The diversity, community dynamics, and interactions of the microbiome in the world's deepest blue hole: insights into extreme environmental response patterns and tolerance of marine microorganisms.
Blue holes are unique marine sinkholes with extreme environments and biogeochemical processes. However, our understanding of community dynamics, functional profiles, and microbial interactions in blue holes remains limited. We studied the extreme environmental response pattern of the microbiome (Symbiodiniaceae, bacteria, archaea, and fungi) across 14 depths in the world's deepest blue hole, the Sansha Yongle Blue Hole. The α-diversities of Symbiodiniaceae and archaea were stable to extreme environmental conditions, whereas those of bacteria and fungi varied. Physical and nutrient factors primarily influenced the β-diversities of these four microbes, and there were significant differences in microbial communities among water layers. Nine microbial taxa of Cladocopium sp, γ-proteobacteria, Nanoarchaeota, and Ascomycota representing the core microbiome occurred in all water layers. These four microbial groups exhibited potential interactions, with a positive correlation between Symbiodiniaceae and archaea α-diversities. The microbial biogeochemical profiles exhibited notable enrichment characteristics among distinct water layers. Archaea metabolized sulfides in the oxic and upper deep layers, while bacteria dominated sulfide decomposition in the chemocline and lower deep layers. These findings suggest the acclimation of Symbiodiniaceae to an extreme environment may rely on archaea, as a result of a partial niche overlap. The bacterial communities exhibited an environmental response pattern consistent with the Anna Karenina effects, whereas fungal communities displayed an opposite trend. The wide tolerance of the core microbiome to environmental gradients may be linked to evolution, acclimatization, and symbiosis. Bacteria, archaea, and fungi have distinct ecological niches and biogeochemical functions in the Sansha Yongle Blue Hole. IMPORTANCE This study comprehensively examined the community dynamics, functional profiles, and interactions of the microbiome in the world's deepest blue hole. The findings revealed a positive correlation between the α-diversities of Symbiodiniaceae and archaea, indicating the potential reliance of Symbiodiniaceae on archaea in an extreme environment resulting from a partial niche overlap. The negative association between the α-diversity and β-diversity of the bacterial community suggested that the change rule of the bacterial community was consistent with the Anna Karenina effects. The core microbiome comprised nine microbial taxa, highlighting their remarkable tolerance and adaptability to sharp environmental gradient variations. Bacteria and archaea played significant roles in carbon, nitrogen, and sulfur cycles, while fungi contributed to carbon metabolism. This study advanced our understanding of the community dynamics, response patterns, and resilience of microorganisms populating the world's deepest blue hole, thereby facilitating further ecological and evolutional exploration of microbiomes in diverse extreme environments.


Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant.
The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).


Unexplained lymphadenopathy in family practice. An evaluation of the probability of malignant causes and the effectiveness of physicians' workup.
This study reported here was undertaken to determine the probability of malignancy in patients presenting with unexplained lymphadenopathy in primary care practice and to estimate the effectiveness of current referral patterns by family physicians in relation to malignant disease. Clinical characteristics that may be discriminatory for malignant causes were also investigated. A retrospective analysis was performed of 82 patients who underwent biopsy for unexplained lymphadenopathy from 1982 to 1984; data regarding the incidence of unexplained lymphadenopathy and the referral rate for this problem were obtained from registration projects. A total of 29 malignant lymphadenopathies were identified for a prior probability of 1.1 percent and a posterior (after referral) probability of 11 percent. The ability of the family physician to refer malignant cases within four weeks after initial consultation (sensitivity of referral) was 80 to 90 percent; 91 to 98 percent of benign cases were not referred (specificity of referral). An increased likelihood of malignancy was associated with age over 40 years (4 percent) and supraclavicular lymphadenopathy (50 percent). The incidence of malignancy in patients presenting with unexplained lymphadenopathy to the family physicians is very low (1 to 2 percent). Nevertheless, despite the paucity of validated discriminatory factors, the family physicians perform a reasonably effective selection process toward referral and biopsy.


Nimodipine and microsurgery induced recovery of the vocal cord after recurrent laryngeal nerve resection.
Transection of the recurrent laryngeal nerve leads to permanent palsy of the vocal cord. Experimental studies have confirmed that nimodipine increases the pace of axonal regeneration. We present a case of a 19-year-old male, suffering a thyroid cancer disease, who was subjected to unilateral resection of the recurrent laryngeal nerve during surgery. The nerve was repaired with a nerve graft and the patient further treated with nimodipine for 3 months. Evaluation of the patient showed normalization of voice, movement of the vocal cord on the injured side, and electromyography evidence of reinnervation of the larynx muscles at 15 months after surgery.


MORPHOLOGIC CHARACTERISTICS OF MACULAR HOLE AND MACULAR HOLE RETINAL DETACHMENT ASSOCIATED WITH EXTREME MYOPIA.
To investigate the surgical results and morphologic characteristics of macular hole (MH) and macular hole retinal detachment (MHRD) associated with extreme myopia. We retrospectively reviewed consecutive cases with axial length ≥28 mm who were treated with pars plana vitrectomy for MH or MHRD. The choroidal and scleral thickness at the fovea, presence of dome-shaped macula, and the height of posterior staphyloma 3 mm from the fovea were measured from postoperative optical coherence tomography images. Significant improvement in visual acuity was obtained postoperatively in both MH (16 eyes; 15 patients) and MHRD (19 eyes; 18 patients) groups (P < 0.05). Final MH closure rate was not significantly different between the groups (MH: 15/16, MHRD: 14/19, P = 0.19). Axial length was not significantly different between the groups (MH: 30.5 ± 1.5 mm, MHRD: 29.6 ± 1.3 mm, P = 0.098). Eyes with MH had significantly greater choroidal thickness (MH: 61.9 ± 66.0 μm, MHRD: 24.1 ± 19.8 μm, P = 0.045), greater scleral thickness (MH: 294 ± 77 μm, MHRD: 232 ± 89 μm, P = 0.008), higher frequency of dome-shaped macula (MH: 6/16, MHRD: 1/19, P = 0.032), and lower staphyloma height (MH: 190 ± 113 μm, MHRD: 401 ± 156 μm, P < 0.001). Surgical outcomes were generally favorable. The pathogenetic differences between the two conditions may be attributable to differences with respect to eye morphology.


Galectin-3 and HBME-1 expression in oncocytic cell tumors of the thyroid.
Oncocytic cell tumors (OCTs) of the thyroid include oncocytic cell adenomas (OCAs) and oncocytic cell carcinomas (OCCs). Oncocytic variant of papillary carcinoma (OVPC) has also been described. These tumors may present similar diagnostic problems as their non-oncocytic counterparts, in both conventional histology and fine-needle aspiration biopsies. Several markers were shown able to distinguish benign from malignant thyroid follicular tumors, galectin-3 and HBME-1 being the most promising ones. Controversial data have been reported on their discriminatory potential in the small series of OCTs so far analyzed. We aimed to assess the role of galectin-3 and HBME-1 in a large series of 152 OCTs (including 50 OCAs, 70 OCCs and 32 OVPCs). The expression of PPARgamma protein was also evaluated. Using a biotin-free detection system, the sensitivity of galectin-3 was 95.1%, while that for HBME-1 was nearly 53%. The combination of galectin-3 and HBME-1 increased the sensitivity up to 99%. However, for both markers, the specificity was 88%, lower than that reported for non-oncocytic follicular tumors. PPARgamma protein overexpression was absent in all OCAs tested and present in only 10% of OCCs, confirming previous reports on the low prevalence of PAX8-PPARgamma translocations in OCT and ruling out its role as a potential diagnostic marker of malignancy.


Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.
Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list.


Antibody response and clinical reactions in children given measles vaccine with immunoglobulin.
Antibody responses and clinical reactions to three measles vaccines (Attenuvax, Mevilin, and Rimevax) injected into the opposite arm to immunoglobulin were assessed in 45 children with brain disorders making them susceptible to fits if given measles vaccine alone. In this small study no unacceptable reactions occurred and in only three cases was the antibody response minimal or absent. More children in this special category should be considered for vaccination against measles in this way.


[Otosclerosis. A paramyxovirus-induced inflammatory reaction].
Despite intensive investigation the cause of otosclerosis remains unknown. Recent immunohistochemical and electron microscopic studies of otosclerotic stapes have revealed a possible viral aetiology. Therefore we investigated the histology, ultrastructure and immunohistochemistry of fragments of otosclerotic footplates. Immunoglobulins G (IgG) and A (IgA) were found in plasma cells, oseocytes, chondrocytes and connective tissue of the active lesions. Polyclonal and monoclonal antibodies against paramyxovirus and rubella virus antigens produced reproducible reactions with these antigens at different sites of otosclerotic stapes, especially in the epithelial cells of the overlying middle ear mucosa. Using specific T-lymphocyte and B-lymphocyte markers about 80% of the lymphocytes present in the otosclerotic footplate proved to be T-lymphocytes. There was neither deposition of immunoglobulins nor any expression of viral antigens in non-otosclerotic footplates which were investigated as controls. Our results indicate that otosclerosis is an inflammatory reaction of the otic capsule initiated or caused by paramyxovirus and/or rubella virus. The silent progress of the disease and its onset under certain conditions, e.g. endocrine upsets, show similarity to slow viral infections.


HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.
The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.


