROPHOSPHORYLASE ACTIVITIES IN POTATOES.
Pyrophosphorylytic kinetic constants (S(0.5), V(max)) of partially purified UDP-glucose- and ADP-glucose pyrophosphorylases from potato tubers were determined in the presence of various intermediary metabolites. The S(0.5) of UDP-glucose pyrophosphorylase for UDP-glucose (0.17 millimolar) or pyrophosphate (0.30 millimolar) and the V(max) were not influenced by high concentrations (2 millimolar) of these substances. The most efficient activator of ADP-glucose pyrophosphorylase was 3-P-glycerate (A(0.5) = 4.5 x 10(-6) molar). The S(0.5) for ADP-glucose and pyrophosphate was increased 3.5-fold (0.83 to 0.24 millimolar) and 1.8-fold (0.18 to 0.10 millimolar), respectively, with 0.1 millimolar 3-P-glycerate while the V(max) was increased nearly 4-fold. The magnitude of 3-P-glycerate stimulation was dependent upon the integrity of key sulfhydryl groups (-SH) and pH. Oxidation or blockage of -SH groups resulted in a marked reduction of enzyme activity. Stimulations of 3.1-, 2.9-, 4.8-, and 9.5-fold were observed at pH 7.5, 8.0, 8.5, and 9.0, respectively, in the presence of 3-P-glycerate (2 millimolar). The most potent inhibitor of ADP-glucose pyrophosphorylase was orthophosphate (I(0.5) = 8.8 x 10(-5). molar). This inhibition was reversed with 3-P-glycerate (1.2 x 10(-4) molar), resulting in an increased I(0.5) value of 1.5 x 10(-3) molar. Likewise, orthophosphate (7.5 x 10(-4) molar) caused a decrease in the activation efficiency of 3-P-glycerate (A(0.5) from 4.5 x 10(-6) molar to 6.7 x 10(-5) molar). The significance of 3-P-glycerate activation and orthophosphate inhibition in the regulation of alpha-glucan biosynthesis in Solanum tuberosum is discussed.


Cation-Doping in Organic-Inorganic Perovskites to Improve the Structural Stability from Theoretical Prediction.
With outstanding photoelectric properties, organic-inorganic perovskites have become promising materials in the application of solar cells. However, their low stability limits their high conversion efficiency. On the basis of first-principles calculations, we screened out the optimal dopant into MAPbI3 from a variety of organic cations, and further revealed the mechanism underneath for the improved stability of cations doping. Our results have demonstrated that the doping of large-size cations (i.e., IPA+, TriMA+, and GA+) could efficiently inhibit the formation and diffusion of structural defects with high defect formation energies and large migration barriers, which is associated with the lattice expansion and greater hydrogen-bond formation. Our theoretical findings address crucial guidelines to design and synthesize the organic-inorganic perovskite materials with high stability, and provide valuable insights in understanding the stability mechanism, which may enhance the photovoltaic efficiency of perovskite materials and extend their wide applications.


Localisation and distribution of hyaluronan in normal bone marrow matrix: a novel method to evaluate impending fibrosis?
Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women aged 18-60 yr were obtained for identification and localisation of hyaluronan (HYA). Fixation, decalcification and embedding were performed by two different methods, with identical results in both. For comparison bone marrow trephine biopsies from three patients with different haematological diseases and known fibrosis were studied. All bone marrow specimens were also stained for reticulin grading. HYA was found in the bone marrow specimens from healthy individuals in a pattern that was concordant with the reticulin staining, the common way of visualising bone marrow fibrosis. In bone marrow from the patients with known fibrosis the HYA and reticulin staining were both more intense and abundant. Interestingly, HYA was also found intracellularly in eosinophilic cells in normal bone marrow. HYA is a polysaccharide unique both in structural and biological properties, and in excess it may predict bone marrow fibrosis.


High-throughput approaches for screening and analysis of cell behaviors.
The rapid development of new biomaterials and techniques to modify them challenge our capability to characterize them using conventional methods. In response, numerous high-throughput (HT) strategies are being developed to analyze biomaterials and their interactions with cells using combinatorial approaches. Moreover, these systematic analyses have the power to uncover effects of delivered soluble bioactive molecules on cell responses. In this review, we describe the recent developments in HT approaches that help identify cellular microenvironments affecting cell behaviors and highlight HT screening of biochemical libraries for gene delivery, drug discovery, and toxicological studies. We also discuss HT techniques for the analyses of cell secreted biomolecules and provide perspectives on the future utility of HT approaches in biomedical engineering.


False neighbors and false strands: a reliable minimum embedding dimension algorithm.
The time-delay reconstruction of the state space of a system from observed scalar data requires a time lag and an integer embedding dimension. We demonstrate a reliable method to estimate the minimum necessary embedding dimension that improves upon previous methods by correcting for systematic effects due to temporal oversampling, autocorrelation, and changing time lag. The method gives a sharp and reliable indication of the proper dimension. With little computational cost, the method also distinguish easily between infinite-dimensional colored noise-including noisy periodicity-and low-dimensional dynamics.


[Orbital phlegmone caused by acute exacerbation of chronic fungal pansinusitis in a child].
Invasive fungal rhinosinusitis is an aggressive, destructive process most commonly affecting immunocompromised hosts with mortality rate of approximately 60-80%. The authors present a child's recovery of orbital phlegmone due to acute exacerbation of chronic fungal pansinusitis. They call the attention to the possibility of ever more frequent fungal sinusitis in our country. Retrospective case report of an 8 years old boy presented with photos. The recovery was promoted by supposing the chance of fungal origin in time. No orbital abscess was found by surgery despite of typical clinical appearance and MRI results. After beginning of antibacterial treatment and functional endoscopic sinus surgery (FESS) the even worsening clinical status of orbital phlegmone raised the possibility of fungal origin, which was verified by mycological examination. The antimycotic treatment, which had been started in time was followed by complete recovery. Due to scarring in the medial rectus muscle, diplopia was the only complication which needs further ophthalmological controls. Supposition and verification of chance of fungal origin is essential in cases of chronic inflammation of paranasal sinus and/or their complications for complex recovery.


Xanthoma disseminatum: a child with respiratory system involvement and bronchiectasis.
Xanthoma disseminatum (XD) is a rare normolipemic mucocutaneous xanthomatosis due to the proliferation of non-x histiocytes. Occasional involvement of the upper respiratory system has been reported, but lower respiratory tract involvement is very rare. Here, we present a child with severe involvement of the upper and lower respiratory tract by XD and bronchiectasis in the lower lobes of both lungs. The patient was an 8-year-old boy who was admitted to our hospital because of red-brown papules which developed on the skin and progressive dyspnea. He was diagnosed as having XD by skin biopsy. Physical examination revealed disseminated, numerous yellow-reddish brown papular xanthomas on the forehead and eyelids, around the neck and axillary area, and in the oral cavity and pharynx. He had respiratory distress and clubbing of the fingers. Chest x-rays showed hyperaeration and segmental atelectasis. High-resolution CT of the thorax revealed diffuse thickening of the whole tracheal and bronchial wall, and bronchiectasis in the lower lobes. Flexible fiberoptic bronchoscopy revealed numerous xanthomatous lesions in the nasal cavity, nasopharynx, oropharynx, subglottic area, trachea, bifurcation, both main bronchi, and smaller bronchi. To the best of our knowledge, this is the first report of a child with typical lesions of XD with severe involvement of the lower respiratory tract and bronchiectasis.


Vernal keratoconjunctivitis in school children in Rwanda and its association with socio-economic status: a population-based survey.
Vernal keratoconjunctivitis (VKC) is an allergic eye disease and an important cause of hospital referral among children in Africa and Asia. Hospital-based studies have suggested a role for parasites in its pathogenesis. To determine the prevalence and risk factors for VKC in Central Africa, we conducted a nested population-based case control study in Rwanda, involving randomly selected primary schools from different environments (rural/urban) and climate. A prevalence of VKC of 4.0% (95% confidence interval 3.3-4.7%) was found among 3,041 children studied (participation rate 94.7%). The intestinal parasitic burden was not related to VKC. Besides hot dry climate (odds ratio [OR] = 1.5, P = 0.05) and male gender (OR = 1.7, P = 0.005), multivariate analysis identified higher economic status as a risk for VKC (OR = 1.4, P = 0.005). The effect on VKC of higher economic status appears not to act through differences in parasitic intestinal load.


