Regressive Changes Research Articles

Ultrastructure of Granulosa Cells of Bovine Ovarian Antral Follicles in Relation to Atresia

Abstract The aim of this study was to describe the most common forms of ovarian follicle atresia in large antral follicles of cows and quantify the occurrence of different cell structures in each form. Atresia of antral follicles in ovaries was determined on the basis of ultrastructural images acquired by electron microscopy of ultrathin sections contrasted with uranyl acetate and lead citrate to visualize cell organelles. All forms of atresia in large follicles are accompanied by regressive changes of the granulosa cells. The initial form of atresia is characterized by enlarged intercellular spaces after the disruption of the gap junctions and desmosomes. Small collapsed cells with pyknotic nuclei, substantially reduced the cytoplasm and a higher incidence of lysosomes are located on the surface of the granulosa layer. The stratum granulosum wall collapses and the basal membrane is swollen with a rupture of the lamina basalis. Obliterative atresia is characterized by a multiplied loose connective tissue consisting of collagen fibers, fibroblasts, histiocytes, blood capillaries and sporadically granulocytes. The cystic form of atresia is characterized by small collapsed, pyknotic granulosa cells settled in one or two layers. In luteinization-associated atresia, granulosa cells are hypertrophied, their cytoplasm contains smooth endoplasmic reticulum and mitochondria with tubules. In conclusion, the initial atresia of large antral ovarian follicles is associated with processes of cell death, followed by multiplication of the loose connective tissue cells, its dystrophy and hyalinization of the collagen fibers. Ultrastructural examination could be used as a complementary method to improve histopathological diagnostics of cow reproductive organs in veterinary practice.

Differences in price of flavoured and non-flavoured tobacco products sold in the USA, 2011–2016

BackgroundLimited data exist on whether there is differential pricing of flavoured and non-flavoured varieties of the same product type. We assessed price of tobacco products by flavour type.MethodsRetail scanner data...

Answer to September 2020 Photo Quiz

Answer: Chronic pulmonary coccidioidomycosis. An IgG antibody to Aspergillus fumigatus was not present in the patient’s serum, and Aspergillus fumigatus was not detected in either BAL sample by PCR. However, a serum Coccidioides IgG complement fixation titer was positive at 1:32. Coccidioides immitis/Coccidioides posadasii was isolated from culture of the BAL fluid and was also detected by a specific PCR assay. Treatment with fluconazole was initiated (1). The patient’s lengthy history of pulmonary illness suggests that she had acquired her infection in Mexico or Arizona, but autochthonous coccidioidomycosis has also been reported in Washington State (2). Most coccidioidal pneumonia is self-limited, and fewer than 1% of patients develop chronic progressive pulmonary infections, which may be indistinguishable from other chronic fungal or mycobacterial infections (3). Diabetes mellitus is a risk factor for chronic infection. Radiologic manifestations of chronic disease include residual nodules, chronic cavities, persistent pneumonia with or without lymphadenopathy, pleural effusion, and regressive changes such as localized fibrosis, bronchiectasis, and calcification (4). The pulmonary imaging in this patient was not specific for Coccidioides infection; however, the presence of the air crescent sign in the dependent area of the cavitating lesion was not felt to be typical for an aspergilloma, and sparing of the lung apex reduced the likelihood of tuberculosis.

Phylogenetic analysis and expression differences of eye-related genes in cavefish genus Sinocyclocheilus.

