Complications following single-stage bilateral total knee arthroplasty and unilateral procedures: experience of a high-volume community hospital.
The safety of single-stage bilateral total knee arthroplasty (SSBTKA) compared to unilateral total knee arthroplasty (TKA) remains controversial. The present study compares the 90-day postoperative complications encountered following SSBTKA and unilateral TKA in an unselected cohort of patients performed at a high-volume community hospital. The perioperative electronic medical records of an unselected consecutive cohort of 1032 patients (1345 knees) having undergone unilateral or SSBTKA were reviewed. Ninety-day postoperative complications or need for additional procedures were compared between unilateral and SSBTKA groups. A total of 719 and 313 patients underwent unilateral and SSBTKA, respectively. There were no significant differences in age or BMI between groups. Patients undergoing SSBTKA were more likely to be male (p = 0.019), have longer lengths of stay (p < 0.001) and were less likely to discharge directly home (13.1%) compared to unilateral patients (80.9%) (p < 0.001). Patients undergoing SSBTKA were more likely to require a transfusion (14.7%) compared to unilateral patients (2.2%) (p < 0.001). Interestingly, mortality rate following unilateral TKA (1.7%) was significantly higher than SSBTKA (0.0%) (p = 0.013). There were no significant differences regarding other complications or need for additional procedures within 90 days following surgery. SSBTKA did not result in greater complications when compared to unilateral TKA in this particular cohort. As expected, transfusion rates will likely be higher and there will be a greater need for acute inpatient care following surgery for SSBTKA patients.


Near-total pancreatectomy for hyperinsulinism. Spontaneous remission of resultant diabetes.
Persistent hyperinsulinism in the newborn may warrant surgical intervention to prevent neurologic sequelae. Subtotal pancreatectomy may not be adequate, necessitating near-total pancreatectomy with subsequent development of diabetes mellitus. We report an infant with hyperinsulinemic hypoglycemia who underwent near-total pancreatectomy. The postoperative period was characterized by insulin-dependency and extreme insulin sensitivity. Clinical follow-up and C-peptide determinations showed a return of insulin secretory capacity permitting the discontinuation of insulin therapy after five months. This experience reaffirms the potential for a favorable outcome after near-total pancreatectomy in the newborn period for severe hyperinsulinism.


Data set of in-silico analysis and 3D modelling of boiling stable stress-responsive protein from drought tolerant wheat.
Boiling stable proteins are widespread, evolutionary conserved proteins from several kingdoms including plants, fungi and bacteria. Accumulation evidences in response to dehydration, suggest a wide spread adaptation and an evolutionary role of these protein families to protect cellular structures from water loss effects in a wide range of water potentials. Boiling stable proteins, although represents just 0.1% of total plant proteins, resist coagulation upon boiling and believed to be involved in water stress adaptation in plants. The present data profiles in-silico analysis of cloned boiling stable protein encoding gene wBsSRP from drought tolerant cultivar of wheat. The data presented here was of a gene isolated from total RNA/mRNA samples of wheat variety PBW 175 subjected to drought stress. The gene is available with EMBL data repository with accession number LN832556.


[Immediate and long term complications of episiotomy].
The objective of this review was to describe the complications of episiotomy. A systematic review on Medline Database set was performed with the key words: episiotomy, dyspareunia, fecal incontinence, urinary incontinence, maternal morbidity, pelvic floor defects and sexual function. Four hundred seventy two articles were selected. When performed liberally, episiotomy appears to increase the risk of post partum bleeding. More restrictive use does not appear to increase the risk of serious perineal injury. In the event of instrumental extraction, use of episiotomy appears to be associated with more severe damage. Medial episiotomy does not appear to be associated with third or fourth degree tears. Following delivery, patients who had an episiotomy complain of perineal pain more than those with an intact perineum or first or second degree tears. Three months after delivery, there is no difference. While episiotomy appears to be a source of dyspareunia during the first weeks after delivery in comparison with spontaneous tears, this does not appear to be true later after delivery. Episiotomy appears to be the cause of more perineal pain and dyspareunia during the early post partum weeks.


HIV treatment adherence, patient health literacy, and health care provider-patient communication: results from the 2010 AIDS Treatment for Life International Survey.
Little is known about patients' health literacy regarding antiretroviral therapy (ART) adherence and drug resistance and patient-provider communication about these topics. The AIDS Treatment for Life International Survey was a multicountry cross-sectional study (January-March 2010) including 2035 HIV-infected adults. A 40-minute interview was conducted using a standardized self-report adherence questionnaire. Overall, 57% of patients reported a 30-day recall of 100% adherence (Latin America: 89%; Africa: 73% vs North America: 45% and Asia Pacific: 47%; P < .01). Overall, 18% identified HIV drug resistance as a "good thing" in North America (35%) and Africa (24%). Only 71% said their health care providers had offered practical recommendations about adherence, 62% of the patients in North America and 80% in Latin America and Africa. Optimal ART adherence remains a challenge globally. There is a critical need to improve patient-provider communication about the importance of ART adherence and its benefits for patient's health.


Generation of a genetically-modified induced pluripotent stem cell line harboring a Noonan syndrome-associated gene variant MRAS p.G23V.
Patients harboring causative gene variants in RAS GTPase MRAS develop Noonan syndrome and early-onset hypertrophic cardiomyopathy. Here, we describe the generation of a human iPSC line harboring the Noonan syndrome-associated MRAS p.G23V variant by using CRISPR/Cas9 technology. The established MRASG23V iPSC line allows to study MRAS-specific pathomechanisms and to test novel therapeutic strategies in various disease-relevant cell types and tissues.


Nature of the rate-determining steps of the reaction catalyzed by the Yersinia protein-tyrosine phosphatase.
Product inhibition and 18O exchange experiments suggest that the Yersinia protein-tyrosine phosphatase-catalyzed phosphate monoester hydrolysis proceeds through at least two different chemical steps, i.e. the formation and breakdown of a covalent phosphoenzyme intermediate. The pH dependence of kcat values is bell-shaped, with the apparent pKa derived from the acidic limb of the profile at 4.6 for both p-nitrophenyl phosphate and beta-naphthyl phosphate, whereas the apparent pKa derived from the basic limb of the profile is substrate-dependent, with apparent pKa values of 5.2 and 5.8 for p-nitrophenyl phosphate and beta-naphthyl phosphate, respectively. Twelve aryl phosphates with leaving groups having pKa values from approximately 7 to 10 are also examined as substrates at two pH values. At pH 4.0, the beta lg values is effectively zero, whereas at pH 7.5, a beta lg value of 0.16 is observed. Collectively, our results suggest that the rate-determining step under acidic conditions corresponds to the breakdown of the phosphoenzyme intermediate, whereas under more alkaline conditions, substrate effects also contribute to the rate-limiting step. A model is proposed for the mechanism of the Yersinia protein-tyrosine phosphatase-catalyzed reaction.


Parental attitudes toward organ transplantation.
We investigated parental attitudes toward organ donation by surveying the parents of 106 children attending a general pediatric, cystic fibrosis, hematology or nephrology clinic using a printed questionnaire. Only 64% of parents knew that cessation of brain function is the definition of death. Most people (73%) obtained information about organ transplantation from the mass media and significantly fewer (37%) from medical personnel (P less than 0.05). Blacks were less likely than whites to express a desire to be living-related and/or cadaveric donors (P less than 0.05).


The Medical Home and Use of Mental and Non-mental Specialty Services Among Children with Autism Spectrum Disorder (ASD).
This study assessed the relationship between the medical home and use of health services among children with autism spectrum disorder (ASD). Data from 2016 to 2018 National Survey of Children's Health was analyzed. Outcome measures were receipt of mental and non-mental specialty care, difficulty receiving needed mental and non-mental specialty care and unmet need for mental care. Having a medical home was associated with significantly lower odds of having unmet mental health need for children with ASD ages 11-17 (OR 0.14, 95% CI 0.07-0.30) but not for those ages 3-10 (OR 0.54, 95% CI 0.21-1.43). Having a medical home was also associated with lower odds of difficulty getting needed mental health care (OR 0.38, 95% CI 0.22-0.66) as well as non-mental specialty care (OR 0.24, 95% CI 0.13-0.44).


Prospectively randomized trial using perioperative low dose octreotide to prevent organ related and general complications following pancreatic surgery and pancreatico-jejunostomy.
The aim of the study was to evaluate the influence of low dose perioperative Octreotide on the prevention of complications (pancreatic fistula and general complications) in patients undergoing pancreatic surgery followed by pancreatico-jejunostomy. 105 patients were randomized to receive either Octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no Octreotide. The primary endpoints were the occurrence of a pancreatic fistula and/or general complications including the length of hospital stay. There were 25 surgical draining procedures performed and 80 duodeno-pancreatectomies with or without preservation of the pylorus. Twenty-six (24.8%) of the patients were treated for chronic pancreatitis, 8 (7.6%) for benign tumoral disease and 71 (67.6%) for carcinoma. All patients underwent pancreatico-jejunostomy. 56 patients received Octreotide and 49 did not. The incidence of fistula formation in the Octreotide group was 8.9% (n=5) and in the control group 8.2% (n=4) for a total incidence of 8.5%. The difference between the two groups was not statistically significant. There was one death in the Octreotide group and none in the control group for an overall mortality of 0.9%. The morbidity, except fistulas, was 10.7% in the Octreotide group and 12.2% in the control group. The length of hospital stay was 23.1 +/- 15.1 days in the group receiving Octreotide vs 20.4 +/- 8.1 days in the control group (p = 0.808). Stratifying the data for duodenopancreatectomy and for draining procedures there was no difference between the groups either. In patients undergoing pancreatic surgery and pancreatico-jejunostomy, the perioperative use of 3 x 0.1 mg Octreotide for 7 days does not reduce general complications nor fistula formation.


