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1.
Climacteric ; 27(2): 171-177, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37942806

ABSTRACT

OBJECTIVE: This study aimed to compare the efficacy and safety of oral and transdermal estradiol in alleviating menopausal symptoms. METHOD: A total of 257 recently menopausal women were randomized into two groups. The t-E2 group received transdermal estradiol (2.5 g per day) (n = 128) and the o-E2V group received oral estradiol valerate (2 mg per day) (n = 129) for 24 weeks; both groups received micronized progesterone (200 mg per day). The primary outcome measure is the change in the modified Kupperman Menopausal Index (KMI) after 24 weeks of treatment. Menopausal symptoms were recorded at screening and at 4, 12 and 24 weeks using both the KMI and the Menopause Rating Scale (MRS). RESULTS: Significant amelioration was observed by KMI and MRS scores for both groups after treatment (p < 0.001). The mean KMI scores showed no difference between the two groups. The mean MRS scores were similar between the two groups at baseline and after 4 weeks of treatment. The results showed statistical differences after 12 weeks and 24 weeks of treatment (p = 0.005 and p = 0.011). Both the after-treatment scores minus the baseline scores of KMI and MRS and the incidence of adverse effects showed no difference between the two groups. CONCLUSIONS: This study shows that both transdermal and oral estradiol are effective in relieving menopausal symptoms, with little difference in treatment efficacy and safety. CLINICAL TRIAL NUMBER: ChiCTR2300073146.


Subject(s)
Estradiol , Menopause , Female , Humans , Progesterone , Estrogen Replacement Therapy/methods , Treatment Outcome , Administration, Cutaneous
2.
Diagn Cytopathol ; 51(4): 221-229, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36700488

ABSTRACT

INTRODUCTION: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is an established system with reproducible risk of malignancies (ROM) for salivary gland fine needle aspiration (SGFNA). No studies have reviewed the relationship between Milan categories and the resection rate (RR) and time to resection (TTR). METHODS: We searched our database (January 1, 2011 to January 4, 2021) for non-lymphoma SGFNAs and assigned appropriate MSRSGC categories. RR and TTR were calculated and compared for each category. A literature search was performed; RRs and TTRs were compared. RESULTS: Seven hundred and eighty SGFNAs were identified, 333 with follow-up. RR was highest in suspicious for malignancy (SUS, V; 70.6%, n = 12/17), followed by the salivary gland neoplasm of uncertain malignant potential (SUMP, IVb; 69.6%, n = 80/115) and malignant (M, VI; 55.6%, n = 75/135). Among M, primary tumors had a higher RR (65.1%, n = 41/63) than metastases (47.2%, n = 34/72, p = .36). In literature review, SUS had the highest RR (69.3%, n = 233/336) followed by M (61.6%, n = 821/1332) and SUMP (60.2%, n = 632/1050). TTR was shorter in SUS (mean = 32.3 days, median = 25 days). Within the benign neoplasms (BN, IVa), Pleomorphic adenomas (PAs) had a higher RR than Warthin tumors (WTs) (66.3% vs. 37.2%, p < .00001), and a shorter TTR (median = 63 days vs. 90 days). CONCLUSIONS: Tumors classified as SUS had higher RR and at shorter intervals than those classified as SUMP. PAs have higher RRs and more expedient surgery than WTs. Cases classified as M are less likely to undergo follow-up than SUS, perhaps due to a lower RR for metastases.


Subject(s)
Adenolymphoma , Adenoma, Pleomorphic , Salivary Gland Neoplasms , Humans , Adenolymphoma/pathology , Adenoma, Pleomorphic/pathology , Biopsy, Fine-Needle , Retrospective Studies , Salivary Gland Neoplasms/surgery , Salivary Gland Neoplasms/pathology , Salivary Glands/surgery , Salivary Glands/pathology
3.
Nat Neurosci ; 25(11): 1481-1491, 2022 11.
Article in English | MEDLINE | ID: mdl-36216999

ABSTRACT

The dentate gyrus (DG) gates neocortical information flow to the hippocampus. Intriguingly, the DG also produces adult-born dentate granule cells (abDGCs) throughout the lifespan, but their contribution to downstream firing dynamics remains unclear. Here, we show that abDGCs promote sparser hippocampal population spiking during mnemonic processing of novel stimuli. By combining triple-(DG-CA3-CA1) ensemble recordings and optogenetic interventions in behaving mice, we show that abDGCs constitute a subset of high-firing-rate neurons with enhanced activity responses to novelty and strong modulation by theta oscillations. Selectively activating abDGCs in their 4-7-week post-birth period increases sparsity of hippocampal population patterns, whereas suppressing abDGCs reduces this sparsity, increases principal cell firing rates and impairs novel object recognition with reduced dimensionality of the network firing structure, without affecting single-neuron spatial representations. We propose that adult-born granule cells transiently support sparser hippocampal population activity structure for higher-dimensional responses relevant to effective mnemonic information processing.


