Perimesencephalic Subarachnoid Hemorrhage Has a Unique Peripheral Blood Leukocyte Profile Compared To Aneurysmal Subarachnoid Hemorrhage.
The authors sought to investigate if peripheral blood leukocyte profiles on admission differed between perimesencephalic, angio-occult, and aneurysmal subarachnoid hemorrhage cohorts. We performed a retrospective analysis of 202 consecutive patients with spontaneous subarachnoid hemorrhage. We classified spontaneous subarachnoid hemorrhage as either aneurysmal or nonaneurysmal origin. Nonaneurysmal subarachnoid hemorrhage was subclassified as either perimesencephalic or angio-occult according to the distribution of hemorrhage on the initial imaging. Patient demographics, clinical parameters, radiographic metrics, and laboratory values were obtained on admission. In-hospital data including acute hydrocephalus, shunt dependence, vasospasm, and delayed cerebral ischemia were collected. Comparative analyses were conducted between cohorts. The perimesencephalic subarachnoid hemorrhage cohort exhibited significantly lower neutrophil (7.76 vs. 10.06; P = 0.004), lymphocyte (1.40 vs. 1.90; P = 0.024), and monocyte counts (0.52 vs. 0.73; P = 0.031) than the aneurysmal subarachnoid hemorrhage cohort. There were no significant differences in peripheral blood leukocyte profiles between the angio-occult and aneurysmal subarachnoid hemorrhage cohorts. The nonaneurysmal cohort exhibited significantly lower neutrophil (8.33 vs. 10.06; P = 0.005) and lymphocyte counts (1.47 vs. 1.90; P = 0.011) as well as a lower lymphocyte-to-monocyte ratio (2.80 vs. 4.51; P = 0.018) than the aneurysmal subarachnoid hemorrhage cohort. Perimesencephalic subarachnoid hemorrhage exhibits a unique peripheral blood leukocyte profile compared to aneurysmal subarachnoid hemorrhage. Moreover, these preliminary data demonstrate that blood leukocytes may be affected by the burden of cisternal subarachnoid hemorrhage or the presence of a ruptured aneurysm. Further large-scale prospective studies and validation are required to confirm these preliminary findings.


A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding.
To determine whether visceral fat reduction in connection with bariatric surgery could improve weight loss and metabolic profile of obese subjects. In a one-center, randomized and controlled pilot trial we assigned 50 subjects with severe obesity (body mass index >35 kg/m(2)) to either adjustable gastric banding (AGB) alone (11 men and 14 women), or AGB plus surgical removal of the total greater omentum (11 men and 14 women). The patients were followed at regular intervals for 2 y and examined at 0 and 24 months with respect to body composition and metabolic profile. No significant differences between control and omentectomized patients were observed at baseline. The removed greater omentum constituted 0.8+/-0.4% (mean+/-s.d.) of total body fat. At 2 y follow-up there was an expected decrease in body weight and an improvement in metabolic profile in both groups. Although omentectomized subjects tended to lose more weight than control subjects the difference was not statistically significant and changes in waist-to-hip ratio and saggital diameter did not differ between groups. However, the improvements in oral glucose tolerance, insulin sensitivity and fasting plasma glucose and insulin were 2-3 times greater in omentectomized as compared to control subjects (P from 0.009 to 0.04), which was statistically independent of the loss in body mass index. No differences in blood lipids between the groups were recorded. No adverse effects related to omentectomy were observed. Omentectomy, when performed together with AGB, has significant positive and long-term effects on the glucose and insulin metabolic profiles in obese subjects.


An evaluation of the tuberculosis agglutination test.
The tuberculosis agglutination titre as described by Nicholls (1975) was measured without prior knowledge of the diagnosis in 27 patients with open pulmonary tuberculosis, 100 patients with other diseases and 14 control patients with no apparent disease. Reproducibility of the test, as judged by repeat estimations on split samples, was poor. When attempting to distinguish between the disease categories the test gave 29% false negatives in patients with tuberculosis and 52% false positives in patients with other disease. Therefore the tuberculosis agglutination titre cannot be recommended for use in distinguishing tuberculosis from other conditions.


Associations between social engagement, internalizing symptoms, and delusional ideation in the general population.
Delusions are a hallmark feature of psychotic disorders and lead to significant clinical and functional impairment. Internalizing symptoms-such as symptoms of depression, anxiety, and trauma exposure-are commonly cited to be related to delusions and delusional ideation and are often associated with deficits in social functioning. While emerging studies are investigating the impact of low social engagement on psychotic-like experiences, little work has examined the relationship between social engagement, internalizing symptoms, and delusional ideation, specifically. Using general population data from the Nathan Kline Institute-Rockland (NKI-Rockland) database (N = 526), we examined the relationships between self-reported delusional ideation, internalizing symptoms, and social engagement and tested four indirect effect models to understand how these factors interrelate. Delusional ideation was significantly associated with both increased internalizing symptoms (r = 0.41, p < 0.001) and lower social engagement (r = - 0.14, p = 0.001). Within aspects of social engagement, perceived emotional support showed the strongest relationship with delusional ideation (r = - 0.17, p < 0.001). Lower social engagement was also significantly associated with increased internalizing symptoms (r = - 0.29, p < 0.001). Cross-sectional models suggest that internalizing symptoms have a significant indirect effect on the association between delusional ideation and social engagement. These findings reveal that elevated delusional ideation in the general population is associated with lower social engagement. Elevated internalizing symptoms appear to play a critical role in reducing engagement, possibly exacerbating delusional thinking. Future work should examine the causal and temporal relationships between these factors.


Choosing and Doing wisely: triage level I resuscitation a possible new field for starting palliative care and avoiding low-value care - a nationwide matched-pair retrospective cohort study in Taiwan.
The association between palliative care and life-sustaining treatment following emergency department (ED) resuscitation is unclear. This study aims to analyze the usage of palliative care and life-sustaining treatments among ED triage level I resuscitation patients based on a nationally representative sample of patients in Taiwan. A matched-pair retrospective cohort study was conducted to examine the association between palliative care and outcome variables using multivariate logistic regression and Kaplan-Meier survival analyses. Between 2009 and 2013, 336 ED triage level I resuscitation patients received palliative care services (palliative care group) under a universal health insurance scheme. Retrospective cohort matching was performed with those who received standard care at a ratio of 1:4 (usual care group). Outcome variables included the number of visits to emergency and outpatient departments, hospitalization duration, total medical expenses, utilization of life-sustaining treatments, and duration of survival following ED triage level I resuscitation. The mean survival duration following level I resuscitation was less than 1 year. Palliative care was administered to 15% of the resuscitation cohort. The palliative care group received significantly less life-sustaining treatment than did the usual care group. Among patients who underwent level I resuscitation, palliative care was inversely correlated with the scope of life-sustaining treatments. Furthermore, triage level I resuscitation status may present a possible new field for starting palliative care intervention and reducing low-value care.


The development of dental education in the United Kingdom with special reference to orthodontics.
The history of the developments in Dental Education in the British Isles is discussed starting in the middle of the eighteenth century with the work by John Hunter, and many to the present day. Stress is laid in the preservation of these improvements in both undergraduate and postgraduate education and the needs for close contact with bodies outside of orthodontics.


Novel aspects of macromolecular repair and relationship to human disease.
Cellular and humoral defence mechanisms are essential for the survival of individuals and species. Thus, DNA repair prevents mutations and cytotoxicity from DNA damage, thereby reducing the risks of inappropriate cell death, developmental defects, premature ageing and cancer. Similarly, antigen-dependent acquired immune responses prevent infections and also have a role in cancer prevention. DNA repair is highly complex and functions in an intricate network that also involves transcription, replication, cell cycle regulation, and the immune system. DNA damage is repaired by at least four major mechanisms, each requiring many different proteins. In addition there are "subpathways", and back-up mechanisms both within and between pathways. Various defects in DNA repair result in different forms of cancer, e.g. the rare syndrome Xeroderma pigmentosum and the more common diseases early-onset breast cancer and hereditary non-polyposis colon cancer. Surprisingly, recent research has revealed molecular interactions between the ancient DNA repair mechanisms and the much younger acquired immune system. Thus, the classical base excision enzyme uracil-DNA glycosylase encoded by the UNG gene is also involved in somatic hypermutation and class switch recombination, e.g. from IgM antibodies to IgG, yielding secreted high affinity antibodies. Mutations in both alleles of UNG result in a hyper-IgM syndrome with life-threatening infections. Furthermore, it has recently become clear that not only DNA, but also RNA and proteins are repaired. Thus, certain aberrant methylations in RNA are repaired by oxidative demethylation in one step restoring the normal base, and at least in a bacterial model system this increases survival several-fold after exposure to methylating agents. Proteins are repaired both at the peptide amino acid level and at the structural level. RNA and protein repair are likely to be important to prevent the formation of cytotoxic protein aggregates of the types known to cause neurodegenerative diseases e.g. Alzheimer's, Parkinson's and Huntington's diseases, and other diseases as well. In conclusion, recent research has demonstrated an unexpected complexity of cellular defence mechanisms that function in intricate networks, rather than as independent mechanisms. The new knowledge opens for interventions that are based on a deeper understanding of the mechanisms of defence.


