Miracle-dz/UniFAR-FTUs huggingface dataset:
pRb, p16, and cyclin D1 in small cell carcinoma of the uterine cervix.

To the Editor: With interest, we recognized the response of Dr. Herrington (1) to our previous study about the expression of cell cycle regulatory proteins in small cell neuroendocrine carcinoma (SmCC) of the cervix uteri (2). Regarding their previous results (3,4), Dr. Herrington stressed the very interesting hypothesis that early integration events of high-risk human papillomavirus DNA with consecutive related high-level E7 expression in SmCC, in conjunction with the absence of cyclin D1 expression (2), are related to a disruption of the retinoblastoma protein (pRb) pathway. This idea has been supported by in vitro (5) and in vivo results on cervical intraepithelial neoplasia lesions (4) and in several human malignancies (for review, see (6)). Concerning this hypothesis, and the suggestion of Herrington (1) for completing the data on SmCC of the uterine cervix, we have evaluated pRb-1 expression in the SmCC of our previous study (2) and in 1 additional case using a monoclonal pRb-1 antibody (clone Rb-10, catalogue no. R 6878, 1:500, pretreatment: cooking in a microwave oven for 20 minutes at pH6; Sigma-Aldrich Inc, St Louis, MO). Nine of the 10 tested SmCC showed negative staining results (90%). However, all tumors, inclusive of the additional one, were positive for p16 and high-risk human papillomavirus. It has been found that pRb was phosphorylated in synchrony with the cell cycle (7). These data suggested that pRb may be a general cell cycle regulator. This hypothesis was initially supported by the observations that exogenous unphosphorylated pRb could arrest cells in the G1 phase of the cell cycle (8) and that depletion of pRb led to an accelerated G1/S transition (9), improving cellular proliferation and tumor growth. In conclusion, the available data on SmCC of the uterine cervix show a marked overexpression of p16 in all cases but a loss of cyclin D1 and pRb1 in most cases, which might indicate a widespread disruption of the Rb pathway. These alterations are not completely understood at time but might be responsible for the very aggressive behavior of SmCC of the cervix uteri.
Scale of protection and the various types of sports mouthguard

Objectives: To present a grading system of the protection offered by various types of mouthguard, together with an indication of associated risks, in order to make athletes aware of the consequences of improper or no mouth protection. Methods: A review of the literature on mouthguards, mouthguard materials, and novel laminates for mouthguards was carried out as it was apparent that information on mouthguards was lacking. Studies on stock (or unfitted) mouthguards, mouth formed (boil and bite) mouthguards, and custom mouthguards are reviewed. Results: A scale of protection offered by various mouthguards and novel laminates has been produced, where 0 indicates no mouthguard and 10 indicates a custom made mouthguard offering excellent protection. Conclusions: From work carried out on laminates and the manufacturing processes of mouthguards, it became apparent that information was lacking to enable athletes make informed decisions about the best oral protection for their chosen sport.
Micronutrient Metabolism in Hemodialysis Patients

Patients with end stage renal diseases (ESRD) that require long-term dialysis treatment still have high morbidity and mortality rates. Risk factors that are associated with outcomes and survival rates include long dialysis duration, medical complications, oxidative stress, infection, inflammation, and impaired immune responsiveness. Some studies have been investigated associations of disturbances of certain micronutrients in patients undergoing dialysis. However, the homeostasis of these micronutrients plays a critical role in the maintenance of antioxidant status and immune function, and the amelioration of infection. This chapter will focus on the associations between micronutrients (trace elements and vitamins) status and these risk factors and their potential therapeutic uses in hemodialysis patients. In addition, we review other special nutrients (substrates) that are essential for patient management.
TLR2 Is Necessary to Inflammatory Response in Coxiella burnetii Infection

Abstract: The resolution of Q fever, a zoonosis caused by Coxiella burnetii, depends on efficient innate and adaptive immune responses. Such responses are influenced by Toll‐like receptors (TLRs). TLR4 is involved only in part in immune responses against C. burnetii, suggesting a role for TLR2. We investigated C. burnetii infection in wild‐type and TLR2−/− mice. C. burnetii organisms were similarly eliminated by wild‐type and TLR2−/− mice. In contrast, the formation of granulomas, a marker for efficient cell‐mediated immunity, was markedly impaired. These results show that TLR2 is required for inflammatory and immune response to C. burnetii, but is dispensable for bacterial clearance.
Preprogrammed reactions in individuals with Down syndrome: the effects of instruction and predictability of the perturbation.