The automatic processing of social information in working memory.
Working memory has been considered an active buffer for processing perceptual representations in a progressive manner, integrating information involuntarily to form structured mental representations. The automatic integration of objects' physical features in working memory has been well documented, although its social aspect remains unknown. The current study examines whether working memory would automatically process social information, that is, extract social information from memory content to form a higher-level social representation. Through four experiments, we demonstrate that participants could spontaneously infer personality traits when required to hold the social information implying others' traits in working memory, without the explicit goal of trait inference or awareness of the inference processes. Results show that participants mistook the memorized words for inferred trait words; such "errors" were then accumulated and amplified when the information was transmitted from person to person, during which the social information was briefly stored in working memory and reproduced after a short time. These findings indicate that working memory may automatically integrate social information into hierarchically structured mental representations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[False aneurysm and bleeding caused by a secondary dislocated lesser trochanter fragment].
A 92-year-old woman incurred an unstable pertrochanteric hip fracture with avulsion of the lesser trochanter (type 31-A2 according to the AO classification). The fracture was treated by gliding nail osteosynthesis, without fixing the minimally displaced lesser trochanter. No intra- or postoperative complications were detected. Suddenly, after 30 days, a swelling of the proximal femoral region, accompanied by signs of haemorrhage, occurred.CT-scans showed a false aneurysm of the deep femoral artery and a dorsal laceration of the artery proximal to the aneurysm. X-rays showed a further dislocation with rotation of the lesser trochanter fragment. Intraoperatively, the tip of the lesser trochanter fragment was identified to be responsible for the laceration of the artery. The false aneurysm was resected and the defect bridged by a vascular prosthesis while the fragment was removed. Follow-up showed no further complications. According to case reports from the literature, false aneurysms and laceration of the deep femoral artery caused by dislocated lesser trochanter fracture fragments are rare.


Fibrinolytic activity in the abdominal cavity of rats with faecal peritonitis.
Generalized peritonitis causes a reduction in abdominal fibrinolytic activity, resulting in persistence of intraabdominal fibrin with subsequent adhesion and abscess formation. The activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) were measured in the peritoneal fluid of rats with faecal peritonitis and correlated with the extent of peritoneal damage to determine the cause of decreased fibrinolysis. Activity of tPA was low during the study period of 8 days, but higher in rats with peritonitis than in controls. The activity of PAI in rats with peritonitis was significantly increased compared with that of controls during the whole study period (P < 0.001). Histological signs of damage to the peritoneum were similar in rats with peritonitis and controls. There was no correlation between the extent of peritoneal damage and tPA or PAI activity. The increased activity of PAI in the peritoneal fluid of rats with faecal peritonitis may be the main cause of reduced fibrinolysis in the abdominal cavity. Activities of tPA and PAI may originate not only from the mesothelium but from other sources.


General practitioners learning qualitative research: A case study of postgraduate education.
Qualitative research is increasingly being recognised as a vital aspect of primary healthcare research. Teaching and learning how to conduct qualitative research is especially important for general practitioners and other clinicians in the professional educational setting. This article examines a case study of postgraduate professional education in qualitative research for clinicians, for the purpose of enabling a robust discussion around teaching and learning in medicine and the health sciences. A series of three workshops was delivered for primary healthcare academics. The workshops were evaluated using a quantitative survey and qualitative free-text responses to enable descriptive analyses. Participants found qualitative philosophy and theory the most difficult areas to engage with, and learning qualitative coding and analysis was considered the easiest to learn. Key elements for successful teaching were identified, including the use of adult learning principles, the value of an experienced facilitator and an awareness of the impact of clinical subcultures on learning.


Acute colonic pseudo-obstruction (Ogilvie syndrome) leading to respiratory compromise and death.
Here, we present an unusual case of acute colonic pseudo-obstruction (ACPO), also known as Ogilvie syndrome, which resulted in respiratory failure and sudden death. The patient was a 19-year-old man with a history of cerebral palsy (CP) and severe autism who experienced marked abdominal distension that progressed over several days in his skilled nursing facility. He developed shortness of breath and episodic diarrhea, before having an unwitnessed cardiac arrest and subsequently expiring after prehospital and emergency department care. Autopsy revealed developmental deformities consistent with CP, rectal prolapse, and significant abdominal distension. Postmortem radiography showed diffuse bowel distension with bilateral upward displacement of the diaphragm and consequent lung compression. Thorough examination of the gastrointestinal tract failed to reveal any perforation or obstruction. The cause of death was determined to be respiratory compromise secondary to diaphragmatic compression as a result of ACPO, a condition defined as colonic distension without a mechanical explanation for obstruction. This case highlights the challenges that ACPO can pose to a forensic pathologist at autopsy, and serves as a teaching point to clinicians on the warning signs and treatment measures for ACPO.


Phosphorylation of glutamate receptors: a potential mechanism for the regulation of receptor function and psychostimulant action.
Ionotropic glutamate receptors, N-methyl-d-aspartate receptors (NMDARs) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), are densely distributed in the mammalian brain and actively regulate a variety of cellular activities. Expression and function of these receptors are also under a tight regulation by many molecular mechanisms. Protein phosphorylation represents one of the important mechanisms for the posttranslational modulation of these receptors. Constitutive and regulatory phosphorylation occurs at distinct sites (serine, threonine, or tyrosine) on the intracellular C-terminal domain of almost all subunits capable of assembling a functional channel. Several key protein kinases, such as protein kinase A, protein kinase C, Ca(2+)/calmodulin-dependent protein kinases, and tyrosine kinases are involved in the site-specific catalyzation and regulation of NMDAR and AMPAR phosphorylation. Through the phosphorylation mechanism, these protein kinases as well as protein phosphatases control biochemical properties (biosynthesis, delivery, and subunit assembling), subcellular distribution, and interactions of these receptors with various synaptic proteins, which ultimately modify the efficacy and strength of excitatory synapses containing NMDARs and AMPARs and many forms of synaptic plasticity. Emerging evidence shows that psychostimulants (cocaine and amphetamine) are among effective agents that profoundly alter the phosphorylation status of both receptors in striatal neurons in vivo. Thus, psychostimulants may modulate NMDAR and AMPAR function through the phosphorylation mechanism to shape the excitatory synaptic plasticity related to additive properties of drugs of abuse.


Design and development of a compact ion implanter and plasma diagnosis facility based on a 2.45 GHz microwave ion source.
A project on developing a 2.45 GHz microwave ion source based compact ion implanter and plasma diagnostic facility has been taken up by the Central University of Punjab, Bathinda. It consists of a double-wall ECR plasma cavity, a four-step ridge waveguide, an extraction system, and an experimental beam chamber. The mechanical design has been carried out in such a way that both types of experiments, plasma diagnosis and ion implantation, can be easily accommodated simultaneously and separately. To optimize microwave coupling to the ECR plasma cavity, a four-step ridge waveguide is designed. Microwave coupling simulation for the ECR plasma cavity has been performed at different power inputs using COMSOL Multiphysics. An enhanced electric field profile has been obtained at the center of the ECR plasma cavity with the help of a four-step ridge waveguide compared to the WR284 waveguide. The magnetic field distribution for two magnetic rings and the extraction system's focusing properties have been simulated using the computer simulation technique. A tunable axial magnetic field profile has been obtained with a two permanent magnetic ring arrangement. The dependency of the beam emittance and beam current on accelerating voltages up to 50 kV has been simulated with different ions. It shows that ion masses have a great impact on the beam emittance and output current. This facility has provision for in situ plasma diagnosis using a Langmuir probe and optical emission spectroscopy setups. This system will be used for ion implantation, surface patterning, and studies of basic plasma sciences.


Acquired zinc deficiency in alcoholic liver cirrhosis: report of two cases.
Acquired zinc deficiency in two patients suffering from alcoholic liver cirrhosis is reported. Skin changes included bullae and erosions on the heels, desquamating dermatitis on feet, hands and shins, and localized alopecia. Following oral zinc therapy the skin changes disappeared and Beau lines were later seen on the finger nails. Concomitantly with the rise in the depressed plasma zinc levels, serum alkaline phosphatase and prothrombin levels rose and serum bilirubin decreased. The observations are in agreement with earlier reports dealing with congenital and conditioned zinc deficiency and oral zinc therapy in alcoholic liver cirrhosis.


Knowledge-based educational systems.
In knowledge-based educational systems, the key concept is that information and procedures are represented in the same data structure. These structures can search for each other in flexible and, consequently, very robust ways. At the Air Force Human Resources Laboratory (AFHRL), our researchers are building computer environments that know what they know, know how people can best use them, and know how to draw inferences about their state--self-referential electronic tutors. In September 1986, artificial intelligence researchers participated in AFHRL's Research Planning Forum for Intelligent Tutorial Systems (ITS). This essay reviews the state of the philosophy, art, and science of artificial intelligence (AI) approaches to education. Then it summarizes the research issues which were presented, discussed, and better defined in this Forum--namely the nature and representation of 1) expertise modules, 2) student diagnostic modules, 3) adaptive instructional and curriculum modules, 4) instructional environments, and 5) man-machine interfaces. Advances in artificial intelligence, cognitive science, and instructional discourse have provided a means for investigating human learning, for representing an individual's own "knowledge processing." Research and development in knowledge-based educational systems seems promising, not only for helping people learn how to perform complex tasks, but also for explicitly expressing how people learn to learn. Therefore, would it not be wise to establish a scientific legacy for the development of effective knowledge-based tutorial systems which is informed by the best studies of mind and meaning, language and thought, purpose and paradox?


CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis.
Replication-coupled destruction of a cohort of cell cycle proteins ensures efficient and precise genome duplication. Three proteins destroyed during replication via the CRL4(CDT2) ubiquitin E3 ligase, CDT1, p21, and SET8 (PR-SET7), are also essential or important during mitosis, making their reaccumulation after S phase a critical cell cycle event. During early and mid-S phase and during DNA repair, proliferating cell nuclear antigen (PCNA) loading onto DNA (PCNA(DNA)) triggers the interaction between CRL4(CDT2) and its substrates, resulting in their degradation. We have discovered that, beginning in late S phase, PCNA(DNA) is no longer sufficient to trigger CRL4(CDT2)-mediated degradation. A CDK1-dependent mechanism that blocks CRL4(CDT2) activity by interfering with CDT2 recruitment to chromatin actively protects CRL4(CDT2) substrates. We postulate that deliberate override of replication-coupled destruction allows anticipatory accumulation in late S phase. We further show that (as for CDT1) de novo SET8 reaccumulation is important for normal mitotic progression. In this manner, CDK1-dependent CRL4(CDT2) inactivation contributes to efficient transition from S phase to mitosis.


Stress following extinction learning leads to a context-dependent return of fear.
It has been suggested that extinction-based therapy benefits from administration of the stress hormone cortisol. However, it is unclear whether similar effects can be obtained by inducing stress instead of administering cortisol, and whether the effects also persist if memory is tested in a different context (renewal test) or after exposure to an aversive stimulus (reinstatement). The present study therefore applied a fear conditioning (context A, day 1) and extinction (context B, day 2) paradigm in healthy men. After fear extinction, participants were exposed to a stress or control procedure (n = 20 each). Fear retrieval was tested in contexts A and B on day 3. Postextinction stress increased skin conductance responses to the extinguished stimulus in the retrieval and reinstatement test especially in the acquisition context. The context-dependent return of fear may reflect enhancing effects of stress on the consolidation of contextual cues.


Improving Patient Safety through the Use of Nursing Surveillance.
Surveillance and monitoring each represent a distinct process in patient care. Monitoring involves observation, measurement, and recording of physiological parameters, while surveillance is a systematic, goal-directed process based on early detection of signs of change, interpretation of the clinical implications of such changes, and initiation of rapid, appropriate interventions. Through use of an illustrative clinical example based on Early Warning System scoring and rapid response teams, this article seeks to distinguish between nurse monitoring and surveillance to demonstrate the impact of surveillance on improving both care processes and patient care. Using a clinical example, differences between surveillance and monitoring as a trigger for deployment of the rapid response team were reviewed. The use of surveillance versus monitoring resulted in a mean reduction in rapid response team deployment time of 291 minutes. The median hospital length of stay for patients whose clinical care included using surveillance to initiate the deployment of the rapid response team was reduced by 4 days. Monitoring relies on observation and assessment while nursing surveillance incorporates monitoring with recognition and interpretation of the clinical implications of changes to guide decisions about subsequent actions. The clinical example described here supports that the use of an automated surveillance system versus monitoring had a measurable impact on clinical care.


DNA methylation level in blood and relations to breast cancer, risk factors and environmental exposure in Greenlandic Inuit women.
Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case-control study evaluated blood methylation level of two repetitive elements and selected breast cancer-related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE-1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE-1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.


Comparison of the Sensititre YeastOne and CLSI M38-A2 Microdilution Methods in Determining the Activity of Amphotericin B, Itraconazole, Voriconazole, and Posaconazole against Aspergillus Species.
This study compared the YeastOne and reference CLSI M38-A2 broth microdilution methods for antifungal susceptibility testing of Aspergillus species. The MICs of antifungal agents were determined for 100 Aspergillus isolates, including 54 Aspergillus fumigatus (24 TR34/L98H isolates), 23 A. flavus, 13 A. terreus, and 10 A. niger isolates. The overall agreement (within 2 2-fold dilutions) between the two methods was 100%, 95%, 92%, and 90% for voriconazole, posaconazole, itraconazole, and amphotericin B, respectively. The voriconazole geometric mean (GM) MICs were nearly identical for all isolates using both methods, whereas the itraconazole and posaconazole GM MICs obtained using the YeastOne method were approximately 1 dilution lower than those obtained using the reference method. In contrast, the amphotericin B GM MIC obtained using the YeastOne method was 3.3-fold higher than that observed using the reference method. For the 24 A. fumigatus TR34/L98H isolates assayed, the categorical agreement (classified according to the CLSI epidemiological cutoff values) was 100%, 87.5%, and 83.3% for itraconazole, voriconazole, and posaconazole, respectively. For four A. niger isolates, the itraconazole MICs were >8 μg/ml using the M38-A2 method due to trailing growth, whereas the corresponding itraconazole MICs obtained using the YeastOne method were all ≤0.25 μg/ml without trailing growth. These data suggest that the YeastOne method can be used as an alternative for azole susceptibility testing of Aspergillus species and for detecting the A. fumigatus TR34/L98H isolates but that this method fails to detect A. niger isolates exhibiting trailing growth with itraconazole. Additionally, for isolates with azole MICs that approach or that are at susceptibility breakpoints or with high amphotericin B MICs detected using the YeastOne method, further MIC confirmation using the reference CLSI method is needed.


Functional neuroanatomy of speech processing within the temporal cortex.
The phonemic structure of the maternal language determines the way of perceiving speech signals. A typical example is that native Japanese listeners map two English phonemes, /r/ and /l/, onto the same /R/. This perceptual assimilation of speech sounds has been associated with the left and/or right posterior perisylvian region, but the precise functional anatomy is unknown. Using functional magnetic resonance imaging and a repetition priming paradigm, we identified three subregions in the left temporal cortex: an anterior division sensitive to language-specific phonological knowledge, and a midlateral and a posterior division related to other vocal stimuli features. Dynamic causal modeling supports the scheme by which the anterior pathway processes perceptual assimilation; the posterior pathway processes lexico-semantic information.


Influence of supplementary fish oil and rumen-protected methionine on milk yield and composition in dairy cows.
The effects of a daily supplement of 300 ml fish oil and 20 g rumen-protected methionine, alone or in combination, were investigated in mid-lactation cows receiving a maize silage-based diet ad lib. Fish oil significantly decreased feed intake, increased milk yield, decreased protein and casein concentrations, and especially fat concentration (by 13.1 g/kg) and output. Fat concentration decreased more in primiparous than in multiparous cows. Methionine supplementation increased protein and casein concentrations and outputs. No significant interaction between oil and methionine supplementation was found on milk composition. Treatments did not modify live weight or body condition changes, or lactose and non-casein nitrogenous compounds in milk. Oil plus methionine supplementation made it possible to decrease milk fat content without changing protein content.


Clinical effects of serotonin reuptake inhibitors in the treatment of depressive illness.
The serotonergic hypothesis of depression has stimulated the development of a range of chemically diverse compounds that have an exclusive effect on this neurotransmitter for potential use as antidepressant drugs. The group of serotonin reuptake inhibitors are at various stages of clinical development. The authors review the efficacy, side effect profiles, and toxicity of zimelidine, fluvoxamine, and citalopram in detail and ifoxetine, fluoxetine, indalpine, paroxetine, and sertraline in brief. Evidence suggests that, compared with tricyclic antidepressants, these drugs may cause fewer anticholinergic effects and lower cardiotoxicity in the treatment of major depressive disorders. These advantages need to be weighed against an emerging pattern of gastrointestinal complaints, insomnia, and akathisia. The place of serotonin reuptake inhibitors in therapy can be fully evaluated only after further studies, particularly those involving long-term use. The adverse experience associated with zimelidine suggests that caution and vigilance should be exercised in future studies of agents in this class. These drugs will undoubtedly provide important insights into depressive illness and some anxiety disorders and may fulfill their initial promise.


Folic acid consumption among Missouri women in the periconceptional period.
Periconceptional folic acid consumption significantly reduces the risk for neural tube defects. The purpose of this study was to identify the risk factors for poor periconceptional folic acid supplementation among Missouri women. Sixty-five percent of Missouri women reported not taking periconceptional multivitamins regularly. Unintended pregnancy (aOR = 0.49), maternal adolescent age (aOR = 0.44) and smoking before pregnancy (aOR = 0.53) were significantly associated with poor periconceptional multivitamin use. Folic acid interventions targeting specific sub-groups of women are needed in Missouri.


Detection of two atypical rotaviruses in the province of Misiones, Argentina.
Out of 317 human gastroenteritis cases studied between August 1988-August 1989, two atypical antigenically distinct rotaviruses (pararotaviruses) were detected in faecal samples among 19 rotaviruses shedding children from Misiones province, North-Eastern Argentina. A 1 3/4 year old girl a 3 years old boy, both with vomiting and normal temperature, shed these atypical rotaviruses. Their morphology by electron microscopy was identical to other rotaviruses; they contained 11 double-stranded RNA segments detected by polyacrylamide gel electrophoresis and failed to react with the antibody directed against the rotavirus group specific antigen (Rotazyme II ELISA). The electrophoretic migration of these RNAs (electropherotype) in polyacrylamide gels did not coincide with the typical pattern of distinct size classes observed in most human rotaviruses reported, instead, they appeared to be related to patterns of rotaviruses group C.


MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells.
The TAM family of receptor tyrosine kinases (TYRO3, AXL, and MERTK) is known to be expressed on antigen-presenting cells and function as oncogenic drivers and as inhibitors of inflammatory responses. Both human and mouse CD8+ T cells are thought to be negative for TAM receptor expression. In this study, we show that T-cell receptor (TCR)-activated human primary CD8+ T cells expressed MERTK and the ligand PROS1 from day 2 postactivation. PROS1-mediated MERTK signaling served as a late costimulatory signal, increasing proliferation and secretion of effector and memory-associated cytokines. Knockdown and inhibition studies confirmed that this costimulatory effect was mediated through MERTK. Transcriptomic and metabolic analyses of PROS1-blocked CD8+ T cells demonstrated a role of the PROS1-MERTK axis in differentiation of memory CD8+ T cells. Finally, using tumor-infiltrating lymphocytes (TIL) from melanoma patients, we show that MERTK signaling on T cells improved TIL expansion and TIL-mediated autologous cancer cell killing. We conclude that MERTK serves as a late costimulatory signal for CD8+ T cells. Identification of this costimulatory function of MERTK on human CD8+ T cells suggests caution in the development of MERTK inhibitors for hematologic or solid cancer treatment.


DNA markers for Portuguese olive oil fingerprinting.
The certification of olive oil has led to the definition of Protected Denomination of Origin (PDO) producing regions in European countries. PDO products should be protected, and a solution could be by using DNA fingerprinting. In this work we evaluate the efficiency of RAPD, ISSR, and SSR molecular markers for olive oil varietal identification and their possible use in certification purposes. Twenty-three Portuguese olive oil samples (11 obtained monovarietal and 12 purchased commercial oils) were screened by means of two RAPD, four ISSR, and four SSR markers. The quality of amplified products was used to evaluate the reproducibility and the level of polymorphism. Principal component analysis was performed with DCENTER using unweighted pair group mathematical average (UPGMA) that allowed group formation according to olive oil varietal geographic origin.


[Two cases of advanced pancreas cancer treated with GTX: combined use of gemcitabine, docetaxel and capecitabine].
Two cases of advanced pancreas cancer were treated with GTX. One cycle was 3 weeks, capecitabine (1,000 mg/m(2)/day) was administered from day 1 to 14, and GEM 750 mg/m(2) and DOC 30 mg/m(2) were drip-infused on day 4 and 11. A 62-year-old man with pancreas head cancer and 2 liver metastases was treated with GEM 1,000 mg/m(2)/week at weeks 1, 2, and 3, and drug-free week 4 for 3 cycles, but was PD. After 3 cycles of GTX, the liver metastases decreased in size, and thereafter tumor markers became lowest after 7 cycles. The patient was shifted to another regimen after 14 cycles for 9 months of GTX. A 75-year-old man with pancreas head cancer and vascular invasion has been treated with GTX. As leukopenia was seen after the first cycle, the administration doses were reduced and GTX has been continued for a total 13 cycles. The tumor reduced in size and tumor markers decreased. GTX is suitable for outpatient chemotherapy with mild adverse effects.


Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells.
Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients. Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism. The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay. The gene was silenced by small interfering RNA. The cellular morphology was observed by using an optical microscope. The viable cell numbers were counted by trypan blue staining assay. The OSI-resistant HCC827/OSIR cells were established on HCC827 cells with naive EGFR-sensitive mutation, and the resistant effects of HCC827/OSIR cells were confirmed through MTT and colony formation assays. The IC50s of HCC827/OSIR cells to other EGFR TKIs, such as gefitinib, erlotinib, afatinib, and rociletinib was higher than that of the HCC827 cells. The anti-proliferative effects of paclitaxel, pemetrexed, doxorubicin, and fluorouracil in HCC827 and HCC827/OSIR cells were similar. The expression of inositolrequiring enzyme 1α (IRE1α) was increased after the cells developed resistance to OSI. The number of viable cells in both cell lines, particularly in HCC827/OSIR cells, was decreased through knockdown of IRE1α or pretreatment with STF-083010, an IRE1α inhibitor. An increased expression of IRE1α may be one of the resistant mechanisms for OSI-resistant NSCLC.


Quantification of Graph Complexity Based on the Edge Weight Distribution Balance: Application to Brain Networks.
The aim of this study was to introduce a novel global measure of graph complexity: Shannon graph complexity (SGC). This measure was specifically developed for weighted graphs, but it can also be applied to binary graphs. The proposed complexity measure was designed to capture the interplay between two properties of a system: the 'information' (calculated by means of Shannon entropy) and the 'order' of the system (estimated by means of a disequilibrium measure). SGC is based on the concept that complex graphs should maintain an equilibrium between the aforementioned two properties, which can be measured by means of the edge weight distribution. In this study, SGC was assessed using four synthetic graph datasets and a real dataset, formed by electroencephalographic (EEG) recordings from controls and schizophrenia patients. SGC was compared with graph density (GD), a classical measure used to evaluate graph complexity. Our results showed that SGC is invariant with respect to GD and independent of node degree distribution. Furthermore, its variation with graph size [Formula: see text] is close to zero for [Formula: see text]. Results from the real dataset showed an increment in the weight distribution balance during the cognitive processing for both controls and schizophrenia patients, although these changes are more relevant for controls. Our findings revealed that SGC does not need a comparison with null-hypothesis networks constructed by a surrogate process. In addition, SGC results on the real dataset suggest that schizophrenia is associated with a deficit in the brain dynamic reorganization related to secondary pathways of the brain network.


[Development of germ cells in the ovaries of human fetuses in the early periods].
Histological methods were used for studying 30 ovaries of early human embryos from 7 to 11 weeks of development. It was shown that in the process of development of the ovary the number of mitotically dividing oogonia decreased from 76% in 7-8 weeks to 41% in the period of 10-11 weeks. The mototic division of oogonia was characterized by high activity from 3,6% to 6,8%. However, as early as in the ovaries of 7-8 week embryos there occurred transition of a part of oogonia into oocytes of preleptotene stages which were characterized by processes of spiralization and despiralization of chromatin in the nuclei. The amount of such oocytes increases in the process of development of the embryo. The amount of oocytes at the stage of condensation of chromatin "prochromosomes" increases from 7,6% to 14,4%, the amount of oocytes at the stage of the following despiralization increased from 2,1% to 21% when comparing the ovaries of embryos of 7-8 and 10=11 weeks of development. The size of nucleoli was found to change in the period of preleptotene transformations in the oocyte nuclei. Photographs of the stages in question are presented made from histological and total preparations.


[Racemic and optically active alpha-tocopherol analogues with a modified side chain: synthesis and biological activity].
Information on the synthesis and biological activity of natural and synthetic analogues of alpha-tocopherol with a modified side chain is systematized. These compounds are of interest as vitamin E metabolites, hydrophilic antioxidants, and precursors of drugs with combined pharmacological properties useful in therapy of pathological disorders caused by oxidative stress.


Clinicopathologic findings in a patient with serpiginous choroiditis and treated choroidal neovascularization.
We present the ocular clinicopathologic features of the left eye of a patient who, during a 29-year period, developed the characteristic features of progressive serpiginous choroiditis. Two areas of choroidal neovascularization were successfully treated by laser photocoagulation. The larger area of neovascularization, located in and inferior to the maculopapillary bundle area and treated with argon laser, resulted in a scar composed of hyperplastic retinal pigment with persistence of neovascularization and full-thickness destruction of the retina. A smaller area of neovascularization, located temporal to the fovea and treated by krypton laser, resulted in a fibrous scar with obliteration of the new vessels and preservation of the inner retinal layers. A diffuse and focal infiltrate of lymphocytes was present in the choroid. Often, larger aggregates of lymphocytes were present at the margin of the serpiginous lesions. The serpiginous lesions were characterized by loss of retinal pigment epithelium and the photoreceptor cell layer. The margins of most lesions had variable degrees of hyperplastic retinal pigment epithelium and some had defects in Bruch's membrane, through which fibroglial scar tissue extended into the choroid.


Intrahepatic cholangiocarcinoma patients without indications of lymph node metastasis not benefit from lymph node dissection.
To investigate the necessity of routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) patients without indications of lymph node metastasis (LNM) preoperatively. 422 consecutive ICC patients who undergone curative resection from January 2009 to December 2014 were enrolled and categorized as two groups (hepatectomy only or hepatectomy plus LND). Clinicopathologic data was compared between the groups by χ2 or Fisher's exact test. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method and differences were analyzed using the log-rank test. Cox regression model was adopted for multivariable analysis. The median OS time of all 422 patients was 41.4 months. One-, 3-, and 5-year OS was 67%, 47%, and 35%, respectively. A total of 73 patients had undergone curative resection combined with LND, of whom 20.5% (15/73) were confirmed lymph node positive pathologically. The clinicopathologic characteristics between LND and control groups showed no significant differences. Of the 422 patients, 271 patients had recurrence. The recurrence rates were 65.8% for the LND group and 63.9% for the non-LND group. Survival analysis revealed that, neither the OS (LND vs. non-LND: 32.2 months vs. 46.2 months; p = 0.16) nor the RFS (LND vs. non-LND: 23.1 months vs. 17.0 months; p = 0.09) had significant difference. Multivariate analysis revealed that tumor size, tumor number, carbohydrate antigen19-9, carcinoembryonic antigen, and gamma-glutamyl transpeptidase were independent predictive factors for OS and RFS. Routine LND may not improve survival in resectable ICC patients with negative LNM diagnosis before operation.