The adaptive evolution of visual systems has been observed in many cavefish. However, little is known about the molecular mechanisms underlying these adaptations, which include regressive changes such as eye degeneration. Here, we analyzed phylogenetic and expression patterns of 6 eye-related genes (crx, foxg1b, opn1sw2, otx2, rho and sox2) in 12 Sinocyclocheilus species from China, including 8 stygobionts and 4 stygophiles, and examined photoreceptor cell morphology of these species. Those eye-degenerated species of Sinocyclocheilus were polyphyletic and showed different degrees of photoreceptor defects in responses to cave environments. The eye loss and degeneration are the result of convergent evolution. Although S. anophthalmus grouped with the eye-normal species, it displayed not only a high degree of eye degeneration but also significant expression differences in eye-related genes compared with the eye-normal species. The gene foxg1b, which was determined to be under positive selection, might play an important role in the process of eye degeneration in S. anophthalmus based on differential expression. Eye-related gene expression and selection may have contributed to the polyphyly of the cave species. We examined gene expression and duplication in 6 eye-related genes and revealed that these genes displayed considerable diversity in relative expression in Sinocyclocheilus fishes. Otx2 and sox2 were significantly up-regulated in individual cave species, while the other 4 genes (crx, foxg1b, opn1sw2 and rho) were significantly down-regulated. These findings provide a valuable resource for elucidating molecular mechanisms associated with visual system evolution in cavefish.

National and State-Level Trends in Nontraumatic Lower-Extremity Amputation Among U.S. Medicare Beneficiaries With Diabetes, 2000-2017.

Diabetes is a leading cause of nontraumatic lower-extremity amputation (NLEA) in the U.S. After a period of decline, some national U.S. data have shown that diabetes-related NLEAs have recently increased, particularly among young and middle-aged adults. However, the trend for older adults is less clear. To examine NLEA trends among older adults with diabetes (≥67 years), we used 100% Medicare claims for beneficiaries enrolled in Parts A and B, also known as fee for service (FFS). NLEA was defined as the highest-level amputation per patient per calendar year. Annual NLEA rates were estimated from 2000 to 2017 and stratified by age-group, sex, race/ethnicity, NLEA level (toe, foot, below-the-knee amputation [BKA], or above-the-knee amputation [AKA]), and state. All rates were age and sex standardized to the 2000 Medicare population. Trends over time were assessed using Joinpoint regression and annual percent change (APC) reported. NLEA rates (per 1,000 people with diabetes) decreased by half from 8.5 in 2000 to 4.4 in 2009 (APC -7.9, P < 0.001). However, from 2009 onward, NLEA rates increased to 4.8 (APC 1.2, P < 0.01). Trends were similar across most age, sex, and race/ethnic groups, but absolute rates were highest in the oldest age-groups, Blacks, and men. By NLEA type, overall increases were driven by increases in rates of toe and foot NLEAs, while BKA and AKA continued to decline. The majority of U.S. states showed recent increases in NLEA, similar to national estimates. This study of the U.S. Medicare FFS population shows that recent increases in diabetes-related NLEAs are also occurring in older populations but at a less severe rate than among younger adults (<65 years) in the general population. Preventive foot care has been shown to reduce rates of NLEA among adults with diabetes, and the findings of the study suggest that those with diabetes-across the age spectrum-could benefit from increased attention to this strategy.

Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice.

BackgroundThe cellular mechanisms underlying the age‐associated loss of muscle mass and function (sarcopenia) are poorly understood, hampering the development of effective treatment strategies. Here, we performed a detailed characterization of age‐related pathophysiological changes in the mouse neuromuscular system.MethodsYoung, adult, middle‐aged, and old (1, 4, 14, and 24–30 months old, respectively) C57BL/6J mice were used. Motor behavioural and electrophysiological tests and histological and immunocytochemical procedures were carried out to simultaneously analyse structural, molecular, and functional age‐related changes in distinct cellular components of the neuromuscular system.ResultsAgeing was not accompanied by a significant loss of spinal motoneurons (MNs), although a proportion (~15%) of them in old mice exhibited an abnormally dark appearance. Dark MNs were also observed in adult (~9%) and young (~4%) animals, suggesting that during ageing, some MNs undergo early deleterious changes, which may not lead to MN death. Old MNs were depleted of cholinergic and glutamatergic inputs (~40% and ~45%, respectively, P < 0.01), suggestive of age‐associated alterations in MN excitability. Prominent microgliosis and astrogliosis [~93% (P < 0.001) and ~100% (P < 0.0001) increase vs. adults, respectively] were found in old spinal cords, with increased density of pro‐inflammatory M1 microglia and A1 astroglia (25‐fold and 4‐fold increase, respectively, P < 0.0001). Ageing resulted in significant reductions in the nerve conduction velocity and the compound muscle action potential amplitude (~30%, P < 0.05, vs. adults) in old distal plantar muscles. Compared with adult muscles, old muscles exhibited significantly higher numbers of both denervated and polyinnervated neuromuscular junctions, changes in fibre type composition, higher proportion of fibres showing central nuclei and lipofuscin aggregates, depletion of satellite cells, and augmented expression of different molecules related to development, plasticity, and maintenance of neuromuscular junctions, including calcitonin gene‐related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor‐β1. Overall, these alterations occurred at varying degrees in all the muscles analysed, with no correlation between the age‐related changes observed and myofiber type composition or muscle topography.ConclusionsOur data provide a global view of age‐associated neuromuscular changes in a mouse model of ageing and help to advance understanding of contributing pathways leading to development of sarcopenia.

Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

ObjectiveThe efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox‐Gastaut syndrome, and two in Dravet syndrome.MethodsEach trial of CBD (Epidiolex® in the US; Epidyolex® in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic regression for the 50% responder rate, where the principle analysis combined both indications and CBD doses in a stratified meta‐analysis. Pharmacokinetic data were examined for an exposure/response relationship based on CLB presence/absence. Safety data were analyzed using descriptive statistics.ResultsThe meta‐analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68; P < .0001) with CLB and 0.85 (0.73, 0.98; P = .0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71; P < .0001) with CLB and 2.40 (1.38, 4.16; P = .0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite.ConclusionsThese results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB show a lower rate of certain AEs than with CLB.

Evaluation of secondary dentin deposition in lower first molars to indicate a legal age threshold of 14 years using receiver operating characteristic curves.

The age threshold of 14 years has become vital in proving legal violations involving children, particularly in cases of suspected child labour, child pornography and the minimum age of criminal responsibility. In recent years, there has been great interest in the evaluation of age in children and sub-adults using analysis of regressive changes in teeth, with a particular focus on age thresholds that are of medico-legal importance. This research aimed to compare the sensitivity and specificity of stages of root pulp visibility by Olze etal. in a sample of South Indian children aged between 12 and 16 years, with an age threshold of 14 years, using receiver operating characteristic curves and the area under the curve (AUC). Among the four stages of root pulp visibility, stage 2 showed the highest AUC in both female and male cohorts. For stage 2, lower sensitivity and higher specificity values were recorded, indicating the possibility of type II errors (i.e. false negatives). In both sexes, stage 2 had a higher AUC (i.e. 0.696 in females and 0.706 in males, respectively). Based on our findings, it can be concluded that this staging method in lower first molars is of limited value in indicating the legal age threshold of 14 years. Future research should validate the proposed approach in a larger sample and consider how to improve predictions in this area.

The political economy of peace processes and the Women, Peace and Security agenda

ABSTRACT This article examines why the Women, Peace and Security (WPS) agenda has been so challenging to implement and argues that the political economy of war and peace, driven by a complex network of power, is a deterrent to sustainable and gender-just peace. However, peace initiatives are not a zero-sum game. They are dialectical, offering possibilities for both regressive and transformative change. Although inclusion of women and gender concerns in current peace processes lags behind expectations, the WPS agenda has been instrumental in changing the negotiation landscape and empowering women beyond the peace table. It has also exposed the need for a paradigm shift in the understanding of peace and security that effectively responds to power asymmetries and the neo-liberal environment that shapes policy and practice. Given their marginalised positioning vis-à-vis hegemonic power structures, women stand to contribute towards this end.