Potential Drug-Drug Interactions in a Cardiac Center: Development of Simple Software for Pattern Identification.
Patients with cardiovascular disorders (CVD) are at higher risk for potential drug-drug interactions (pDDIs) due to complex treatment regimens. This study aimed to evaluate pDDI patterns in physicians' prescriptions in a specialized heart center using simple software. This cross-sectional study identified severe and related interactions during a 2-stage survey of experts. The data collected included age, sex, the date of admission and discharge, the length of hospital stay, drug names, inpatient wards, and the final diagnosis. The extracted drug interactions were used as a source of software knowledge. The software was designed using the SQL Server and the C # programming language. Of 24 875 patients included in the study, 14 695 (59.1%) were male. The average age was 62 years. Based on the survey of experts, only 57 pairs of severe pDDIs were identified. The designed software evaluated 185 516 prescriptions. The incidence of pDDIs was 10.5%. The average number of prescriptions per patient was 7.5. The highest frequency of pDDIs was detected in patients with lymphatic system disorders (15.0%). Aspirin with heparin (14.3%) and heparin with clopidogrel (11.7%) were the most common documented pDDIs. This study reports the prevalence of pDDIs in a cardiac center. Patients with lymphatic system disorders, male patients, and older patients were at higher risk of pDDIs. This study shows that pDDIs are common among CVD patients and highlights the need to use computer software to screen patients' prescriptions to assist in detection and prevention.


Stimulation of lymphocytes in patients with psoriasis under photochemotherapy. A study of lymphocyte transformation.
Lymphocyte-transformation by phytohaemagglutinine (PHA) was examined in 21 patients with generalized psoriasis during photochemotherapy (PUVA). Lymphocyte-transformation-tests (LTT) were performed before and after 8-methoxypsoralen (8-MOP) medication, before and after the initial irradiation and before and after the first maintenance irradiation four to six weeks later. Spontaneous and PHA-induced lymphocyte-transformation was not altered by 8-MOP alone or in combination with UVA irradiation.


Attenuation correction for PET/MRI to measure tracer activity surrounding total knee arthroplasty.
Positron emission tomography (PET) in combination with magnetic resonance imaging (MRI) could allow inflammatory complications near total knee arthroplasty (TKA) to be studied early in their development. However, attenuation of the PET signal by the metal TKA implants imparts substantial error into measurements of tracer activity, and conventional MR-based attenuation correction (AC) methods have large signal voids in the vicinity of metal implants. To evaluate a segmentation-based AC approach to measure tracer uptake from PET/MRI scans near TKA implants. A TKA implant (Triathlon, Stryker, Mahwah, USA) was implanted into a cadaver. Four vials were filled with [18F]fluorodeoxyglucose with known activity concentration (4.68 MBq total, 0.76 MBq/mL) and inserted into the knee. Images of the knee were acquired using a 3T PET/MRI system (Biograph mMR, Siemens Healthcare, Erlangen, Germany). Models of the implant components were registered to the MR data using rigid-body transformations and the other tissue classes were manually segmented. These segments were used to create the segmentation-based map and complete the AC. Percentage error of the resulting measured activities was calculated by comparing the measured and known amounts of activity in each vial. The original AC resulted in a percentage error of 64.1% from the known total activity. Errors in the individual vial activities ranged from 40.2 to 82.7%. Using the new segmentation-based AC, the percentage error of the total activity decreased to 3.55%. Errors in the individual vials were less than 15%. The segmentation-based AC technique dramatically reduced the error in activity measurements that result from PET signal attenuation by the metal TKA implant. This approach may be useful to enhance the reliability of PET/MRI measurements for numerous applications.


Using the Neuroscience of Obesity, Eating Behavior, and Sleep to Inform the Neural Mechanisms of Night Eating Syndrome.
The development and maintenance of night eating syndrome (NES) is likely influenced by physiological, psychological, and social factors. Within the physiological domain, neural mechanisms (e.g., neurotransmitters and specific brain region functioning) remain understudied in contrast to other eating disorders and obesity. The serotonin system has been hypothesized to contribute to NES based on one single photon emission computed tomography (SPECT) study and supportive pharmacologic treatment outcome findings, but additional neural models are plausible. Functional magnetic resonance imaging (fMRI) is a brain imaging tool that is increasingly being used to study obesity, eating behavior, and sleep. Converging data from these literatures using food motivation and decision making fMRI paradigms suggest that the prefrontal and limbic brain systems might also play a role in the development and/or maintenance of NES. We use these data to support a new neural model of NES for future testing and validation.


To vaccinate or not to vaccinate: A comprehensive study of vaccination-subsidizing policies with multi-agent simulations and mean-field modeling.
We combined the elements of evolutionary game theory and mathematical epidemiology to comprehensively evaluate the performance of vaccination-subsidizing policies in the face of a seasonal epidemic. We conducted multi-agent simulations to, among others, find out how the topology of the underlying social networks affects the results. We also devised a mean-field approximation to confirm the simulation results and to better understand the influences of an imperfect vaccine. The main measure of a subsidy' performance was the total social payoff as a sum of vaccination costs, infection costs, and tax burdens due to the subsidy. We find two types of situations in which vaccination-subsidizing policies act counterproductively. The first type arises when the subsidy attempts to increase vaccination among past non-vaccinators, which inadvertently creates a negative incentive for voluntary vaccinators to abstain from vaccination in hope of getting subsidized. The second type is a consequence of overspending at which point the marginal cost of further increasing vaccination coverage is higher than the corresponding marginal cost of infections avoided by this increased coverage. The topology of the underlying social networks considerably worsens the subsidy's performance if connections become random and heterogeneous, as is often the case in human social networks. An imperfect vaccine also worsens the subsidy's performance, thus narrowing or completely closing the window for vaccination-subsidizing policies to beat the no-subsidy policy. These results imply that subsidies should be aimed at voluntary vaccinators while avoiding overspending. Once this is achieved, it makes little difference whether the subsidy fully or partly offsets the vaccination cost.


Colonic involvement in inflammatory bowel diseases: spotlight on the role of magnetic resonance enterography.
The large bowel can be affected by inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, with the latter occurring either as a unique localization or in conjunction with simultaneous ileal involvement. The differential diagnosis among these conditions is challenging and relies on clinical symptoms, laboratory tests and endoscopy with biopsy. However, as these features can overlap, a conclusive diagnosis is not always achievable, and the underlying cause remains indeterminate. Currently, endoscopy is the reference standard for colonic assessment, although its invasiveness limits its use and repetition within a short timeframe. Magnetic Resonance Enterography is a non-invasive, radiation-free technique that has been extensively and effectively employed in the intestinal evaluation of patients with Crohn's disease in recent years. Although the main goal of this technique is generally focused on evaluating small bowel loops, it can also provide important information about the large bowel if an adequate fulfillment by the oral contrast medium is achieved. The purpose of this work is, therefore, to put emphasis on the potential role of Magnetic Resonance Enterography in assessing the large bowel. In fact, this imaging modality is capable of providing valuable information for comprehensive staging and follow-up of inflammatory bowel diseases within the large bowel, thus complementing the clinical picture and the endoscopic features in the context of a differential diagnosis.


Extending impact beyond the community: Protocol for a scoping review of evidence of the impact of communities of practice on teaching and learning in higher education.
The disruption in higher education caused by the COVID-19 pandemic has led to renewed interest in implementing communities of practice (CoPs) as a feasible mechanism for delivering faculty development. The construct of community of practice is cited in the literature among the most important strategies for professional development. However, empirical evidence of the impact of CoPs on teaching and learning is scarce and we still know little about the extent to which faculty participation in CoPs affect their teaching practices and students' learning and achievement. This scoping review aims to collect, synthesize, and map existing evidence about the impact of CoPs in higher education. The review is guided by a conceptual framework, which incorporates six elements underlying the purpose and expected outcomes of CoPs: resources and the capacity to mobilize them, knowledge management activities and the expansion of knowledge, changes in policy and practice, and impact on higher education outcomes.


The density of epidermal p53 clones is higher adjacent to squamous cell carcinoma in comparison with basal cell carcinoma.
It is well accepted that ultraviolet radiation from the sun can induce and promote growth of skin tumours. Skin cancer develops as a consequence of multiple genetic hits, where an initial, important step includes proliferation of cells susceptible to malignant transformation. Foci of morphologically normal epidermal keratinocytes overexpressing p53 protein are common in chronically sun-exposed skin. Such foci have previously been shown to represent expanding clones of p53-mutated keratinocytes. Although several characteristics concerning epidermal p53 clones remain to be resolved, an important role in skin carcinogenesis is anticipated. The density of epidermal p53 clones in human skin is largely unknown. To compare the occurrence of epidermal p53 clones in skin surrounding cancers with that in skin surrounding benign melanocytic naevi. To assess the influence of age on frequency and size of epidermal p53 clones in human facial skin. We have analysed the number and sizes of epidermal p53 clones in skin specimens from patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and benign melanocytic naevi. Cases included normal facial skin from four different age groups. Tissue sections were immunohistochemically stained and the presence of p53 clones was recorded. Approximately 1.4 m of epidermis from a total of 112 biopsies was analysed. We found 128 epidermal p53 clones in biopsy specimens from 112 patients. The results showed that the number and size of p53 clones increase with age. In normal skin adjacent to SCC p53 clones were significantly more numerous and greater in size in comparison with those in normal skin both adjacent to benign naevi and adjacent to BCC. Interestingly, normal skin in the close vicinity of BCC and melanocytic naevi showed similar results regarding both number and size of epidermal p53 clones. Our findings suggest a connection between development of epidermal p53 clones and SCC.


Effects of Allopurinol as a xanthine oxidase inhibitor on depressive-like behavior of rats and changes in serum BDNF level.
Depression is a psychiatric disorder characterized by low mood and loss of interest in daily activities. Allopurinol, a xanthine oxidase blocker, is widely administered for the treatment of hyperuricemia. Recently, its effects on serotonin and depressive like behaviors have been reported. On the other hand, the level of brain-derived neurotrophic factor (BDNF), a protective and regenerative neurotrophic, has been increased by many antidepressants. The purpose of this study was to evaluate the antidepressant effects of allopurinol and changes in serum level of BDNF compared to those of fluoxetine. Thirty-five male Wistar albino rats divided into five groups (control, 10 mg/kg fluoxetine, 25, 50 and 100 mg/kg allopurinol; n = 7 per group), that received all treatments intraperitoneally, every day. Forced swimming tests (FST), tail suspension test (TST) and open field test (OFT) were performed after 21 days of drug administration. Finally, the serum BDNF levels were measured using the sandwich ELISA method. All doses of allopurinol and fluoxetine reduced the duration of immobility time in FST and TST. No significant changes were observed in the number of lines crossed in OFT between either allopurinol or fluoxetine groups and control group. Serum level of BDNF were significantly higher in fluoxetine and allopurinol 50 and 100 mg/kg groups. Long-term administration of allopurinol 50 and 100 mg/kg have shown antidepressant effects in behavioral tests along with an increase in the amount of serum BDNF concentration. The OFT results suggested that allopurinol did not have any significant effects on motor activity. The increased serum level of the BDNF in the allopurinol group was correlated with FST and TST results. However, it is still not clear whether the antidepressant effects of allopurinol are due to a direct effects on serotonin and/or BDNF or an indirect effect related to its xanthin oxidase inhibition.