Visualizing the Geography of the Diseases of China: Western Disease Maps from Analytical Tools to Tools of Empire, Sovereignty, and Public Health Propaganda, 1878-1929.
Argument This article analyzes for the first time the earliest western maps of diseases in China spanning fifty years from the late 1870s to the end of the 1920s. The 24 featured disease maps present a visual history of the major transformations in modern medicine from medical geography to laboratory medicine wrought on Chinese soil. These medical transformations occurred within new political formations from the Qing dynasty (1644-1911) to colonialism in East Asia (Hong Kong, Taiwan, Manchuria, Korea) and hypercolonialism within China (Tianjin, Shanghai, Amoy) as well as the new Republican Chinese nation state (1912-49). As a subgenre of persuasive graphics, physicians marshaled disease maps for various rhetorical functions within these different political contexts. Disease maps in China changed from being mostly analytical tools to functioning as tools of empire, national sovereignty, and public health propaganda legitimating new medical concepts, public health interventions, and political structures governing over human and non-human populations.


High-consistency fiber-optic Fabry-Perot sensor based on MEMS for simultaneous temperature and liquid refractive index measurement.
We proposed a hybrid Fabry-Perot fiber-optic sensor based on the microelectromechanical system (MEMS) technique for measuring temperature and liquid refractive index simultaneously, and we verify the consistency of four sensors in the same batch. The sensor consists of a groove-array structured glass wafer and two silicon wafers, which are connected by double-sided anodic bonding. The three parts form two independent Fabry-Perot cavities for temperature and liquid refractive index sensing, respectively. We randomly selected three sensors in the same batch and conducted temperature and refractive index experiments to establish the sensing equation. The experimental results demonstrate their high consistency with temperature sensitivities of 81.6, 81.8, and 81.4 pm/°C in the range of 10°C to 80°C, and refractive index sensitivities of 1040.11, 1044.24, 1042.91 nm/RIU in the range of 1.333-1.374. The sensors have low cross-sensitivities that are less than 5.86×10-6 RIU/°C and high precisions of 0.047°C, 2.14×10-6RIU, respectively. To verify the validity of the sensing equation, we made another sensor in the same batch and got maximum errors of 0.36°C and 7.7×10-5RIU, respectively.


Predicting Parkinson's Disease Progression: Evaluation of Ensemble Methods in Machine Learning.
Parkinson's disease (PD) is a complex neurodegenerative disease. Accurate diagnosis of this disease in the early stages is crucial for its initial treatment. This paper aims to present a comparative study on the methods developed by machine learning techniques in PD diagnosis. We rely on clustering and prediction learning approaches to perform the comparative study. Specifically, we use different clustering techniques for PD data clustering and support vector regression ensembles to predict Motor-UPDRS and Total-UPDRS. The results are then compared with the other prediction learning approaches, multiple linear regression, neurofuzzy, and support vector regression techniques. The comparative study is performed on a real-world PD dataset. The prediction results of data analysis on a PD real-world dataset revealed that expectation-maximization with the aid of SVR ensembles can provide better prediction accuracy in relation to decision trees, deep belief network, neurofuzzy, and support vector regression combined with other clustering techniques in the prediction of Motor-UPDRS and Total-UPDRS.


Talker differences in clear and conversational speech: vowel intelligibility for older adults with hearing loss.
To establish the range of talker variability for vowel intelligibility in clear versus conversational speech for older adults with hearing loss and to determine whether talkers who produced a clear speech benefit for young listeners with normal hearing also did so for older adults with hearing loss. Clear and conversational vowels in /bVd/ context produced by 41 talkers were presented in noise for identification by 40 older (ages 65-87 years) adults with sloping sensorineural hearing loss. Vowel intelligibility within each speaking style and the size of the clear speech benefit varied widely among talkers. The clear speech benefit was equivalent to that enjoyed by young listeners with normal hearing in an earlier study. Most talkers who had produced a clear speech benefit for young listeners with normal hearing also did so for the older listeners with hearing loss in the present study. However, effects of talker gender differed between listeners with normal hearing and listeners with hearing loss. The clear speech vowel intelligibility benefit generated for listeners with hearing loss varied considerably among talkers. Most talkers who produced a clear speech benefit for normal-hearing listeners also produced a benefit for listeners with hearing loss.


Pelvic organs in premenarcheal girls: real-time ultrasonography.
Age-related changes in uterine and ovarian morphology and size were studied in 114 normal premenarcheal girls using a real-time mechanical sector scanner. Reference growth values were obtained for total uterine length, anteroposterior diameters of the corpus and cervix, corpus/cervix ratio, and uterine and ovarian volumes. Up to 7 years of age uterine size was not influenced by age and there was a relative predominance of the cervix over the corpus. Thereafter the uterus underwent a regular increase in size and the corpus gradually became larger than the cervix. Ovarian volume was relatively stable up to 5 years, when regular age-related growth started, associated with an increase in cystic functional changes in the ovary. As uterine and ovarian morphology and size are reliable indicators of the degree of sex-hormone stimulation, real-time ultrasound offers a rapid method of studying normal and abnormal pubertal development in girls.


The effect of inattention on form perception.
A state of inattention was achieved by having subjects selectively attend to one of two overlapping novel figures in a series of such overlapping figures. Recognition of form directly afterward was good for figures that had been attended to but was essentially nil for the unattended figures. Recognition failed to occur even if a familiar figure was in the unattended series and even if that figure was presented 1 sec before the test. A further experiment showed that certain general characteristics of the unattended figures other than form were recognized. The results are interpreted as indicating that attention is necessary for form perception, not merely for memory of form. It is suggested that a cognitive process of description constitutes the essence of form perception. Diverting attention eliminates the cognitive operation of describing the spatial relations that characterize a figure.


Targeting Viral Entry for Treatment of Hepatitis B and C Virus Infections.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major health problems worldwide, with 400-500 million chronically infected people worldwide. Chronic infection results in liver cirrhosis and hepatocellular carcinoma, the second leading cause of cancer death. Current treatments for HBV limit viral replication without efficiently curing infection. HCV treatment has markedly progressed with the licensing of direct-acting antivirals (DAAs) for HCV cure, yet limited access for the majority of patients is a major challenge. Preventative and curative treatment strategies, aimed at novel targets, are needed for both viruses. Viral entry represents one such target, although detailed knowledge of the entry mechanisms is a prerequisite. For HBV, the recent discovery of the NTCP cell entry factor enabled the establishment of an HBV cell culture model and showed that cyclosporin A and Myrcludex B are NTCP-targeting entry inhibitors. Advances in the understanding of HCV entry revealed it to be a complex process involving many factors, offering several antiviral targets. These include viral envelope proteins E1 and E2, virion-associated lipoprotein ApoE, and cellular factors CD81, SRBI, EGFR, claudin-1, occludin, and the cholesterol transporter NPC1L1. Small molecules targeting SR-BI, EGFR, and NPC1L1 have entered clinical trials, whereas other viral- and host-targeted small molecules, peptides, and antibodies show promise in preclinical models. This review summarizes the current understanding of HBV and HCV entry and describes novel antiviral targets and compounds in different stages of clinical development. Overall, proof-of-concept studies indicate that entry inhibitors are a promising class of antivirals to prevent and treat HBV and HCV infections.


Using the electronic medical record to improve education in patients at risk for adrenal insufficiency.
Background. Adrenal insufficiency is a life-threatening event. It is recommended that patients with known adrenal insufficiency and their families receive careful and repeated education on sick-day glucocorticoid management. We hypothesized that the electronic medical record (EMR) can be used to improve patient education through automated provider notification. Methods. We established an automated electronic alert in the EMR that triggered in the outpatient endocrine clinic. The alert asked if stress dose education was reviewed at the visit. The response to this alert was evaluated between July 15, 2009 and February 19, 2010. Results. 128 unique patients had visits both prior to and following the implementation of the EMR alert. The alert was acknowledged in 58 unique patient visits. After the alert was implemented, 87/128 (68%) of the patients had documentation in their record that stress dosing was reviewed. In the visit just prior to implementation of the alert, 48/128 (38%) of the patient encounters showed written documentation of stress dose review. Conclusion. This report documents that an automated alert in the EMR can promote improved provider adherence to recommendations regarding ongoing education of patients for stress dosing of glucocorticoids. Whether this translates into better outcomes for patients remains to be seen.


[The frequency of cytomegalovirus infection (CMV) in patients immunocompromised patients with malignant and nonmalignant blood disorders].
Studies on CMV infection were carried out in a group of 110 patients, aged from 15 to 78 (average 38), treated in the Department of Haematology. During the course of observation most of the patients were examined repeatedly. Diagnosis was based on serology (CFT, ELISA) and virus isolation from the clinical material. Primary infection (seroconversion) was confirmed in 4 (21%) out of 19 seronegative patients. Seropositive patients comprised 83 per cent. Active CMV infection was determined in 20 (22%) of those patients.