Preprogrammed reactions to unexpected loadings and unloadings of an elbow joint resisting an extending bias load were studied in subjects with Down syndrome. The subjects were instructed to either "let go" or "return back as fast as possible. " Both predictable and unpredictable perturbation directions were used. Integrated electromyograms of the two elbow flexors and two elbow extensors were used to characterize the preprogrammed reactions. All the subjects were able to modulate their preprogrammed reactions in response to a change in the instruction. They were also able to grade the preprogrammed responses corresponding to the magnitude of the perturbation. Two basic patterns of modulation were observed, "reciprocal" and "coactivation. " There were no effects of the predictability of the perturbation direction. Reconstructed joint compliant characteristics suggested an unchanged gain in the arc of the tonic stretch reflex. We propose that there are no abnormalities in the preprogrammed reactions of some individuals with Down syndrome. The apparent "clumsiness" of individuals with Down syndrome in a changing environment is assumed to reflect an adaptation to their impaired decision-making ability. The high variability of motor performance in subjects with Down syndrome may result from mixing different strategies for solving motor tasks.
Enhanced Molecular Mobility of Ordinarily Structured Regions Drives Polyglutamine Disease*

Background: Polyglutamine tract expansion within disease-associated proteins leads to protein aggregation and disease. Results: Molecular mobility of a single α-helix within ataxin-3 positively scales with polyglutamine tract length and drives misfolding and aggregation. Conclusion: Polyglutamine expansion allosterically enhances the molecular dynamics of folded regions to trigger amyloid-like fibril formation. Significance: This work resolves the mechanistic link between polyglutamine tract length and aggregation. Polyglutamine expansion is a hallmark of nine neurodegenerative diseases, with protein aggregation intrinsically linked to disease progression. Although polyglutamine expansion accelerates protein aggregation, the misfolding process is frequently instigated by flanking domains. For example, polyglutamine expansion in ataxin-3 allosterically triggers the aggregation of the catalytic Josephin domain. The molecular mechanism that underpins this allosteric aggregation trigger remains to be determined. Here, we establish that polyglutamine expansion increases the molecular mobility of two juxtaposed helices critical to ataxin-3 deubiquitinase activity. Within one of these helices, we identified a highly amyloidogenic sequence motif that instigates aggregation and forms the core of the growing fibril. Critically, by mutating residues within this key region, we decrease local structural fluctuations to slow ataxin-3 aggregation. This provides significant insight, down to the molecular level, into how polyglutamine expansion drives aggregation and explains the positive correlation between polyglutamine tract length, protein aggregation, and disease severity.
Long-term effects of low-calorie diet on the metabolic syndrome in obese nondiabetic patients.

The prevalence of obesity is increasing among western populations, bringing about a parallel rise in the prevalence of the metabolic syndrome (1), which is strictly related to overweight (2). There is full agreement that lifestyle changes primarily focused on weight reduction are the first-line approach to patients with the metabolic syndrome (3). In short-term trials, even a modest weight reduction has been shown to favorably affect the components of the metabolic syndrome such as hypertension, lipid abnormalities, and glycemic control (4–8). The long-term effects of weight loss on the cluster of factors that comprise the metabolic syndrome have been studied in both overweight (9) and mildly obese (10) patients. We report here the extent to which a 2-year treatment program with a low-calorie, low-fat diet altered components of the metabolic syndrome in obese, nondiabetic patients presenting with the syndrome. The local ethics committee reviewed and approved the study, and each eligible participant gave written informed consent. We enrolled 41 patients (30 women and 11 men, age 58.7 ± 11.27 years [means ± SD]) with the metabolic syndrome as diagnosed according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) (2). The inclusion criteria were age >18 years, BMI ≥30 kg/m2, and a willingness to adhere to the prescribed diet. The exclusion criteria …
The different impacts of socio-economic factors on suicide between males and females