Hydrogen as a GC/MS carrier and buffer gas for use in forensic laboratories.
A custom set of ion volumes was manufactured in order to investigate the gain and byproducts using hydrogen as a buffer gas following electron ionization in a quadrupole ion trap mass spectrometer as compared with helium. Analyses of illicit drugs such as cocaine, codeine, and oxycodone, and explosives such as TNT, RDX, and HMTD with ion volume exit orifices of 1mm, 2mm, 4mm, 6mm, 8mm and 10mm were performed using GC/MS. Strong similarities between hydrogen and helium spectra of illicit drugs and explosives provide evidence that hydrogen can be used effectively as a buffer gas in an ion trap mass spectrometer.


Comparison of triceps surae structural stiffness and material modulus across sex.
Dynamic joint stability is derived, in part, from active muscle stiffness. Previous research has identified greater structural musculotendinous stiffness in males than in females, suggesting potential sex differences in joint stability. However, structural stiffness is influenced by anthropometrics, and it is currently unclear if sex differences in musculotendinous stiffness are purely functions of anthropometrics or related to additional factors. The purpose of this investigation was to compare structural stiffness and material modulus of the triceps surae between sexes to determine the relative influence of anthropometrics. It was hypothesized that males would demonstrate greater structural stiffness and material modulus. Twenty male and 20 female individuals volunteered for participation. Active triceps surae structural stiffness was estimated from the damped frequency of oscillation of the shank about the ankle. Material modulus was calculated as the ratio of stress to strain, derived from estimates of triceps surae length and physiological cross-sectional area. Structural stiffness was significantly greater in males [mean (SD)] [137.41 (26.99) N/cm] than females [91.06 (20.10) N/cm]. Similarly, material modulus was significantly greater in males [2778.51 (549.95) Pa] than females [1968.58 (439.61) Pa]. Greater structural stiffness in males identified in previous literature appears to be a true phenomenon. Identification of greater material modulus in males suggests that these differences are likely attributable to sex differences in tendon stiffness and muscle architecture. These results indicate that male musculature is more effective at resisting changes in its length, a finding which may have implications for joint stability.


Location and Size of Preterm Cerebellar Hemorrhage and Childhood Development.
To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (β = -0.095, 95% confidence interval = -0.184 to -0.005), with a standardized β coefficient (-0.16) that was similar to that of white matter injury volume (standardized β = -0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion-symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095-1108.


Pain, depression, and illness behavior in a pain clinic population.
The relationship between depression, illness behavior and persistent pain was studied in 100 patients referred to the University of Washington Hospital Pain Clinic. The instruments used were the Illness Behavior Questionnaire (IBQ) and the Levine-Pilowsky Depression Questionnaire (LPD). To delineate those aspects of illness behavior characteristic of the Pain Clinic group, their scores were compared to those attained on the IBQ by a Family Medicine Clinic sample. The Pain Clinic group showed greater conviction of disease and somatic preoccupation than the comparison group. Further, they were reluctant to consider their health problems in psychologic terms, and denied current life problems. The Pain Clinic group's performance on the LPD indicated a low degree of depressive affect overall and few patients manifesting a depressive syndrome. The association between IBQ and depression scores suggests that the predominant clinical pattern presented by pain clinic patients is best characterized as a form of "abnormal illness behavior".


[Fractures of the glenoid surface of the scapula].
The communications of literature regarding osteosynthesis in glenoid fractures of the scapula are reviewed, and six own cases are presented. The results are better than expected even in case of comminuted fractures. The indication for surgical reconstruction should therefore be adopted in dislocated fractures of the shoulder joint surface. Although the adequate operation technique is still under discussion, there seems to be a trend towards screwing and a narrow DC plate.


Geographical differences in the composition of tetrodotoxin and 5,6,11-trideoxytetrodotoxin in Japanese pufferfishes and their origins.
Tetrodotoxin (TTX)-bearing fish are thought to accumulate TTXs in their bodies through a food chain that begins with marine bacteria. However, the mechanism of TTXs transfer between prey and predators in the food chain remains unclear and the reasons for regional differences in pufferfish toxicity are also unknown. To investigate these matters, we collected juveniles of four species of pufferfish, Takifugu alboplumbeus, Takifugu flavipterus, Takifugu stictonotus, and Chelonodon patoca, from various locations in the Japanese Islands, and subjected them to liquid chromatography-tandem mass spectrometry analysis for TTX and its analog 5,6,11-trideoxyTTX (TDT). Concentrations of these substances tended to be higher in pufferfish juveniles collected from the Sanriku coastal area (Pacific coast of northern Japan) than in those from other locations. Juveniles had higher concentrations of TTX at all locations than of TDT. Mitochondrial cytochrome c oxidase subunit I (COI) sequences specific to the TTX-bearing flatworm, Planocera multitentaculata, were detected in the intestinal contents of up to 100% of pufferfish juveniles from various sampling sites, suggesting that P. multitentaculata was widely involved in the toxification of the juveniles in the coastal waters of Japan. A toxification experiment was conducted on three species of pufferfish juveniles (T. alboplumbeus, Takifugu rubripes and C. patoca) using TTX-bearing flatworm eggs harboring equal amounts of TTX and TDT. The TTX content of juveniles fed on flatworm eggs was found to be more than twice that of TDT, suggesting that pufferfish preferentially incorporate TTX compared to TDT.


Clinical outcomes of robotic-assisted and manual total hip arthroplasty in the same patient: A case report.
Total hip arthroplasty (THA) is an effective treatment for advanced osteonecrosis of the femoral head, which can significantly relieve pain and improve patients' quality of life. Robotic-assisted THA enhances the accuracy and stability of THA surgery and achieves better clinical outcomes than manual THA. We report the clinical outcomes of robotic-assisted THA and manual THA in the same patient with osteonecrosis of the femoral head. A 49-year-old male patient attended our hospital due to more than 3 years of pain in both hip joints. The left hip was treated with robotic-assisted THA. The patient underwent manual THA of the right hip 3 mo after robotic-assisted THA. We obtained postoperative radiograph parameters, Harris hip score and forgotten joint score of the patient 1 year after surgery. Compared with manual THA, the patient's left hip felt better 1 year after robotic-assisted THA. Robotic-assisted THA resulted in a better Harris hip score and forgotten joint score than manual THA in the same patient with osteonecrosis of the femoral head.


[Nursing support in a housing association apartment].
A transferable lease project jointly run by the municipal authorities, the departmental council, the local mental health council and the hospital, has been set up for the benefit of patients in the process of reintegration. In this context, the work of the nurse is based around the individual support of the patient, integration within networks and the establishment of the project within the community.


Comparison of different quantitative evaluation protocols for peri-device leak detection using cardiac computed tomography angiography after left atrial appendage closure.
This study seeks to propose and compare different quantitative evaluation methods for identifying patients with peri-device leak (PDL) using cardiac computed tomography angiography (CCTA). Patients who had undergone left atrial appendage (LAA) closure and both transesophageal echocardiography (TEE) and CCTA were enrolled. Hounsfield units (HU) were measured in the proximal and distal regions of the left atrial appendage (p-LAA, d-LAA) on the CCTA, and the average of the two was determined (a-LAA). The relative HU ratios of the LAA to the center of the left atrium (LA) were calculated (p-LAA/c-LA, d-LAA/c-LA, a-LAA/c-LA). The area under the curve (AUC) for the LAA HU and the LAA/LA HU ratio were analyzed and compared. Fifty-one patients were included in this study. Pairwise comparisons showed a statistically significant difference (p = 0.029) in diagnostic performance between the d-LAA (AUC = 0.868) and a-LAA (AUC = 0.972). There were no significant differences between the a-LAA and p-LAA (p = 0.549) or between the d-LAA and p-LAA (p = 0.053). At the optimal cutoff for a-LAA of 115.5 HU, the sensitivity was 100%, the specificity was 88%. At the optimal cutoff for p-LAA of 109 HU, the sensitivity was 100%, the specificity was 84%. The LAA/LA HU ratio did not exhibit better diagnostic performance than HU attenuation in the LAA (p > 0.05). The a-LAA > 115.5 is useful in identifying PDL. Due to its convenience and intuitiveness, p-LAA > 109.0 can also be used as an alternative protocol for a-LAA.


Function of nitric oxide and superoxide anion in the adventitious root development and antioxidant defence in Panax ginseng.
The involvement of NO in O(2)(.-) generation, rootlet development and antioxidant defence were investigated in the adventitious root cultures of mountain ginseng. Treatments of NO producers (SNP, sodium nitroprusside; SNAP, S-nitroso-N-acetylpenicillamine; and sodium nitrite with ascorbic acid), and NO scavenger (PTIO, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl3-oxide) revealed that NO is involved in the induction of new rootlets. Severe decline in number of new rootlets compared to the control under PTIO treatment indicates that NO acts downstream of auxin action in the process. NO producers (SNP, SNAP and sodium nitrite with ascorbic acid) activated NADPH oxidase activity, resulting in greater O(2)(.-) generation and higher number of new rootlets in the adventitious root explants. Moreover, treatment of diphenyliodonium chloride, a NADPH oxidase inhibitor, individually or along with SNP, inhibited root growth, NADPH oxidase activity and O(2)(.-) anion generation. NO supply also enhanced the activities of antioxidant enzymes that are likely to be responsible for reducing H(2)O(2)levels and lipid peroxidation as well as modulation of ascorbate and non-protein thiol concentrations in the adventitious roots. Our results suggest that NO-induced generation of O(2) (.-) by activating NADPH oxidase activity is related to adventitious root formation in mountain ginseng.