Atrial function is altered in lone paroxysmal atrial fibrillation in male endurance veteran athletes.
Intensive endurance sport practice is associated with an increased risk of atrial fibrillation (AF) in male veteran athletes. Paroxysmal AF (PAF) is the very beginning step of this disease. The description of atrial remodelling occurring at this early stage might enable to depict predictive factors of AF in veteran athletes in order to give them personalized recommendation according to their sport practice. Twenty-seven male endurance veteran athletes with documented PAF were retrospectively enrolled and compared with 30 control endurance athletes without documented AF, with similar training level, age, and cardiovascular risk factors. All subjects underwent a resting-electrocardiogram (ECG) to assess the electric remodelling of P-waves as well as an echocardiography, to evaluate the left and right atrial (LA, RA) anatomical and functional (assessed by 2D strain) remodelling. No difference was noted between groups for the ECG P-wave parameters. Atrial function was decreased in the PAF group, particularly the peak atrial longitudinal strain (L-ɛ-Max) of LA (29.3 ± 7.9% vs. 49.1 ± 7.8% respectively in the PAF group and in controls, P < 0.0001) and RA (36.5 ± 7.0% vs. 50.6 ± 10.2%, P < 0.0001). LA and RA volumes were also larger in the PAF group. Receiver operating characteristic analysis demonstrated that L-ɛ-Max of LA [area under curve (AUC): 0.957 ± 0.023] and RA (AUC: 0.901 ± 0.042) had the best ability to identify the athletes with PAF, far better than the anatomical parameters (AUC < 0.75 in all). Atrial function analysed by strain in echocardiography is strongly associated with PAF and might enable to identify male endurance veteran athletes at risk to develop AF.


Clinical development of onercept, a tumor necrosis factor binding protein, in psoriasis.
Tumor necrosis factor (TNF)-α plays a critical role in psoriasis pathogenesis, and several anti-TNF agents have been developed as therapeutic drugs in this indication. To present the preclinical rationale and clinical data for onercept, a novel anti-TNF agent developed for the treatment of moderate-to-severe psoriasis, and to critically evaluate the onercept clinical development program. Onercept was shown in preclinical studies to inhibit TNF-α and suppress clinical signs in several inflammatory conditions. In phase II studies onercept demonstrated a therapeutic benefit in psoriasis and psoriatic arthritis and no safety issues were identified. Based on these results, a phase III program comprising three multicenter, randomized, double-blind, placebo-controlled studies examining onercept in moderate-to-severe plaque psoriasis was initiated. Following the occurrence of two cases of systemic inflammatory response syndrome (SIRS) and lower than expected efficacy results, an independent Data Safety Monitoring Board (DSMB) determined that the risk-benefit ratio was not sufficiently favorable to justify continued development, and all clinical studies were promptly terminated. Although not initially diagnosed as such by the investigators, two further SIRS events were reported, one after study discontinuation. Although an increased incidence of infection and sepsis-like events has been associated with other anti-TNF therapies, an increased risk of infection was not observed with onercept treatment. Moreover, no infectious etiology was determined in the SIRS cases. The data suggest that the SIRS reactions were due to a systemic inflammatory response. Despite promising early clinical results, onercept showed many of the expected risks associated with other anti-TNF agents and proved not to have an exceptional efficacy and safety profile. The clinical development of onercept highlights the critical importance of DSMBs and closely monitoring patient safety and evaluating risk-benefit profiles in large clinical programs.


Antimicrobial resistance in Neisseria gonorrhoeae in the UK: surveillance and management.
Successful antimicrobial therapy is fundamental to the public health control of gonorrhea, in the absence of a protective immune response. Neisseria gonorrhoeae, the causative agent, has presented a constant challenge for the provision of such therapy as it has demonstrated the ability to become resistant to successive highly active agents chosen for first-line treatment. Acquisition of plasmids from other bacteria and long-term use of a single agent has selected both single step high-level and low-level resistance due to multiple mutations. While therapeutic failure of the current recommended agents cefixime and ceftriaxone begins to emerge, choice of alternative therapies is limited. Guidelines for therapy will be dependent on surveillance programs but individual patient management will require a viable organism to detect emerging resistance. Advances in molecular detection, while advantageous for the diagnosis of gonorrhea, fail to provide a viable organism, posing even greater challenges for the definition of treatment failure, and appropriate end points for test of cure. Innovative and collaborative approaches will be essential to maintain gonorrhea as a treatable infection.


Erratum: Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing.
The author's email has been corrected in the publication of Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing. There was an error with the author, Jerry Zhou's, email. The author's email has been updated to: firstname.lastname@example.com from: email@example.com.


LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness.
One aim of cancer therapies is to induce apoptosis of tumor cells. Efficient removal of the apoptotic cells requires coordinated efforts between the processes of efferocytosis and LC3-associated phagocytosis (LAP). However, this activity has also been shown to produce anti-inflammatory and immunosuppressive signals that can be utilized by live tumor cells to evade immune defense mechanisms, resulting in tumor progression and aggressiveness. In the absence of LAP, mice exhibit suppressed tumor growth during efferocytosis, while LAP-sufficient mice show enhanced tumor progression. Little is known about how LAP or its regulators directly affect efferocytosis, tumor growth and treatment responses, and identifying the mechanisms involved has the potential to lead to the discovery of novel approaches to target cancer cells. Also incompletely understood is the direct effect of apoptotic cancer cells on LAP. This is particularly important as induction of apoptosis by current cytotoxic cancer therapies can potentially stimulate LAP following efferocytosis. Herein, we highlight the current understanding of the role of LAP and its relationship with efferocytosis in the tumor microenvironment with a view to presenting novel therapeutic strategies.


Gene expression pathway analysis to predict response to neoadjuvant docetaxel and capecitabine for breast cancer.
Neoadjuvant chemotherapy has been shown to be equivalent to post-operative treatment for breast cancer, and allows for assessment of chemotherapy response. In a pilot trial of docetaxel (T) and capecitabine (X) neoadjuvant chemotherapy for Stage II/III BC, we assessed correlation between baseline gene expression and tumor response to treatment, and examined changes in gene expression associated with treatment. Patients received four cycles of TX. Tumor tissue obtained from Mammotome core biopsies pretreatment (BL) and post-cycle 1 (C1) of TX was FLash frozen and stored at -70 degrees C until processing. Gene expression analysis utilized Affymetrix HG-U133 Plus 2.0 GeneChip arrays. Statistical analysis was performed using BRB Array Tools after RMA normalization. Gene ontology (GO) pathway analysis used random variance t tests with a significance level of P\0.005. For gene categories identified byGO pathway analysis as significant, expression levels of individual genes within those pathways were compared between classes using univariate t tests; those genes with significance level of P\0.05 were reported. PAM50 analyses were performed on tumor samples to investigate biologic subtype and risk of relapse (ROR). Using GO pathway analysis, 39 gene categories discriminated between responders and non-responders,most notably genes involved in microtubule assembly and regulation. When comparing pre- and post-chemotherapy specimens, we identified 71 differentially expressed gene categories, including DNA repair and cell proliferation regulation. There were 45 GO pathways in which the change in expression after one cycle of chemotherapy was significantly different among responders and nonresponders. The majority of tumor samples fell into the basal like and luminal B categories. ROR scores decreased in response to chemotherapy; this change was more evident in samples from patients classified as responders by clinical criteria. GO pathway analysis identified a number of gene categories pertinent to therapeutic response, and may be an informative method for identifying genes important in response to chemotherapy. Larger studies using the methods described here are necessary to fully evaluate gene expression changes in response to chemotherapy.


[Liver transplantation for liver metastases of colorectal cancer].
Because of the critical shortage of donor organs, liver transplantation for metastatic tumors should be reserved for patients in whom long-term survival is possible. Transplantation in patients with metastatic tumors from colorectal cancer has resulted only in short disease-free intervals, and palliation was achieved in only a few patients. In patients with symptomatic neuroendocrine tumors unresponsive to conventional therapy, on the other hand, reasonably good disease-free intervals and prolonged survival may justify liver transplantation.