I used the national panel data of Japan to investigate the determinants of suicide. The major findings are twofold. First, the social capital that enhances community integration had a greater effect on the suicide of females than that of males. This is probably because females are less likely to have full-time jobs and thus have more spare time, leading them to seek social involvement in their neighbourhoods and participate in community activities. Second, divorce causes the propensity to commit suicide among males to become about two times higher than that among females because of the compensation costs that males are more likely to pay to females.
Assessing culturally competent diabetes care with unannounced standardized patients.

BACKGROUND AND OBJECTIVES More effective diabetes care is desperately needed, especially for ethnic minority populations. Provider cultural competence promises to be an important means for reducing disparities in outcomes for patients with diabetes. The objectives of this study were to understand the role of cultural competence in the diabetes office visit. METHODS Unannounced standardized patients (SPs) were sent to the offices of 29 family and internal medicine residents and practicing physicians. The SPs portrayed a Mexican American woman newly diagnosed with type 2 diabetes. Using a checklist developed with the input of experts in Hispanic/Latino health care and cultural competence, the SPs evaluated physicians' cultural competence, diabetes care, and general communications skills. RESULTS The average total SP Checklist score was 70.7-11.0%, with a range of 43.9% to 90.2%. Physicians scored highly on items that measured general communication skills (95.9%) but were less likely to ask about social history (ie, family and community support issues, 51.9% and 48.1%, respectively). Sixty-seven percent of physicians ordered a hemoglobin A1c, 44% referred to ophthalmology, and 15% performed a monofilament exam. Physicians' inquiry into SPs explanatory model of disease (ie, asking about the SPs' views regarding their disease and its treatment) correlated with the performance of several diabetes treatment-related behaviors, Spearman's rho=. 466. CONCLUSIONS The findings provide support for a relationship between inquiry into patients' explanatory models of disease and effective diabetes care. Social history and explanatory model elicitation skills are vital parts of cultural competence training programs and potentially valuable tools for mitigating health disparities.
Evaluation of 18 F-FDG PET in Patients with Advanced , Metastatic , or Recurrent Gastric Cancer

1Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; 2Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; 3Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan; and 4Department of Diagnostic Radiology, Tohoku University Hospital, Tohoku University, Sendai, Japan
Vacuum birefringence in strong inhomogeneous electromagnetic fields

Birefringence is one of the fascinating properties of the vacuum of quantum electrodynamics (QED) in strong electromagnetic fields. The scattering of linearly polarized incident probe photons into a perpendicularly polarized mode provides a distinct signature of the optical activity of the quantum vacuum and thus offers an excellent opportunity for a precision test of nonlinear QED. Precision tests require accurate predictions and thus a theoretical framework that is capable of taking the detailed experimental geometry into account. We derive analytical solutions for vacuum birefringence which include the spatio-temporal field structure of a strong optical pump laser field and an x-ray probe. We show that the angular distribution of the scattered photons depends strongly on the interaction geometry and find that scattering of the perpendicularly polarized scattered photons out of the cone of the incident probe x-ray beam is the key to making the phenomenon experimentally accessible with the current generation of FEL/high-field laser facilities.
An analysis of the axon populations in the nerves to the pelvic viscera in the rat

