Nevin Manimala

Mult Scler Relat Disord. 2022 Mar 31;62:103775. doi: 10.1016/j.msard.2022.103775. Online ahead of print.

ABSTRACT

BACKGROUND: The strong link between innate immunity and thrombosis/coagulation has recently been investigated in the light of antibodies directed against serine proteases of the coagulation pathway. The antibodies have been proposed as contributing factors to venous thromboembolism development and as key molecules in the initiation of signaling inflammatory pathways in neuroinflammatory diseases. Preliminary studies of Multiple Sclerosis (MS) progression characteristics with the reactivity of antibodies against coagulant components are limited. Considering the development of thrombosis at the early onset of MS, our study aimed to detect antibodies against coagulant components in MS and evaluate their possible association with the clinical profile of the disease.

METHOD: A cross-sectional study was carried out to identify antibodies to factor(F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C in serum samples from 167 patients with MS and 40 healthy controls using the enzyme-linked immunosorbent assay. Statistical analysis was performed for the evaluation of the data.

RESULTS: The analysis revealed a significantly higher prevalence of IgG in MS patients (n = 72, 43%) compared to HCs (n = 8, 20%, p < 0.01). Specifically, elevated anti-FVIIa (n = 19, 11.4%, mean activity p < 0.0001), anti-FXII (n = 12, 7.2%, mean activity p < 0.001) and anti-plasmin (n = 20, 12%, mean activity p < 0.01) levels were observed in patients compared to controls. Additionally, the highest scores of clinical characteristics like the expanded disability status scale and MS severity score were linked with IgG seropositivity against thrombin, whilst anti-FXII levels corresponded with the lowest disease progression.

CONCLUSION: The findings of our study illustrate the presence of antibodies against serine proteases of the coagulation cascade in MS and demonstrate the association of antibody activity with disease progression. In particular, thrombin IgG seropositivity was demonstrated to be associated with worse outcomes and a severe disease phenotype. These observations suggest the implication of antibodies in patient monitoring and prognosis, and further evaluation may elucidate inflammatory cascades in which antibodies act as key mediators.

PMID:35417817 | DOI:10.1016/j.msard.2022.103775

Transl Oncol. 2022 Apr 10;20:101410. doi: 10.1016/j.tranon.2022.101410. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.

METHODS: The Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.

RESULTS: In total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03-7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.

CONCLUSIONS: Histological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.

PMID:35417814 | DOI:10.1016/j.tranon.2022.101410

Mar Pollut Bull. 2022 Apr 10;178:113634. doi: 10.1016/j.marpolbul.2022.113634. Online ahead of print.

ABSTRACT

The groundwater salinization is a global problem that degrades water quality and endangers sustainable use of water resources, particularly in coastal areas. In this paper, 24 water samples were collected from 12 monitoring wells during the dry (January) and wet (June) seasons for analyzing the salinization and hydrogeochemical characteristics of groundwater in Dongshan Island of China through combined hydrogeochemical and multivariate statistical approaches. Results showed that groundwater in the study area is primarily Cl-Na and followed by Cl-Ca·Mg type in the dry season, Cl-Na and followed by Cl-Ca·Mg and HOC₃·Cl-Na type in the wet season. The groundwater chemistry is predominantly controlled by carbonate, gypsum, and silicate dissolution. However, some areas are strongly influenced by seawater intrusion, sewage infiltration and reverse ion exchange process. Around 40% of water samples from the dry season and 50% from the wet season are at injuriously, highly and severely saline levels while other samples at slightly and moderately saline levels, suggesting that groundwater in the area is partially recharged by seawater. Furthermore, the NO₃^–/Cl^– versus Cl^– diagram and principal component analysis (PCA) indicated nitrate pollution in groundwater that is subjected to anthropogenic activities such as domestic sewage, agricultural and industrial practices, which lead to degradation of groundwater quality in the area. The findings of this study provide helpful insights for understanding the genesis and hydrogeochemical evolution of groundwater in those coastal areas.

PMID:35417808 | DOI:10.1016/j.marpolbul.2022.113634

Pathol Res Pract. 2022 Apr 6;233:153888. doi: 10.1016/j.prp.2022.153888. Online ahead of print.