Subject(s)
Dentate Gyrus , Hippocampus , Animals , Mice , Dentate Gyrus/physiology , Hippocampus/physiology , Neurons/physiology , Memory/physiology
4.
Neurochirurgie ; 68(6): e53-e59, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35940925

ABSTRACT

BACKGROUND: Intraventricular hemorrhage (IVH) is a severe form of stroke. Studies of existing treatment options are controversial. Therefore, we aimed to evaluate the safety and efficacy of extra ventricular drainage (EVD) combined with uPA administration for the treatment of IVH. METHODS: The clinical data of 157 IVH patients admitted to our department during 2019-2022 were retrospectively analyzed. Based on the Glasgow Outcome Score (GOS) after 30 days, patients were categorized into favorable outcome (GOS4-5) and poor outcome (GOS1-3), and factors with prognostic impact were screened by univariate and multifactorial analysis, followed by propensity score matching and screening of paired patients for comparative analysis between the uPA and non-uPA groups. RESULTS: Patient age, uPA use, initial GCS score, and intracranial hematoma volume can all influence the patient's GOS. After propensity score-matched screening, 72 patients were finally included, 36 each in the uPA and non-uPA groups. Analysis revealed that at the follow-up after 30 days, 50.0% of patients with a GOS score of 4-5 were in the uPA group compared with 30.6% in the non-uPA group; however, they were not statistically significantly different. In contrast, the mean clearance of hematoma after four days was significantly higher in the uPA group than in the non-uPA group (P<0.05) and did not increase the incidence of postoperative complications (P>0.05). CONCLUSION: uPA treatment may eliminate hematomas faster and reduce the rate of obstruction. However, its effectiveness in improving patient prognosis does not appear to be significant. Therefore, studies with larger samples may be needed to further validate its effectiveness.


Subject(s)
Cerebral Hemorrhage , Urokinase-Type Plasminogen Activator , Humans , Urokinase-Type Plasminogen Activator/therapeutic use , Retrospective Studies , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/surgery , Hematoma/surgery , Drainage
5.
Cancer Cytopathol ; 130(10): 800-811, 2022 10.
Article in English | MEDLINE | ID: mdl-35640089

ABSTRACT

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) reports a 25% rate of malignancy (ROM) for the Milan I: Nondiagnostic (ND) category. We clarify the ROM of ND salivary gland fine-needle aspirations (SGFNAs) based on our institutional experience and review of the literature. METHODS: Overall risk of malignancy (OROM) and that for those with surgical/flow cytometric follow-up (FROM) for each category and "all-comers" were calculated for Emory SGFNAs from January 2010 through March 2021. From a literature review of 50 articles using MSRSGC, distribution of diagnoses, rates of follow-up, FROM, and OROM by category were calculated. FROMs and OROMs between ND FNAs and all-comers were compared. Milan I rate was compared with the ratio of Milan I OROM to all-comer OROM. RESULTS: Of 819 SGFNAs at Emory, 12.8% (n = 105/819) were ND. Thirty-two had known follow-up, with 12 (37.5%) being malignant. Nonmucinous cyst contents accounted for 26.7% of ND SGFNAs (n = 28/105); all 7 with surgical follow-up were benign. Of 50 MSRSGC studies, 18.2% (n = 2384/13,129) of SGFNAs were classified as ND, 26.6% (n = 635/2384) with known follow-up. Total FROM and OROM for ND FNAs (15.7% and 4.1%, respectively) were significantly lower than those for all-comers (24.9% and 11.4%, respectively) (p < .001). There was no relationship between rate of ND SGFNA and ND ROM. CONCLUSIONS: The ND category is associated with a lower ROM than that of all-comer SGFNA patients. The "true" ROM for ND SGFNAs is likely best estimated by the 4.1% OROM. SGFNAs showing nonmucinous cyst contents have a particularly low ROM. Rate of ND SGFNAs does not influence ND ROM.