Robot-assisted radical cystectomy and urinary diversion in female patients: technique with preservation of the uterus and vagina.
After performing more than 500 robotic radical prostatectomy and robotic radical cystoprostatectomy in men, we attempted to develop the technique of robot-assisted radical cystectomy in women. This article describes two techniques of robot-assisted radical cystectomy for women, conventional and with preservation of the uterus and vagina. To the best of our knowledge, this is the first case series of robot-assisted radical cystectomy and urinary diversion in women. Robot-assisted radical cystectomy was undertaken in three female patients with transitional cell carcinoma of the urinary bladder. The operation was performed with the conventional anterior approach in one patient and with a new technique in two patients, which allows preservation of urethra, uterus, vagina, and both ovaries. As planned, the radical cystectomy was done robotically, using the da Vinci Surgical System (Intuitive Surgical). The bladder was entrapped in an Endocatch bag and removed through a small subumbilical incision. Urinary reconstruction was performed extracorporeally after exteriorizing the bowel through the incision used for retrieving the specimen. In two patients, the reconstructed pouch was placed in the pelvis and the abdominal incision was closed. Urethroneovesical anastomosis was done robotically, using a technique described previously for men. The average operating time for the robotic radical cystectomy was 160 minutes and the mean operating times for ileal conduit and orthotopic neobladder were 130 minutes and 180 minutes, respectively. The mean blood loss was less than 100 mL. The mean number of lymph nodes removed was 12 (range 3 to 21). Surgical margins were free of tumor in all three patients. This approach incorporates advantages of minimally invasive and open surgery. Performing the radical cystectomy with the robot allows precise and rapid removal of the bladder with minimal blood loss. Extracorporeal reconstruction of the urinary tract reduces operative time at this stage of evolution of laparoscopic and robotic instrumentation. In the future, with the development of technology, instrumentation, and with additional refinement of our technique, the entire procedure may be done completely intracorporeally with equal efficiency.


Firearm injury survival is only the beginning: The impact of socioeconomic factors on unplanned readmission after injury.
Firearm trauma remain a national crisis disproportionally impacting minority populations in the United States. Risk factors leading to unplanned readmission after firearm injury remain unclear. We hypothesized that socioeconomic factors have a major impact on unplanned readmission following assault-related firearm injury. The 2016-2019 Nationwide Readmission Database of the Healthcare Cost and Utilization Project was used to identify hospital admissions in those aged >14 years with assault-related firearm injury. Multivariable analysis assessed factors associated with unplanned 90-day readmission. Over 4 years, 20,666 assault-related firearm injury admissions were identified that resulted in 2,033 injuries with subsequent 90-day unplanned readmission. Those with readmissions tended to be older (31.9 vs 30.3 years), had a drug or alcohol diagnosis at primary hospitalization (27.1% vs 24.1%), and had longer hospital stays at primary hospitalization (15.5 vs 8.1 days) [all P<0.05]. The mortality rate in the primary hospitalization was 4.5%. Primary readmission diagnoses included: complications (29.6%), infection (14.5%), mental health (4.4%), trauma (15.6%), and chronic disease (30.6%). Over half of the patients readmitted with a trauma diagnosis were coded as new trauma encounters. 10.3% of readmission diagnoses included an additional 'initial' firearm injury diagnosis. Independent predictors of 90-day unplanned readmission were public insurance (aOR 1.21, P = 0.008), lowest income quartile (aOR 1.23, P = 0.048), living in a larger urban region (aOR 1.49, P = 0.01), discharge requiring additional care (aOR 1.61, P < 0.001), and discharge against medical advice (aOR 2.39, P < 0.001). Here we present socioeconomic risk factors for unplanned readmission after assault-related firearm injury. Better understanding of this population can lead to improved outcomes, decreased readmissions, and decreased financial burden on hospitals and patients. Hospital-based violence intervention programs may use this to target mitigating intervention programs in this population.


Subcutaneous rupture of the superficial branch of the radial nerve at the wrist. A case report and review of literature.
Isolated neuropathy of the superficial branch of the radial nerve (SBRN) is a rarely recognized pathology. It was initially described by Wartenberg in 1932. Various causes have been published. We report a case of an unusual injury of the SBRN at the wrist, never been previously reported in the literature. A 40-year-old woman presented with pain and paresthesia over the area of the lateral aspect of the wrist, thumb and first web two months after a blunt trauma of the left forearm. After failure of conservative treatment, surgical exploration found a neuroma of one branch of the SBRN. No distal nerve stump was found. Neuroma resection was performed and the nerve was transposed and embedded into the flexor pollicis longus muscle. With a six months follow-up, the result was satisfactory.


Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer.
CD30 is highly expressed on Hodgkins lymphoma and anaplastic large cell lymphoma, making it an attractive target for therapy. We describe the generation of serum-stabilized ssDNA aptamers that bind CD30 via a hybrid SELEX methodology. The selected aptamer bound CD30 with high affinity and specificity. Further optimization of the aptamer led to a short, truncated variant with a 50-fold higher affinity than its longer counterpart. The multivalent aptamer was able to induce oligomerization of CD30 receptors and, in effect, activate downstream signaling, which led to apoptosis of ALCL cells. Immunotherapy using aptamer-based co-stimulation provides an alternative to antibodies, and has potential to transform cancer treatment.


Experiences of informal caregiving among older lesbian and gay adults in Australia.
This study examined older lesbian and gay adults' experiences regarding informal caregiving, including challenges and positive aspects of caregiving. Interviews were conducted with 16 lesbian women and gay men in Australia, aged 60+, who were engaged in informal caregiving. Analyses involved a qualitative thematic approach. Most participants were caring for a friend or partner and regarded caregiving as a form of love and did not seek external support despite noting several impacts. Some participants found that they too were beginning to require care. For some, formal care was being considered, but with a degree of reluctance. Older lesbian and gay adult caregivers experience a range of challenges and support needs in relation to their experiences with the caregiving role. This research highlights a need for ensuring that caregiving policies and practices be responsive to the experiences and challenges faced by older lesbian and gay people.


Publisher Correction: A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Malaria: toxins, cytokines and disease.
In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglycaemia may be due to direct effects of similar molecules on glucose metabolism. These molecules appear to be phospholipids and we suggest that when fully characterized they might form the basis of antitoxic therapy for malaria.


Testing the effects on information use by older versus younger women of modality and narration style in a hospital report card.
Hospital report cards (HRCs) are usually presented in a textual and factual format, likely hampering information processing. This study aimed to investigate the effects of audiovisual and narrative information in HRCs on user responses, and to test differences between older and younger women. A 2 (modality [textual vs. audiovisual]) × 3 (narration style [factual vs. process narrative vs. experience narrative]) online experiment was conducted. Information about breast cancer care was used as a case example. Age (younger [<65] vs. older [≥65]) was included as a potential effect modifier. A total of 631 disease-naïve women (Mage = 56.06) completed an online survey. The outcomes were perceived cognitive load, satisfaction, comprehension, information recall and decisional conflict. Data were analysed using AN(C)OVAs. Audiovisual (vs. textual) information resulted in higher information satisfaction across age groups, but was associated with lower comprehension in older women. An experience narrative (vs. factual information) increased satisfaction with attractiveness and emotional support of the information only in older women. A three-way interaction effect was found, suggesting that older women were most satisfied with the comprehensibility of audiovisual factual or textual process narrative information. Younger women were most satisfied with the comprehensibility of audiovisual process narrative or textual factual information. Audiovisual and narrative information in an HRC showed beneficial effects on satisfaction measures. In particular, audiovisual information could be incorporated into HRCs to increase satisfaction with information. Lay persons helped in optimizing the visuals used in the stimulus materials by checking for clarity.


Holmium:YAG laser ureteroscopic lithotripsy for ureteric calculi in children: predictive factors for complications and success.
To evaluate the impact of age, stone size, location, radiolucency, extraction of stone fragments, size of ureteroscope and presence and degree of hydronephrosis on the efficacy and safety of holmium:YAG (Ho:YAG) laser lithotripsy in the ureteroscopic treatment of ureteral stones in children. Between October 2011 and May 2013, a total of 104 patients were managed using semirigid Ho:YAG ureterolithotripsy. Patient age, stone size and site, radiolucency, use of extraction devices, degree of hydronephrosis and size of ureteroscope were compared for operative time, success and complications. In all, 128 URS were done with a mean age of 4.7 years. The mean stones size was 11 mm. Success rate was 81.25 %. Causes of failure were 12.5 % access failure, 1.5 % extravasation and 4.7 % stone migration. Overall complications were 23.4 %. Failure of dilatation and extravasation were detected only in children <2 years old. Extravasation was significantly higher in smaller ureters and cases with stone size >15 mm. Stone migration was significantly higher in upper ureteric stones. Failure and complications rates in Ho:YAG ureterolithotripsy were significantly affected by younger age (<2 years), upper ureteric stones and smaller ureters but were not related to stone radiolucency or degree of hydronephrosis. Larger stones (>15 mm) were associated with increased complications. After multivariate analysis, the age of the patients remained significant predictor for failure of dilatation and stone migration, while size of the ureter was the only significant predicting factor for failure.