Effects of modifiable, non-modifiable and clinical process factors in ventral hernia repair surgical site infections: A retrospective study.
The hypothesis of this study is that non-modifiable factors are more important in ventral hernia repair (VHR) surgical site infection (SSI) than care process factors. All VHR's which were reviewed retrospectively for both NSQIP-recorded data, and also: preoperative hospitalization, existing mesh, enterocutaneous fistula, open wound, case month, case day, case length, prophylactic antibiotics, skin preparation, other procedure performed, re-do operation, estimate blood loss, hernia size, repair approach, repair type, mesh used, skin closure, suture type, use of drains, and dressing. 7% of 223 VHR's had an SSI. Factors associated with SSI: presence of mesh (24% vs. 4%), recurrent VHR (15% vs. 3%), operation time >120 min (15% vs. 3%), hernia size >200 cm2 (<25 cm2 2%, 26-200 cm2 4% and >200 cm2 11%), and EBL >100 ml (21% vs. 3%). Other factors did not affect SSI rates. Factors associated with a more difficult operation were associated with SSI. Factors considered modifiable played limited roles. This has implications for choices of interventions made to reduce SSI rates.


Characterization of the molecular parameters determining charge transport in anthradithiophene.
The molecular parameters that govern charge transport in anthradithiophene (ADT) are studied by a joint experimental/theoretical approach involving high-resolution gas-phase photoelectron spectroscopy and quantum-mechanical methods. The hole reorganization energy of ADT has been determined by an analysis of the vibrational structure of the lowest ionization band in the gas-phase photoelectron spectrum as well as by density-functional theory calculations. In addition, various dimers and clusters of ADT molecules have been considered in order to understand the effect of molecular packing on the hole and electron intermolecular transfer integrals. The results indicate that the intrinsic electronic structure, the relevant intramolecular vibrational modes, and the intermolecular interactions in ADT are very similar to those in pentacene.


SALMATcor: microagglutination for Salmonella flagella serotyping.
Salmonella is a complex bacterial group with more than 2400 serovars widely distributed in nature; they are considered zoonotic because they can infect a variety of animals and be transmitted to humans. Usually, they cause alimentary acquired diseases such as gastroenteritis, typhoid fever, and others that can lead to severe complications and death. Serotyping is useful to differentiate among Salmonella, because it shows an important correlation with their clinical and epidemiological patterns; consequently, it is of high value for public health, animal health, agriculture, and industry. To characterize all known Kauffmann-White Salmonella serovars, over 250 antisera are required. Due to this and to high prices antisera, many laboratories worldwide have limitations in establishing Salmonella surveillance. Therefore, we developed and validated a Salmonella flagella microagglutination test (SALMATcor) that significantly reduces laboratory requirements of antisera. SALMATcor is based on scaling down, by fivefold, the antigen:antiserum volumes actually required for the reference method: flagella standard tube agglutination technique (STAT). Antigen preparation, temperatures, and incubation periods remained as established for STAT. The SALMATcor was validated according to ISO/DIS 16140:1999 protocol, which included 1187 comparisons of flagella determinations conducted by SALMATcor and STAT, on 141 Salmonella isolates of 12 common serotypes and the use of antiserum recommended for STAT. SALMATcor concordance was excellent (Cohen's kappa index 0.9982), obtaining relative accuracy >99.9% and relative specificity >99.9%. Additionally, SALMATcor has been used by CNRB-INCIENSA since 2004 to respond to all 40 Salmonella proficiency testing strains, provided by World Health Organization-Global Salmonella Surveillance Network, obtaining 100% concordance on serovar identification. On the basis of the results achieved with SALMATcor and considering that it also significantly reduces antiserum expenses, hand labor, glassware, and bench top and water bath space requirements (microtiter plates and micropipette tips are the only additional supplies), we envision that SALMATcor will contribute to establish a sustainable Salmonella serovar surveillance worldwide.


Identification of peptides released from hot water insoluble fraction of edible bird's nest under simulated gastro-intestinal conditions.
For centuries, edible bird's nest (EBN) has been consumed as a Chinese delicacy. In the past decades, numerous studies reported that water soluble extract of the EBN not only possessed epidermal growth factor, but also associated with a wide range of health-promoting effects. However, based on the traditional Chinese way of EBN preparation and consumption, the bioactive components should be originated from both its hot water soluble and insoluble fractions. Nevertheless, information on the hot water insoluble fraction (HWIF) of EBN is not currently available. In this study, peptides released from the HWIF of EBN under simulated gastro-intestinal conditions were identified for the first time by de novo sequencing using a combination of MALDI TOF/TOF MS and ESI-ion-trap MS/MS. The released peptides were found to share very high similarities to mucin, NADH dehydrogenase, acidic mammalian chitinase-like protein, immunoglobulin, proline-rich protein, von Willebrand factor and epidermal growth factor domain-containing protein.


Diabetes in urban African-Americans. VI. Utility of fasting or random glucose in identifying poor glycemic control.
African-Americans have an increased prevalence of both diabetes and diabetes complications, creating an imperative for improved metabolic control. Because American Diabetes Association guidelines recommend that action be taken when HbA1c is > 8.0%, but access to rapid-turnaround HbA1c assays remains limited, we tested the utility of fasting and random plasma glucose cutoffs as indicators of HbA1c > 8.0%. Using receiver operating characteristics (ROC) analysis, we evaluated the sensitivity, specificity, and predictive value of fasting and random plasma glucose measurements in identifying an HbA1c > 8.0% (fasting n = 974, random n = 552). The population studied was predominantly African-American, middle-aged, and non-insulin-dependent. Fasting plasma glucose was a significant indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.87, 0.90, 0.87, and 0.84, respectively (all P < 0.0001). A fasting plasma glucose cutoff of > 9.2 mmol/l (165 mg/dl) provided a sensitivity of 80% and a specificity of 83% for the whole group and a 77% positive predictive value. Random plasma glucose was also a good indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.85, 0.91, 0.85, and 0.77, respectively (all P < 0.0001). A cutoff > 9.8 mmol/l (177 mg/dl) provided a sensitivity of 78% and a specificity of 77% for the whole group and a 78% positive predictive value. Overall, a plasma glucose > 11.1 mmol/l (200 mg/dl) identified an HbA1c > 8.0% with a predictive value of approximately 90% if done while fasting and a predictive value of approximately 80-85% if random. The utility of both fasting and random plasma glucose cutoffs was subsequently confirmed in a prospective study of another 2,309 and 1,396 patients, respectively. Although glucose levels cannot replace HbA1c determinations, measurement of fasting or random plasma glucose may be used during a clinic visit to identify poorly controlled type 2 patients with reasonable certainty and allow timely patient education and therapeutic intervention.


Acid-responsive properties of fibrils from heat-induced whey protein concentrate.
The heat-induced fibrils of whey protein concentrate (WPC) have demonstrated an acid-responsive property; that is, the fibrils went through formation-depolymerization-reformation as pH was adjusted to 1.8, 6.5, and back to 1.8. We investigated the microstructure, driving force, and thermal stability of 3.0% (wt) WPC nanofibrils adjusted between pH 6.5 and 1.8 twice. The results showed that the nanofibrils had acid-responsive properties and good thermal stability after reheating for 10h at 90°C and adjusting pH from 1.8 to 6.5 to 1.8. The content of WPC fibril aggregates was not much different with the prolongation of heating times during pH variation. Although the nanofibrils' structure could be destroyed only by changing the pH, the essence of this destruction might only form fiber fragments, polymers that would restore a fibrous structure upon returning to pH 1.8. A described model for the acid-responsive assembly of fibrils of WPC was proposed. The fibrils went through formation-depolymerization-reformation by weaker noncovalent interactions (surface hydrophobicity) as pH changed from 1.8 to 6.5 back to 1.8. However, the fibrils lost the acid-responsive properties because much more S-S (disulfide) formation occurred when the solution was adjusted to pH 6.5 and reheated. Meanwhile, fibrils still possessed acid-responsive properties when reheated at pH 1.8, and the content of fibrils slightly increased with a further reduction of α-helix structure.


Can EMF exposure during development leave an imprint later in life?
People in industrialized nations live in an environment of ubiquitous electromagnetic field (EMF) exposure, both natural and anthropogenic. The intensity, variety, and geographic distribution of anthropogenic EMF exposures have grown dramatically since the mid 20th century, with many uses serving, and in close proximity to, human populations, such as electric power distribution, radio and television transmission, and more recently, personal cell phone communication units and transmitting towers. Thus, it is reasonable to ask if this EMF exposure could cause alterations in the physiology of developing organisms, since they are generally assumed to be the most sensitive to chemical stressors. In this report, we review work published beginning in the late 1980s. Initial reports indicated that exposure of chicken eggs during embryonic development to power-line electric fields of 50 and 60 Hz, at 10 V/m in air (which is frequently in locations inhabited by humans), could cause the brain tissues of the hatched chickens to respond differently in a particular test. More recently, an anecdotal report of human sensitivity to EMF has appeared that shows a health-related influence of prior exposure history to particular power-line frequencies in chemically sensitized individuals. These reports open the question of whether the ambient electromagnetic environment can leave an imprint on developing organisms and if such imprint changes have the potential for health consequences.