Implementing a teenage health service in primary care.
The health of teenagers is currently a priority of the NHS, with many schemes and projects being developed. There are documented difficulties for teenagers in accessing health care, especially within general practice. This article describes the development and evaluation of a tailor-made clinic in the primary care setting.


Crystal structures of the Arabidopsis thaliana abscisic acid receptor PYL10 and its complex with abscisic acid.
Abscisic acid (ABA) is one of the most essential phytohormones, and plays an important role in growth and development regulation, as well as in stress responses. The PYR/PYL/RCAR family (PYL for short)-comprised of 14 proteins in Arabidopsis-was recently identified as soluble ABA receptors that function in the perception and transduction of ABA signaling. In this work, the crystal structures of PYL10 were determined in the apo- and ABA-bound states, with respective resolutions of 3.0 and 2.7Å. Surprisingly, a closed CL2 conformation was observed in the apo-PYL10 structure, which was different from a previously reported open CL2 conformation. A putative two-conformation dynamical equilibrium model was proposed to explain PYL10's constitutive binding to PP2Cs in the apo-state and its increased PP2C binding ability in the ABA-bound state.


Results of salvage abdominoperineal resection for anal cancer after radiotherapy.
Nonsurgical treatment of anal cancer by radiotherapy alone or combined with chemotherapy is the standard therapy for epidermoid carcinoma of the anal canal. Surgery is only recommended for treatment failures. Very few studies have been devoted to the outcome of this salvage surgery. The aim of this study is to evaluate these results. A retrospective review from 1986 to 1995 revealed 21 patients with residual or recurrent anal canal carcinoma after initial radiotherapy, operated on by abdominoperineal resection. Patients were reviewed as to age, gender, initial treatment, any symptoms of recurrence, duration until recurrence, any diagnosis imaging, treatment, and outcome. None of these 21 patients had known lymph node involvement or metastases at radiotherapy or at salvage abdominoperineal resection. Eleven patients had residual disease (positive biopsy less than 6 months after the end of radiotherapy) and 10 had tumor recurrence (more than 6 months after cessation of treatment). Recurrence occurred at a mean of 15 (range, 9-41) months after radiotherapy. All 21 patients underwent an abdominoperineal resection. Pathologic examination of the 21 specimens showed complete excision in all cases except one and lymph node metastases in two cases. There was no perioperative mortality. The mean follow-up after surgery was 40 months; no patients were lost to follow-up. Of the 21 patients, 10 died and 11 lived, of whom 9 are disease free. The overall survival rate at three years after salvage abdominoperineal resection was 58 percent. The overall survival rate for patients with residual disease (vs. recurrence) at three years was 72 percent (vs. 29 percent) and at five years was 60 percent (vs. 0 percent; P = 0.06). Salvage abdominoperineal resection for anal cancer can be expected to yield a number of survivors from residual disease, but the low rate of survival after abdominoperineal resection for recurrent disease suggests the need for additional postoperative treatment if salvage abdominoperineal resection is performed.


Heparin cofactor II inhibits thrombin-stimulated release of tissue plasminogen activator from cultured human endothelial cells in the presence of dermatan sulfate.
To investigate the involvement of heparin cofactor II (HC II) in fibrinolytic system, endothelial cells from human umbilical vein were cultured in the presence of HC II or antithrombin III (AT III) combined with or without thrombin. Although AT III significantly inhibited thrombin-induced increase in tissue plasminogen activator antigen (t-PA:Ag) release, HC II did not exhibit such a suppressive effect. In contrast, in the presence of dermatan sulfate, HC II inhibited thrombin stimulation of t-PA:Ag release more strongly than AT III did. The release of plasminogen activator inhibitor-1 antigen (PAI-1:Ag) was also stimulated by thrombin; this stimulation was inhibited only by the combination of HC II and dermatan sulfate. Comparatively high concentrations of HC II significantly suppressed thrombin stimulation of t-PA:Ag and PAI-1:Ag release but did not cause an obvious change of both release in the absence of thrombin. Based on these results, it was suggested that HC II may inhibit an increase in fibrinolytic activity mediated by thrombin-stimulated endothelial cells in the liquid phase through a suppression of thrombin stimulation of t-PA:Ag release, when plasma is exposed to vascular smooth muscle cells or fibroblasts which synthesize a significant amount of dermatan sulfate.


Malpractice Litigation in the Setting of Prostate Cancer Diagnosis.
Medical malpractice and prostate cancer screening are important issues in the current landscape of health care. We identified factors contributing to litigation in the diagnosis of prostate cancer. We used the Westlaw® database to search for jury verdict reports using the term medical malpractice combined with prostate cancer with dates ranging from January 2000 to December 2013. Each case was examined for trial year, patient age, prostate specific antigen at alleged breach of duty and at diagnosis, defendant specialty, alleged cause of malpractice, whether there was metastasis, the outcome of cases that went to trial or were otherwise settled, and the plaintiff award. The initial search produced 256 results, which was narrowed to 106 cases. Of these cases 64.1% went to trial, including 66.2% that were decided for the defendant. The mean out of court settlement was $945,000, significantly lower than the mean plaintiff verdict award of $2.1 million (p = 0.0009). Primary care physicians (74.1%) were the most commonly named defendants, followed by urologists (19.6%). The most common cause was failure to perform an initial prostate specific antigen test (26.8%), followed by failure to follow elevated prostate specific antigen (22.3%). Causes of malpractice revolved mostly around prostate specific antigen testing. Primary care physicians and urologists must continue to educate patients to minimize malpractice claims made in this setting. It will be important to follow data to see trends following recent guidelines.


Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma.
Esophageal adenocarcinoma (EA) is characterized by a poor prognosis making the identification of clinically targetable proteins essential for improving patient outcome. We report the involvement of multiple alterations of the MET pathway in EA development and progression. Microarray analysis of Barrett's metaplasia, dysplasia, and EA revealed overexpression of the MET oncogene in EAs but only those with MET gene amplification. STS-amplification mapping revealed that the boundary of the MET amplicon in these EAs is defined by fragile site FRA7G. We also identified an amplicon at 11p13 that resulted in amplification and overexpression of CD44, a gene involved in MET autophosphorylation upon HGF stimulation. Tissue microarrays with phospho-MET-specific antibodies demonstrated a uniformly high abundance of MET activation in primary EA and cells metastatic to lymph nodes but to a lesser extent in a subset of metaplastic and dysplastic Barrett's samples. Increased expression of multiple genes in the MET pathway associated with invasive growth, for example, many MMPs and osteopontin, also was found in EAs. Treatment of EA-derived cell lines with geldanamycin, an inhibitor for tyrosine kinases including MET receptor kinase, reduced cell migration and induced EA cell apoptosis. The data indicate that upregulation of the MET pathway may contribute to the poor outcome of EA patients and that therapeutic agents targeting this pathway may help improve patient survival.


Impact of end-of-life respiratory modalities on quality of dying and death and symptom relief in patients with interstitial lung disease: a multicenter descriptive cross-sectional study.
Respiratory modalities applied at the end of life may affect the burden of distressing symptoms and quality of dying and death (QODD) among patients with end-stage interstitial lung disease (ILD); however, there have been few studies into respiratory modalities applied to these patients near death. We hypothesized that high-flow nasal cannula (HFNC) might contribute to improved QODD and symptom relief in patients with end-stage ILD. This multicenter study examined the proportion of end-of-life respiratory modalities in a hospital setting and explored its impact on QODD and symptom relief among patients dying with ILD. Consecutive patients with ILD who died in four participating hospitals in Japan from 2015 to 2019 were identified and divided into four groups according to end-of-life respiratory modality: conventional oxygen therapy (COT), HFNC, non-invasive ventilation (NIV), and invasive mechanical ventilation (IMV). In addition, a mail survey was performed to quantify the QODD and symptom relief at their end of life from a bereaved family's perspective. QODD and symptom relief were quantified using the Good Death Inventory (GDI) for patients with a completed bereavement survey. The impact of end-of-life respiratory modalities on QODD and symptom relief was measured by multivariable linear regression using COT as a reference. Among 177 patients analyzed for end-of-life respiratory modalities, 80 had a completed bereavement survey. The most common end-of-life respiratory modality was HFNC (n = 76, 42.9%), followed by COT (n = 62, 35.0%), NIV (n = 27, 15.3%), and IMV (n = 12, 6.8%). Regarding the place of death, 98.7% of patients treated with HFNC died outside the intensive care unit. Multivariable regression analyses revealed patients treated with HFNC had a higher GDI score for QODD [partial regression coefficient (B) = 0.46, 95% CI 0.07-0.86] and domain score related to symptom relief (B = 1.37, 95% CI 0.54-2.20) than those treated with COT. HFNC was commonly used in patients with end-stage ILD who died in the hospital and was associated with higher bereaved family ratings of QODD and symptom relief. HFNC might contribute to improved QODD and symptom relief in these patients who die in a hospital setting.


Making impressions count: An evaluation of the quality of information provided by orthodontic practices in London in response to the COVID-19 pandemic.
As a result of the coronavirus disease 2019 (COVID-19) pandemic, primary care specialist orthodontic practices have been limited to providing emergency treatment only. This has resulted in a cessation of normal face-to-face services and patient advice can only be offered by remote means. A service evaluation was carried out to assess the quality of information published on websites and social media pages of specialist orthodontic practices in London, against General Dental Council guidance on communication and advertising and the British Orthodontic Society (BOS) COVID-19 specific guidance for orthodontics in primary care in relation to Coronavirus Disease 2019 (COVID-19) pandemic. This study also aimed to provide a gold standard template for orthodontic practices to aid in the delivery of information on a digital platform during the current (COVID-19) pandemic and future possible spikes. All orthodontic practices providing care in the London region were identified from a CQC Database and subsequently checked against predetermined criteria based on the BOS guidance and the GDC Guidance on Ethical Advertising. Of the 83 orthodontic practices sampled; 78 had a website of which 18 (23.1%) were non-compliant with GDC guidance. Facebook pages were identified for 62 orthodontic practices. 17 practices did not provide any update in relation to the COVID-19 pandemic. This was more frequently carried out on practice websites (78.2%) compared to Facebook pages (33.9%). A number of practices were identified as having novel strategies to manage communication during the COVID-19 pandemic. Variation was observed in information published by practices despite the regularly updated, blanket information provided by the BOS. Communication may have been delivered by a different means during the pandemic which this study did not account for. In addition, the sampling method may not have identified all practices within the London region, however the sample size seems appropriate to draw meaningful conclusions. The checklist created should help improve the delivery of future information.