The present study uses selective surgical ablations combined with electron microscopic analyses to determine the number of axons in yarious catagories in rat hypogastric, pelvic, and pudendal nerves, these being the nerves to the pelvic viscera in this animal. Unmyelinated fibers predominate in all of these nerves. One of the most significant findings is that the pelvic nerve contains almost as many postganglionic sympathetic fibers as the hypogastric nerve. Previous investigators thought that the pelvic nerve supplied the parasympathetic inflow and the hypogastric nerve the sympathetic inflow to the pelvic viscera. The finding that there is a sizable sympathetic component in the pelvic nerve negates this idea, at least for the rat, and presumably calls for a reevaluation of the syndromes that arise from pelvic as opposed to hypogastric nerve section. Other findings of interest are (1) that there are unmyelinated efferent axons in the pudendal nerve, indicating that the pudendal is not a typical somatic nerve, (2) that the hypogastric nerve has a very small sensory component, and (3) that there are fibers surviving in the distal stumps of all these nerves, particularly the pelvic and hypogastric nerves.
Presence of a simple lateral extramural diverticulum at the junction of second and third parts of the duodenum – a case report

Extramural duodenal diverticulum along the convex margin of the duodenum is a rare entity. Though its exact etiology is not clear, diverticulum of duodenum usually occurs at weak spots in duodenal walls near the major and minor duodenal papillae. Here we present a case, where we found an unusual diverticulum at the junction of the second and third parts of the duodenum. This was unique as it was very prominent with about 3 cm diameter and was along the lateral convex margin. Gastroenterologist and surgeons who deal with gastrointestinal obstructions or infections should be alert about this particular variation.
Abnormal localisation and hyperclustering of α V β 3 integrins and associated proteins in Src-deficient or tyrphostin A 9-treated osteoclasts

Osteoclasts are highly differentiated bone resorbing cells of hematopoietic origin. Bone resorption is a multistep process, initiated by osteoclast adherance to bone matrix leading to cytoskeletal reorganisation, cellular polarisation and formation of unique membrane areas for bone resorption (Suda et al., 1997; Roodman, 1999). During resorption osteoclastic microfilaments form a specific ring structure, called the sealing zone, which mediates tight attachment of the cell to mineralised bone matrix (Lakkakorpi et al., 1989; Lakkakorpi and Väänänen, 1991). The sealing zone surrounds a convoluted membrane area, called the ruffled border, formed as a result of active, directional secretion. Protons and proteases secreted into the compartment between the cell and the bone matrix dissolve mineral and organic components of bone (see review in Chambers and Hall, 1991). During active resorption, degraded bone matrix is endocytosed into the osteoclast, transported through the cell and secreted at the basal plasma membrane facing bone marrow (Nesbitt and Horton, 1997; Salo et al., 1997). The non-receptor tyrosine kinase c-Src has been shown to be essential for osteoclast function, since targeted disruption of c-Src in mice caused osteopetrosis (Soriano et al., 1991). The number of osteoclasts appears to be normal in Src-deficient mice, but these cells are not able to form ruffled border, which leads to impaired bone resorption in vivo and in vitro (Lowe et al., 1993). In addition, c-Src is largely localised to the ruffled border membrane and to vacuoles in osteoclasts (Boyce et al., 1992; Tanaka et al., 1992). αvβ3 integrin, which is the major integrin in osteoclasts, is also important for osteoclast function. Targeted disruption of β3 integrin in mice induces progressive osteosclerosis without an apparent reduction in osteoclast number (McHugh et al., 2000). αvβ3 integrin is suggested to mediate the initial adhesion of osteoclasts to bone matrix and to be necessary for osteoclast migration and progress of bone r sorption (Davies et al., 1989; Sato et al., 1990; Lakkakorpi et al., 1991; Nakamura et al., 1999). Engagement of αvβ3 integrin in osteoclasts, induces tyrosine phosphorylation of PYK2 (also known as CAK β, RAFTK or CADTK), a member of the focal adhesion kinase family, and of the adaptor protein p130Cas (Duong et al., 1998; Lakkakorpi et al., 1999). Both PYK2 and p130 Cas localise in the sealing zone in resorbing osteoclasts. Activation and tyrosine phosphorylation of PYK2 and p130Cas are Src-dependent, since their tyrosine phosphorylation is markedly reduced in osteoclasts derived from Src−/− mice (Duong et al., 1998; Nakamura et al., 1998; Lakkakorpi, 1999). Furthermore, PYK2 activity is reduced when osteoclasts are treated with bone resorption inhibiting agents, such as echistatin, calcitonin and cytochalasin D 149
Management of Blebitis by Members of the American Glaucoma Society: A Survey