Temporal Lobe Cavernous Malformation Caused Epileptic Amnesic Episodes and Mild Cognitive Impairment.
Neuropathological features in Alzheimer's disease (AD) are amyloid β (Aβ) deposits and neurofibrillary changes. AD is characterized by memory impairment and cognitive dysfunction, with some reports associating these impairments with hyperexcitability caused by Aβ in the medial temporal lobe. Epileptic seizures are known to be common in AD. We encountered a 65-year-old patient with cavernous malformation (CM) in the right temporal lobe who exhibited epileptic amnesia (EA) and AD-like symptoms. Scalp electroencephalography (EEG), including long-term video-EEG, showed no interictal discharges, but intraoperative subdural electrode (SE) recording from the right parahippocampal area showed frequent epileptiform discharges. Neuropathologically, senile plaques were found in the surrounding normal cortex of the CM. Postoperatively, the patient has remained free of EA and AD-like symptoms since total removal of the CM. This is the first surgical case report to confirm temporal lobe hyperexcitability associated with EA and AD-like symptoms.


Mucoepidermoid carcinoma of the vocal cord. Report of a case.
A case of mucoepidermoid carcinoma of the vocal cord is described in a 51-year-old man who presented with a thickened right vocal cord at the midportion without any limitation of movement. Histological examination revealed a mucoepidermoid carcinoma of low-grade malignancy. Partial laryngectomy was performed, but 10 months after the operation a squamous cell carcinoma developed on the other vocal cord. Primary vocal cord involvement of this tumor is rare. The literature is reviewed.


Three-Year Follow-up of Hyperopic LASIK Using a 500-Hz Excimer Laser System.
To evaluate the long-term visual, refractive, and corneal aberrometric outcomes and regression of the achieved correction of hyperopia with a sixth-generation excimer laser. This retrospective, consecutive, observational case series study comprised 86 eyes of 44 patients who underwent LASIK to correct hyperopia with a postoperative follow-up of 3 years. LASIK procedures were performed using the sixth-generation Amaris excimer laser (Schwind eye-tech-solutions GmbH and Co., Kleinostheim, Germany). Visual acuity, manifest refraction, corneal topography, and aberrometry were evaluated in the follow-up. Three years postoperatively, 65 eyes (76%) had an uncorrected distance visual acuity of 20/20 or better. Five eyes (6.2%) lost one or more lines of corrected distance visual acuity. Sixty eyes (70%) had a spherical equivalent within ± 0.50 diopters (D). There was regression of 0.47 D between 3 and 36 months postoperatively. Statistically significant differences were found in spherical equivalent between 3 and 36 months (P < .01), but no differences were observed between 12 and 36 months (P = .08). A flattening of 0.16 D was observed between 3 and 36 months after surgery in the mean simulated keratometry. A significant increase of root mean square spherical-like, coma-like, and higher-order aberrations (P < .01) were observed postoperatively. Twenty-five eyes (29%) required re-treatment. Treatment of hyperopia using the sixth-generation Amaris excimer laser provides good results in terms of efficacy, safety, predictability, and visual outcomes after 3 years. The refractive stability shows a significant regression in the first 12 months after surgery with more stable results from 12 months postoperatively.


Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia.
Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.


Specific immune responses against airway epithelial cells in a transgenic mouse-trachea transplantation model for obliterative airway disease.
Immune injury to airway epithelium is suggested to play a central role in the pathogenesis of obliterative bronchiolitis (OB) after clinical lung transplantation. In several studies, a rejection model of murine trachea transplants is used, resulting in obliterative airway disease (OAD) with similarities to human OB. To focus on the role of an immune response specifically against airway epithelium, we transplanted tracheas from transgenic mice expressing human epithelial glycoprotein (hEGP) on epithelial cells. We hypothesized that the immune response against the hEGP-2 antigen would result in OAD in the trachea transplants. Tracheas from hEGP-2 transgenic and control nontransgenic FVB/N mice were heterotopically transplanted into FVB/N mice and harvested at week 1, 3, 6, and 9. Anti-hEGP-2 antibodies were determined in the recipient blood. The trachea grafts were analyzed for cellular infiltration, epithelial cell injury, and luminal obliteration. Recipients of transgenic tracheal grafts gradually developed anti-hEGP-2 antibodies. In the transgenic grafts, the submucosa was infiltrated predominantly by CD4+ T cells. Epithelial cells remained present but showed progressive abnormality. The tracheal lumen showed a mild degree of obliteration. All these changes were absent in nontransgenic FVB/N trachea transplants. The hEGP-2 antigen on the epithelial cells of transgenic trachea transplants induces specific humoral and cellular immune responses, leading to a mild form of OAD. It provides a suitable model for further investigation of the role of epithelial cells in the development of OAD in animals and OB in human-lung transplantation.


Effect of a seminar on pharmacy student attitudes toward residency training.
Students at a college of pharmacy were surveyed before and after a one-hour seminar on residency training to determine whether the information changed their opinions of pursuing a residency and identify predisposing factors and barriers to pursuit of a residency. Attendance at the seminar was mandatory for students in professional years 1 through 3 (P1-P3). Before the seminar, students provided information on demographics, grade point average (GPA), involvement in organizations, and previous pharmacy experience, degrees, and careers. They were asked to choose from a list of reasons they were or were not considering residency training and to answer yes or no questions about the residency application process. Students numbered their preseminar form for matching with their postseminar form. Before and after surveys were obtained for 221 students. Thirty-nine percent of the students before the seminar and 40% afterward were considering residency training, not a significant difference. Students with a GPA greater than 3.5, those in the P1 class, those with a previous career, and those involved in multiple organizations or holding office in an organization were more likely to consider a residency. Students' knowledge about the residency application process was significantly greater after the seminar. The most commonly cited barriers to residency were availability of pharmacy jobs without a residency, "burnout with school," lack of interest, and financial and family obligations. A mandatory one-hour seminar on residencies did not influence pharmacy students' opinions of and plans for residency training, but it did identify factors affecting their decisions.


Effects of centrally and systemically administered indomethacin on body temperature in exercising rats.
Subcutaneous and intracerebroventricular (icv) injections of indomethacin were used to test whether prostaglandin synthesis is essential for the exercise-induced increase in a rat's body temperature. At an air temperature of 24 degrees C, male Wistar rats ran on a treadmill at 10-15 m/min 20 min after 300-micrograms icv injection or 60 min after 15-mg/kg sc injection of indomethacin or of control vehicle. The rectal temperature (Tre) of control rats in 17 control experiments increased by 1.0 degree C during exercise, whereas the Tre of the rats pretreated with intracerebroventricular indomethacin increased by only 0.4 degrees C. Threshold Tre for tail vasodilation was significantly lower in rats pretreated with indomethacin than the control rats (38.4 +/- 0.1 vs. 38.9 +/- 0.1 degrees C), but O2 uptake did not differ between indomethacin-pretreated and control rats. Subcutaneous injection of indomethacin did not affect the body temperature, tail vasomotor activity, or O2 uptake of exercising rats. Intracerebroventricular indomethacin did not affect Tre or tail vasomotor activity of rats resting at ambient temperatures of 24 and 28 degrees C. Present results suggest that prostaglandin synthesis is required for the vasoconstrictive effect of exercise on skin blood vessels and thus for the exercise-induced elevation of body temperature.


Primary malignant melanoma of left buccal mucosa with metastasis in thyroid: a case report.
Primary oral malignant melanomas are rare with an incidence of .2 to 8% of all melanomas. Less than 1% of them arise on buccal mucosa. Grossly they arise as a black macule with irregular borders & are commonly of mucosal lentiginous type. They appear at a higher stage and are aggressive with a 5 yr survival rate of 10-25%. 39% of metastasis in thyroid occur from skin (melanomas) and melanomas produce a thyroid mass while the original source remains occult. We report a case of oral malignant melanoma of left buccal mucosa for its rarity and its spread to cervical lymph nodes and thyroid.


Discrepant Parent-Adolescent Reports of Parenting Practices: Associations with Adolescent Internalizing and Externalizing Symptoms.
Discrepancies in multi-informant reports of parenting practices represent a meaningful clinical construct that can be harnessed to predict adolescent mental health outcomes and shed light on the nature of parent-adolescent relationships. To date, however, no research has sought to examine discrepancies in perceptions of parenting practices among adolescents with histories of substance use disorders, a population for whom supportive parenting is a critical protective factor during the recovery process. This study examined parent-adolescent informant discrepancies of parenting practices and their associations with externalizing and internalizing symptomology among a sample of adolescents with substance use disorder histories. Data were analyzed from 294 adolescents (M adolescent age = 16 years; 45% female, 72% white) and their parents (87% female, 83% white) from a larger longitudinal study. Parenting practices of interest were positive parenting, inconsistent discipline, and poor monitoring. Polynomial regression analyses were used to test the discrepancy hypotheses. The results generally suggested null associations between single informant reports and internalizing and externalizing symptoms. Discrepancies were noted, however, in multi-informant reports of positive parenting, such that higher levels of adolescent-reported positive parenting were associated with higher levels of internalizing symptoms at high (but not low) levels of parent-reported positive parenting. Similarly, discrepancies were noted in multi-informant reports of poor monitoring, such that lower levels of adolescent-poor monitoring were associated with higher externalizing symptoms at low levels of parent-reported poor monitoring. The findings are discussed in terms of research and clinical implications of collecting and utilizing multi-informant data among clinical samples of adolescents with unique risk profiles.