EFEK SUB LETHAL AMONIA AMBIEN TERHADAP HISTOPATOLOGIS IKAN NILA (Oreochromis niloticus) YANG DIPELIHARA DALAM SISTEM BIOFLOK

The purpose of this research were to measure the increasing of unionized ammonia during start-up period of biofloc system for growing Nile Tilapia and to figure out its effect on histopathological changes. There was only one treatment that designed with three replication, which was 40 liters of water that contained eight fishes of each weighed 22.. The biofloc system was treated with C/N ration 12:1. Total Ammonia Nitrogen, pH and temperature were measured daily as long as 14 days. the tissue of gill, liver and kidney were cut off at the end of the experiment for histopathological examination. The result of the experiment showed that the peak of unionized ammonia concentration achieved 0.34±0.05 mg/l at 10th day. Then, decreased rapidly to 0.003±0.0009 mg/l at 14th day. The gill, liver, and kidney had regressive changes as physiologic sub lethal response of unionized ammonia expose. Keywords : Biofloc, unionized ammonia, Nile Tilapia, histopatholocal

Spatial modeling, risk mapping, change detection, and outbreak trend analysis of coronavirus (COVID-19) in Iran (days between February 19 and June 14, 2020)

ObjectivesCoronavirus disease 2019 (COVID-19) represents a major pandemic threat that has spread to more than 212 countries with more than 432,902 recorded deaths and 7,898,442 confirmed cases worldwide so far (on June 14, 2020). It is crucial to investigate the spatial drivers to prevent and control the epidemic of COVID-19. MethodsThis is the first comprehensive study of COVID-19 in Iran; and it carries out spatial modeling, risk mapping, change detection, and outbreak trend analysis of the disease spread. Four main steps were taken: comparison of Iranian coronavirus data with the global trends, prediction of mortality trends using regression modeling, spatial modeling, risk mapping, and change detection using the random forest (RF) machine learning technique (MLT), and validation of the modeled risk map. ResultsThe results show that from February 19 to June 14, 2020, the average growth rates (GR) of COVID-19 deaths and the total number of COVID-19 cases in Iran were 1.08 and 1.10, respectively. Based on the World Health Organisation (WHO) data, Iran’s fatality rate (deaths/0.1M pop) is 10.53. Other countries’ fatality rates were, for comparison, Belgium – 83.32, UK – 61.39, Spain – 58.04, Italy – 56.73, Sweden – 48.28, France – 45.04, USA – 35.52, Canada – 21.49, Brazil – 20.10, Peru – 19.70, Chile – 16.20, Mexico– 12.80, and Germany – 10.58. The fatality rate for China is 0.32 (deaths/0.1M pop). Over time, the heatmap of the infected areas identified two critical time intervals for the COVID-19 outbreak in Iran. The provinces were classified in terms of disease and death rates into a large primary group and three provinces that had critical outbreaks were separate from the others. The heatmap of countries of the world shows that China and Italy were distinguished from other countries in terms of nine viral infection-related parameters. The regression models for death cases showed an increasing trend but with some evidence of turning. A polynomial relationship was identified between the coronavirus infection rate and the province population density. Also, a third-degree polynomial regression model for deaths showed an increasing trend recently, indicating that subsequent measures taken to cope with the outbreak have been insufficient and ineffective. The general trend of deaths in Iran is similar to the world's, but Iran’s shows lower volatility. Change detection of COVID-19 risk maps with a random forest model for the period from March 11 to March 18 showed an increasing trend of COVID-19 in Iran’s provinces. It is worth noting that using the LASSO MLT to evaluate variables’ importance, indicated that the most important variables were the distance from bus stations, bakeries, hospitals, mosques, ATMs (automated teller machines), banks, and the minimum temperature of the coldest month. ConclusionsWe believe that this study's risk maps are the primary, fundamental step to take for managing and controlling COVID-19 in Iran and its provinces.

Cyclophosphamide, a cancer chemotherapy drug-induced early onset of reproductive senescence and alterations in reproductive performance and their prevention in mice

Although, cyclophosphamide (CP) treatment is known to cause degeneration of the ovarian follicular reserve, which may have a serious consequence of the onset of early reproductive senescence, thus far there is no experimental study either to demonstrate CP-induced early onset of reproductive senescence or its prevention. Intraperitoneal administration (ip) of CP [100 mg/kg body weight (bw)/mouse] resulted in a drastic reduction in reproductive life span as shown by the onset of reproductive senescence at a significantly early age (258 days) compared to controls (349 days), whereas treatment with the root extract of the herb Decalepis hamiltonii (DH) (200 mg/Kg bw/day for 7 days), a cocktail of anti-oxidants prior to CP administration maintained normal reproductive life span in mice. Further, the CP treated mice showed a significant increase in pre-coital interval and a significant reduction in parturition index coupled with regressive changes in the uterine endometrium, whereas DH co-treatment prevented these changes. The results for the first time, demonstrate that the ovarian toxicity of CP could be prevented by an anti-oxidant to maintain a normal reproductive life span as well as reproductive outcome using mice model.