Effect of fish paste products "Hanpen" intake in Sprague-Dawley rats.
Fish paste product, "Hanpen," is a traditional type of Japanese food made from minced fish as well as imitation crab and kamaboko, and a marshmallow-like soft texture is characteristic of hanpen. Hanpen is known as a high-protein and low-fat food. However, there is a lack of evidence on its health benefits. The aim of this study was to investigate the effects of hanpen intake on organ weight and biomarker levels in Sprague-Dawley rats with diets consisting of hanpen for 84 days as an initial study. Male, 6-week-old Sprague-Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5% dried hanpen. Throughout the 84-day treatment period, we checked body weight and food intake, and after 84 days, we performed organ weight and blood biochemical analyses. No significant differences were seen in body weight, food intake, organ weight, and most biochemical parameters between group I and group II. Interestingly, total cholesterol (T-CHO) and high-density lipoprotein cholesterol (HDL-C) levels of group II were significantly higher than those of group I after administration for 84 days. Moreover, lactate dehydrogenase (LDH) level of group II was marked lower than that of group I, and other liver function parameters of group II tended to be lower than those of group I. As conclusion, "Hanpen," a Japanese traditional food, could be effective as a functional food for human health management worldwide.


[Circulation of intestinal infection in the families of patients with rheumatic diseases and the state of humoral immunity to enterobacterial antigens].
ELISA quantitation of antibodies to Klebsiella pneumonia, Proteus mirabilis, and Yersinia enterocolitica was conducted in 75 ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) probands and in 262 of their first-degree relatives. The control group comprised 28 healthy donors. Sixteen (64 per cent) AS probands (12 with B27+) and 26 (30.2 per cent) their relatives (14 with B27+) were found to have high titres of antibodies to Klebsiella pneumonia. In 18 (60 per cent) active RA probands and 27 (23.7 per cent) relatives, antibodies to Proteus mirabilis were found. The obtained results suggest the presence of genetic determinants of the increased immune response to various infectious agents, at least in the AS cases. The possibility of Enterobacteriaceae acting as polyclonal stimulators is not excluded.


The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II.
A fine mapping study of the MHC region in a Swedish case-control population sample reported a novel type 1 diabetes (T1D) association from the inositol 1-, 4-, 5-trisphosphate receptor type 3 gene (ITPR3) in a case-control study, reportedly independent of the HLA class II effect. We attempted to replicate this novel association in a family-based study of 1120 T1D families with at least one affected child, an approach immune to population stratification. We found association of the ITPR3 single nucleotide polymorphisms (SNPs) rs2296336 with T1D but in a direction opposite to that reported. Moreover, rs2296336 was in linkage disequilibrium (LD) with specific alleles of the HLA DQB1 gene. Conditional regression showed that all of the ITPR3 SNP T1D association could be accounted for by the DQB1 effect. Therefore, our findings do not support an obvious role of genetic variation of the ITPR3 gene in T1D risk.


Dynamic coronary fibrinolysis evaluation in patients with myocardial infarction and unstable angina by specific plasma fibrin degradation product determination.
It has been shown that myocardial infarction (MI) is caused by thrombotic occlusion of a coronary artery. A thrombotic process is also involved in the flow obstruction associated with peripheral embolization in unstable angina (UA). In UA, a local fibrinolytic process should occur, but biological evidence has never been reported. Therefore, we measured sequential changes in plasma fibrin degradation products (FDP) in patients with stable and unstable angina pectoris without MI and compared the levels to those in patients with MI. FDP determination was carried out by ELISA using a D neo monoclonal antibody allowing low amounts of FDP to be reliably and precisely detected. Our results show an early increase in FDP in UA indicating a thrombolytic process. In patients who presented only one episode of chest pain, a prompt decrease of FDP was noted whereas in patients with recurrent chest pain, the levels of FDP remained high. On the contrary, during the first 3 days of uncomplicated MI, FDP levels were not significantly different from those of normal control suggesting an absence of clot dissolution. This study underlines the important function of fibrinolysis in the spontaneous evolution of acute coronary syndrome.


Monocytes and smooth muscle cells cross-talk activates STAT3 and induces resistin and reactive oxygen species production [corrected].
During the early phase of atherosclerosis, monocytes attach to and migrate through the vessel wall where they activate and communicate with smooth muscle cells (SMC) affecting plaque progression by largely unknown mechanisms. Activation of STAT3 transcription factor is suggested to be critically involved in dedifferentiation, migration, and proliferation of SMC in the neointima formation after vascular injury. Monocytes-SMC cross-talk induces an inflammatory phenotype of the resident SMC, but the involvement of STAT3 in phenotype switching is not known. Resistin is a cytokine found in human atheroma associated to monocytes/macrophages with role in inflammation associated with cardiovascular disease. The aim of this study was to follow the effect of activated monocytes-SMC cross-talk on STAT3 activation and subsequent resistin and reactive oxygen species (ROS) production. Our results showed that the interaction of activated monocytes with SMC determines: (i) phosphorylation of STAT3 and reduction of SOCS3 expression in both cell types; (ii) intracellular ROS production dependent on NADPH oxidase (by increased Nox1 expression) and STAT3 activation in SMC; (iii) up-regulation of resistin expression in monocytes dependent on STAT3 activation. Furthermore, exposure of SMC to resistin induces ROS by increasing NADPH oxidase activity and the p22phox and Nox1 expression. In conclusion, the cross-talk between SMC and monocytes activates STAT3 transcription factor and lead to resistin up-regulation in monocytes and ROS production in SMC. Moreover, resistin increases the ROS levels in SMC. These data indicate that monocyte-SMC communication may represent an important factor for progression of the atherosclerotic lesion.


Comparison of efficacy and safety of tranexamic acid mesotherapy versus oral tranexamic acid in patients with melasma undergoing Q-switched fractional 1064-nm Nd:YAG laser: A blinded RCT and follow-up.
Melasma is a common hyperpigmentation disorder. This study aimed to compare the efficacy of Nd-Yag fractional 1064 plus microinjection of tranexamic acid versus Nd-Yag fractional 1064 plus oral tranexamic acid in patients with melasma. This is a prospective, randomized study with a sample size of 40 patients, 20 in each treatment arm, which was done six times with 2-week intervals. Twenty patients were administered localized microinjections (4 mg/ml) of tranexamic acid and Q-switched 1064 laser every 2 weeks in one arm, while in the other arm, 20 were given oral tranexamic acid 250 mg three times a day and Q-switched 1064 laser every 2 weeks per visit. Twenty-one patients with mean SD 40.52+-4.95 y/o were treated with oral tranexamic acid, and 20 patients with 43.3+-5.87 y/o treated with microinjection of tranexamic acid were analyzed. There was no statistically significant difference between the two groups in terms of demographic and clinical characteristics at the baseline (p > 0.05). The patients MASI score and ∆E decrease over the study period in both treatments significantly (p < 0.001). However, patient's MASI score (p = 0.99) and ∆E (p = 0.53) did not differ significant between the two group over the time. Satisfaction (p = 0.41) and complication during the study period (p = 0.09) were not significantly different between the two group. The combination treatment method can be a viable option for Middle Eastern patients having melasma disorder, and tranexamic acid appears to be an effective and safe treatment for melasma, irrespective of its route of administration. Tranexamic acid can increase the permeability locally by non-invasive methods such as microneedling which is less painful than microinjection and can also increase patient satisfaction. Although the oral method is more tolerable for the patient, it may have systemic side effects, and its combination with Q-switch laser increases its effect regardless of the type of prescription. Therefore, it is recommended to use of this drug topically (cream or lotion) by non-invasive methods like microneedling to reduce pain and laser treatment in future studies.


Multilocus sequence typing of Ochrobactrum spp. isolated from gastric niche.
The human stomach is colonized by diverse bacterial species. The presence of non-Helicobacter pylori bacteria in urease-positive biopsies of individuals has been reported. Bacteria belonging to the Ochrobactrum genus have been documented in the human gastric niche. The co-occurrence of Ochrobactrum spp. with H. pylori was previously reported in an antral biopsy of a non-ulcer dyspeptic (NUD) subject from Northern India. There is no information on the genetic diversity of Ochrobactrum spp. isolated from the gastric niche in the stomach. We aimed to study the species distribution and diversity of Ochrobactrum spp. with and without H. pylori in urease-positive biopsies across three different geographical regions in India. Sixty-two Ochrobactrum isolates recovered from patients with an upper gastric disorder (n=218) were subjected to molecular identification and multilocus sequence typing. H. pylori DNA was found in the majority of biopsies, which had a variable degree of Ochrobactrum spp present. Interestingly, some of the urease-positive biopsies only had Ochrobactrum without any H. pylori DNA. Based on phylogenetic analysis, the Ochrobactrum isolates were distributed into the O. intermedium, O. anthropi and O. oryzae groups. This indicates there are multiple species in the gastric niche irrespective of the presence or absence of H. pylori. Antibiotyping based on colistin and polymyxin B could differentiate between O. intermedium and O. anthropi without revealing the resistance-driven diversity. Considering the prevalence of multiple Ochrobactrum spp. in the human gastric niche, it is important to evaluate the commensal and/or pathogenic nature of non-H. pylori bacteria with respect to their geographical distribution, lifestyle and nutrition needs.


Identifying attendance patterns in a smoking cessation treatment and their relationships with quit success.
While important for substance use outcomes, knowledge about treatment attendance patterns, and their relation with clinical outcomes is limited. We examined the association between attendance patterns and smoking outcomes in a randomized, controlled smoking cessation intervention trial. In addition to standard smoking cessation treatment, participants were randomized to 15 weeks of an exercise intervention (n=72) or an education control condition (n=64). Latent class growth analysis (LCGA) tested whether intervention attendance would be better modeled as qualitatively distinct attendance patterns rather than as a single mean pattern. Multivariate generalized linear mixed modeling (GLMM) was used to evaluate associations between the attendance patterns and abstinence at the end of treatment and at 6-month follow-up. The LCGA solution with three patterns characterized by high probability of attendance throughout (Completers, 46.3%), gradual decreasing probability of attendance (Titrators, 23.5%), and high probability of dropout within the first few weeks (Droppers, 30.1%) provided the best fit. The GLMM analysis indicated an interaction of attendance pattern by treatment condition, such that titration was associated with lower probability of quit success for those in the control condition. Probability of quit success was not significantly different between Titrators and Completers in the exercise condition. These findings underscore the importance of examining how treatment efficacy may vary as a function of attendance patterns. Importantly, treatment discontinuation is not necessarily indicative of poorer abstinence outcome.


Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation.
The effect of food on the relative bioavailability of an erythromycin particles-in-tablet formulation was studied in 27 healthy volunteers, using a four-way, crossover study design with the following treatments: one or two erythromycin capsules USP (Eryc, Parke-Davis), or one polymer-coated erythromycin particles-in-tablet (PCE, Abbott) administered fasting or with a high-fat meal. Under fasting conditions the erythromycin particles-in-tablet and erythromycin capsule formulations are bioequivalent based on similar tmax and dose-normalized Cmax and AUC values. The rate and extent of absorption from the particles-in-tablet formulation, however, are dramatically reduced following administration with a meal. Mean Cmax and AUC values decreased by 73% and 72%, respectively, and seven subjects had no detectable erythromycin plasma concentrations for 16 hours following administration of the particles-in-tablet formulation with the high-fat meal. Greater than 40% of the subjects had nonfasting Cmax and AUC values that were less than 10% of those values following administration of the dose fasting. Cmax and AUC values in nonfasting subjects were within 75% to 125% of fasting values in only two and one of 27 subjects, respectively. The erythromycin particles-in-tablet formulation therefore should not be administered with meals.


Somatic Embryogenesis in Horse Chestnut (Aesculus hippocastanum L.).
Embryogenic cultures of horse chestnut (Aesculus hippocastanum L.) can be obtained from different organs and tissues. We describe here the induction from stamen filaments and the procedures applied for the successive phases of somatic embryo development and maturation. Embryogenic tissues are obtained on Murashige and Skoog medium containing 9.0 μM 2,4-dichlorophenoxyacetic acid. Somatic embryos develop after transfer to hormone-free medium enriched with glutamine. Maturation and germination of isolated embryos are achieved by transfer to medium containing polyethylene glycol 4000 and activated charcoal, successive desiccation treatment, and cold storage at 4 °C for 8 weeks.


Mouse strain differences in induction of micronuclei by base analogues and nucleosides.
The frequency of induced micronucleated polychromatic erythrocytes (MNPCEs) was compared in BALB/c, C57BL/6, and DBA/2 mice after intraperitoneal (i.p.) injection of 5-bromodeoxyuridine (BUdR), 5-fluorodeoxyuridine (FUdR), cytosine arabinoside (Ara-C), 6-mercaptopurine (6-MP), 5-bromouracil (5-BU), thymidine (TdR), uridine (UdR), adenosine (AdR) and guanosine (GdR). The experimental procedure was a single i.p. injection followed by harvest at 30 h. The frequency of MNPCEs was significantly increased in all strains by treatment with BUdR, FUdR, Ara-C and 6-MP compared to vehicle control. TdR and UdR induced MNPCEs slightly in BALB/c mice but showed no effect on C57BL/6 and DBA/2 mice. 5-BU, AdR, and GdR did not increase the frequency of MNPCEs in any mouse strain used. These results suggest that BALB/c mice are more susceptible to induction of MNPCEs by clastogenic base analogues and nucleosides than are C57BL/6 or DBA/2 mice.


The impact of corporate environmental disclosure practices and board attributes on sustainability: Empirical evidence from Asia and Europe.
This study analyzes the impact of environmental disclosure, board attributes, and firms' specifics on the levels of environmental and ESG performance in Europe and Asia. The study utilizes secondary data from Refinitiv Eikon database for 8094 firms for the period between 2016 and 2021. The study employs panel data analysis using fixed effect models to estimate the results. The findings suggest that disclosure on emissions, innovations, environmental controversies, environmentally friendly products, proactive environmental investments, environmental expenses, and fines charged by authorities have a positive and significant influence on the level of firms' environmental and ESG performance. Furthermore, the study identifies board tenure, independence, size, and meetings as being associated with greater levels of environmental disclosures, reporting, and sustainability score. However, board diversity is found to have a limited contribution to environmental disclosures, especially in Asian countries. Additionally, the results reveal that companies with higher revenue growth, larger size and market capitalization, and better performance have greater and better disclosure of environmental and sustainability issues. The study provides practical implications for policymakers to establish comprehensive guidelines for environmental and sustainability reporting based on the analysis of institutional, regulatory frameworks, legislation, and sustainability score enforcement status of the country.


A 10-Year Case Series of Surgically Managed Periurethral Masses at a Single Tertiary Care Institution.
This study aimed to present the evaluation, diagnoses, and surgical management of symptomatic periurethral masses of women at an academic institution. This study is an institutional review board-approved retrospective case series of women who presented with a symptomatic periurethral mass and scheduled for surgery within the Department of Urology and Female Pelvic Medicine and Reconstructive Surgery over a 10-year period (October 2003-July 2014). Fifty-nine women (mean age, 46 years; range, 22-73 years) were evaluated during the study period. Final pathology revealed 38 (64%) urethral diverticula and 21 (36%) from other benign etiologies. Of the 38 urethral diverticula, 2 (5%) were associated with adenocarcinoma and 4 (11%) with previous bulking agents. Of the 21 nondiverticula, there were 7 (12%) Skene duct cysts/abscesses, 3 (5%) Gartner duct cysts, 2 (3%) vaginal wall inclusion cysts, 2 (3%) bulking agents, 2 (3%) urethral polyps, and one (2%) of each of the following: leiomyoma, angiomyofibroblastoma, redundant vaginal mucosa epithelium, suture abscess, and encapsulated mesh remnant. Fifty-seven women underwent surgical excision (97%), and 2 elected observation. Most (78%) reported resolution of symptoms after excision. Of the patients surgically managed, 7% had postoperative stress urinary incontinence and 12% had persistent lower urinary tract symptoms. Of the 38 women with urethral diverticula, 17% had recurrence and were more likely to have multiple diverticula (44% vs 8%, P = 0.03). Although urethral diverticulum was the most common cause of a periurethral mass, final pathology revealed a variety of benign diagnoses in more than one-third of cases, demonstrating the importance of a thorough investigation for accurate diagnosis.


Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males.
A genetic risk score (GRS) was developed for predicting fracture risk based on lifetime prevalence of femoral fractures in 924 consecutive autopsies of Japanese males. A total of 922 non-synonymous single nucleotide polymorphisms (SNPs) located in 62 osteoporosis susceptibility genes were genotyped and evaluated for their association with the prevalence of femoral fracture in autopsy cases. GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores estimated from logistic regression coefficients (weighted GRS). Five SNPs (α-ʟ-iduronidase rs3755955, C7orf58 rs190543052, homeobox C4 rs75256744, G patch domain-containing gene 1 rs2287679, and Werner syndrome rs2230009) showed a significant association (P < 0.05) with the prevalence of femoral fracture in 924 male subjects. Both the unweighted and weighted GRS adequately predicted fracture prevalence; areas under receiver-operating characteristic curves were 0.750 [95 % confidence interval (CI) 0.660-0.840] and 0.770 (95 % CI 0.681-0.859), respectively. Multiple logistic regression analysis revealed that the odds ratio (OR) for the association between fracture prevalence and unweighted GRS ≥3 (n = 124) was 8.39 (95 % CI 4.22-16.69, P < 0.001) relative to a score <3 (n = 797). Likewise, the OR for a weighted GRS of 6-15 (n = 135) was 7.73 (95 % CI 3.89-15.36, P < 0.001) relative to scores of 0-5 (n = 786). The GRS based on risk allele profiles of the five SNPs could help identify at-risk individuals and enable implementation of preventive measures for femoral fracture.


Principles of Immunotherapy in Melanoma.
Advanced/metastatic melanoma is an aggressive cancer with a low survival rate. Traditional cytotoxic chemotherapies do not appreciably extend life and systemic cytokine/chemokine administration produces toxic side effects. By harnessing the surveillance and cytotoxic features of the immune system, immunotherapies can provide a durable response and are proved to improve disease outcomes in patients with advanced/metastatic melanoma and other cancers. Close monitoring is necessary, however, to identify and treat immune system-related adverse events before they become life-threatening. Because metastatic lesions can respond differently to immunotherapies, modified response criteria have been developed to assist physicians in tracking patient response to treatment.


Histopathological classification of lesions associated with natural paratuberculosis infection in cattle.
Paratuberculosis-associated lesions in 116 naturally infected adult cows, with or without clinical signs, were classified histopathologically. Tissue samples obtained focused on gut-associated lymphoid tissue. Lesions were divided into five categories. Focal lesions (n=68 cases), consisted of small granulomas in the ileal and jejunal lymph nodes or the ileocaecal lymphoid tissue. In the multifocal type (n=13 cases), small granulomas or scattered giant cells appeared in some intestinal villi, as well as in the lymph nodes. Diffuse multibacillary lesions (n=15 cases), associated with severe granulomatous enteritis affecting different intestinal locations and lymph nodes, were formed by macrophages containing large numbers of acid-fast bacilli. In diffuse lymphocytic lesions (n=3 cases), lymphocytes were the main inflammatory cells, with some macrophages or giant cells containing few if any mycobacteria. In diffuse intermediate forms (n=17 cases), the infiltrate was formed by abundant lymphocytes and macrophages, and mycobacteria were present to varying degrees related to the number of macrophages. Clinical signs and gross lesions were mainly associated with diffuse forms. Thickening of the intestinal wall, which was the most common macroscopical finding, was related to the degree of submucosal change. Mycobacterium avium subsp. paratuberculosis was identified by culture or PCR in all cows with diffuse lesions, and in 55.5 and 37% of those with multifocal or focal forms, respectively. The importance of sampling the ileal and caudal jejunal lymph nodes to find histological lesions of paratuberculosis in cattle is emphasized.