Surgical resection of a giant pericardial cyst showing a rapidly growing feature.
This report presents an extremely rare case of a rapidly growing giant pericardial cyst which was surgically removed 20 years after the first detection. A 38-year-old asymptomatic male was referred because of rapidly growing mass on the right diaphragm. This lesion was detected about 20 years earlier and checked by a chest roentgenogram once a year. However, this lesion showed rapid growth over the last year, therefore surgical removal was performed. A pathological examination revealed this lesion as a giant pericardial cyst without inflammatory, hemorrhage or malignant cells. Therefore, there was no pathological explanation for the rapid growth of this cyst. In conclusion, general thoracic surgeons should be aware of the possibility of rapid growth, even if the diagnosis is a pericardial cyst.


Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats.
Mild traumatic brain injuries (mTBIs) are the most common form of acquired brain injury. Symptoms of mTBI are thought to be associated with a neuropathological cascade, potentially involving the dysregulation of neurometabolites, lipids, and mitochondrial bioenergetics. Such alterations may play a role in the period of enhanced vulnerability that occurs after mTBI, such that a second mTBI will exacerbate neuropathology. However, it is unclear whether mTBI-induced alterations in neurometabolites and lipids that are involved in energy metabolism and other important cellular functions are exacerbated by repeat mTBI, and if such alterations are associated with mitochondrial dysfunction. In this experiment, using a well-established awake-closed head injury (ACHI) paradigm to model mTBI, male rats were subjected to a single injury, or five injuries delivered 1 day apart, and injuries were confirmed with a beam-walk task and a video observation protocol. Abundance of several neurometabolites was evaluated 24 h post-final injury in the ipsilateral and contralateral hippocampus using in vivo proton magnetic resonance spectroscopy (1H-MRS), and mitochondrial bioenergetics were evaluated 30 h post-final injury, or at 24 h in place of 1H-MRS, in the rostral half of the ipsilateral hippocampus. Lipidomic evaluations were conducted in the ipsilateral hippocampus and cortex. We found that behavioral deficits in the beam task persisted 1- and 4 h after the final injury in rats that received repetitive mTBIs, and this was paralleled by an increase and decrease in hippocampal glutamine and glucose, respectively, whereas a single mTBI had no effect on sensorimotor and metabolic measurements. No group differences were observed in lipid levels and mitochondrial bioenergetics in the hippocampus, although some lipids were altered in the cortex after repeated mTBI. The decrease in performance in sensorimotor tests and the presence of more neurometabolic and lipidomic abnormalities, after repeated but not singular mTBI, indicates that multiple concussions in short succession can have cumulative effects. Further preclinical research efforts are required to understand the underlying mechanisms that drive these alterations to establish biomarkers and inform treatment strategies to improve patient outcomes.


Impact of preoperative ultrasonography for predicting the prognosis of deceased donor kidney transplantation.
This study evaluated the role of donor kidney ultrasonography (US) for predicting functional kidney volume and identifying ideal kidney grafts in deceased donor kidney transplantation. In total, 272 patients who underwent deceased donor kidney transplantation from 2000 to 2020 at Samsung Medical Center were enrolled. Donor kidney information (i.e., right or left) was provided to the radiologist who performed US image re-analysis. To binarize each kidney's ultrasound parameters, an optimal cutoff value for estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation was selected using the receiver operating characteristic curve with a specificity >60%. Cox regression analysis was performed for an eGFR less than 30 mL/min/1.73 m2 within 1 year after kidney transplantation and graft failure within 2 years after kidney transplantation. The product of renal length and cortical thickness was a statistically significant predictor of graft function. The odds ratios of an eGFR less than 30 mL/min/1.73 m2 within a year after kidney transplantation and the hazard ratio of graft failure within 2 years after kidney transplantation were 5.91 (P=0.003) and 5.76 (P=0.022), respectively. Preoperative US of the donor kidney can be used to evaluate donor kidney function and can predict short-term graft survival. An imaging modality such as US should be included in the donor selection criteria as an additional recommendation. However, the purpose of this study was not to narrow the expanded criteria but to avoid catastrophic consequences by identifying ideal donor kidneys using preoperative US.


Improved stress response in bipolar affective disorder with adjunctive spironolactone (mineralocorticoid receptor antagonist): case series.
The psychopathologies underlying affective disorders are thought to involve persistent changes in the expression and function of both mineralocorticoid receptors and glucocorticoid receptors in the hippocampus. In addition, exposure to stressful stimuli can precipitate episodes in vulnerable individuals. The aim of this study is to determine if spironolactone as an adjunctive therapy is effective in improving residual symptoms in bipolar disorder. Four cases of euthymic bipolar disorder (BD) patients were treated with spironolactone as an adjunctive therapy in a private treatment sector. All patients met the DSM-IV diagnosis criteria for bipolar disorder. Clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement. Spironolactone was effective in all patients. The four cases illustrate a clinical response to residual symptoms and improvement in stress response after use of spironolactone as an adjunctive therapy in BD. This pilot case series suggests reducing in residual symptoms, with spironolactone as an adjunctive therapy in these DSM-IV BD patients. Mineralocorticoid receptors antagonists' role in reducing stress-induced symptoms deserves further investigation through placebo-controlled trials.


Distinct Interaction of Lytic Polysaccharide Monooxygenase with Cellulose Revealed by Computational and Biochemical Studies.
A distinct interaction pattern of lytic polysaccharide monooxygenases (LPMOs) with their insoluble substrate, cellulose, was revealed through the combination of computational and biochemical approaches. The results indicated that the enzymes can stably bind on the flat hydrophobic surface of cellulose via the interactions of the key residues located in the axis across the conserved distal tyrosine residue and copper ion with two adjacent cellulose chains. Further studies on the correlation of substrate binding and H2O2 accumulation suggested that LPMOs involved in the productive binding on the insoluble polysaccharides not only fail to accumulate H2O2 but also consume the H2O2 produced by the unbound molecules under the lab condition. This was further substantiated by quantum-mechanical calculations. These findings broadened our knowledge of the interaction between enzymes and insoluble substrates and deepened our understanding of the role that H2O2 plays in LPMO activity.


[Clinical characteristics and outcome of patients with primary central nervous system lymphoma].
To investigate the characteristics, treatment and outcome of patients with primary central nervous system lymphoma (PCNSL). A total of 37 patients with PCNSL treated in Peking Union Medical College Hospital from June 1999 to June 2012 were enrolled into this retrospective study. The clinical characteristics, results of treatment and prognostic factors were analyzed. The median age of 37 patients with PCNSL at diagnosis was 57 years(range 17 to 78 years) with a male to female ratio of 2.7:1. The symptoms or signs of elevated intracranial pressure and cognitive dysfunction were the most common initial manifestations. The median time period between onset of symptoms and diagnosis was 1.5 months. The majority of lesions were located in the cerebral hemisphere. At a median follow-up of 50 months, the median overall survival for all treated patients was 36.0 months (95% CI 21.7-50.3 months), with a progression-free survival of 18.0 months(95% CI 9.1-26.9 months). The 3-year cumulative survival rate was 46.9%. Compared to chemotherapy alone, combined-modality regimens which did not improve outcome were associated with a greater risk of neurotoxicity. The prognosis of PCNSL was still poor, and the optimal treatment strategy for these patients should be explored in the future clinical trials.


Wide-angle point-to-point x-ray imaging with almost arbitrarily large angles of incidence.
The paper describes a new scheme for wide-angle point-to-point x-ray imaging with almost arbitrarily large angles of incidence by a matched pair of spherically bent crystals to eliminate the astigmatism, which is a well-known imaging error of spherical mirrors. In addition to x rays, the scheme should be applicable to a very broad spectrum of the electromagnetic radiation, including microwaves, infrared and visible light, as well as UV and extreme UV radiation, if the crystals are replaced with appropriate spherical reflectors. The scheme may also be applicable to the imaging with ultrasound.


Impact of Multiple Single-Nucleotide Polymorphisms Within mprF on Daptomycin Resistance in Staphylococcus aureus.
A number of single nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) have been associated with daptomycin-resistance (DAP-R) in Staphylococcus aureus. Such SNPs have been found throughout the mprF ORF, although there are clearly preferred "hot spots" within this gene frequently linked to DAP-R phenotype. These mprF SNPs are often correlated with a gain-in-function phenotype, either in terms of increased production (synthase activity) and/or enhanced translocation (translocase activity) of lysyl-phosphatidylglycerol (L-PG) within its cell membrane. However, it is unclear if multiple hot spot mprF SNPs can accumulate within mprF ORFs and cause additive elevations of DAP minimum inhibitory concentrations (MICs). In this study, we used a previously well-characterized plasmid complementation system in S. aureus Newman ΔmprF mutant to express: (1) single point-mutated forms of mprF ORFs cloned from two DAP-R S. aureus strains (mprFS295L or mprFT345A) and (2) dual point-mutated forms of mprF ORFs simultaneously harboring SNPs in the central bifunctional domain and synthase domain in MprF, respectively (mprFS295L+L826F or mprFT345A+L826F). The current study revealed that, although individual hot spot point mutations within mprF ORF can recapitulate signature DAP-R-associated phenotypes (i.e., increased DAP MICs, enhanced surface positive charge, and increased L-PG synthesis), accumulation of such hot spot point mutations paradoxically caused reduction in these latter three metrics.


Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.
To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease.


Clinical factors and clinical variation influencing the reproducibility of interocclusal recording methods.
The reproducibility of clinical records of the occlusion was assessed in three dimensions using mounted casts. Three distinct areas were examined: 1) mandibular positions (intercuspal position (IP) or retruded contact position (RCP)), 2) materials used in recording the occlusion, 3) clinical variation. Interocclusal records were made in a random order of three patients: one fixed prosthodontics case, one removable partial denture case and one complete denture case, with two different types of waxes, record rims, two different brands of vinyl polysiloxanes and one irreversible hydrocolloid. Private practice and Karolinska Institute, Huddinge, Sweden. One general dental practitioner and three voluntary patients. Point estimation of variance components indicate that 70-93% of the variation of the positions of the mounted casts are caused by: 1) clinical variation for all three cases and in three directions, 2) the influence of recording materials 0-29%, and 3) mandibular positions (IP/RCP) 0-11%. The ranges of the positions of the mounted casts were lower for the dentate case (0.04-1.39 mm) than for the partially dentate case (0.17-2.65 mm), which in turn was lower than those for the edentulous case (1.42-5.59 mm). Clinical variation seems to dominate the variation in positions of mounting casts when making interocclusal records, rather than mandibular position or the recording materials used. Therefore a dentist who makes one single interocclusal record cannot presume that it will reproduce the interocclusal relationship intended, which in the present study was most obvious for the edentulous case. The results showed that impression materials stabilised by a tray did not differ significantly from waxes and record rims concerning the reproducibility. Therefore the stabilised impression materials are an alternative, which also give additional advantages like reduction of appointments as well as superior accuracy.


Emergence of Highly Multidrug-Resistant Bacteria Isolated from Patients with Infections Admitted to Public Hospitals in Southwest Iran.
The emergence of multidrug-resistant (MDR) microorganisms causing infections is increasing worldwide and becoming more serious in developing countries. Among those, Acinetobacter species are becoming prominent. The aim of this study was to determine the rate of antimicrobial resistance of the bacteria causing infections, Acinetobacter species in particular, in local public hospitals in Firuzabad, Fars province, Iran. This cross-sectional study was performed on different clinical specimens collected from patients who were suspected of infections hospitalized from March 2016 to March 2019 in local hospitals of Firuzabad, Fars province, Iran. The bacterial isolates were identified following standard microbiological methods. Clinical and Laboratory Standards Institute guidelines were used to identify the antibiotic susceptibility of these isolates. Overall, 1778 bacterial etiologies were isolated from 1533 patients diagnosed with infection. Of these, 1401 (78.8%) were Gram-negative and the remaining were Gram-positive bacteria. Escherichia coli (37.1%), Klebsiella spp. (13.9%), and Acinetobacter species (10.4%) were the most common isolated bacteria. Antibiotic sensitivity testing in this study showed a high resistance rate of Acinetobacter species to all antibiotics tested except Colistin. During the study period, the rate of infection with highly multidrug-resistant Acinetobacter species increased from 7.2% to 13.3%. This study highlights the emergence of MDR bacterial agents such as Acinetobacter species as a new threat in our region. However, a decrease in the rate of infection with Pseudomonas aeruginosa was noticeable.


The putative Arabidopsis zinc transporter ZTP29 is involved in the response to salt stress.
Salt stress leads to a stress response, called the unfolded protein response (UPR), in the endoplasmic reticulum (ER). UPR is also induced in a wide range of organisms by zinc deficiency. However, it is not clear whether regulation of zinc levels is involved in the initiation of the UPR in plant response to salt stress. In this study, a putative zinc transporter, ZTP29, was identified in Arabidopsis thaliana. ZTP29 localizes to the ER membrane and is expressed primarily in hypocotyl and cotyledon tissues, but its expression can be induced in root tissue by salt stress. T-DNA insertion into the ZTP29 gene led to NaCl hypersensitivity in seed germination and seedling growth, leaf etiolation, and widening of cells in the root elongation zone. In addition, in ztp29 mutant plants, salt stress-induced upregulation of the UPR pathway genes BiP2 and bZIP60 was inhibited. Furthermore, under conditions of salt stress, upregulation of BiP2 and bZIP60 was inhibited by treatment with high concentrations of zinc in both control and ztp29 plants. However, zinc chelation restored salt stress-induced BiP2 and bZIP60 upregulation in ztp29 mutant plants. These experimental results suggest that ZTP29 is involved in the response to salt stress, perhaps through regulation of zinc levels required to induce the UPR pathway.


Identifying Stuttering in Arabic Speakers Who Stutter: Development of a Non-word Repetition Task and Preliminary Results.
Stuttering and other conditions that affect speech fluency need to be identified at an early age in order that effective interventions can be given before the problems becomes chronic. This applies in countries where several languages are spoken including those in which English and Arabic are both widely used which calls for assessment procedures that work across these languages. The 'universal' non-word repetition task (UNWR) has been established as an effective screening tool for discriminating between children who stutter (CWS) and children with word-finding difficulty for a number of languages. However, the UNWR does not apply to languages such as Arabic and Spanish. The present study aimed to: (1) introduce an Arabic English NWR (AEN_NWR); which was developed based on the same phonologically informed approach used with UNWR; (2) present preliminary non-word repetition data from Arabic-speaking CWS and adults who stutter (AWS). The AEN_NWR items comprises twenty-seven non-words that meet lexical phonology constraints across Arabic and English. The set of items includes non-words of two, three and four syllables in length. Preliminary non-word repetition data were collected from ten CWS between the ages of 6;5 and 16;7 (M age = 12:1) and fourteen AWS between the ages of 19;2 and 31;0 (M age = 24). Participants performed the non-word repetition task and provided a sample of spontaneous speech. The spontaneous speech samples were used to estimate %stuttered syllables (%SS). To validate that AEN_NWR performance provides an alternative way of assessing stuttering, a significant correlation was predicted between %SS and AEN_NWR performance. Also, word length should affect repetition accuracy of AEN_NWR. As predicted, there was a significant negative correlation between the AEN_NWR and %SS scores (r (25) = -0.5), p < 0.000). Overall, CWS were less accurate in their repetition than AWS at all syllable lengths. The AEN_NWR provides a new assessment tool for detecting stuttering in speaker of Arabic and English. Future studies would benefit from a larger sample of participants, and by testing a population-based sample. These studies would allow further investigation of the AEN_NWR as a screening measure for stuttering in preschool children.


Computational Search for Possible Mechanisms of 4-Thiazolidinones Anticancer Activity: The Power of Visualization.
Public databases of NCI-60 tumor cell line screen results and measurements of molecular targets in the NCI-60 panel give the opportunity to assign possible anticancer mechanism to compounds with positive outcome from antitumor assay. Here, the novel protocol of NCI databases mining where inferences are based on the visualization is presented and utilized with the aim to identify putative biological routes of 4-thiazolidinones anticancer effect. As a result, highly potent 4-thiazolidinone-pyrazoline-isatin conjugates show the similarity of activity patterns with puromycin and CBU-028 and their pattern is also highly correlated with fraction of methylated CpG sites in CD34, AF5q31 and SYK. Several compounds from this group show strong negative correlation with fraction of methylated CpG sites in HOXA5. Thiopyrano[2,3-d][1,3]thiazol-2-ones bearing naphtoquinone fragment were found to possess the same activity pattern as fusarubin does. But none of the studied 4-thiazolidinone derivatives has activity fingerprint similar to standard anticancer agents. The obtained results bring medicinal chemistry closer to the understanding of basic nature of 4-thiazolidinones effect on cancer cells.


Synthesis, antiplatelet and vasorelaxing activities of xanthone derivatives.
A series of omega-aminoalkoxylxanthones was synthesized and tested in vitro for their ability to inhibit platelet aggregation and cause vasorelaxing action. Compounds 4, 5, 12, 17, and 18 showed significant antiplatelet effects on thrombin-, arachidonic acid (AA)-, collagen-, and platelet activating factor (PAF)-induced washed rabbit platelet aggregation and exhibited inhibition of primary and secondary aggregation induced by adenosine-5'-diphosphate (ADP) in human platelet-rich-plasma (PRP). Compounds 4, 17, and 18 revealed vasorelaxing activities in rat thoracic aorta. We concluded that these compounds may be developed as new antithrombotic agents.


[Clinicotherapeutic aspects of neurosis-like states in elderly patients with a psychoorganic syndrome of vascular genesis].
The neurosis-like manifestations take up an important place in the clinical symptomatology of elderly patients with a psychoorganic syndrome of vascular genesis. The objective of this study consisted in identifying the predictors of the therapy effectiveness for similar patients. 109 patients with the mean age equal to 68.3+/-1.4 years were evaluated. The complex therapy included correctors of the cerebral blood circulation, neurometabolic stimulators, psychotropic drugs as well as psychocorrective interventions. It was found that in neurosis-like states with predominance of anxiety, the peculiarities of patients' psychoemotional life conditions exert the greatest influence on the effectiveness of treatment. And in case of asthenic manifestations' leading position in the symptomatology of the above-mentioned states, in the foreground within this context the predictors connected with the intensity of cerebroorganic changes proper are situated. Modern antidepressants as well as their combinations with neuroleptics, which possess a "soft" effect, and nootropic drugs, have occupied a principal place in the effective pharmacotherapy of neurosis-like manifestations.