Are targeted prostate biopsies ready to replace systematic prostate biopsies?
To evaluate the efficacy and efficiency of systematic prostatic biopsy (SPB) and cognitive fusion PB (CFPB) to diagnose prostate cancer (PCa) and significant PCa (SPCa), and to analyse if CFPB could safely replace SPB. A cohort of 314 consecutive men having PI-RADS ≥2 in a pre-biopsy 3T mp-MRI were prospectively subjected to trans-rectal ultrasound CFPB (two cores per suspicious area until a maximum of three areas) and a 12 peripheral core SPB. SPCa was considered when the WHO grade was higher than 2 (Gleason 4+3 or higher). PCa was diagnosed in 133 patients (42.4%), being 83 (62.4%) SPCa. SPB detected PCa in 114 men (85.7%) while CFPB in 103 (77.4%), P<.001. SPB detected SPCa in 64 men (77.1%) while CFPB in 71 (85.5%), P<.001. In 52 of the 81 men (64.2%) SPCa was detected in SPB and CFPB. In 19 men SPCa was only detected in CFPB (23.5%) while in 10, it was only detected in SPB (12.3%). 33.1 cores were needed to diagnose one PCa in SPB while 8.5 in CFPB, P<.001. 58.9 cores were needed to diagnose one SPCa in SPB, while 12.4 in CFPB, P<.001. CFPB are more effective and also more efficient than SPBs in detecting SPCa. However, CFPBs still can't safely replace SPBs because they are not able to detect up to 15% of SPCa.


An integrative analysis to predict the active compounds and explore polypharmacological mechanisms of Orthosiphon stamineus Benth.
Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.


Determination of Kα,β excitation factors in thin target for selected elements from Y to Te at 59.54 keV excitation energy.
The paper presents the first measurements of the Kα and Kβ excitation factors for some selected elements from Y to Te. To determine the Kα and Kβ excitation factors, the experimental values of K shell X-ray production cross sections and total absorption photoelectric cross sections were used. The measurements were performed using a Si(Li) detector coupled with 2048 multichannel analyzer and an Am-241 annular radioisotope source which is emitted 59.54 keV γ-photons. It is observed that the Kα excitation factors are 5-6 times larger than the Kβ excitation factors. The measured excitation factors were compared only with theoretical calculated ones since there are no other experimental reports for the present elements in the literature. The present experimental values of Kα and Kβ excitation factors are in satisfactory agreement with the theoretical results.


SEPHS1 is dispensable for pluripotency maintenance but indispensable for cardiac differentiation in mouse embryonic stem cells.
Embryonic stem cells (ESCs) are derived from the inner cell mass of developing blastocysts, which have self-renewal ability and have the potential to develop or reconstitute into all embryonic lineages. Selenophosphate synthetase 1 (SEPHS1) is an essential protein in mouse early embryo development. However, the role of SEPHS1 in mouse ESCs remains to be elucidated. In this study, we generated Sephs1 KO ESCs and found that deficiency of SEPSH1 has little effect on pluripotency maintenance and proliferation. Notably, SEPHS1 deficiency impaired differentiation into three germ layers and gastruloid aggregation in vitro. RNA-seq analysis showed SEPHS1 is involved in cardiogenesis, verified by no beating signal in Sephs1 KO embryoid body at d10 and low expression of cardiac-related and contraction markers. Taken together, our results suggest that SPEHS1 is dispensable in ESC self-renewal, but indispensable in subsequent germ layer differentiation especially for functional cardiac lineage.


High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.
Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs). We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD-10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli. Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41-77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ-resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL-producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90-days and history of a multi-drug resistant pathogen were associated with FQ-resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04-3.51, and OR 6.93, 95% CI: 4.95-9.70, respectively). Of the patients who had FQ-resistant E. coli or an ESBL-producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance. FQ-resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments.


[Observations of the surface of the articular cartilage after treatment with hyaluronidase (author's transl)].
1. The articular surfaces of the femoral head of rats have been studied by scanning electron microscopy after in vitro treatment with hyaluronidase. 2. The cartilage surface has been digested mildly by the buffer medium (control). 3. The matrix of the cartilage has selectively been removed by the hyaluronidase. 4. Chondrocytes have been seen on the surface after treatment with hyaluronidase for a longer period. 5. We discuss the result of enzymatic digestion.


Early mitochondrial dysfunction occurs in motor cortex and spinal cord at the onset of disease in the Wobbler mouse.
The Wobbler mouse is recognized as an animal model for motoneuron disease that exhibits motoneuron pathology. We have recently demonstrated the occurrence of mitochondrial dysfunction in the Wobbler mouse brain. The aim of the present study was to evaluate whether mitochondrial dysfunction occurred at an early age at the time where disease symptoms appear, and whether it was more pronounced in the motor cortex or in the spinal cord. We report here a significant decrease in mitochondrial state 3 and 4 respiration rates at an early age in the Wobbler spinal cord. In addition, there was a pronounced decrease in oxidative phosphorylation in mitochondria isolated from both spinal cord and motor cortex in both age groups. This mitochondrial dysfunction was accompanied by impairment of complex I activity in mitochondria isolated from spinal cord at an early age. Decreases in complex III and IV activities were observed only in mitochondria isolated from the motor cortex at an early age, but impairment of complex III activity prevailed until later in the disease. We conclude that mitochondrial dysfunction ensues at an early stage of the disease and is more pronounced in the spinal cord, which correlates with previous studies that reported degeneration of spinal cord motorneurons.


Determination of nutrients in the presence of high chloride concentrations by column-switching ion chromatography.
Determination of inorganic anions in waters of high salinity is one of the most difficult task in analytical chemistry. A simple column-switching method, based on an original chromatographic set-up, for the determination of nutrients (nitrate, nitrite and phosphate) in chloride rich aqueous matrices is presented. A pre-separation system (made of two in line pre-columns, Dionex AG9-HC 4 mm) connected to an analytical column (Dionex AS9-HC 4 mm) by a four way pneumatic valve, allows chloride to be eluted off into the waste and nutrients to be separated and detected by a conductimeter and/or a UV spectrophotometer. Neither chemical pre-treatment nor sample dilution are required; sample matrices presenting a large range of chloride concentrations can be investigated. Moreover by using this technology, automation for routine analysis, low analysis time and low costs can be achieved. LODs of 100, 300, 1000 microg/l for nitrate, nitrite and phosphate, respectively, have been obtained by spiking a synthetic sea water sample containing 20,000 mg/l of chloride and 3000 mg/l of sulphate. Analyte calibration curves of analytes are linear (r>0.99) in the range between the LODs and 60 mg/l. This method was applied to nutrients determination in sea water samples collected near a river outlet.


Studies on the interaction between apolipoprotein A-II-enriched HDL3 and cultured bovine aortic endothelial (BAE) cells.
The specific binding of high-density lipoproteins (HDL) to a number of cell and membrane types has been reported. The aim of this study was to investigate the ligand specificity of HDL binding sites on bovine aortic endothelial (BAE) cells and in particular to investigate the role of apo A-II in the interaction. In order to do this we prepared AII-HDL3 particles by incubating HDL3 with apo HDL. These particles were enriched in apo A-II, contained virtually no apo A-I, and were similar to HDL3 in terms of size and lipid composition. As these particles resemble the native HDL3 structure we believe they are probably a more suitable model for investigation of ligand specificity than artificial recombinants. AII-HDL3 particles were shown to bind to cells with similar affinity and capacity as HDL3. Further experiments indicated that HDL3 and AII-HDL3 competed with each other for binding and displayed similar affinities for a common binding site(s). The results suggest that apo A-II, as well as apo A-I, play an important role in the process of HDL recognition by putative HDL receptors on endothelial cells.


Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients.
The rate of hepatitis B virus transmission via organs from with isolated hepatitis B virus core antibody-positive (HBcAb+) donors in kidney transplant recipients seems very low. Over 4 years, we performed 36 transplants from Ig HBcAb+, hepatitis B surface antigen (HBsAg)-negative donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination (28 patients) and in recipients who were not immunized and received a pretransplant prophylaxis with hepatitis B immunoglobulins. We examined the HBV-related outcomes in these 36 patients in comparison with 40 recipients of allografts from HBcAb- donors. No patient receiving an allograft from an HBcAb+ donor developed clinical HBV infection or HBSAg positivity. The rate of seroconversion was 14.2% in immunized patients, 12.5% in nonimmunized patients, and 0% in the control group. The 17.8% of immunized patients developed elevated transaminases after transplant, in comparison with 25% and 10% in the nonimmunized patients and the control group, respectively. Graft and patient survival was 93% and 93% for immunized patients, 100% and 100% for nonimmunized patients, and 98% and 95% for the control group, respectively. The use of anti-HBc antibody-positive kidneys was associated with no risk of transmission of HBV infection, without affecting graft and patient survival, and could be considered a safe way to expand the donor pool. Our preliminary results suggest that such kidneys could be safely transplanted even in not immunized patients who underwent a prophylaxis with hepatitis B immunoglobulins.


Gorham-Stout disease involving ipsilateral clavicle and scapula in a child - a case report focusing on imaging and histopathological features of this extremely rare condition.
Gorham-Stout disease (GSD) is a very rare entity of unknown etiology, characterized by excessive intra-osseous proliferation of blood or lymphatic vessels, resulting in progressive resorption of bone matrix and destruction of bone. To date we have found only seven published cases concerning fully confirmed GSD of the shoulder girdle bones in children. Our case concerns an 8-year-old boy with involvement of the left clavicle and scapula. The knowledge of imaging and histopathological features is crucial for establishing the diagnosis of GSD, therefore the exchange of experiences in this field is essential for improving the care of affected patients.