Congenital infiltrating lipomatosis of the face with hemimegalencephaly.
Congenital infiltrating lipomatosis of the face (CILF) is a rare disorder, causing unilateral facial asymmetry characterized by enlargement of the cheek or chin. Hemimegalencephaly is a unique malformation characterized by enlargement of a cerebral hemisphere. The association of CILF and hemimegalencephaly has rarely been reported. We present a case of unilateral facial swelling in a 1.5-year-old boy in whom magnetic resonance imaging and computed tomography revealed CILF associated with unilateral megalencephaly.


Improvement of extraction system geometry with suppression of possible Penning discharge ignition.
During the past two years, a new ECR 2.45 GHz type ion source has been developed especially dedicated to intense light ion injector project like IPHI (Injecteur Proton Haute Intensité), IFMIF (International Fusion Materials Irradiation Facility), to reduce beam emittance at RFQ entrance by shortening the length of the LEBT. This new ALISES concept (Advanced Light Ion Source Extraction System) is based on the use of an additional LEBT short length solenoid very close to the extraction aperture. The fringe field of this new solenoid produces the needed magnetic field to create the ECR resonance in the plasma chamber. Such geometry allows first putting the solenoid at ground potential, while saving space in front of the extraction to move the first LEBT solenoid closer and focus earlier the intense extracted beam. During the commissioning of the source in 2011-2012, ALISES has produced about 20 mA extracted from a 6 mm diameter plasma extraction hole at 23 kV. But the magnetic configuration combined to the new extraction system geometry led to important Penning discharge conditions in the accelerator column. Lots of them have been eliminated by inserting glass pieces between electrodes to modify equipotential lines with unfavorable ExB vacuum zones where particles were produced and trapped. To study Penning discharge location, several 3D calculations have been performed with OPERA-3D/TOSCA code to simulate the possible production and trapping of electrons in the extraction system. The results obtained on different sources already built have shown very good agreement with sparks location observed experimentally on electrodes. The simulations results as well as experimental measurements are presented and solutions to prevent possible Penning discharge in future source geometries are established.


Frequency discrimination in noise: comparison of cat performances with auditory-nerve models.
Pure-tone frequency discrimination (delta F) performances were measured in cats and compared to neural models of these delta F performances based on auditory-nerve data in cats. Animal psychophysical techniques were used to train cats to discriminate frequency changes for pulsed pure tones in background noise at both 1.0 and 3.0 kHz. A go-left, go-right procedure was employed, and delta F's were measured in noise as a function of signal level at a constant signal-to-noise ratio. In contrast to human listeners, cats showed increases in delta F at 1.0 kHz with increasing signal level. Model estimates of delta F's based on rate responses in the cat auditory nerve predict increasing delta F with increasing signal level, the trend observed in the cat psychophysical data. Model estimates of delta F's based on temporal (phase-locking) properties in cat auditory nerve, on the other hand, predict decreases in delta F that have been observed in previous data from human listeners [Dye and Hafter, J. Acoust. Soc. Am. 67, 1746-1753 (1980)]. These results suggest that for cats, average rate, rather than phase-locking, may be used by the central nervous system in performing frequency discrimination in background noise at 1.0 kHz. At 3.0 kHz cats showed little change in delta F as a function of signal level, a result similar to the trend for human listeners to show no change or slight increases in delta F with increases in signal level for tones in the 2- to 3-kHz range.


Current Management of Neonatal Neuroblastoma.
Neonatal neuroblastoma accounts for less than 5% of all cases of neuroblastoma but carries a favorable prognosis with most patients being stratified into low- or intermediate-risk groups for recurrence of disease. The epidemiology of neonatal (age less than 30 days) neuroblastoma contrasts greatly with patients older than 30 days. Owing to the unique potential for spontaneous regression of this tumor type, several groups have sought to reduce therapy given to neonates with neuroblastoma and use a watch-and-wait approach for many low-risk patients. Ongoing studies also seek to reduce therapy for some intermediate-risk patients in an attempt to lessen exposure to surgical intervention and cytotoxic chemotherapy. In this review, we discuss the epidemiology, clinical presentation, staging, and treatment for neonates with neuroblastoma.


[Prognostic implication of plasma N-terminal-pro-brain natriuretic peptide in weaning from mechanical ventilation].
To explore the relationship between plasma N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels of patients before weaning and outcome of weaning from mechanical ventilation (MV) in patients. A total of 126 intensive care unit (ICU) patients with MV were enrolled from August 2008 to December 2009, and the cause composition was recorded. Plasma NT-proBNP levels were measured in patients with MV, in whom the clinical data had fulfilled the criteria for weaning from MV, spontaneous breathing trial, weaning and extubation were performed successively. The enrolled patients were divided into two groups namely success group and failure group according to weaning outcome within 48-hour. The plasma NT-proBNP levels in two groups were compared, and receiver operating characteristic (ROC) curve for predicted weaning outcome was plotted to find the cut-off point value of NT-proBNP. The major causes of MV were pulmonary infection (33.3%) and surgical operations (30.2%), and heart failure accounted for only 11.9%. The plasma NT-proBNP levels before weaning were negatively correlated with the consequences of weaning. The plasma NT-proBNP levels in failure group (n=38) were significantly higher than those in success group (n=88, lg NT-proBNP: 3.97+/-0.48 vs. 2.99+/-0.67 ,P<0.05). The NT-proBNP area under ROC curve was 0.875+/-0.043 [95% confidence interval (95% CI) was 0.792-0.959]. The cut-off point value which could be used to predict the outcome of weaning was 3 914.5 ng/L. The sensitivity and specificity of the cut-off point value were 78.3% and 91.1%, respectively. Irrespective of the causes of institution of MV, the cardiac function must be considered as an important factor in affecting the outcome of weaning. The plasma NT-proBNP level of 3 914.5 ng/L can be used to predict weaning outcome. The cardiac function should be improved to a point within the range of cut-off point value in order to improve the success rate of weaning.


"Winter" aggregations, colony cycle, and seasonal phenotypic change in the paper wasp Polistes versicolor in subtropical Brazil.
Social wasps from temperate zones have clear annual colony cycles, and the young queens hibernate during winter. In the subtropics, the only previously reported evidence for the existence of "hibernation" is the facultative winter aggregations of females during harsh climate conditions. As in temperate-zone species analyzed so far, we show in this study that in the paper wasp, Polistes versicolor, a subtropical species, body size increases as an unfavorable season approaches. Our morphological studies indicate that larger females come from winter aggregations--that is, they are new queens. Multivariate analyses indicate that size is the only variable analyzed that shows a relationship to the differences. Given the absence of a harsh climate, we suggest that the occurrence of winter aggregations in tropical P. versicolor functions to allow some females to wait for better environmental conditions to start a new nest, rather than all being obliged to start a new nest as soon as they emerge.


Interference of immune globulin with measles and rubella immunization.
Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (> 10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.


Intracellular trehalase of a hybrid yeast.
1. The trehalase found in an extract prepared from a yeast strain that cannot ferment trehalose was studied and characterized. The enzyme is highly specific for trehalose with K(m) 1.02x10(-2)m, and an optimum pH of 6.9. 2. It is inhibited by glucose and by trehalose 6-phosphate, and does not facilitate any significant transglucosylations. 3. pK values 7.7 and 5.8 were detected for the groups associated with binding of the non-ionized substrate to the enzyme. 4. The trehalase was found to be highly labile and was inhibited by thiol-binding reagents. 5. The possible role of this enzyme in the trehalose-dissimilation patterns in the yeast cell was evaluated.


The role of endovascular treatment in unruptured basilar tip aneurysms.
Objective This study was to evaluate the safety and efficiency of endovascular treatment of unruptured basilar tip aneurysms. Methods We retrospectively reviewed consecutive 79 cases of unruptured basilar tip aneurysms in our center between 2009 and 2014. The patients' clinical and imaging information were recorded. Complications, initial occlusion rate, clinical outcomes and the predictors were retrospectively analyzed. Results Thirty-five cases received conservative treatment and 44 cases were treated by endovascular embolization. In the conservative treatment group, six (19.4%) of 31 basilar tip aneurysms ruptured and resulted in five deaths (16.1%) during the mean 18.1-month follow-up (range from 1 to 60 months). Among the endovascularly treated cases, 24 (54.5%) achieved initial complete occlusion and no delayed hemorrhagic events occurred during the mean 33.6-month follow-up (range from 10 to 68 months). For 20 (45.5%) incompletely occluded cases, five postoperative or delayed hemorrhagic events and two mass effect events resulted in six deaths. There were no statistical significant differences in hemorrhagic events ( p = 0.732) and mortality ( p = 0.502) between the incomplete occlusion group and untreated group. Large aneurysm size (≥10 mm) was an independent predictor for incomplete occlusion ( p = 0.002), which had a potential risk of postoperative or delayed hemorrhage. On univariate analysis, initial occlusion rate and aneurysm size were found to be associated with clinical outcomes ( p = 0.042 and 0.015). Conclusion Complete occlusion for unruptured basilar tip aneurysm proved to be a safe and effective therapeutic method that could eliminate the potential risk of postoperative or delayed hemorrhage.