Subject(s)
Cysts , Salivary Gland Neoplasms , Biopsy, Fine-Needle , Cysts/pathology , Humans , Retrospective Studies , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/pathology , Salivary Glands/pathology
6.
Zhonghua Zhong Liu Za Zhi ; 44(4): 334-340, 2022 Apr 23.
Article in Chinese | MEDLINE | ID: mdl-35448921

ABSTRACT

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 µmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 µmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 µmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.


Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cyclin D1 , Female , Flavonoids , Humans , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , MicroRNAs/genetics , RNA, Messenger , Urinary Bladder Neoplasms/genetics
7.
J Magn Reson Imaging ; 55(3): 681-697, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33682266

ABSTRACT

Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States with the incidence rate more than doubling in 20 years. HCC is unique since a noninvasive diagnosis can be achieved with imaging alone when specific clinical criteria and imaging characteristics are met, obviating the need for tissue sampling. However, HCC is a highly heterogeneous neoplasm. Atypical HCC subtypes vary significantly in their morphology, which can be attributed to specific histologic and molecular features, and can cause deviations from the classic imaging characteristics. The different morphologic subtypes of HCC frequently present a diagnostic challenge for radiologists and pathologists since their imaging and pathologic features can overlap with those of non-HCC malignancies. Identifying an atypical subtype can have important clinical implications. Liver transplant, albeit a scarce and limited resource, is the optimal treatment for conventional HCC, potentially curing both the tumor and the underlying pre-malignant condition. Some HCC subtypes as well as mimickers are associated with unacceptably high recurrence and poor outcome after transplant, and there remains limited data on the role and prognosis of liver transplantation for treatment of rare HCC subtypes. Other subtypes tend to recur later than classic HCC, potentially requiring a different follow-up scheme. This review will discuss the appearance of different HCC subtypes in relation to their histopathologic features. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Radiology , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Prognosis
8.
Transl Psychiatry ; 11(1): 588, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34782594

ABSTRACT

Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest-activity profiles of GluA1-knockout mice (Gria1-/-). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest-activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1-2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides-vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)-differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts' short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia.


Subject(s)
Circadian Rhythm , Receptors, AMPA , Animals , Cues , Mice , Suprachiasmatic Nucleus , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
9.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: mdl-34556572

ABSTRACT

Light provides the primary signal for entraining circadian rhythms to the day/night cycle. In addition to rods and cones, the retina contains a small population of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). Concerns have been raised that exposure to dim artificial lighting in the evening (DLE) may perturb circadian rhythms and sleep patterns, and OPN4 is presumed to mediate these effects. Here, we examine the effects of 4-h, 20-lux DLE on circadian physiology and behavior in mice and the role of OPN4 in these responses. We show that 2 wk of DLE induces a phase delay of ∼2 to 3 h in mice, comparable to that reported in humans. DLE-induced phase shifts are unaffected in Opn4-/- mice, indicating that rods and cones are capable of driving these responses in the absence of melanopsin. DLE delays molecular clock rhythms in the heart, liver, adrenal gland, and dorsal hippocampus. It also reverses short-term recognition memory performance, which is associated with changes in preceding sleep history. In addition, DLE modifies patterns of hypothalamic and cortical cFos signals, a molecular correlate of recent neuronal activity. Together, our data show that DLE causes coordinated realignment of circadian rhythms, sleep patterns, and short-term memory process in mice. These effects are particularly relevant as DLE conditions-due to artificial light exposure-are experienced by the majority of the populace on a daily basis.


Subject(s)
Circadian Rhythm , Light , Memory, Short-Term/physiology , Retinal Ganglion Cells/physiology , Rod Opsins/physiology , Sleep/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Retinal Ganglion Cells/cytology
10.
Nat Neurosci ; 24(9): 1210-1215, 2021 09.
Article in English | MEDLINE | ID: mdl-34341585

ABSTRACT

Cortical and subcortical circuitry are thought to play distinct roles in the generation of sleep oscillations and global state control, respectively. Here we silenced a subset of neocortical layer 5 pyramidal and archicortical dentate gyrus granule cells in male mice by ablating SNAP25. This markedly increased wakefulness and reduced rebound of electroencephalographic slow-wave activity after sleep deprivation, suggesting a role for the cortex in both vigilance state control and sleep homeostasis.