Antagonism of thromboxane receptors by diclofenac and lumiracoxib.
Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesic and anti-inflammatory by virtue of inhibition of the cyclooxygenase (COX) reaction that initiates biosynthesis of prostaglandins. Findings in a pulmonary pharmacology project gave rise to the hypothesis that certain members of the NSAID class might also be antagonists of the thromboxane (TP) receptor. Functional responses due to activation of the TP receptor were studied in isolated airway and vascular smooth muscle preparations from guinea pigs and rats as well as in human platelets. Receptor binding and activation of the TP receptor was studied in HEK293 cells. Diclofenac concentration-dependently and selectively inhibited the contraction responses to TP receptor agonists such as prostaglandin D2 and U-46619 in the tested smooth muscle preparations and the aggregation of human platelets. The competitive antagonism of the TP receptor was confirmed by binding studies and at the level of signal transduction. The selective COX-2 inhibitor lumiracoxib shared this activity profile, whereas a number of standard NSAIDs and other selective COX-2 inhibitors did not. Diclofenac and lumiracoxib, in addition to being COX unselective and highly COX-2 selective inhibitors, respectively, displayed a previously unknown pharmacological activity, namely TP receptor antagonism. Development of COX-2 selective inhibitors with dual activity as potent TP antagonists may lead to coxibs with improved cardiovascular safety, as the TP receptor mediates cardiovascular effects of thromboxane A2 and isoprostanes.


Difficulty with surgical site identification: what role does it play in dermatology?
The potential for wrong-site surgery is a growing concern in dermatology. The purpose of this study was to determine the incidence of difficulty with surgical site identification and possible confounding factors. This was a prospective study on 333 Mohs cases performed between April 1, 2009, and February 9, 2010. Data collection forms were used on the day of surgery to record the difficulty associated with surgical site identification and potential confounding factors. Of the 333 patients evaluated, 9% were unable to identify their surgical sites. The majority of cases (88.5%) were located on the head and neck. When comparing patients who were able to identify their site and those who were not, there was a statistically significant difference (P = .035) in the percentage of lesions residing in a location visible to the patient. Those who were able to see their biopsy sites were 3.5 times more likely to identify their surgical site. Of the 47.6% of patients with chart notes, only 5% of these cases were photographs and 23% had high-quality diagrams. Although a delay in treatment of greater than 3 months from the original biopsy site was higher among those with difficulty in identifying their surgical site, this was not found to be statistically significant. We believe our sample size was not large enough to show a significant link between difficulty with surgical site identification and several likely confounding factors. We have shown that at least 9% of patients presenting for Mohs micrographic surgery are unable to confidently identify their surgical sites.


How a functional soil animal-earthworm affect arbuscular mycorrhizae-assisted phytoremediation in metals contaminated soil?
Phytoremediation is a promising and sustainable technology to remediate the risk of heavy metals (HMs) contaminated soils, however, this way is limited to some factors contributing to slow plant growth and low remediation efficiency. As soil beneficial microbe, arbuscular mycorrhizal fungi (AMF) assisted phytoremediation is an environment-friendly and high-efficiency bioremediation technology. However, AMF-symbiotic formation and their functional expression responsible for HMs-polluted remediation are significantly influenced by edaphic fauna. Earthworms as common soil fauna, may have various effects on formation of AMF symbiosis, and exhibit synergy with AMF for the combined remediation of HMs-contaminated soils. For now, AMF-assisted phytoremediation incorporating earthworm coexistence is scarcely reported. Therefore, the main focus of this review is to discuss the AMF effects under earthworm coexistence. Effects of AMF-symbiotic formation influenced by earthworms are fully reviewed. Moreover, underlying mechanisms and synergy of the two in HMs remediation, soil improvement, and plant growth were comprehensively elucidated. Phenomenon of "functional synergism" between earthworms and AMF may be a significant mechanism for HMs phytoremediation. Finally, this review analyses shortcomings and prescriptions in the practical application of the technology and provides new insights into AMF- earthworms synergistic remediation of HMs-contaminated soils.


Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease.
Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.


Fertilization of human oocytes in relation to varying delay before insemination.
Fertilization and pregnancy rates in an in vitro fertilization and embryo transfer program were studied after a range of insemination times of between 1 and 26 hours after oocyte recovery. There was no significant variation in fertilization rate across this range. The pregnancy rate showed no significant variation for insemination between 3 and 16 hours after aspiration. However, it was disappointing at 2 hours (3%), and no pregnancies were achieved from the nine patients whose ova were inseminated 20 or more hours after aspiration. It is concluded that mature oocytes can be inseminated in vitro at any time between 3 and 16 hours after aspiration and still retain the same potential to produce a pregnancy.


Messenger RNA for the Ad2 DNA binding protein: DNA sequences encoding the first leader and heterogenity at the mRNA 5' end.
During the early stage of Ad2 infection of human cells, RNA is transcribed from five separate transcription units. Early region II encodes the mRNA for a 72K single-stranded DNA binding protein (DBP) which functions in DNA replication. This report describes the structure of the first leader of the DBP mRNA and the flanking sequences in the DNA. The leader, labeled in vivo with 32P, was isolated by DNA filter hybridization to the viral restriction fragment Eco RI F, and its RNAase T1 and RNAase A oligonucleotides were analyzed by RNA fingerprinting techniques. Comparison of this RNA sequence information with the DNA sequence of Eco RI F has located a 68 nucleotide region of the Hae III C subfragment at coordinate 75.1 that encodes the leader. This position is near the coordinate to which nascent chain analysis and ultraviolet transcription mapping have mapped an RNA initiation site, or promoter, for the DBP mRNA. The DNA sequence that overlaps the leader on the 3' side contains a donor sequence for splicing this leader to a second downstream leader. The splicing sequence shows a seven base homology with the comparable structure of the Ad2 major late leader, and a mouse globin mRNA splicing sequence. The DNA sequence upstream from the cap, the region oof the potential promoter site does not, however, contain a "TA-TAAA"-type homology of the sort noted by D. Hogness, M. Goldberg and R. Lifton (personal communication) for many cellular transcription units, and by other investigations for the Ad2 major late transcription unit. Also, the leader is found with two distinct capped 5' termini, 7meGpppA and 7meGpppG, which are encoded at adjacent positions in the DNA and thus are from mRNAs which are staggered by one nucleotide in length at the 5' end. The staggering at the 5' terminus and the lack of the upstream homolgy distinguish the DBP mRNA from many viral and cellular messenger. In both these respects, however, the DBP mRNA resembles the late messengers of SV40 and polyoma viruses. In this paper, we discuss the implications of these findings for the mechanism of specifying mRNA 5' ends.


DNA damage repair gene germline profiling for metastatic prostate cancer patients of different ancestries.
Germline and somatic mutations in DNA damage repair genes (DDRg) are now recognized as new biomarkers for the management of metastatic prostate cancers (mPC). We evaluate the frequency of germline DDRg mutations among French mPC patients of European and African ancestries. Targeted next-generation sequencing of 21 DDRg was performed on germline DNA from 557 mPC patients, including 15.1% of cases with an African origin. Forty-seven germline mutations in 11 DDR genes were identified in 46 patients of the total cohort (8.3%). BRCA2 (4.1%) and ATM (2.0%) were the most frequently mutated genes. There was no difference in DDRg mutation frequency between mPC patients of European ancestry and those of African origin. Germline mutations of BRCA2 were associated with a positive family history of breast cancer (p = 0.02). The mean age at metastatic stage (59.7 vs. 67.0; p = 0.0003) and the mean age at death (65.2 vs. 73.9; p = 0.0003) were significantly earlier for carriers of BRCA2 mutation than for non-carriers. Moreover, the Cox model showed that BRCA2 positive status was statistically associated with poorer survival (hazard ratio: 0.29; 95% confidence interval 0.18-0.48; p < 0.0001). We showed that, in France, BRCA2 and ATM are the main predisposing DDR genes in mPC patients, with a particular aggressiveness for BRCA2 leading to early metastatic stage and death.


A review of the clinical presentation and laboratory findings in two uncommon hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency.
Two hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate-cysteine disulfideuria and sulfite oxidase deficiency, were described twenty years ago. Other examples of these disorders have been limited to about 5 of each in the world literature since then. Reasons for the apparent rarity of these conditions are discussed and the analytical procedures to identify them are reviewed. The detection of the first depends on the positive result of a cyanide-nitroprusside test followed by positive identification of the specific mixed disulfide. The enzyme mercaptopyruvate sulfur transferase has been shown to be deficient. In the second disorder of sulfite oxidase deficiency, the clinical presentation with progressive dystonia and dislocated lenses in an infant should suggest further laboratory investigations for this disorder which would not be detected by conventional laboratory screening procedures. Laboratory diagnosis can be obtained by use of the Merckoquant sulfite test on a fresh urine sample. Quantitative thiosulfate and taurine measurements can also be made. Positive identification of the specific amino acid S-sulfo-L-cysteine should also be made. The enzyme sulfite oxidase is missing from such organs as liver, kidney and brain. This latter condition may also be associated with xanthinuria. For this combined disorder of sulfite oxidase and xanthine oxidase, a deficiency of a molybdenum-containing cofactor has been demonstrated.