106-OR: National Trends in Lower Extremity Amputation among U.S. Medicare Beneficiaries with Diabetes, 2000-2017

Diabetes is the leading cause of non-traumatic lower extremity amputation (NLEA) in the United States. After a period of decline, some U.S. data show that diabetes-related NLEA has recently increased, particularly among young and middle-aged adults. However, the trend for older adults is less clear. To examine NLEA trends among older adults with diabetes (≥67 years), we used 100% Medicare claims for beneficiaries enrolled in Parts A and B during 2000-2017. NLEA was defined as the highest-level amputation per patient per calendar year. NLEA rates were stratified by sex, race and ethnicity, and NLEA level. All rates were age-sex standardized to the 2000 Medicare population. Trends over time were assessed using Joinpoint regression and annual percent change (APC) reported. NLEA rates (per 1,000 persons) halved from 8.5 in 2000 to 4.4 in 2009 (APC -7.9, p value<0.001). However, from 2009 to 2017 NLEA rates increased slightly to 4.8 (APC 1.2, p-value<0.001). Trends were similar across most sex and race/ethnic groups, however absolute rates were highest in blacks and men (Figure A). By NLEA level, overall increases were driven by increases in rates of toe and foot NLEAs. This study of the U.S. Medicare population shows that recent increases in diabetes-related NLEA are also occurring in the older population but at a less severe rate.

Changing HER2-status of the primary gastric tumor after neoadjuvant trastuzumab-based therapy.

e16529 Background: Aproximetly 16 % of patients with metastatic gastric cancer (GC) have HER2+ tumors. With localized stages, the detection rate of HER2+ is known to be lower. Addition of trastuzumab (T) to chemotherapy (CT) improved survival in metastatic, HER2+ GC. Unlike the metastatic disease, Her-2 did not represent an independent prognostic biomarker for early stages during exploratory analysis of MAGIC trial. The aim of the study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer, to evaluate the contribution of trastuzumab to the effectiveness of neoadjuvant treatment in this rare patient population. Methods: We assessed HER2 expression using immunohistochemistry in pre-treatment biopsied specimens and post-treatment resected specimens obtained from 10 patients with locally advanced HER2-positive (3+) gastric cancer receiving trastuzumab-based neoadjuvant chemotherapy: 8 men (80%) and 2 women (20%), from 30 to 80 years old, the median age was 63,5 years. Included 7 patients with resectable adenocarcinoma of the stomach and 3 patients with adenocarcinoma of the esophageal-gastric junction. All patients received neoadjuvant therapy with trastuzumab (100%) + chemotherapy: FLOT (2 patients), FOLFOX (7 patients), XELOX (1 patient). All patients underwent R0 gastrectomy. Tumor regression grading (TRG) after treatment were determined according to Mandard system. Results: Two patients showed a complete pathomorphological response of the tumor (20%,TRG1), therefore, the determination of postoperative HER2 status was not possible. Two patients (20%) maintained the HER2-positive status and six patients (60%) had a change in HER2 expression from positive to negative. Three patients had a (y)pT3 and 5 had a (y)pN+ tumor. Basing on histological changes the tumor regression TRG3 ( &lt; 10% residual tumor cells) was observed in 5 patients (50%). TRG 4-5(preponderance of tumor cells/tumors without changes of regression) observed in 3 patients (30%). The follow-up period is too short for disease-free survival or overall survival to be assessed. Conclusions: HER2 expression can change after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after neoadjuvant treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

Significance of tumour regression in lymph node metastases of gastric and gastro‐oesophageal junction adenocarcinomas