Fetus as Human Being: Where is the Cut-off Point?
Abortion is one of the controversial issues discussed in medical ethics. We can formulate the argument which is put forward by the opponents of abortion as follows: 1) fetus has to be regarded as human being; 2) killing an innocent human being is morally wrong; 3) aborting is an example of killing and terminating a human being's life. So, being engaged in aborting is morally wrong. In this paper, I am going to argue that the proponents' argument with regard to the implausibility of categorizing fetus as human being is unjustified and wanting. In other words, the way in which the proponents of abortion talk about the idea of personhood is, inadequate and vague, semantically speaking. The outline of the argument is as follows. The proponents of abortion are confronted with a dilemma. According to the first horn of the dilemma, the proponents have to subscribe to infanticide which is morally wrong, intuitively speaking. According to the second horn of the dilemma, there is a semantic story which needs to be expressed by the proponents with regard to the cut-off point of the concept 'personhood'. Otherwise, the first premise will not be convincing if raised in favour of the plausibility of committing abortion.


[Genetic testing and prenatal diagnosis for thirteen Chinese pedigrees affected with oculocutaneous albinism].
To identify the causative variants in 13 Chinese pedigrees affected with oculocutaneous albinism (OCA) so as to provide genetic counseling and prenatal diagnosis to them. Thirteen unrelated pedigrees with clinically diagnosed OCA were collected and classified based on the manifestation of skin and eyes. With informed consent obtained from the participants, peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate variants were screened by targeted capture and next generation sequencing, and the results were validated by Sanger sequencing. Prenatal diagnosis was provided to the families upon their subsequent pregnancies. Causative variants were detected in all probands, including 10 with compound heterozygotes or homozygotes for TYR gene variants and 3 with compound heterozygotes for OCA2 gene variants. Among these, two variants [TYR: c.650G>C (p.Arg217Pro) and OCA2: c.516-2A>T] were unreported previously. The pathogenicity of the novel TYR: c.650G>C (p.Arg217Pro) variant was verified through bioinformatic analysis and prediction of three dimensional structure of the protein. Prenatal diagnosis was provided to 6 fetuses with a high risk for OCA. Four fetuses were found to be carriers, one did not carry the variants of the proband, and one was affected with OCA. Identification of the pathogenic variants in the 13 probands, including 2 novel ones, has expanded the mutational spectrum of OCA and enabled genetic counseling and prenatal diagnosis for the families.


[Enhancement of susceptibility of sulbactam/cefoperazone-treated bacteria to phagocytes].
Effects of sulbactam/cefoperazone (SBT/CPZ) on the host-parasite relationship were studied using an established mouse macrophage cell line. Since SBT inactivates some types of beta-lactamase strongly, a combination of SBT with CPZ shows marked antibacterial activities against the bacteria producing beta-lactamases. In addition, sub-MIC levels of SBT/CPZ made Escherichia coli more susceptible to bactericidal activity of macrophage. This study provides evidence that SBT/CPZ works in partnership with host defense mechanism against bacterial infections in clinical situations.


Racial Justice Curricula in Family Medicine Residency Programs: A CERA Survey of Program Directors.
Structural racism is a cause of health disparities. Graduate medical education is tasked with training physicians who understand and address disparities. Addressing health disparities includes education on racism, such as racial justice curricula (RJC). We surveyed program directors (PDs) about the prevalence and characteristics of RJC in family medicine residency programs (FMRPs). RJC questions were included in the 2020 Council of Academic Family Medicine Educational Research (CERA) survey of FMRP PDs. We calculated univariate and bivariate statistics to describe respondent characteristics and attitudes, program characteristics, curriculum characteristics, and barriers to implementation. Of 624 PDs, 312 (50%) responded and 283/312 (90.7%) completed RJC questions. Less than one-third of FMRPs reported RJC, of which 98.9% focused on implicit/unconscious bias. Program characteristics associated with RJC included location, percent underrepresented minorities in medicine (URMM) residents and faculty, and percent patients identifying as Black, Latino/a, and Native American. FMRPs with RJC were more likely to have PDs who reported favorable attitudes toward including RJC and believed it is important for family physicians to understand structural racism. The greatest barrier to implementation of RJC was lack of faculty training. In this national survey, most FMRPs reported no RJC. Most respondent PDs endorsed that it is important for family physicians to understand structural racism and that RJC should be included in residency. Lack of faculty training was the greatest barrier to implementation. Research is needed to evaluate existing RJC and explore strategies for overcoming barriers to implemention.


Controlled-release formulations of propranolol and verapamil.
The in vitro and clinical behavior of new controlled-release formulations of propranolol and verapamil are reviewed. In vitro dissolution studies have proved to be of little value in determining the clinical activity of these new dosage forms. There is a difference between the blood levels found with the new formulations and those of the reference products. The once-daily verapamil product was evaluated in black hypertensive patients with promising results and suggests that this dosage form of verapamil may be successful as monotherapy for treating this patient population.


Mucin gene structure and expression: protection vs. adhesion.
The cloning of mucin cDNAs brought about by the application of molecular biology and molecular analyses constitutes a major step in understanding mucin structure and function. Here two classes of mucins are described: epithelium-associated and endothelium/leukocyte-associated mucins, which have thus far been described separately in the literature. The epithelial mucins are generally believed to play a role in cytoprotection. The endothelial and leukocyte class of mucins are adhesion molecules involved in lymphocyte homing and lymphocyte activation or are part of the adhesion cascade that plays a role in the initiation of inflammation. Mucins in general contain many threonine and serine residues, which are extensively O-glycosylated. Due to this profound glycosylation, mucins have a filamentous conformation. By virtue of their extended filamentous, and often negatively charged, structure, mucins can act as a barrier protecting the cell. However, when an opposing cell has specific receptors for mucins, adhesion can override the barrier function. Therefore, mucins may be powerful two-edged swords: they are both protective and adhesive.


Arithmetic processing with a joint-transform correlator.
A technique for realizing arithmetic operations that uses a joint-transform correlator is presented. Optical implementations of the technique using a single and a multichannel joint-transform correlator are suggested. The performance of the proposed systems is verified by computer simulation.


Effect of the vertical and horizontal distances between adjacent implants and between a tooth and an implant on the incidence of interproximal papilla.
The interproximal dental papilla is considered an essential component of the anterior and posterior regions of the maxilla and mandible. The absence of this structure has esthetic and phonetical consequences and lateral food impaction problems occur with the implant-supported prosthesis. The aims of the present study were to: 1) evaluate the effect of the vertical and horizontal distances between adjacent implants (group 1) and between a tooth and an implant (group 2) on the presence of the interproximal dental papilla; and 2) determine whether the interaction between the vertical and horizontal distances might be associated with the incidence of the papilla. In 48 patients, 96 interproximal sites in group 1 and 80 in group 2 were examined. The distance from the base of the contact point to the bone crest (D1), the distance between tooth and implant or between two implants (D2), and the distance from the base of the contact point to the tip of the papilla (D3) were measured. In both groups, when D2 was 3, 3.5, or 4 mm, the papilla was present most of the time (P < 0.05), and when D2 was 2 or 2.5 mm, the papilla was absent 100% of the time (P < 0.05). Further, in group 2, when D1 was between 3 and 5 mm, the papilla was present most of the time (P < 0.05). However, in Group 1, only when D1 was 3.0 mm was the papilla present most of the time (P < 0.05). For both groups, analysis of the interaction between D1 and D2 showed that when D2 was < or = 2.5 mm, the papilla was absent; otherwise, when D2 was > or = 3 mm, there was an interaction between D1 and D2. We conclude that the ideal distance from the base of the contact point to the bone crest between adjacent implants is 3 mm and, between a tooth and an implant, 3 mm to 5 mm. The ideal lateral spacing between implants and between tooth and implant is 3 mm to 4 mm. Further, there is an interaction between horizontal and vertical distances when the lateral spacing is greater than 3 mm.