Increases in cholinergic neurotransmission measured by using choline-sensitive microelectrodes: enhanced detection by hydrolysis of acetylcholine on recording sites?
Previous experiments demonstrated that second-based transient increases in choline concentrations measured by electrodes coated with choline oxidase (ChOx) and the amperometric detection of hydrogen peroxide validly indicate the depolarization-dependent release of acetylcholine (ACh) and its hydrolysis by endogenous acetylcholinesterase (AChE). Therefore, choline-sensitive microelectrodes have become valuable tools in neuropharmacological and behavioral research. The present experiments were designed to test the possibility that co-immobilization of ChOx plus AChE on recording sites increases the level of detection for evoked ACh release in the brain. If newly released ACh is not completely hydrolyzed by endogenous AChE and capable of reaching the extracellular space, currents recorded via sites equipped with both enzymes should be greater when compared with sites coated with ChOx only. Pairs of platinum-recording sites were coated either with AChE plus ChOx or ChOx alone. Potassium or nicotine-evoked currents were recorded throughout the entire dorsal-ventral extent of the medial prefrontal cortex (mPFC). The amplitudes of evoked cholinergic signals did not differ significantly between AChE+ChOx and ChOx-only coated recording sites. Additional experiments controlling for several potential confounds suggested that, in vivo, ACh levels > or =150fmol were detected by recordings sites featuring dual enzyme coating. Collectively, these results indicate that co-coating of microelectrodes with AChE does not enhance the detection of cholinergic activity in the cortex compared with measurements via recording sites coated only with ChOx.


Pyocystis in patients on chronic dialysis. A potentially misdiagnosed syndrome.
Pyocystis is an important complication of non-functioning urinary bladder, which often poses diagnostic difficulties. We present a case of pyocystis in a patient on chronic hemodialysis who was anuric for one year. The patient was initially diagnosed with diverticulitis. An abdominal C-T scan suggested the diagnosis of pyocystis, which was confirmed by bladder catheterization. The patient was treated with bladder drainage and a prolonged antibiotic course, followed by intermittent saline washing of the bladder.


Death after acute myocardial infarction: interrelation between left ventricular dysfunction, arrhythmias and ischemia.
Patients who survive an acute myocardial infarction face an increased risk of sudden death for approximately 6 months after hospital discharge; their prognosis is determined by the severity of their coronary arteriosclerosis and the degree of left ventricular dysfunction. Frequent ventricular premature complexes and evidence of ischemia either spontaneously or on treadmill are also markers for early morbidity and mortality in patients who are discharged from the hospital after acute myocardial infarction. The degree of left ventricular dysfunction is the strongest predictor of mortality; patients who have both left ventricular dysfunction, frequent premature ventricular beats and evidence of ischemia are at the highest risk of mortality after hospital discharge. It appears likely that all 3 of these risk factors interact and that therapy to reduce morbidity and mortality after myocardial infarction should aim at the amelioration of each of these risk factors. A model for the interaction of these risk factors is proposed and an approach to treatment for patients at high risk of mortality after hospital discharge after myocardial infarction is suggested.


Tissue-localizing properties of some photosensitizers studied by in vivo fluorescence imaging.
Using fluorescence imaging, the tissue-localizing properties of five photosensitizers were studied in vivo in tumours in 'sandwich' observation chambers and in tumours growing on thigh muscle. The preliminary results indicate that of the three photodynamically active dyes tested (haematoporphyrin derivative, Photofrin II and aluminium phthalocyanine tetrasulphonate), the phthalocyanine possesses the best tumour-localizing properties. This makes it possible to combine tumour fluorescence detection and photodynamic therapy with reduced skin photosensitivity. The two photodynamically inactive dyes tested (uroporphyrin I and acridine red) may be useful for application in fluorescence imaging to localize superficial tumours without inducing skin photosensitivity. In particular, acridine red has remarkable tumour-localizing properties, but is rather toxic.


Synthesis of benzocycloalkane derivatives as new conformationally restricted ligands for melatonin receptors.
Benzocycloalkane derivatives 1-4 were synthesized as new conformationally restricted melatoninergic ligands. They were prepared by the reaction of the ketones 5 with diethylcyanophosphonate and the reduction of the corresponding cyano compounds or by the Wittig reaction and Curtius degradation to obtain the amines 8. The 1-Cyanobenzocyclobutane derivative was obtained by the benzyne cyclisation reaction. The amines 8 were acylated with acetyl, propionyl or butyryl groups. The affinity of the compounds for chicken brain melatonin receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. The indanyl (2b,c), tetralin (3a-c) and benzocycloheptane (4c) derivatives were potent compounds with nanomolar affinity and an important enantioselectivity of the receptor was observed with the (+) enantiomers 2b and 3b.


Sepsis: time has come to focus on the later stages.
Despite numerous advances in intensive care medicine, sepsis remains a deadly disease. Today, conventional therapeutic approaches and mainstream scientific research mostly focus on symptomatic early goal directed organ support therapy. This includes fluid resuscitation, choice and timing of antibiotics and vasopressors, mechanical ventilation, and renal replacement strategies. Furthermore, great effort has been undertaken to investigate whether tightly controlled blood glucose levels, the application of corticosteroids, and early medication using activated protein C improves survival. However, most of these mainstream approaches have recently been shown unsuccessful in large-scale clinical trials. Current data now suggest that besides giving fluids, antibiotics, and symptomatic organ support, little - if at all - can be done to improve mortality from sepsis. This might be due to the fact that in the presence of modern intensive care medicine, most patients with severe sepsis or septic shock will survive the early "shock phase" of the disease. Mounting evidence suggests that in the course of the disease, most septic patients are then subjected to a secondary phase, which is characterised by a failure of cell-mediated immunity. This leads to repeated and uncontrolled infections, "chronic" multiple organ failure, and death in a large number of cases. Here we hypotheses that in order to profoundly influence survival from sepsis, future therapeutic efforts in the field should concentrate on this later "hypo-immune" stage of sepsis, associated immune phenomena, and novel immunomodulatory strategies. This may lead to the development of advanced immunomodulatory therapies available for widespread clinical use. Today, in the era of antibiotics and advanced organ system support therapy, it is not the bug that kills you- survival has become a matter of whether your cellular immune system can cope.


Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study.
Activity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort. Patients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy. Seventeen patients completed the program with average participation duration of 21.3 weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1 N to 21.2 N over 20 weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline. A weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI.


Peptide Cyclization by the Use of Acylammonium Species.
Although cyclic peptides have become increasingly important as drugs, the most conventional peptide cyclization method using moderately active coupling agents suffers from a lot of waste and high cost as well as long reaction times and burdensome purification. Herein, we report an unconventional approach to peptide cyclization that uses acylammonium species generated from inexpensive and less wasteful Me2 NBn and ClCO2 i-Pr. Using this approach, we observed the desired rapid activation of the C-terminus of cyclization precursors by an acylammonium ion for rapid and epimerization/dimerization-free cyclization of synthetically challenging peptides, including a difficult cyclization involving N-methyl amide bond formation. The ease of purification, productivities, and reaction mass efficiencies of our approach were significantly superior to those in previous reports. We synthesized a previously reported versicotide D analogue, and our data indicated that its assigned stereostructure should be revised.


[Glycerinized models of enterocytes and several of their properties].
The method for the preparation of glycerol-treated models of the enterocytes with preserved membrane has been described. Using such a simplified model of the enterocyte suspension allows membrane digestion and enzyme properties to be studied. Moreover, preserving the important properties of the native isolated cells the glycerol-treated enterocytes have a number of essential advantages as compared with other known preparations of the small intestinal mucosa. Some characteristics of the glycerol-treated models of the enterocytes have been described in the paper.


Effect of naproxen, a non-selective cyclo-oxygenase inhibitor, on pentylenetetrazol-induced kindling in mice.
1. Epilepsy is one of the major neurological disorders of the brain, affecting approximately 0.5-1.0% of the population worldwide. Various neurotransmitter abnormalities, especially of GABA and glutamate, have been reported to play a key role in the pathophysiology of epilepsy. 2. Cyclo-oxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins and, as such, is a key target for many anti-inflammatory drugs. Cyclo-oxygenase has been reported to play a significant role in neurodegeneration. Recent studies have reported that COX plays a significant role in the pathophysiology of epilepsy. 3. The aim of the present study was to explore the possible role of COX and the effect of COX inhibitors in epilepsy. 4. Kindling is a chronic model of epilepsy. In the present study, kindling was induced in mice by chronic administration of a subconvulsive dose of pentylenetetrazole (PTZ; 40 mg/kg) on every other day for a period of 15 days. Naproxen was administered daily 45 min before PTZ or vehicle. The kindling score was recorded after PTZ administration. Seizure severity was measured according to a prevalidated scoring scale. Biochemical estimations were performed immediately after recording behavioural parameters on the 16th day of PTZ treatment. 5. Chronic treatment with PTZ significantly induced kindling in mice. Pretreatment with the non-selective COX inhibitor naproxen (7 and 14 mg/kg, i.p.) showed significant protection against PTZ-induced kindling in mice. Biochemical analysis revealed that chronic treatment with PTZ significantly increased lipid peroxidation and nitrite levels (NO levels), but decreased reduced glutathione (GSH) levels in brain homogenates. 6. In conclusion, the results of the present study strongly suggest that COX plays an important role in the pathophysiology of PTZ-induced kindling in mice and that COX inhibitors could be a useful neuroprotective strategy for the treatment of epilepsy.