The presence of lymph node (LN) metastases is one of the most important negative prognostic factors in upper gastrointestinal carcinomas. Tumour regression similar to that in primary tumours can be observed in LN metastases after neoadjuvant therapy. We evaluated the prognostic impact of histological regression in LNs in 480 adenocarcinomas of the stomach and gastro‐oesophageal junction after neoadjuvant chemotherapy. Regressive changes in LNs (nodular and/or hyaline fibrosis, sheets of foamy histiocytes or acellular mucin) were assessed by histology. In total, regressive changes were observed in 128 of 480 patients. LNs were categorised according to the absence or presence of both residual tumour and regressive changes (LN−/+ and Reg−/+). 139 cases were LN−/Reg−, 28 cases without viable LN metastases revealed regressive changes (LN−/Reg+), 100 of 313 cases with LN metastases showed regressive changes (LN+/Reg+), and 213 of 313 metastatic LN had no signs of regression (LN+/Reg−). Overall, LN/Reg categorisation correlated with overall survival with the best prognosis for LN−/Reg− and the worst prognosis for LN+/Reg− (p < 0.001). LN−/Reg+ cases had a nearly significant better outcome than LN+/Reg+ (p = 0.054) and the latter had a significantly better prognosis than LN+/Reg− (p = 0.01). The LN/Reg categorisation was also an independent prognostic factor in multivariate analysis (HR = 1.23; 95% CI 1.1–1.38; p < 0.001). We conclude that the presence of regressive changes after neoadjuvant treatment in LNs and LN metastases of gastric and gastro‐oesophageal junction cancers is a relevant prognostic factor.

Digital dermoscopic changes during follow-up of de-novo and nevus-associated melanoma: a cohort study.

Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up. A cohort of melanomas excised at follow-up was retrospectively and consecutively selected. NAMs and DNMs were compared according to baseline features and main dermoscopic changes occurring during follow-up. Univariate and multivariable logistic and Cox's regression analysis were performed to respectively define factors associated with NAM diagnosis and those influencing the risk for excision. Eighty-six melanomas were enrolled, of which 21 (24.4%) were nevus-associated. During follow-up NAMs mainly underwent atypical network modifications (47.6%), followed by inverse network (28.6%) and dermoscopic island (23.8%) worsening or appearance. DNMs were also mainly characterized by atypical network modifications (47.7%), however, a significant proportion of cases underwent irregular pigmentation/dots/globules or regression changes (29.2%), which were rarely seen among NAMs. Furthermore, both multivariable logistic and Cox's regression analysis demonstrated a significant association between NAM and a longer follow-up. We demonstrated that among melanomas excised at follow-up, different patterns of dermoscopic changes may be found between NAMs and DNMs. This finding, together with the association of NAM with a longer follow-up time, supports the hypothesis of different biological behavior of these two entities.

Tumor volume regression during neoadjuvant chemoradiotherapy for esophageal cancer: a prospective study with weekly MRI

Background: Neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer causes tumor regression during treatment. Tumor regression can induce changes in the thoracic anatomy, with smaller target volumes and displacement of organs at risk (OARs) surrounding the tumor as a result. Adaptation of the radiotherapy treatment plan according to volumetric changes during treatment might reduce radiation dose to the OARs, while maintaining adequate target coverage. Data on the magnitude of the volumetric changes and its impact on the thoracic anatomy is scarce. The aim of this study was to assess the volumetric changes in the primary tumor during nCRT for esophageal cancer based on weekly MRI scans.Material and methods: In this prospective study, patients with adeno- or squamous cell carcinoma of the esophagus treated with neoajduvant chemoradiotherapy according to the CROSS regimen (carboplatin + paclitaxel + 23 × 1.8 Gy) were included. Of each patient, six sequential MRI scans were acquired: one prior to nCRT, and five in each subsequent week during nCRT. Tumor volumes were delineated on the transversal T2 weighted images by two radiation oncologists. Volumetric changes were analyzed using linear mixed effects models.Results: A total of 170 MRI scans from 29 individual patients were included. The mean (± standard deviation (SD)) tumor volume at baseline was 45 cm3 (± 23). Tumor volume regression started after the first week of nCRT with a significant decrease in tumor volumes every subsequent week. A decrease to 42 cm3 (91% of initial volume), 38 cm3 (81%), 35 cm3 (77%), and 32 cm3 (72%) was observed in the second, third, fourth and fifth week of nCRT, respectively.Conclusion: Based on weekly MRI scanning during nCRT for esophageal cancer, a considerable decrease in tumor volume was observed during treatment. Volume regression and consequential anatomical changes suggest the possible benefit of adaptive radiotherapy.