Correlation of transrectal sonographic findings in patients with suspected and unsuspected prostatic disease.
Previous reports describing the diagnostic accuracy of transrectal sonography have not documented the specificity of differentiating abnormal internal echoes of the prostate. To determine the specificity of the examination, a prospective study was designed to correlate sonographic findings with histological diagnoses. Gray scale transrectal sonography was performed on 228 patients and the scans were reviewed without clinical information. The sensitivity (true positive rate) was confirmed by histological evaluation in 121 cases to be 90 per cent. The specificity (true negative rate) was determined by histological evaluation as well as subsequent clinical followup to be 60 per cent. Our experience is similar to that of others showing transrectal sonography as a sensitive diagnostic tool. The relatively low specificity demonstrates the difficulty in differentiating the abnormal internal echoes of the prostate, representing malignant and nonmalignant prostatic disease processes.


Effects of progestins on the progesterone receptor in guinea pig uterus.
We examined the effects of progesterone and some synthetic progestins and other steroids on the physical properties of the progesterone receptor of guinea pig uterine cytosol and on the binding of the receptor by nuclei. Progestational potency seemed to correlate with the ability to keep the receptor in the 7S form and to prevent dissociation into smaller subunits. The rate of activation prior to nuclear binding was slower with steroids of increasing progestational activity. Therefore activation in vitro may be unrelated to biological activity. Concentration of the cytosol led to a decrease in the equilibrium association constant. The extent of the decrease was less with progesterone than with its metabolite, 5 alpha-pregnanedione. When cytosol and nuclei were incubated in the absence of ligand measureable progesterone receptor was bound by the nuclei. The uncomplexed nuclear receptor bound [3H]-progesterone of [3H]-R5020 rapidly at 0 degrees, but progesterone-receptor complexes exchanged [3H]-progestin slowly at 0 degrees. Progesterone increased the amount of nuclear receptor at concentrations of 10(-9) and 10(-8)M, but decreased binding at higher concentrations. 5 alpha-Pregnanedione had the same effect as progesterone, but other metabolites of progesterone that had little affinity for the 7S progesterone receptor in cytosol had no effect on nuclear binding at any concentration. Glucocorticoids, testosterone and estradiol-17 beta increased the nuclear binding of the progesterone receptor when present at concentration of 10(-8)M and greater.


Effects of hypertonic saline replacement on colonic anastomosis in experimental hemorrhagic shock model in rats.
Inadequate intestinal perfusion resulting from hemorrhagic shock negatively affects wound healing. In this experimental study, we aimed to evaluate the effects of resuscitation with hypertonic saline on colonic anastomosis in rats with controlled hemorrhagic shock. A total of 24 male Wistar albino rats weighing between 200 and 250 g were used in this study. The rats were divided into four groups as: Control, hypotonic, isotonic, and hypertonic. Median laparotomy, colon resection, and colocolonic anastomosis were performed to the rats in the control group. After creating controlled hemorrhagic shock to rats in other three groups, resuscitation was achieved with hypotonic, isotonic, and hypertonic saline. After resuscitation, median laparotomy, colon resection, and colocolonic anastomosis were performed on rats in these three groups. On the 5th post-operative day, a median laparotomy was applied to the rats in all groups and anastomosis lines were evaluated. Anastomotic bursting pressure, tissue hydroxyproline level, and tissue fibrosis degree were compared between the groups. There was no statistically significant difference between the groups in terms of anastomotic bursting pressure, tissue hydroxyproline level, and tissue fibrosis degree (respectively; p=0.320, p=0.537, p>0.05). In rats with controlled hemorrhagic shock, resuscitation with hypertonic saline does not differ significantly from isotonic or hypotonic saline in terms of healing of colonic anastomosis.


Myospherulosis of maxillary sinus--a case report with review of literature.
Myospherulosis is a rare condition. The authors report a unique case of this entity arising in paranasal sinus. The review of literature with emphasis on pathogenesis is also discussed.


Bleeding aneurysm of the axillary artery, managed by a combined approach: interventional radiology and extra-anatomic bypass.
Twenty-two years after an obvious radical mastectomy with axillary lymph node dissection and postoperative conventional radiotherapy for carcinoma of the right breast, an 80-year-old lady was admitted because of the third bleeding episode within one year originating from the axilla. An aneurysm from the axillary artery was identified as the source of hemorrhage. Since the sites of irradiation had to be avoided, an extra-anatomic reversed saphenous vein graft was run from the right common carotid to the brachial artery. In the same session the bleeding was finally controlled by therapeutic embolization of the aneurysm using Gianturco-Anderson-Wallace coils. The postoperative angiogram showed the patent graft. Bleeding did not reoccur during the follow-up period of 17 months.


An outbreak of isoniazid resistant tuberculosis in Glasgow 1981-1988.
An increase in the number of patients attending the Victoria Infirmary, Glasgow with isoniazid resistant tuberculosis, prompted a survey of the incidence of the condition in Glasgow. There was a clustering of cases among the homeless and/or alcoholic population of the city, particularly between the years 1982 and 1986. This suggests an outbreak of isoniazid resistance among that population, probably spread from a single, but unidentified source.


18F-fluorodeoxyglucose positron emission tomography-computed tomography imaging of leiomyomatosis peritonealis disseminata.
Leiomyomatosis peritonealis disseminata (LPD) is a rare benign condition characterized by multiple smooth muscle implants in the peritoneal cavity. The clinical presentation is usually nonspecific abdominal discomfort and nontender abdominal mass. Preoperative imaging usually points to suggests malignancy due to its unusual location, but the diagnosis can only be confirmed by histopathological examination. We share 18F-Fluorodeoxyglucose positron emission tomography-computed tomography images of a 43-year-old woman diagnosed with LPD and briefly discuss the clinical aspects of this disease.


[Preparation of salbutamol polyclonal antibodies and development of indirect competitive enzyme-linked immunoassay].
To prepare the antibodies against salbutamol (SAL) with high sensitivity and to develop an indirect competitive enzyme-linked immunoassay (ic-ELISA) for fast detection of SAL. The New Zealand white rabbits were immunized with SAL in a small dose and long period mode. The method of ic-ELISA was optimized and adopted for the detection of a series of SAL samples, then the standard curve of SAL was established. The precision and the recoveries of the method were determined. The antibodies with high sensitivity towards SAL were prepared with a IC50 of 12.21 ng/ml. The ic-ELISA method for SAL measurement was established, the recoveries of measurement was between 95%-105% and the CV was <3%. The antibodies against salbutamol have been prepared and an indirect competitive enzyme-linked immunoassay for fast and specific detection of SAL has been developed.


Foliar application is an effective method for incorporating selenium into peanut leaf proteins with antioxidant activities.
Proteins were extracted from Se-enriched peanut leaves, an agro-byproduct, and the foliar application of sodium selenite was indicated to be an effective method to incorporate Se into leaf selenoproteins with 75-80% incorporation rates. After trypsin digestion, the most abundant proteins from Se-enriched peanut leaf (PSPL) were identified as pathogenesis-related class 10 proteins, Ara h 8 allergen and its isoforms, using LC-MS/MS. The Se species in both the low Se PSPL and high Se PSPL were determined to be selenomethionine (SeMet), methylselenocysteine (MeSeCys) and selenocystine (SeCys2) with SeMet (15.6 mg/g) dominated the high Se PSPL. Their antioxidant activities were also evaluated using free radical scavenging assay, reducing power assay and ferric thiocyanate (FTC) test. As results, the PSPL exhibited potent DPPH radical (96.2%) and superoxide anion radical (98.4%) scavenging activities and showed strong reducing power in a Se-concentration-dependent manner, indicating that PSPL can be used as antioxidants and Se sources to improve health.


Neurodevelopmental functioning of infants with untreated single-suture craniosynostosis during early infancy.
Single-suture craniosynostosis (SSC) is a congenital craniofacial disorder, in which premature fusion of one of the skull sutures restricts and distorts growth of the cranium and underlying brain. This disorder of prenatal onset occurs during a critical phase of rapid growth and development of the immature brain. Craniosynostosis carries a known risk of developmental impairment. The neurodevelopmental sequelae of SSC prior to treatment remains however incompletely understood. This study sought to determine the neurodevelopmental sequelae of untreated single-suture craniosynostosis during early infancy. Fifty-six consecutive patients with unoperated SSC (sagittal, metopic and unicoronal) comprised the sample cohort. Patients were aged between 4 and 16 months (M = 8.9 months, SD = 2.9 months). Neurodevelopmental functioning was assessed with the mental (Mental Development Index) and motor (Psychomotor Development Index) scales of the Bayley Scales of Infant Development, second edition. Children with SSC displayed significantly lower mean mental (M = 97.7, SD = 6.7, p < 0.05) and motor (M = 87.7, SD = 13.0, p < 0.001) scores than normative population averages. The distribution of these scores also differed significantly from the normative distribution; an increased rate of significant motor developmental delay was found, and none of the children displayed accelerated development. Subgroup comparisons between the primary diagnostic subtypes in this sample revealed no significant differences in mental or motor skill functioning. Untreated SSC is associated with an increased incidence of developmental delay during early infancy, with motor skills appearing the most vulnerable to impairment during this developmental phase.


Amino acid synthesis deficiencies.
Defects in the synthesis pathways of amino acids have only been discovered in recent years and are relatively unknown to most clinicians. In this chapter disorders neurological symptoms caused by genetic defects in the synthesis of the amino acids serine, glutamine and proline are discussed. Patients with serine deficiency invariably suffer from severe neurological symptoms such as microcephaly, psychomotor retardation and intractable seizures. The same is true for patients with a defect in the synthesis of glutamine who present with hypotonia and epileptic encephalopathy. Patients with a disorder in the synthesis proline have mental retardation in combination with symptoms of connective tissue disease. All amino acids synthesis disorders, except for one of the proline defects, can be diagnosed by routine amino acid analysis. Given the fact that the disorder discussed here lead to deficiencies of amino acids opens up possibilities to treat these patients with the amino acids that can't be synthesised. Prompt recognition and treatment of amino acid synthesis disorders are of outmost importance to obtain satisfactory treatment results.