Subject(s)
Dentate Gyrus/physiology , Neocortex/physiology , Neurons/physiology , Sleep/physiology , Wakefulness/physiology , Animals , Male , Mice , Mice, Transgenic , Synaptosomal-Associated Protein 25/deficiency
11.
Sustain Sci ; 16(2): 703-708, 2021.
Article in English | MEDLINE | ID: mdl-33686348

ABSTRACT

Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11625-021-00909-y.

12.
Biochem Pharmacol ; 191: 114404, 2021 09.
Article in English | MEDLINE | ID: mdl-33412102

ABSTRACT

Acute exposure to light exerts widespread effects on physiology, in addition to its key role in photoentrainment. Although the modulatory effect of light on physiological arousal is well demonstrated in mice, its effect on memory performance is inconclusive, as the direction of the effect depends on the nature of the behavioural task employed and/or the type of stimulus utilised. Moreover, in all rodent studies that reported significant effects of light on performance, brain activity was not assessed during the task and thus it is unclear how brain activity was modulated by light or the exact relationship between light-modulated brain activity and performance. Here we examine the modulatory effects of light of varying intensities on recognition memory performance and frontoparietal waking electroencephalography (EEG) in mice using the spontaneous recognition memory task. We report a light-intensity-dependent disruptive effect on recognition memory performance at the group level, but inspection of individual-level data indicates that light-intensity-dependent facilitation is observed in some cases. Using linear mixed-effects models, we then demonstrate that EEG fast theta (θ) activity at the time of encoding negatively predicts recognition memory performance, whereas slow gamma (γ) activity at the time of retrieval positively predicts performance. These relationships between θ/γ activity and performance are strengthened by increasing light intensity. Thus, light modulates θ and γ band activities involved in attentional and mnemonic processes, thereby affecting recognition memory performance. However, extraneous factors including the phase of the internal clock at which light is presented and homeostatic sleep pressure may determine how photic input is translated into behavioural performance.


Subject(s)
Brain/physiology , Gamma Rhythm/physiology , Memory/physiology , Photic Stimulation/methods , Recognition, Psychology/physiology , Theta Rhythm/physiology , Animals , Electroencephalography/methods , Male , Mice , Mice, Inbred C57BL , Odorants , Smell/physiology
13.
Front Neurosci ; 15: 832535, 2021.
Article in English | MEDLINE | ID: mdl-35082600

ABSTRACT

Light is known to exert powerful effects on behavior and physiology, including upon the amount and distribution of activity across the day/night cycle. Here we use home cage activity monitoring to measure the effect of differences in home cage light spectrum and intensity on key circadian activity parameters in mice. Due to the relative positioning of any individually ventilated cage (IVC) with regard to the animal facility lighting, notable differences in light intensity occur across the IVC rack. Although all mice were found to be entrained, significant differences in the timing of activity onset and differences in activity levels were found between mice housed in standard versus red filtering cages. Furthermore, by calculating the effective irradiance based upon the known mouse photopigments, a significant relationship between light intensity and key circadian parameters are shown. Perhaps unsurprisingly given the important role of the circadian photopigment melanopsin in circadian entrainment, melanopic illuminance is shown to correlate more strongly with key circadian activity parameters than photopic lux. Collectively, our results suggest that differences in light intensity may reflect an uncharacterized source of variation in laboratory rodent research, with potential consequences for reproducibility. Room design and layout vary within and between facilities, and caging design and lighting location relative to cage position can be highly variable. We suggest that cage position should be factored into experimental design, and wherever possible, experimental lighting conditions should be characterized as a way of accounting for this source of variation.