A "turn-on" fluorescent chemosensor for zinc ion with facile synthesis and application in live cell imaging.
Compound 1 was facilely synthesized through a one step reaction from commercially available materials. As a sensitive and selective "turn-on" fluorescent chemosensor for Zn(II), 1 exhibits a 40-fold fluorescence enhancement response to Zn(II) over other physiological relevant metal ions in aqueous solution at neutral pH. Furthermore, 1 could be efficiently delivered to live cells for bioimaging of Zn(II).


Experimental infection by Chlamydia pneumoniae in the hamster.
We report that intraperitoneal injection of Chlamydia pneumoniae purified elementary bodies (EBs) in the hamster causes a systemic infection allowing the isolation of viable chlamydiae from several organs for several days post-infection (p.i.). In particular, spleen infection occurred up to Day 7 p.i. in 100% of animals. Systemic infection probably occurs via macrophages as intraperitoneally injected chlamydiae which are taken up by the hamster macrophages remain viable and can infect in vitro cell cultures. Immunization of 18 hamsters with heat-inactivated purified EBs, completely protected the spleens of 16 animals and substantially reduced infection levels in the remaining two. This model, therefore, provides a robust screening tool for the assessment of the protective activity of potential vaccine candidates. In a pilot study on five recombinant antigens recently described as EB surface proteins, three gave results undistinguishable from non-immunized, or mock-immunized controls; however two antigens, derived, respectively, from the product of the lcrE gene (a component of the putative TTSS of C. pneumoniae) and the product of Cpn0498 open reading frame, proved to be capable of inducing protective immune responses.


Selective photocleavage of single-stranded nucleic acids by cyclobisintercaland molecules.
Irradiation of mixtures of a single-stranded circular plasmid and of a double-stranded supercoiled DNA in presence of the cyclobisintercaland compounds 2 or 3 shows that these reagents effect the selective photocleavage of the single-stranded entity. Furthermore, 2 also cleaves tRNAasp preferentially at single-stranded domains.


How does garlic exert its hypocholesterolaemic action? The tellurium hypothesis.
The efficacy of garlic as a lipid-lowering agent is being increasingly recognized, but the biochemical mechanisms underlying this action are currently unknown. It is proposed that organic tellurium compounds, which are found in high concentration in fresh garlic buds, may contribute to this action by inhibiting squalene epoxidase, the penultimate enzyme in the synthetic pathway of cholesterol. Weanling rats fed a diet rich in tellurium develop a demyelinating polyneuropathy due to inhibition of this enzyme in peripheral nerves. Chronic exposure to small amounts of tellurium found in garlic might reduce endogenous cholesterol production through inhibition of hepatic squalene epoxidase and so reduce cholesterol levels. Tellurium may also contribute to the characteristic odour of garlic since the most obvious clinical sign of tellurium poisoning is a garlic-like odour.


DYT1 mutation in a cohort of Taiwanese primary dystonias.
To investigate the DYT1 gene mutation in Chinese ethnic, we examined a series of 200 patients with primary dystonias (11 familial and 189 sporadic), 53 of their asymptomatic relatives, 97 patients with familial or early-onset parkinsonism, and 200 healthy subjects. The GAG deletion at codon 946 was only found in three sporadic dystonia patients and seven of their asymptomatic familial members. The frequency of GAG deletion was 1.5% in dystonia patients, and was 6.7% in early-onset dystonias (< or = 26 years). We conclude that DYT1 mutation is a minor cause of primary dystonias in a cohort of Taiwanese population.


Neuroimaging in the brain in HIV-1-infected patients.
The brain may be affected by a variety of abnormalities in association with HIV infection. Knowledge of these abnormalities and their characteristic imaging features is important to neuroradiologists for the detection, diagnosis, and initiation of appropriate treatment. This review attempts to describe the imaging findings associated with brain disorders in HIV-seropositive patients and the rationales for integrating neuroradiologic techniques.


Analysis of Urine Drug Test Results From Substance Use Disorder Treatment Practices and Overdose Mortality Rates, 2013-2020.
Drug overdose deaths in the US are currently the highest ever recorded; data collected from public health surveillance sources can help to identify emerging drug use patterns associated with overdose mortality rates, but the time lag in results often limits utility. Urine drug testing (UDT) is one potentially underused source that could augment surveillance efforts through timely data collection. To evaluate the correlation between real-time UDT results from a proprietary national database and overdose mortality data from the National Vital Statistics System. This retrospective cross-sectional study included 500 000 urine specimens submitted for UDT by substance use disorder (SUD) treatment health care practices and collected between January 1, 2013, and December 31, 2020. Real-time UDT data were obtained from the Millennium Health proprietary national database, and overdose mortality data were obtained from the National Vital Statistics System of the Centers for Disease Control and Prevention (CDC WONDER). Specimens were analyzed for specific drugs in 5 categories (cocaine, heroin, methamphetamine, synthetic opioids, and other opioids) using liquid chromatography-tandem mass spectrometry. Participants were adults aged 18 years and older who provided urine specimens at SUD treatment practices. Urine drug testing. The primary outcome was the correlation between UDT positivity rates and overdose mortality rates at national, state, and county levels. Univariate and multivariate regression models were also used to evaluate the association between state- and county-level overdose mortality and standardized UDT positivity rates. Among 500 000 unique patient specimens collected from SUD treatment practices between 2013 and 2020, 288 534 specimens (57.7%) were from men, and the median age of the study population was 34 years (IQR, 17-51 years). On a national level, synthetic opioids and methamphetamine were highly correlated with overdose mortality (Spearman ρ = 0.96 for both). When synthetic opioids were coinvolved, methamphetamine (ρ = 0.98), heroin (ρ = 0.78), cocaine (ρ = 0.94), and other opioids (ρ = 0.83) were also highly correlated with overdose mortality. In the absence of synthetic opioids, all drug categories were highly correlated (ρ = 0.75 for other opioids, 0.81 for heroin, and 0.88 for methamphetamine), with the exception of cocaine (ρ = -0.37). Synthetic opioids (ρ = 0.77) and methamphetamine (ρ = 0.80) had the strongest state-level correlations over time, whereas other opioids had the lowest correlation for both total positivity (ρ = 0.31) and positivity in the absence of synthetic opioids (ρ = 0.23). In Ohio, county-level correlation was strongest for synthetic opioids (ρ = 0.71), followed by heroin (ρ = 0.69) and methamphetamine (ρ = 0.67). At the state level, the multivariate incidence rate ratio (IRR) for synthetic opioids was 1.16 (95% CI, 1.14-1.19; P < .001), and at the county level, the IRR was 1.13 (95% CI, 1.09-1.17; P < .001), suggesting that for every 1-SD increase in the UDT positivity rate, there were 16.2% and 12.8% increases, respectively, in monthly overdose deaths. Both methamphetamine (11.7% increase per 1-SD increase in UDT positivity rate; IRR, 1.12; 95% CI, 1.09-1.14; P < .001) and cocaine (5.1% increase per 1-SD increase in UDT positivity rate; IRR, 1.05; 95% CI, 1.03-1.07; P < .001) also had significant positive associations with mortality rates, but the effect sizes were smaller than that of synthetic opioids (IRR, 1.16). In this study, UDT results were highly correlated with mortality rates at national, state, and county levels. These findings suggest that real-time UDT surveillance can help to quickly identify changes in drug use patterns that might inform targeted harm reduction strategies designed to prevent overdose deaths.


Bioavailability of cadmium from crab hepatopancreas and mushroom in relation to inorganic cadmium: a 9-week feeding study in mice.
The bioavailability of Cd from boiled crab hepatopancreas and dried mushroom was studied in relation to that of inorganic Cd (CdCl2). Female Balb/c mice were fed with diets containing 0.4 ppm Cd from either boiled crab (Cancer pagurus) hepatopancreas or dried mushroom (Agaricus augustus), or as inorganic Cd (CdCl2). A control group received low Cd (< 0.007 ppm) feed, and did not accumulate detectable levels of Cd during 9 wk of exposure. Using Cd accumulation in the liver and kidney as a measure of Cd absorption, it was indicated that the bioavailability of Cd from boiled crab hepatopancreas is slightly lower than that of Cd from mushroom and inorganic Cd. Fractionation of Cd in boiled crab hepatopancreas and mushroom indicated that Cd in crab hepatopancreas mainly is associated with denaturated proteins with low solubility, whereas a large fraction of Cd in dried mushroom is associated with soluble ligands. This difference in speciation of Cd may be a reason for the lower bioavailability of crab Cd than that of mushroom Cd. The difference in bioavailability is, however, low and as a safety measure it is recommended that human consumption of both crab hepatopancreas and wild mushrooms with high Cd levels should be restricted.