Rates of RNFL Thinning in Patients with Suspected or Confirmed Glaucoma Receiving Unilateral Intravitreal Injections for Exudative AMD.
This study evaluated whether the rate of retinal nerve fiber layer (RNFL) thinning is faster in eyes receiving intravitreal injections than in fellow uninjected eyes among patients suspected of having or confirmed to have glaucoma and exudative age-related macular degeneration (AMD). Retrospective comparative cohort study. Patients with a diagnosis of unilateral exudative AMD and confirmed to have or suspected of having glaucoma in both eyes receiving unilateral intravitreal injections were identified. Those with ≥3 RNFL optical coherence tomography scans and ≥6 injections were included in the study. Rates of RNFL thinning in the injected eye versus the uninjected eye were estimated using linear mixed models. The main outcome measurement was the differences in rates of RNFL thinning in the injected versus the fellow uninjected eye. The effects of postinjection elevation of intraocular pressure (IOP), injection frequency, and number of injections were also evaluated. A total of 53 patients met the inclusion criteria, receiving 26.4 ± 15.9 intravitreal injections. The average rate of RNFL thinning in uninjected eyes was -0.620 μm/year (P = .029). Injected eyes had an additional incremental loss of -0.385 μm/year, but this value was not statistically significant (95% confidence interval [CI]: -1.147 to 0.379 μm/year; P = .324). Subgroup analysis with only glaucoma patients (n = 33) also demonstrated a nonsignificant effect of injections (-0.568 μm/year; 95% CI: -1.454 to 0.319 μm/year; P = .212). Postinjection IOP elevation, injection frequency, and total number of injections were not associated with faster RNFL loss. Among exudative AMD patients with glaucoma or suspected of having glaucoma, the rate of RNFL thinning in eyes receiving intravitreal injections did not significantly differ from that of fellow uninjected eyes.


Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis.
In early-onset myasthenia gravis (EOMG), the thymus usually shows medullary lymph node-type infiltrates, rearranged bands of hyperplastic epithelium and focal fenestrations in the intervening laminin borders. This resemblance to autoimmune target organs may reflect autoantigen expression by rare thymic myoid cells, long ago implicated circumstantially as agents provocateurs. In this quantitative study, they were frequently seen at the laminin fenestrations; if so, germinal centers (GC) were significantly commoner nearby, our most EOMG-specific finding (not seen in a distinct MG patient subset). As autoantibodies became detectable, myoid cell involvement apparently progressed. Our unifying hypothesis--that an early autoantibody attack on myoid cells provokes local GC formation--helps to resolve many puzzles.


Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16.
Coxsackievirus A16 (CA16) is a major causative agent of hand, foot, and mouth disease. Immunization with inactivated whole-virus or recombinant virus-like particles (VLP) of CA16 elicits neutralizing antibodies that protect mice against lethal challenge. However, the epitope/s responsible for this induction has not been determined. In this investigation, we identified six neutralizing linear epitopes of CA16. A panel of 95 synthetic peptides spanning the entire VP1 protein of CA16 were screened by ELISA for reactivity with neutralizing antisera against CA16 VLPs, which were generated in a previous study (Vaccine 30:6642-6648). Fifteen high-binding peptides were selected and further examined for their inhibitory effect on neutralization by anti-VLP sera. Among them, six peptides with no overlap significantly inhibited neutralization. Mice immunized with these six peptides generated peptide-specific serum antibodies. The anti-peptide antisera positively detected CA16 via immunofluorescent staining and Western blot assays. More importantly, they neutralized both homologous and heterologous CA16 strains, indicating that these six peptides represented neutralizing epitopes. Sequence alignment also showed that these epitopes are extremely conserved among CA16 strains of different genotypes. These findings have important implications for the development of peptide-based broadly protective CA16 vaccines.


Ultrasonic-assisted decoration of Ag2WO4, AgI, and Ag nanoparticles over tubular g-C3N4: Plasmonic photocatalysts for impressive removal of tetracycline under visible light.
The development of an efficient, eco-friendly, and low-cost photocatalyst is essential for addressing environmental and energy crises. In this regard, we report novel plasmonic photocatalysts through adorning tubular g-C3N4 with Ag2WO4, Ag, and AgI nanoparticles (TGCN/Ag/Ag2WO4/AgI) fabricated via a facile ultrasonic-irradiation procedure. The TGCN/Ag/Ag2WO4/AgI (20%) nanocomposite presented the excellent photocatalytic ability for removal of tetracycline hydrochloride under visible light, which was almost 45.6, 4.03, and 1.32 times more than GCN, TGCN, and TGCN/Ag/Ag2WO4 (20%) photocatalysts, respectively. Interestingly, the photocatalyst displayed impressive ability for the degradations of amoxicilline, rhodamine B, methyl orange, fuchsine, and methylene blue, which was 14.7, 52.2, 9.8, 13.2, and 7.46 times as much as pure GCN. The outcomes of DRS, PL, EIS, and photocurrent density analyses proved that the impressive activity could be related to the highly promoted harvesting of visible light, segregation of charge carriers, and improved charge migrations. In addition, trapping tests exhibited that •O2- and h+ were active species in the photocatalysis process.


Development and application of an automated air quality forecasting system based on machine learning.
As one of the most concerned issues in modern society, air quality has received extensive attentions from the public and the government, which promotes the continuous development and progress of air quality forecasting technology. In this study, an automated air quality forecasting system based on machine learning has been developed and applied for daily forecasts of six common pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and pollution levels, which can automatically find the best "Model + Hyperparameters" without human intervention. Five machine learning models and an ensemble model (Stacked Generalization) were integrated into the system, supported by a knowledge base containing the meteorological observed data, pollutant concentrations, pollutant emissions, and model reanalysis data. Then five-year data (2015-2019) of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an, Wuhan, and Changchun in China, were used as an application case to study the effectiveness of the automated forecasting system. Based on the analysis of seven evaluation criteria and pollution level forecasts, combined with the forecasting results for the next 3-days, it is found that the automated system can achieve satisfactory forecasting performance, better than most of numerical model results. This implied that the developed system unveils a good application prospect in the field of environmental meteorology.


The relationship of GH and LEP gene polymorphisms with fat-tail measurements (fat-tail dimensions) in fat-tailed Makooei breed of Iranian sheep.
The present study was designed to investigate the association of GH and LEP genes' single-nucleotide polymorphisms with fat-tail measurements (fat-tail dimensions) in Makooei sheep. DNA was extracted from whole blood samples collected from 100 sheep. Polymerase chain reaction (PCR) products were subjected to single-strand conformation polymorphism (SSCP) denaturation and polyacrylamide gel electrophoresis. Data were collected at the Makooei Sheep Breeding Station in Makoo (36°, 35'S and 48°, 22'E) of West Azerbaijan province. Climatically, this location has temperate summers and cold winters and receives a mean annual rainfall of about 400 mm. Ewes are raised in an annual breeding cycle starting in September. In general, the flock is managed under a semi-migratory system. In the tested Makooei sheep population, significant statistical results were found in all traits of fat-tail measurements for GH and LEP genes. Individuals with the G4, L4 genotype of GH and LEP genes had lower tail length (rump length), fat thickness (the thick rump), and tail width (rump width) when compared to those of individuals with other genotypes (P < 0.05). In addition, the results demonstrated that individuals with the G5, L5 genotype of GH and LEP genes had superiority of tail length (rump length) and fat thickness (the thick rump) compared to those individuals with other genotypes (P < 0.05). Individuals with the G2, L2 genotype of GH and LEP genes had superiority of tail width (rump width) compared individuals with other genotypes (P < 0.05). These results confirmed potential usefulness of GH and LEP genes in marker-assisted selection programs of sheep breeding.


The role of a grief support team following stillbirth.
The loss of a baby through stillbirth is a tragic, devastating experience for a woman and her family. Although well intentioned, physicians and nurses are often ill-prepared to provide essential emotional support. We would like to describe our experience with a multidisciplinary perinatal grief support team. In our hospital, such a team has, in part, corrected deficits in the care of these families and has functioned as an invaluable source of education and support for health care providers.


Unawareness of "illnesses": a case of right-sided hemiballism.
The Authors describe a non-demented patient who, after a left subthalamic haemorrhage causing hemiballism, was completely unaware of both neurological (i.e., dyskinesias) and non-neurological (i.e., cough) symptoms occurring after the stroke. In contrast, he was perfectly able to acknowledge pathological conditions affecting him before the brain damage. Neuropsychological assessment showed no cognitive defects, but revealed the presence of frontal behaviours (e.g., perseverations and utilization behaviours). This unusual clinical picture was ascribed to damage of frontal-subcortical circuits involved in conscious representation of current bodily states.


The ompB operon partially determines differential expression of OmpC in Salmonella typhi and Escherichia coli.
Expression of the Escherichia coli OmpC and OmpF outer membrane proteins is regulated by the osmolarity of the culture media. In contrast, expression of OmpC in Salmonella typhi is not influenced by osmolarity, while OmpF is regulated as in E. coli. To better understand the lack of osmoregulation of OmpC expression in S. typhi, we compared the expression of the ompC gene in S. typhi and E. coli, using ompC-lacZ fusions and outer membrane protein (OMP) electrophoretic profiles. S. typhi ompC expression levels in S. typhi were similar at low and high osmolarity along the growth curve, whereas osmoregulation of E. coli ompC in E. coli was observed during the exponential phase. Both genes were highly expressed at high and low osmolarity when present in S. typhi, while expression of both was regulated by osmolarity in E. coli. Complementation experiments with either the S. typhi or E. coli ompB operon in an S. typhi DeltaompB strain carrying the ompC-lacZ fusions showed that both S. typhi and E. coli ompC were not regulated by osmolarity when they were under the control of S. typhi ompB. Interestingly, in the same strain, both genes were osmoregulated under E. coli ompB. Surprisingly, in E. coli DeltaompB, they were both osmoregulated under S. typhi or E. coli ompB. Thus, the lack of osmoregulation of OmpC expression in S. typhi is determined in part by the ompB operon, as well as by other unknown trans-acting elements present in S. typhi.


Secrets of the Hair Follicle: Now on Your iPhone.
Skin development requires communication between epithelial and mesenchymal cells, melanocytes, and neurons. In this issue of Developmental Cell, Sennett et al. (2015) shed new light on these mechanisms by simultaneously profiling multiple different cell types in embryonic mouse skin at the onset of hair follicle formation.