15.
Sci Rep ; 10(1): 20680, 2020 11 26.
Article in English | MEDLINE | ID: mdl-33244132

ABSTRACT

Body temperature is an important physiological parameter in many studies of laboratory mice. Continuous assessment of body temperature has traditionally required surgical implantation of a telemeter, but this invasive procedure adversely impacts animal welfare. Near-infrared thermography provides a non-invasive alternative by continuously measuring the highest temperature on the outside of the body (Tskin), but the reliability of these recordings as a proxy for continuous core body temperature (Tcore) measurements has not been assessed. Here, Tcore (30 s resolution) and Tskin (1 s resolution) were continuously measured for three days in mice exposed to ad libitum and restricted feeding conditions. We subsequently developed an algorithm that optimised the reliability of a Tskin-derived estimate of Tcore. This identified the average of the maximum Tskin per minute over a 30-min interval as the optimal way to estimate Tcore. Subsequent validation analyses did however demonstrate that this Tskin-derived proxy did not provide a reliable estimate of the absolute Tcore due to the high between-animal variability in the relationship between Tskin and Tcore. Conversely, validation showed that Tskin-derived estimates of Tcore reliably describe temporal patterns in physiologically-relevant Tcore changes and provide an excellent measure to perform within-animal comparisons of relative changes in Tcore.


Subject(s)
Body Temperature/physiology , Skin/physiopathology , Animals , Body Temperature Regulation/physiology , Diet Therapy/methods , Feeding Methods , Hot Temperature , Mice , Mice, Inbred C57BL , Reproducibility of Results , Thermography/methods
16.
Endocr Pathol ; 31(3): 239-253, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32488621

ABSTRACT

Better prognostication/stratification of pancreatic neuroendocrine tumors (PanNETs) is needed. In this detailed morpheomic study of 163 resected PanNETs, 11 unusual variants, some of which were not previously recognized, and others scarcely documented in the literature, were identified, and their pathologic characteristics were further analyzed. By behavior and clinicopathologic associations, these variants could be grouped into three prognostically different categories. I. More aggressive (20%). Included in this group were the variants that in average showed higher grade and stage and adverse outcome including oncocytic, plasmacytoid, lipid-rich and previously unrecognized hepatoid variants, which often had a more diffuse/broad-band growth pattern, with some also displaying discohesiveness. They were characterized by abundant cytoplasm and often had prominent nucleoli (as seen in metabolically active cells), thus the provisional name "metabolic cell phenotype." Because of their diversion from classical neuroendocrine cytomorphology, these variants created challenges on original diagnostic workup, particularly hepatoid examples, which revealed Arginase 1/Hep Par-1 expression in 50%. II. Less aggressive (10%). These cases either showed signs of maturation, including nested growth, paraganglioid pattern (which was previously unrecognized), and organoid PanNETs such as "ductulo-insular" growth, or showed symplastic/degenerative changes, and despite their paradoxically disconcerting histology, were more benevolent in behavior. III. Undetermined. There were other variants including mammary tubulolobular-like, pseudoglandular, peliotic, and sclerotic PanNETs, which although diagnostically challenging, their biologic significance could not be determined because of rarity or heterogeneous characteristics. Prognostic associations: Features that were significantly different in the more aggressive group than the less aggressive group were median size (5.0 vs 1.6 cm, p < 0.001), percentage of pT3+T4 cases (72% vs 12%, p < 0.001), Ki67 index (5.3% vs 2.3%, p = 0.001), % G2 and G3 cases (77% vs 27%, p < 0.001), and rate of lymph node and distant metastasis (96% vs 27%, p < 0.001). In stepwise logistic regression model using the 3 established prognosticators of T stage, size, and grade along with morphology, only aggressive-morphology (metabolic cell phenotype) was found to be associated with metastatic behavior with an odds ratio of 5.9 with 95% confidence interval (C.I.) 1.688 to 22.945 and p value 0.007. In conclusion, PanNETs display various morphologic patterns that are not only challenging and important diagnostically but appear to have biologic significance. Tumors with more diffuse growth of cells with nucleoli and abundant cytoplasm and/or discohesion (oncocytic, hepatoid, lipid-rich, plasmacytoid PanNETs), provisionally termed "metabolic cell phenotype," show aggressive characteristics and are an independent determinant of adverse outcome and thus may require closer post-surgical follow-up, whereas variants with more degenerative or mature features (ductuloinsular, pleomorphic, paraganglioma-like) appear to be more benevolent despite their more atypical and worrisome morphology.