Adaptability and Stability of Safflower Genotypes for Oil Production.
The study aimed to analyze the agronomic performance of 11 safflower genotypes using adaptability and stability methods, while identifying safflower genotypes with stable behavior and a high grain yield in different environments of the Brazilian Cerrado. Ten lines and a cultivar of safflower were evaluated in four environments in the Brazilian conditions. Our results revealed the genotypes P30, P35, P9, P11, and P31 to be superior for grain yield and P43, P7, P11, and P31 to be superior for oil content. The lowest Wricke index, an indication of genotype stability, was observed for P9 (0.41%), which is considered the most stable genotype, followed by P35 (1.29%) and P31 (1.98%). For the predictability of the behavior of genotypes in the environments, P7 (80.85%), P35 (86.10%), P31 (85.90%), and P9 (97.42%) were considered predictable genotypes. The genotypes P11 (1045.6 kg ha-1 and 19.7%) and P21 (952.7 kg ha-1 and 20.6%) are recommended for cultivation in this region, considering both their grain yield and oil content. Safflower is viable to use out of season in the Brazilian Cerrado. The crop can generate profits for farmers and be used for oil production in periods of uncertain corn production.


Ringo/cyclin-dependent kinase and mitogen-activated protein kinase signaling pathways regulate the activity of the cell fate determinant Musashi to promote cell cycle re-entry in Xenopus oocytes.
Cell cycle re-entry during vertebrate oocyte maturation is mediated through translational activation of select target mRNAs, culminating in the activation of mitogen-activated protein kinase and cyclin B/cyclin-dependent kinase (CDK) signaling. The temporal order of targeted mRNA translation is crucial for cell cycle progression and is determined by the timing of activation of distinct mRNA-binding proteins. We have previously shown in oocytes from Xenopus laevis that the mRNA-binding protein Musashi targets translational activation of early class mRNAs including the mRNA encoding the Mos proto-oncogene. However, the molecular mechanism by which Musashi function is activated is unknown. We report here that activation of Musashi1 is mediated by Ringo/CDK signaling, revealing a novel role for early Ringo/CDK function. Interestingly, Musashi1 activation is subsequently sustained through mitogen-activated protein kinase signaling, the downstream effector of Mos mRNA translation, thus establishing a positive feedback loop to amplify Musashi function. The identified regulatory sites are present in mammalian Musashi proteins, and our data suggest that phosphorylation may represent an evolutionarily conserved mechanism to control Musashi-dependent target mRNA translation.


Evidence for graft colonization with periodontal pathogens in lung transplant recipients. A pilot study.
Bronchiolitis obliterans syndrome (BOS) is a major cause of late graft dysfunction in lung transplant recipients. There is increasing evidence that beside alloimmunologic injury also non-alloimmunologic inflammatory conditions may raise the risk of acute and chronic rejection. The oral cavity represents a possible reservoir for pathogenic bacteria due to its close anatomical proximity. In this pilot study, the presence of pathogenic periodontal bacteria in the oral cavity as well as in the lungs of lung transplant recipients was investigated for the first time. Eight lung transplant recipients underwent broncho-alveolar lavage, transbronchial biopsies, and endobronchial biopsies. In addition to routinely performed examinations, pulmonary as well as plaque samples were assessed for Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), Porphyromonas gingivalis (Pg), and Treponema denticola (Td) with the aid of a hybridization technique. No or only one periodontal pathogen (solitarily Pg) was found in the gingival plaques of five of the eight patients (group A). In three patients, two or more periodontal pathogens were detetectable in the gingival samples (group B). Whereas group A also had not more than one periodontal pathogen in the lungs, group B had more than one species in the lungs. In group B, all patients suffered from BOS, whereas in group A only one patient was affected. This is the first evidence for the presence of periodontal pathogens in the lungs of lung transplant recipients. Further studies with larger cohorts are required to elucidate potential links between periodontal infection, pulmonary colonization, and rejection.


Ambroxol inhibits mucoid conversion of Pseudomonas aeruginosa and contributes to the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms.
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause severe infections in immunocompromised individuals. Because it forms biofilms, which protect against host immune attack and increase resistance to conventional antibiotics, mucoid P. aeruginosa is nearly impossible to eradicate. Moreover, mucoid conversion of P. aeruginosa in cystic fibrosis (CF) patients leads to poor outcomes. This conversion is mainly due to mucA gene mutation, which is thought to be induced by polymorphonuclear leukocytes (PMNs) and the reactive oxygen species they release. Ambroxol, a mucolytic agent with antioxidant characteristics, is used clinically, and this compound has recently been demonstrated to possess anti-biofilm properties. In this study, we found that ambroxol inhibits the H2 O2 -mediated conversion of P. aeruginosa from a non-mucoid to a mucoid phenotype, an effect that is due to its antioxidant property against H2 O2 . Furthermore, the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms was increased in vitro when used in combination with ambroxol.


How Updates in Chicago Classification Impact Clinical Practice.
Chicago Classification version 4.0 (CC v4.0), published in 2021, presents several modifications largely aimed at minimizing over-diagnosis of inconclusive patterns on high-resolution manometry (HRM). These include: 1) introduction of a standardized HRM protocol for consistency among centers, 2) emphasis on the need for supportive data in instances of inconclusive manometric patterns, 3) required presence of relevant symptoms in certain instances to reduce over-diagnosis and inappropriate interventions, and 4) classification as disorders of EGJ outflow or disorders of peristalsis. These updates aim to improve the clinical application of HRM and patient outcomes.


New transducers for intraoperative spinal sonography. Technical note.
Although ultrasonography during spinal cord surgery has been widely accepted, it still has limitations in clinical application because of the size of the transducers needed and the immersion method. The authors report on newly designed microprobe transducers used to evaluate intramedullary spinal cord lesions and to monitor surgical procedures. This microprobe system permitted the microscopic use of intraoperative ultrasonography without requiring saline immersion.


Hypertonic mannitol ameliorates intracompartmental tamponade in model compartment syndrome in the dog.
Acute compartment syndrome (ACS) is a devastating complication of rhabdomyolysis caused by muscle tamponade secondary to increased intracompartmental pressure (Pi). ACS requires emergency surgical decompression when Pi greater than 30 mmHg (normal less than 4.0 mmHg) and clinical signs exist. The present study was undertaken to examine whether mannitol which has been used extensively for prevention of acute renal failure in rhabdomyiolysis may also improve muscular hemodynamics in ACS. ACS was produced in dogs by injecting dog plasma into the anterolateral compartment of the hind limb. The Pi was directly monitored. Control dogs received saline, whereas experimental dogs received intravenously 20% mannitol (0.15 ml/min/kg) over a period of 1 h. The initial Pi was set arbitrarily at 100 mm Hg. Following the establishment of ACS, the spontaneous mean decrease in Pi in the control group was 40% of initial value over 60 min (n = 5) versus a decrease of 65%/60 min in the experimental (mannitol) group (n = 7, p less than 0.01). The net mean decompressive effect of mannitol treatments was approximately 28 mm Hg (mean control Pi minus mean experimental Pi at time 60 min). Extrapolated to man with ACS, such a decrease in Pi induced by mannitol theoretically could relieve compartmental tamponade noninvasively.


Research Resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant.
Human ovarian cancer BG-1 cells are a valuable in vitro model that has enabled several laboratories to study the estrogenic responses of ovarian cancers. We recently discovered that there are two different BG-1 cell lines being used for experiments, denoted here as BG-1 FR and BG-1 NIEHS, which exhibit striking morphological differences. The objective of this study was to methodically analyze these two BG-1 variants and compare their characteristics. Short tandem repeat analysis revealed that the DNA profile of BG-1 FR cells was unique, yet the Short tandem repeat pattern of BG-1 NIEHS was identical with that of MCF-7 cells. From a cytogenetic analysis, it became apparent that the BG-1 FR line had the same profile as previously reported, whereas the BG-1 NIEHS and MCF-7 cells share a similar genetic display. A significant number of unique chromosomal translocations were observed between the BG-1 NIEHS and MCF-7 cells, suggesting that acquired genotypic differences resulted in the formation of two lines from a common origin. Although all cell types demonstrated a similar estrogen responsiveness in reporter gene assays, a microarray analysis revealed distinct estrogen-responsive gene expression patterns with surprisingly moderate to low overlap. We conclude that BG-1 FR is the original ovarian cancer cell line, whereas the BG-1 NIEHS is a variant from the MCF-7 cells. These findings provide much needed clarification of the identities and characteristics of key cell line models that are widely used to study estrogen action in female reproductive cancers.