The value of reflective journaling in undergraduate nursing education: a literature review.
The purpose of this literature review was to ascertain the evidence for the use of reflective journaling as a tool to promote the pedagogical strategy of reflection for the purpose of learning from practice for practice in undergraduate nursing education. Concept-centric. The literature review involved structured searches of all OVID gateway databases, EBSCO host databases, and Blackwell Synergy. Qualitative and Quantitative Studies from 1992 to 2006 were included if they focused on reflective journaling in undergraduate clinical education. Due to the vast plethora of literature on reflection, keywords were utilized to focus the search. Approximately 150 abstracts were reviewed for primary sources of research. A total of nine studies met the inclusion criteria. The review subsequently divided the literature into four content themes allowing for appraisal and analysis of the findings, followed by summary and key recommendations for nursing education and research. There was evidence that educators struggle to incorporate reflective processes into education; however, the research provided rationale and support for engaging undergraduate students in the reflective process. Researchers found reasonable levels of reflection in undergraduate students' journaling and educators reported students' learning as a result of reflective journaling. Further to this, there was evidence that writing reflectively improved over time; a learned skill also dependent on a good facilitator and trust. Unfortunately, there was a paucity of research that explored the undergraduate nurses' experiences with the process of having to create written communication, with a critical reflective focus on practice. Nursing educators are correct in pursuing the teaching and learning of the reflective process in undergraduate nursing education. Nurse educators need to utilize various tools and strategies for facilitating the growth of undergraduate students into reflective practitioners. Indeed there was only limited evidence to support reflective journaling as an appropriate tool to promote reflection for the purpose of learning from practice for practice in undergraduate nursing education. Research that provides insight into the undergraduate student experience and perceptions of reflective journaling is needed to facilitate the structuring and use of reflective journaling as a tool in undergraduate nursing education.


Characterization of Triton X 100 extracted colipase from porcine pancreas.
Colipase was isolated from porcine pancreas homogenate prepared in the presence of detergent (Triton X 100). After precipitation by ammonium sulfate and ethanol, the cofactor was purified by chromatography on SP-Sephadex in the presence of Triton X 100 and on DEAE-cellulose in the absence of detergent. Two molecular forms of porcine colipase were obtained. They represent 80 per cent (colipase A) and 20 per cent (colipase B), respectively, of the total colipase. Valine is the N-terminal residue of both proteins. Their aminoacid composition is similar to that found by Borgstrom for the two forms of porcine colipase. Determination of the sequence of the first sixteen residues at the N-terminal end of colipase A indicates that the cofactor undergoes no proteolytic degradation in this region of the molecule when extraction is carried out in the presence of detergent. The recovery of colipase is about 30 per cent.


Co-occurrence of psychiatric disorders in child psychiatric patients and nonpatients: a circumplex model.
This study of 106 preadolescent psychiatric inpatients, 101 preadolescent psychiatric outpatients, and 101 preadolescent nonpatients examined the prevalence of psychiatric disorders and co-occurrence of psychiatric diagnoses. The inpatients and outpatients had significantly more co-occurring diagnoses than the nonpatients. For a given diagnosis there are varying frequencies of co-occurring disorders. The similar structure and prevalence among co-occurring diagnoses in this sample of children fit a circumplex model in which variation among disorders appears to be continuous in the form of a closed circle.


Dynamics of absolute and relative disparity processing in human visual cortex.
Cortical processing of binocular disparity is believed to begin in V1 where cells are sensitive to absolute disparity, followed by the extraction of relative disparity in higher visual areas. While much is known about the cortical distribution and spatial tuning of disparity-selective neurons, the relationship between their spatial and temporal properties is less well understood. Here, we use steady-state Visual Evoked Potentials and dynamic random dot stereograms to characterize the temporal dynamics of spatial mechanisms in human visual cortex that are primarily sensitive to either absolute or relative disparity. Stereograms alternated between disparate and non-disparate states at 2 Hz. By varying the disparity-defined spatial frequency content of the stereograms from a planar surface to corrugated ones, we biased responses towards absolute vs. relative disparities. Reliable Components Analysis was used to derive two dominant sources from the 128 channel EEG records. The first component (RC1) was maximal over the occipital pole. In RC1, first harmonic responses were sustained, tuned for corrugation frequency, and sensitive to the presence of disparity references, consistent with prior psychophysical sensitivity measurements. By contrast, the second harmonic, associated with transient processing, was not spatially tuned and was indifferent to references, consistent with it being generated by an absolute disparity mechanism. Thus, our results reveal a duplex coding strategy in the disparity domain, where relative disparities are computed via sustained mechanisms and absolute disparities are computed via transient mechanisms.


The ability of UK offshore workers of different body size and shape to egress through a restricted window space.
404 male offshore workers aged 41.4 ± 10.7 y underwent 3D body scanning and an egress task simulating the smallest helicopter window emergency exit size. The 198 who failed were older (P < 0.01), taller (P < 0.05) and heavier (P < 0.0001) than the 206 who passed. Using all extracted dimensions from the scans, binary logistic regression identified a model (refined using backward elimination) which predicted egress outcome with 75.2% accuracy. Using only weight, bideltoid breadth and maximum chest depth, the model achieved ∼70% accuracy. When anatomical dimensions categorise individuals for small window egress, 25% or more will be misclassified, with false positives (those predicted to fail, but pass) slightly outnumbering false negatives (those predicted to pass, but fail), highlighting the limitations of a predictive approach which treats the body as a rigid object. Differences in flexibility and technique may explain these observations, which may be important considerations for future research.


The differences in metabolites, starch structure, and physicochemical properties of rice were related to the decrease in taste quality under high nitrogen fertilizer application.
Nitrogen fertilizer application is one of the key cultivation practices to improve rice yields. However, the application of high nitrogen fertilizers often leads to a reduction in the stickiness of the rice after cooking, thus reducing the taste quality of rice. Moreover, there are differences in taste quality among rice varieties, and the mechanism has not been studied in depth. In this study, two rice varieties (Meixiangzhan2hao and Exiang2hao) were planted under two nitrogen fertilizer levels. The physicochemical properties and taste quality of the rice were determined after maturity. Our results showed that high nitrogen fertilizer level alters tryptophan metabolism in rice, increasing most amino acid content and protein content in rice. The high content of protein and the higher short-range ordered structure of starch inhibited the gelatinization characteristics of starch and reduced the taste quality of rice. Under high nitrogen fertilizer application, Exiang2hao showed smaller increases in protein content, lower level of amylose and relative crystallinity, and higher content of lipid metabolites. These differences in chemical substances resulted in a less pronounced reduction in the taste quality of Exiang2hao. In this study, the taste quality of different rice varieties under different levels of nitrogen fertilizer application was analyzed, providing new ideas for future improvement of rice taste quality.


Performance of electrical resistance measurements adjunct to visual inspection in the early diagnosis of occlusal caries.
The detection of small carious lesions at occlusal surfaces is a difficult task, particularly in low caries prevalence populations and individuals. The aim of this study was to evaluate the performance of electrical resistance measurements (ERM) in diagnosing small dentinal lesions at one site per occlusal surface in low caries prevalence populations when used adjunct to visual inspection, and to compare the performance of ERM to that of radiographic examination. The occlusal surfaces of 81 third permanent molar teeth extracted from young adolescents were diagnosed by four examiners, who measured the electrical resistance of enamel on a one measurement per surface basis, and furthermore assessed the occlusal surfaces visually and radiographically. The teeth were sectioned for validation by histological examination. The ERM had the highest sensitivity (0.67), and visual inspection had the highest specificity (0.89). ROC analysis showed no statistically significant differences between the performance of the observers when using visual inspection and ERM (z-score test; P > 0.05). One examiner performed statistically significantly better by measuring the electrical resistance of enamel than by radiographic examination (P < 0.05). The average sensitivity and specificity of the three diagnostic systems were used to express the positive and negative predictive values as a function of caries prevalence. At a caries prevalence of 0.2 the negative predictive values for visual inspection, ERM and radiographic examination were 0.88, 0.91 and 0.89, and the positive predictive values were 0.53, 0.48 and 0.42 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


The cellular effects of estrogens on neuroendocrine tissues.
Estrogen action on sensitive neurons in the rat diencephalon has been studied by morphologic techniques; evidence of estrogen action at every level is presented, including tracts, cells, circuitry and subcellular organelles. The demonstration in the arcuate nucleus of estrogen-induced synaptic remodelling, estrogen-induced postsynaptic membrane phenotypes, changes in intracellular membranes and rapid estrogen actions on neuronal endo-exocytosis indicates that cellular estrogen actions may underlie the neuronal control of reproduction.


[Selection by means of KB cells of substances and extracts potentially active in cancer chemotherapy].
Several synthetic, semi-synthetic and natural compounds as well as plant extracts were screened for their growth inhibition activity on KB cells. The most active ones were naphthoquinones and derivatives of pyrido [4,3-b]carbazole alkaloids, with inhibition dose (ID50) less than 4 micrograms/ml. Of the crude extracts of several plants screened, Vellozia caput-ardeae showed to be the most active.


Solar-driven chemical energy source for a Martian biota.
Microorganisms deep in the Martian soil could derive energy indirectly from the sun via chemical reactions involving atmospheric products of the solar ultraviolet flux. The Viking discovery of a chemically uniform regolith which, though poor in organics, is rich in sulfur-containing compounds suggests reaction sequences in which sulfur is recycled through reduced and oxidized states by biologically catalyzed reactions with photochemically-produced atmospheric constituents. One candidate reaction, reduction of soil ssufate minerals by molecular hydrogen, is already exploited on earth by bacteria of the ubiquitous and tenacious Desulfovibrio genus.