PurposeTo investigate the practice patterns among glaucoma subspecialists in the American Glaucoma Society regarding the management of blebitis. MethodsAn anonymous survey incorporating 14 questions regarding the management of blebitis was mailed to all current active American Glaucoma Society members, including provisional members, in October 1999. ResultsA total of 319 physicians received the survey, and 204 members (64%) returned surveys. Sixty-nine percent of respondents do not ask their patients with functioning blebs to use topical antibiotics at home for early symptoms of blebitis. Thirty-four percent never or almost never obtain conjunctival cultures at the onset of isolated blebitis, whereas 44% always or usually do. Fifty-one percent prescribe a topical fluoroquinolone alone as the initial empirical treatment of isolated blebitis. Twenty-three percent use a fluoroquinolone in combination with one or two other antibiotics. Twenty-one percent choose a combination of fortified topical agents, usually including a fortified aminoglycoside, vancomycin, or cephalosporin. Thirty-one percent use fortified agents in some combination with or without a fluoroquinolone. Five percent prescribe some other single agent alone. Only 6% routinely use an oral antibiotic in cases of blebitis. Sixty-two percent use topical corticosteroids in conjunction with antibiotic treatment. Of these, 68% start them after initial antibiotic treatment is established or once improvement of blebitis is noted. Fifty-six percent indicated that a moderate or severe anterior chamber reaction, including fibrin, would prompt treatment as a possible endophthalmitis. In a persistently Seidel-positive bleb, 77% generally attempt surgical bleb revision. ConclusionsMethods of the management of blebitis differ among members of the American Glaucoma Society. Treatment recommendations generated from randomized clinical trials are needed.
(±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Clinical Studies

(±)3,4-Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is a brain serotonergic neurotoxin in experimental animals, including nonhuman primates. It is also an increasingly popular recreational drug of abuse, and doses of MDMA that are used recreationally overlap with those that produce serotonin (5-HT) neurotoxicity in animals. Studies in human MDMA users probing for evidence of brain serotonergic neurotoxicity indicate that some MDMA users may incur MDMA-related 5-HT neural injury and, possibly, functional sequelae. In particular, MDMA users have selective decrements in cerebrospinal fluid 5-hydroxyindoleacetic acid and brain 5-HT transporters, similar to nonhuman primates with documented MDMA-induced neurotoxicity. Functional abnormalities seen in MDMA users that may be related to 5- HT injury include cognitive deficits, altered sleep architecture, altered neuroendocrine function, altered behavioral responses to 5-HT selective drugs, and increased impulsivity. Additional studies in animals, as well as longitudinal and epidemiological studies in MDMA users, are required to confirm and extend the present data, and to determine whether MDMA users are at increased risk for developing neuropsychiatric illness as they age.
Gender, relationship stage, and sexual behavior: The importance of partner emotional investment within specific situations

This study examined the relationship of type of sexually instigating situation (partner behavior conveying emotional investment or not), relationship stage, and gender to self‐reported likelihood of engaging in sexual behavior. Participants (200 female and 122 male college students) read scenarios describing partner behavior in eight hypothetical sexual situations. Five of the sexual situations were proposed to explicitly communicate a sense of emotional investment in the relationship, and three other scenarios were conceived as not explicitly conveying emotional investment. Emotional investment situations were hypothesized to influence likelihood ratings as a function of imagined relationship stage (dating or in a serious relationship), manipulated across participants. Situations not conveying investment were hypothesized to influence ratings as afiinction of both relationship stage and gender. In large part, hypotheses were confirmed. The few exceptions were consistent with other gender‐role considerations related to trust and power.