Treatment of chronic hepatitis C.
Treatment for chronic hepatitis C has changed over the past years achieving higher response rates. The combination treatment with pegylated interferon-a and ribavirin is tailored based on the on-treatment virological responses. With this response-guided therapy, the overall sustained virological response rate is about 55%. Many new antivirals are currently under investigation and some will be commercially available in the near future. These include antiviral molecules acting directly against the hepatitis C virus (HCV) replication machinery, such as the inhibitors of the viral protease, and agents binding to host cofactors of the viral replication, thereby inhibiting HCV in an indirect way (such as cyclophilin inhibitors and nitazoxanide). The advent of these drugs will further ameliorate response rates and facilitate the permanent cure of chronic hepatitis C.


[Was chemotherapy beneficial for the patients with advanced ovarian cancer? A comparison of survival and resource use in two different time periods].
Around 1980, aggressive surgery and combination-chemotherapy were introduced as routine therapy in advanced ovarian cancer. It is interesting to evaluate whether this has been associated with an improvement of survival. A comparison between patients diagnosed in the county of Funen during the period April 1973 to April 1978 with patients diagnosed during the period September 1981 to September 1986 was made. In the last period the patients were treated according to the DACOVA guidelines (Damish Cancer of the Ovaries). An improvement in median survival but not in five-year survival was registered. The number of hospital bed-days during the two periods was calculated. In the second period the number of hospital bed-days was seven days higher per patient than in the first period. The cost per gained year of life was 240,000 Dkr. in 1992 prices.


Investigation of JAK2, STAT3 and CCR6 polymorphisms and their gene-gene interactions in inflammatory bowel disease.
Genome-wide association studies identified many loci associated with the two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Components of the interleukin-23 signalling pathway, such as IL23R, JAK2 and STAT3, have been implicated in both diseases. In addition, emerging evidence supports the role of IL23-driven Th17 cells in inflammation. Here, we studied the susceptibility nature of three components of IL23 signalling and Th17 cell differentiation: JAK2 rs10758669, STAT3 rs744166 and CCR6 rs2301436 initially associated with CD in Hungarian CD and UC patients. A total of 616 unrelated subjects with either form of IBD and 496 healthy controls were genotyped with PCR-RFLP methods. We also tested the genetic interactions of JAK2, STAT3 and CCR6 polymorphisms in a pairwise fashion with regard to disease risk. We could confirm the susceptibility of STAT3 rs744166 TT homozygotes for UC (OR: 1.483, 95% CI: 1.103-1.992, P = 0.009). Data on genetic interaction reveals that the above JAK2 and STAT3 risk alleles contribute to CD susceptibility in combination with each other (OR: 2.218; 95% CI: 1.097-4.487; P = 0.024), while the JAK2 variant shows a tendency to confer UC risk only on a wild-type STAT3 background (OR: 1.997, 95%CI: 0.994-4.009, P = 0.049). Our results may help in understanding how these natural variants contribute to development of IBD through their genetic association.


Bedside video-ophthalmoscopy as an aid in the diagnosis of central vestibular syndromes.
The evaluation of central vestibular syndromes, especially in the acute setting, can pose a challenge even for the most experienced clinician. Of particular importance is the evaluation of ocular torsion and nystagmus, which can be sensitive for central vestibular pathology, but easily missed by the untrained eye. We present two cases of acute vestibular syndrome of central origin in which the use of magnified fundoscopy at the bedside aided the precise anatomical diagnosis to inform appropriate further management. We also review aspects of the pathophysiology and anatomy of vestibular roll plane disorders. In case 1, the finding of position-dependent ocular torsion facilitated a rapid distinction between central skew deviation and a trochlear nerve palsy. In case 2, the fundoscopic magnification identified a pure rotatory nystagmus indicative of a central vestibular disorder. Ophthalmoscopy remains a useful bedside technique in acute vertigo, but the use of inexpensive magnification with a smartphone can provide objective and recordable evidence of central vestibular pathology, aiding therapeutic decisions.


Chemoprophylaxis strategies in high-risk groups with an emphasis on lung cancer.
The incidence of lung cancer in the United States has stabilized in recent years, but it remains a major cause of death in the United States. Whereas the single most effective primary prevention of this disease would be to eliminate tobacco use from society, this is currently an unrealistic goal. Secondary prevention, however--that is, chemoprophylactic treatment of smokers, exsmokers, and others at risk--represents a viable option. Agents proven effective in both laboratory models and humans include vitamin A and its synthetic derivatives, the retinoids and the carotenoids. It is fairly easy to identify patients at risk of lung cancer compared with other cancers. Yet aside from patients who are under a physician's care and aware of their risk, it can be difficult to target individuals for chemoprophylactic treatment, especially those who are healthy but at high risk and not seeing a physician or other health care provider. Screening for the presence of predictive cellular and molecular changes may facilitate more accurate selection of individuals for chemoprophylactic treatment.


Altered inactivation of Ca2+ current and Ca2+ release in mouse muscle fibers deficient in the DHP receptor gamma1 subunit.
Functional impacts of the skeletal muscle-specific Ca2+ channel subunit gamma1 have previously been studied using coexpression with the cardiac alpha1C polypeptide in nonmuscle cells and primary-cultured myotubes of gamma1-deficient mice. Data from single adult muscle fibers of gamma-/- mice are not yet available. In the present study, we performed voltage clamp experiments on enzymatically isolated mature muscle fibers of the m. interosseus obtained from gamma+/+ and gamma-/- mice. We measured L-type Ca2+ inward currents and intracellular Ca2+ transients during 100-ms step depolarizations from a holding potential of -80 mV. Ratiometric Ca2+ transients were analyzed with a removal model fit approach to calculate the flux of Ca2+ from the sarcoplasmic reticulum. Ca2+ current density, Ca2+ release flux, and the voltage dependence of activation of both Ca2+ current and Ca2+ release were not significantly different. By varying the holding potential and recording Ca2+ current and Ca2+ release flux induced by 100-ms test depolarizations to +20 mV, we studied quasi-steady-state properties of slow voltage-dependent inactivation. For the Ca2+ current, these experiments showed a right-shifted voltage dependence of inactivation. Importantly, we could demonstrate that a very similar shift occurred also in the inactivation curve of Ca2+ release. Voltages of half maximal inactivation were altered by 16 (current) and 14 mV (release), respectively. Muscle fiber bundles, activated by elevated potassium concentration (120 mM), developed about threefold larger contracture force in gamma-/- compared with gamma+/+. This difference was independent of the presence of extracellular Ca2+ and likely results from the lower sensitivity to voltage-dependent inactivation of Ca2+ release. These results demonstrate a specific alteration of voltage-dependent inactivation of both Ca2+ entry and Ca2+ release by the gamma1 subunit of the dihydropyridine receptor in mature muscle fibers of the mouse.


No-268-The Diagnosis and Management of Ovarian Hyperstimulation Syndrome.
To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report.


[Value of the study of contingent negative variation in migraine and tension headache].
The aim of this study was to display the result obtained by the contingent negative variation (CNV) recording in patients suffering from headache. Eighty-five patients were taken into account: 59 with migraines (M) and 26 with tension headache (TH). A typical CNV pattern (high CNV amplitude with no habituation) differentiated M from TH. Moreover, psychological data were collected through Rorschach ink blot test among 42 headache sufferers (31 M and 11 TH). The typical Rorschach repressive pattern of alexithymia was found as well in M as in TH while CNV amplitude was significantly higher in the 31 M (-25 microV) than in the 11 TH (-19 microV FP less than 0.04). Biochemical data collected among 28 patients (17 M and 11 TH) revealed a positive correlation between CNV amplitude and plasma level of noradrenaline, regardless of the type of headache (r = 0.58; P less than 0.01). Thus, besides psychological factors, catecholaminergic mechanisms seem implicated in the determination of the CNV pattern in migraine. CNV may help the clinician both to specify diagnosis and to decide between the many therapeutic strategies available.


Effects of GABA compounds injected into the subpallidal regions of rat brain on nucleus accumbens evoked hyperactivity.
The effects of administration of gamma-aminobutyric acid (GABA) compounds into the ventral pallidum and substantia innominata on the locomotor hyperactivity induced by the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) in the nucleus accumbens were investigated in rats. Hyperactivity induced by ADTN was antagonized by the GABA receptor agonists muscimol, isoguvacine, and baclofen. The compounds were equally effective in both subpallidal regions. In contrast, the GABA antagonists picrotoxin and bicuculline injected into subpallidal sites had no effects on accumbens-evoked hyperactivity, although by themselves both antagonists caused a mild and transient locomotor stimulation. It is suggested that GABA receptors in the subpallidal areas are involved in locomotor stimulation elicited from the nucleus accumbens.