Enhancing the effectiveness of Alkaline Phosphatase and bone matrix proteins by tunable metal-organic composite for accelerated mineralization.
The irregular expression of bone matrix proteins occurring during the mineralization of bone regeneration results in various deformities which poses a major concern of orthopedic reconstruction. The limitations of the existing reconstruction practice paved a way for the development of a metal-organic composite [TQ-Sr-Fe] with Metal ions strontium [Sr] and iron [Fe] and a biomolecule Thymoquinone [TQ] in an attempt to enhance the bone mineralization due to their positive significance in osteoblast differentiation, proliferation and maturation. TQ-Sr-Fe was synthesized by in-situ coprecipitation and subjected to various characterization to determine their nature, compatibility and osteogenic efficiency. The crystallographic and electron microscopy analysis reveals sheet like structure of the composite. The negative cytotoxicity of TQ-Sr-Fe in the MG 63 cell line signified their biocompatibility. Cell adhesion and proliferation rate affirmed osteoconductive and osteoinductive nature of the composites and it was further supported by the gene expression of osteoblastic differentiation. The sequential expression of bone matrix proteins such as OCN, SPARC, COL 1, and Alkaline Phosphatase elevate the calcium deposition of MG-63 osteoblast like cells and initiates mineralization compared to control. Thus, the metal-organic composite TQ-Sr-Fe would make a suitable composite for accelerating mineralization process which would leads to faster bone regeneration.


Dacryodes edulis enhances antioxidant activities, suppresses DNA fragmentation in oxidative pancreatic and hepatic injuries; and inhibits carbohydrate digestive enzymes linked to type 2 diabetes.
The leaves of Dacryodes edulis were investigated for their anti-oxidative and anti-diabetic potentials in vitro. Extracts from sequential extraction with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and aqueous) of the leaves were subjected to in vitro antioxidant assays using the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols respectively. Their inhibitory effects were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phospatase activities. Their antioxidant and anti-apoptotic effects on Fe2+ - induced oxidative injuries in pancreatic and hepatic tissues were also investigated ex vivo. The ethanol extract was subjected to Gas chromatography mass spectroscopy (GC-MS) and Fourier transform infrared (FTIR) spectroscopic analysis to identify its bioactive chemical constituents. The extracts showed potent free radical scavenging activity and significantly (p<0.05) inhibited all studied enzymes, with the ethanol extract showing greater activities. Superoxide Dismutase (SOD) and Catalase (CAT) activities were significantly (p<0.05) increased in both pancreatic and hepatic tissues with concomitant elevation of reduced glutathione (GSH) levels as well as reduced levels of malondialdehyde (MDA). The extracts significantly inhibited DNA fragmentation. These activities were dose - dependent. Amongst compounds identified, only Kaur-15-ene, Urs-12-ene-3-ol acetate and 2,3,23-trihydroxyolean-12-en-28-oic acid methyl ester showed strong binding affinities when docked with α-glucosidase (PDB ID:3TON). These results indicate the anti-oxidative, anti-diabetic and anti-obesogenic potentials of D. edulis leaves, which gives credence to its antidiabetic folkloric claims.


Timing, positioning, and sequential staging in esthetic implant therapy: a four-dimensional perspective.
Many articles address the predictability of immediate implant placement into extraction sockets; however, there are only a few reports that mention the indications and limitations of this technique. The aim of this article is to re-examine specific indications for immediate implant placement and to clarify the timing or "fourth dimension" relative to extraction and implant placement. The expanded concept of four-dimensional implant treatment planning involves the new axis of time, which must be considered along with the traditional spatial or three-dimensional management of implant positioning.


Atypical presentation of hemorrhagic shock in pregnancy: a case highlighting the developing field of emergency medicine in Israel.
Occult hemorrhagic shock secondary to uterine rupture represents a true obstetric emergency and can result in significant morbidity and mortality for both the patient and the fetus. Multiparity and prior cesarean sections are known risk factors. Typically, these patients present late in gestation, often secondary to the physiologic stresses on the uterus related to contractions. This pathology is less common earlier in pregnancy and can often be overlooked in the acute setting. We present the case of a 31-year-old female with three prior gestations, two parities and two prior cesarean sections, resulting in three live births, who presented to the Emergency Department (ED) 22-weeks pregnant with acute onset dyspnea and an episode of syncope. Due to her altered mental status there was concern for occult shock, despite normal vital signs. Large amounts of free fluid in the abdomen were noted on bedside ultrasonography with a high suspicion for uterine pathology. She was resuscitated with blood and taken immediately to the operating room for surgical management where she was found to have had a uterine rupture. This case highlights a rare presentation of a well-known obstetric emergency, due to the patient's development of uterine rupture early in gestation. Consequently, emergency physicians should consider atraumatic hypovolemic shock, secondary to this obstetric catastrophe, even at a stage that far precedes its expected presentation. In addition, we make note of how this case validated our department's integrated emergency medicine model, the first in the State of Israel.


Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay.
The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (5-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents.


Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial.
To determine if the use of a 5-mm umbilical incision and laparoscope would result in a higher likelihood of earlier discharge from hospital after total laparoscopic hysterectomy (TLH) compared with a 10-mm umbilical incision and laparoscope. Secondary objectives of the study were to determine if the use of a 5-mm laparoscope would lead to a reduction in postoperative pain scores and a shorter operating time without an increase in complication rates. Prospective, randomized, double-blinded, clinical trial (Canadian Task Force classification I). A tertiary care setting. Seventy-eight patients scheduled for TLH were prospectively recruited. Women undergoing TLH were assigned to either a 5-mm umbilical port and laparoscope (5LH) or a 10-mm umbilical port and laparoscope (10LH). All patients underwent a standardized operative technique and anesthetic protocol. Patients and research assistants responsible for postoperative pain assessment were blinded to group. Analysis was by intention-to-treat. The primary outcome measure was length of hospital stay. Secondary outcome measures were operating time, pain scores on postoperative days 1 and 7, and complication rates. There was no difference in length of hospital stay between the 2 arms. Compared with the 10LH group, the 5LH group had shorter operative times (32.6 vs 40 minutes; p = .01) and less postoperative pain on day 1 (2.5 vs 3.3; p = .03 for "pain with movement") and on day 7 (.92 vs 1.8; p = .002). Complication rates were similar between the 2 groups. TLH with a 5-mm laparoscope resulted in shorter operative times and less pain on postoperative days 1 and 7, compared with a 10-mm laparoscope, with similar length of stay and complications.


Safety and efficacy of Ovaleap® (recombinant human follicle-stimulating hormone) for up to 3 cycles in infertile women using assisted reproductive technology: a phase 3 open-label follow-up to Main Study.
Ovaleap® (follitropin alfa), a recombinant human follicle-stimulating hormone intended for use in controlled ovarian stimulation in women undergoing assisted reproductive technologies (ART), showed therapeutic equivalence to Gonal-f® in a multinational, multicenter, randomized, controlled, assessor-blind phase 3 Main Study. The current study examined safety, including immunogenicity, and efficacy of Ovaleap® in an open-label, uncontrolled, follow-up treatment period of up to 2 additional treatment cycles in patients who did not become pregnant in the phase 3 Main Study. Patients with negative biochemical or clinical pregnancy in the phase 3 Main Study, regardless of treatment group (ie, Ovaleap® or Gonal-f®), were eligible to participate. Patients received Ovaleap® (Merckle Biotec GmbH, Ulm, Germany) for up to 2 additional cycles, administered using a reusable semi-automated pen device. The primary objective was the assessment of safety, including adverse events (AEs), ovarian hyperstimulation syndrome (OHSS), and anti-drug antibodies. Tolerability, patient satisfaction with the Ovaleap® pen device, and efficacy outcomes (as evaluated in the Main Study) were also assessed. One hundred forty-seven patients were included in cycle 2, and 61 patients were included in cycle 3. In cycles 2 and 3, 10.9 % (16/147) and 6.6 % (4/61) of patients experienced treatment-emergent AEs (TEAEs), respectively. Three serious TEAEs (ie, appendicitis, OHSS, and borderline ovarian tumor) were reported and successfully resolved. The OHSS TEAE was the only OHSS reported in the study (0.7 % [1/147]). Positive findings on anti-drug antibody assays in 6 serum samples did not show neutralizing activity or clinical relevance in biochemical pregnancy rate. No hypersensitivity reaction occurred. Most patients reported "very good"/"good" local tolerability. All patients were "very confident"/"confident" about dose accuracy and correctness of the injection. They all found use of the pen "very convenient"/"convenient" and were all "very satisfied"/"satisfied" with the pen device. Efficacy outcomes were consistent with the phase 3 Main Study. These findings further support the safety, including immunogenicity, and efficacy of Ovaleap® for stimulation of follicular development in infertile women undergoing ART. The findings support continued use of Ovaleap® for multiple cycles or a switch to Ovaleap® if pregnancy is initially not achieved with Gonal-f®. EudraCT number: 2009-017674-20. Current controlled trials register number: ISRCTN74772901 .


Recognition of boxA antiterminator RNA by the E. coli antitermination factors NusB and ribosomal protein S10.
The boxA sequences of the E. coli ribosomal RNA (rrn) operons are sufficient to cause RNA polymerase to read through Rho-dependent transcriptional terminators. We show that a complex of the transcription antitermination factors NusB and ribosomal protein S10 interacts specifically with boxA RNA. Neither NusB nor S10 binds boxA RNA on its own, and neither NusA nor NusG affects the interaction of the NusB-S10 complex with boxA RNA. Mutations in boxA that impair its antitermination activity compromise its interaction with NusB and S10, suggesting that ribosomal protein S10 regulates the synthesis of ribosomal RNA in bacteria. RNA containing the closely related boxA sequence from the bacteriophage lambda nutR site is not stably bound by NusB and S10. This probably explains why antitermination in phage lambda depends on the phage lambda N protein and the boxB component of the nut site, in addition to boxA.