Subject(s)
Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Aged , Cell Differentiation , Cell Proliferation , Cohort Studies , Female , Humans , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neuroendocrine Tumors/pathology , Organ Size , Pancreas/pathology , Pancreatic Neoplasms/pathology , Phenotype , Prognosis , Risk Assessment
17.
Ecol Evol ; 9(13): 7425-7437, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31346413

ABSTRACT

The increasing [CO2] in the atmosphere increases crop productivity. However, grain quality of cereals and pulses are substantially decreased and consequently compromise human health. Meta-analysis techniques were employed to investigate the effect of elevated [CO2] (e[CO2]) on protein, zinc (Zn), and iron (Fe) concentrations of major food crops (542 experimental observations from 135 studies) including wheat, rice, soybean, field peas, and corn considering different levels of water and nitrogen (N). Each crop, except soybean, had decreased protein, Zn, and Fe concentrations when grown at e[CO2] concentration (≥550 µmol/mol) compared to ambient [CO2] (a[CO2]) concentration (≤380 µmol/mol). Grain protein, Zn, and Fe concentrations were reduced under e[CO2]; however, the responses of protein, Zn, and Fe concentrations to e[CO2] were modified by water stress and N. There was an increase in Fe concentration in soybean under medium N and wet conditions but nonsignificant. The reductions in protein concentrations for wheat and rice were ~5%-10%, and the reductions in Zn and Fe concentrations were ~3%-12%. For soybean, there was a small and nonsignificant increase of 0.37% in its protein concentration under medium N and dry water, while Zn and Fe concentrations were reduced by ~2%-5%. The protein concentration of field peas decreased by 1.7%, and the reductions in Zn and Fe concentrations were ~4%-10%. The reductions in protein, Zn, and Fe concentrations of corn were ~5%-10%. Bias in the dataset was assessed using a regression test and rank correlation. The analysis indicated that there are medium levels of bias within published meta-analysis studies of crops responses to free-air [CO2] enrichment (FACE). However, the integration of the influence of reporting bias did not affect the significance or the direction of the [CO2] effects.

18.
Transplant Proc ; 50(8): 2398-2400, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316365

ABSTRACT

Chronic antibody-mediated rejection is the most common cause of late graft loss in renal transplant recipients. Visfatin is a pre-B cell colony-enhancing factor secreted by activated lymphocytes. We hypothesize that visfatin may play a role in the augmentation of B cell colonies and facilitate antibody-mediated rejection. Renal transplant recipients were randomly selected for the study. Fasting blood samples were obtained for the assay of visfatin. The participants were prospectively followed up for 3 years. A total of 146 patients were recruited for the study and were divided into 3 groups according to tertile of serum visfatin level. At the end of follow-up, 6 patients had graft loss, including 1 graft loss in tertile 1, 3 in tertile 2, and 2 in tertile 3 (P = .60). Fourteen patients experienced at least 1 episode of acute rejection, while 21 patients were diagnosed as having chronic rejection. The distribution of acute rejection was 10.2% in tertile 1, 10.2% in tertile 2, and 8.3% in tertile 3 (P = .94); chronic rejection occurred in 10.2%, 16.3%, and 16.7%, respectively (P = .59). We conclude that serum visfatin level was not correlated with either graft failure or patient mortality in a 3-year observation period.


Subject(s)
Cytokines/blood , Graft Rejection/blood , Kidney Transplantation , Nicotinamide Phosphoribosyltransferase/blood , Adult , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft Survival/immunology , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Random Allocation
20.
Front Plant Sci ; 9: 924, 2018.
Article in English | MEDLINE | ID: mdl-30158939

ABSTRACT

Elevated atmospheric CO2 (eCO2) enhances the yield of vegetables and could also affect their nutritional quality. We conducted a meta-analysis using 57 articles consisting of 1,015 observations and found that eCO2 increased the concentrations of fructose, glucose, total soluble sugar, total antioxidant capacity, total phenols, total flavonoids, ascorbic acid, and calcium in the edible part of vegetables by 14.2%, 13.2%, 17.5%, 59.0%, 8.9%, 45.5%, 9.5%, and 8.2%, respectively, but decreased the concentrations of protein, nitrate, magnesium, iron, and zinc by 9.5%, 18.0%, 9.2%, 16.0%, and 9.4%. The concentrations of titratable acidity, total chlorophyll, carotenoids, lycopene, anthocyanins, phosphorus, potassium, sulfur, copper, and manganese were not affected by eCO2. Furthermore, we propose several approaches to improving vegetable quality based on the interaction of eCO2 with various factors, including species, cultivars, CO2 levels, growth stages, light, O3 stress, nutrient, and salinity. Finally, we present a summary of the eCO2 impact on the quality of three widely cultivated crops, namely, lettuce, tomato, and potato.

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