Malignant melanoma of the vulva FIGO stage I: Evaluation of prognostic factors in 43 patients with emphasis on DNA ploidy and surgical treatment.
Forty-three cases of malignant melanoma of the vulva FIGO stage I, primary treated from 1956 to 1987, have been reviewed. Initial surgery was local excision in 14 patients, vulvectomy in 14, and radical vulvectomy with inguinal lymph node dissection in 15. Recurrent disease was seen in 27 (63%) patients. The 5-year corrected survival was 63%; 10-year survival was 52%. Independent prognostic factors for disease-free and long-term survival were angioinvasion and DNA nondiploidy. Tumor thickness was of prognostic importance in univariate analysis, but did not obtain independent significance. Initial surgical modality did not influence long-term survival, but affected disease-free survival significantly. Local excision carried the greatest risk of local recurrence, but in some of these patients secondary surgery was successful. Because radical surgery did not improve long-term prognosis, wider local excision or vulvectomy seems to be the recommended surgical approach.


Identification and Characterization of an Isoform Antifreeze Protein from the Antarctic Marine Diatom, Chaetoceros neogracile and Suggestion of the Core Region.
Antifreeze proteins (AFPs) protecting the cells against freezing are produced in response to extremely low temperatures in diverse psychrophilic organisms, and they are encoded by multiple gene families. The AFP of Antarctic marine diatom Chaetoceros neogracile is reported in our previous research, but like other microalgae, was considered to probably have additional genes coding AFPs. In this paper, we reported the cloning and characterization of additional AFP gene from C. neogracile (Cn-isoAFP). Cn-isoAFP protein is 74.6% identical to the previously reported Cn-AFP. The promoter sequence of Cn-isoAFP contains environmental stress responsive elements for cold, thermal, and high light conditions. Cn-isoAFP transcription levels increased dramatically when cells were exposed to freezing (-20 °C), thermal (10 °C), or high light (600 μmol photon m-2 s-1) stresses. The thermal hysteresis (TH) activity of recombinant Cn-isoAFP was 0.8 °C at a protein concentration of 5 mg/mL. Results from homology modeling and TH activity analysis of site-directed mutant proteins elucidated AFP mechanism to be a result of flatness of B-face maintained via hydrophobic interactions.


Dianhydrogalactitol and neural tumors: an in vitro, in vivo preclinical evaluation.
The effects of dianhydrogalactitol on human neuroblastomas in vitro and in vivo as heterotransplants in nude mice were determined. Four neuroblastoma lines and three primitive neuroectodermal tumor lines were found, in vitro, to have different sensitivities to the drug. The most sensitive in in vitro assays was the neuroblastoma line SK-N-Mc. Tumors from patients resistant to cyclophosphamide were sensitive to dianhydrogalactitol in vitro and in nude mice. The lack of increased cytotoxicity in vitro with concentrations greater than 12 micrograms/ml and the lowered degree of weight loss in mice treated with 6 mg/kg/day x 5 consecutive days compared to 15 mg/kg/day x 2 days (either in sequence or with a 3-day interval) suggest that clinical trials with 5-day courses or constant infusions may be more effective than intermittent pulsed doses.


[Foreigners and natives in Switzerland: demographic divergence and convergence].
The native and immigrant populations of Switzerland are examined and compared. "The latter represents today 18% of the total population and its age structure tends to draw nearer to that of the Swiss by an aging process. The sex ratio is much different in the two communities. In fact, the foreign population has a strong masculine predominance, especially among the holders of short duration permits. In addition, the diminution in the number of Italians and Spaniards goes with the arrival of the new nationalities (Yugoslavs, Portuguese and Turks) in the labour market and one can observe, as for the Swiss, that the foreign labour, generally speaking, joins more and more the tertiary industries." (SUMMARY IN ENG AND GER)


Case studies from the use of commercial biomarker/protein test kits.
Large-molecule drugs (therapeutic proteins, peptides, various forms of antibodies) are more frequently being seen in drug-development pipelines, the majority of which are measured using immunochemical/ligand-binding techniques. The assays utilized for analysis of large-molecule drugs rely heavily upon the quality of the components (e.g., reference materials, antibodies) that are critical to the performance of the assays. Commercially available research-grade materials and kits offer a convenient and simple solution, but also present some unique challenges. This article will explore some examples of issues encountered while employing commercially available kits and reagents.


Assessment of Sarcopenia and Obesity in Patients with Myasthenia Gravis Using Dual-Energy X-ray Absorptiometry: A Cross-Sectional Study.
Sarcopenia and obesity can negatively impact quality of life and cause chronic fragility, and are associated with neuromuscular diseases, including myasthenia gravis (MG). The long-term consequences of body composition changes in chronic MG remain unknown; we therefore evaluated changes in body composition, including sarcopenia, obesity, lean body mass, and the prevalence of sarcopenic obesity in patients. In this cross-sectional study, 35 patients with MG (mean age: 56.1 years) and 175 matched controls were enrolled. Body fat mass and skeletal muscle mass were measured using whole body dual-energy X-ray absorptiometry. Patients with MG exhibited a higher prevalence of obesity and higher android adiposity and total body fat percentage than those of controls. Although the prevalence of sarcopenia and sarcopenic obesity did not increase with age, there was a decrease in arm and android muscle mass in patients with MG compared with controls. Lower muscle mass percentages were correlated with increased age and MG severity, but not with corticosteroid use. Thus, MG is associated with increased risk for obesity and decreased muscle mass with aging, regardless of corticosteroid use. Therefore, accurate diagnosis of body composition changes in MG could facilitate the application of appropriate therapies to promote health, improve quality of life, and prevent fragility.


Comparison of nine commercial immunoassays for the detection of rotavirus in fecal specimens.
One hundred fecal specimens obtained from patients with acute gastroenteritis were tested for rotavirus with nine commercial immunoassays to evaluate the sensitivity, specificity, predictive value, and diagnostic accuracy of these assays. Kits evaluated included two monoclonal antibody-based enzyme immunoassays (EIAs) (Rotaclone and Pathfinder Rotavirus), three polyclonal antibody-based EIAs (Rotavirus Immunoassay, Rotazyme II, and Wellcozyme Rotavirus), and four latex agglutination assays (Rotastat, Virogen Rotatest, Meritec-Rotavirus, and The Wellcome Latex Test). Thirty-eight of the 100 specimens were found to contain rotavirus by a reference microplate EIA. The accuracy of the reference assay was determined by RNA electrophoresis and a blocking assay on discordant specimens. The two monoclonal antibody EIAs had superior sensitivities (100%) and identified two positive specimens which were negative by the reference method but positive by the blocking assay. Among the polyclonal EIAs, all had sensitivities of greater than 90%, but specificities were variable; Rotazyme II, with a specificity of 50%, showed considerable discrepancy from other polyclonal EIAs. The latex tests had sensitivities ranging from 70 to 90% and specificities of 80 to 100%. Latex agglutination tests were more rapid than EIAs and did not require expensive equipment. The final choice of assay system will depend on the cost, speed, and accuracy requirements of the clinical laboratory.


Tolerance of a cow's milk-based hydrolyzed formula in patients with eosinophilic esophagitis triggered by milk.
Cow's milk protein, a major food trigger for EoE in both children and adults, should be continuously avoided once identified as such. This study evaluates tolerance of a cow's milk-based extensively hydrolyzed formula (eHF) with regard to disease remission maintenance in adult patients with milk-triggered EoE. Seventeen adult patients in whom cow's milk was consecutively demonstrated to trigger EoE after an empiric six-food elimination diet-based study protocol and who subsequently maintained disease remission were prospectively recruited. They were given 400 ml of a cow's milk-based eHF daily for 8 weeks. Intraepithelial peak eosinophil and blood eosinophil counts, esophageal-related symptoms, serum total and specific IgE to major milk proteins, and eosinophil cationic protein were monitored before and after eHF intake. Thirteen male and four female patients aged 17-56 completed the study protocol. 15 patients (88.24%) achieved and maintained EoE remission, while an infiltration of ≥15 eosinophils/hpf reappeared in the remaining two patients. No differences in age, gender, symptoms, and endoscopic appearance at baseline conditions or personal/family allergic background were observed between those patients who tolerated the eHF and those who did not. Symptom scores did not significantly change after eHF intake and were significantly lower than those documented at baseline conditions or after cow's milk challenge. No differences were documented in blood eosinophil counts or serum markers after eHF intake. Most adult patients with EoE triggered by cow's milk tolerate a cow's milk-based eHF, thus providing them with a safe, economical alternative to cow's milk.