The Impact of Malnutrition on Acute Muscle Wasting in Frail Older Hospitalized Patients.

Very little is known about the effect of malnutrition on short-term changes of body composition, particularly muscle, among older hospitalized patients. We sought to investigate the association of malnutrition as assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria with changes of thigh muscle mass and muscle strength among older patients during hospitalization. Forty-one patients (age range 66–97 years, 73% female) participated in this prospective longitudinal observational study. Nutritional status was evaluated using the GLIM criteria on admission and at discharge. Functional status and mid-thigh magnetic resonance imaging (MRI) measurements of cross-sectional area (CSA) were conducted on admission and before discharge. In all, 17% were malnourished and 83% had no malnutrition. Mean mid-thigh muscle CSA declined by 7.0 cm2 (−9%) in malnourished patients during hospitalization (p = 0.008) and remained unchanged among non-malnourished patients (−1%, p = 0.390). Mean mid-thigh CSA of subcutaneous and intermuscular fat did not change significantly during hospitalization in both groups. Malnourished subjects lost 10% of handgrip strength (−1.8 kg) and 12% of knee extension strength (−1.5 kg) during hospitalization. However, the magnitude of both changes did not differ between groups. In a stepwise multiple regression analysis, malnutrition and changes in body weight during hospitalization were the major independent risk factors for the reduction of muscle CSA. Malnutrition according to the GLIM criteria was significantly and independently associated with acute muscle wasting in frail older patients during 2-week hospitalization.

Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation.

Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC–MS, while F2-isoprostanes and neuroprostanes (NP) were determined by LC–MS. SAH was accompanied by changes in antioxidant capacity in blood plasma, including initially (day 1) an increase in GSH-Px activity, followed by its decrease and a progressive decrease in glutathione (GSH) levels and vitamins A, E, and C. On the other hand, levels of PUFAs cyclization products, F2-isoprostanes, and neuroprostanes were highest on day 1 (two and eight times higher, respectively) and decreased over time. The levels of 4-HNE (4-hydroxynonenal), 4-ONE (4-oxononenal), and MDA (malondialdehyde) changed similarly. In contrast, the 4-HHE (4-hydroxyhexenal) level reduced after SAH increased significantly after a week. It was found that the deterioration of the overall clinical and neurological condition of SAH patients due to cerebral edema, intracranial hemorrhage, or vasoconstriction corresponded to reduced antioxidant defense and, as a consequence, increased lipid peroxidation and slower observed changes in regression. It can be concluded that monitoring the level of lipid peroxidation products (neuroprostanes, 4-ONE, and MDA) can support the monitoring of the clinical status of patients, especially with regard to the assessment of vasospasm.

The Limits of the “Progressive” Institutional Change: Migration and Remittances Experiences

:The financial and business expansion towards both sides of the Mexico-U.S. border, what could be called the financial diaspora that accompanies Mexican´s migration to the United States and U.S. Corporations to Mexico, has been a process full of nuances and components with different characteristics. Beyond the governments and their migratory and investment policies, the characteristics of the different migrant groups and corporations, the cultural gaps, and the “progressive” institutional changes are subject to a dynamic of survival-assimilation-earnings. Even when powerful trials of organization are observed, a strong and imminent current of regressive institutional change (Veblen) has been gaining space. This article is circumscribed to analyze some key aspects of the financial behavior Mexican migrants to the United States, who have become entrepreneurs, have had. Their enormous limitations of financing are exposed, including the different stages to access credit to the businesses of residents in Mexico and to Mexican businesspeople abroad. The article contends the transformation in financing on both sides of the border has been decisive.