ABSTRACT

BACKGROUND: High endothelial venules (HEVs) are vessels specialized in the transport of lymphocytes shown to be implicated in various forms of cancer. They express peripheral node addressin (specifically recognized by the MECA-79 antibody). MECA-79 is also implicated in pregnancy through its expression by epithelial cells of the endometrium. However, the expression of MECA-79 by endothelial or epithelial (cancer) cells has never been studied in endometrial cancer.

MATERIAL AND METHODS: In this retrospective study, we investigated the immunohistochemical expression of MECA-79 in 40 endometrioid adenocarcinoma hysterectomy specimens and compared it with its expression in 30 non-cancer hysterectomies.

RESULTS: HEVs were found in 22% of tumor specimens and in none of the non-cancer hysterectomies (p = 0.005) and were positively associated with higher grade tumors (p = 0.04). MECA-70 was expressed in tumor cells of 70% of carcinomas and in epithelial cells of 46.6% of normal endometria (p = 0.04). It was inversely associated with parametrial invasion (p = 0.03) and larger tumors (statistical trend of p = 0.07). MECA-79 expression was not associated with overall or progression-free survival.

CONCLUSION: MECA-79 is found in HEVs and tumor cells in endometrial endometrioid adenocarcinoma.

PMID:35417805 | DOI:10.1016/j.prp.2022.153888

J Equine Vet Sci. 2022 Apr 10:103947. doi: 10.1016/j.jevs.2022.103947. Online ahead of print.

ABSTRACT

OBJECTIVE: Although equine strangles is reportable in all states, synchronous reporting of this disease does not occur across the country. States have variable regulations on reporting (actionable, notifiable, and monitored) and no mandatory comprehensive databases exist for tracking prevalence. In this study, we solicited veterinarians’ opinions on reporting of strangles and factors influencing their opinion.

SAMPLES: 250 veterinarians practicing within the United States PROCEDURES: A structured survey was administered online.

RESULTS: A total of 250 veterinarians participated: 84 participants (34%) believed that strangles should continue to be nationally monitored and that individual states should have jurisdiction over laboratory confirmed positive cases; 58 (23.2%) believed strangles should become nationally monitored with mandatory notification of positive cases to a central forum; 24 participants (9.6%) thought strangles should become notifiable nationally; and 44 (17.6%) thought strangles should become notifiable and actionable. While not quite achieving statistical significance, we noted that there was a large effect of currently reporting strangles on the desire for increased reporting (87% more likely, P = 0.054), as did veterinarians who ranked strangles as “very important” or “important” relative to other infectious disease (OR 3.77, P = 0.037). Veterinarians practicing in the Southwest (P=0.01) and West (P = 0.04) were significantly less likely than northeast practitioners to rank strangles of higher importance.

CLINICAL RELEVANCE: Opinions on equine strangles and desire for increased reporting were varied in the sampled veterinary community. Information obtained in this study regarding veterinarians’ current views on strangles reporting could inform future policy regarding the disease.

PMID:35417769 | DOI:10.1016/j.jevs.2022.103947

Int J Radiat Oncol Biol Phys. 2022 Apr 10:S0360-3016(22)00319-4. doi: 10.1016/j.ijrobp.2022.04.006. Online ahead of print.

ABSTRACT

PURPOSE: To report on the early toxicities and quality of life (QOL) of localized prostate cancer radiotherapy in a randomized trial comparing moderate hypofractionation (MHF) to ultrahypofractionation (UHF) MATERIALS AND METHODS: Intermediate to high risk localized prostate cancer patients were randomized to radiotherapy with MHF (70 Gy in 28 daily fractions) or UHF (36.25 Gy in 5 weekly fractions). Early toxicities (CTCAE and RTOG/SOMA scales) and patient reported QOL (EPIC questionnaire) were analysed when all patients had a minimum of 6 months follow-up.

RESULTS: Eighty participants were randomized but two withdrew from radiotherapy. Analysis was done on 78 patients. The two arms were balanced in key patient and disease characteristics except for a statistically worse baseline urinary function in the UHF arm (IPSS > 7: 68% vs 36% p = 0.004). There are no statistically significant differences between the two arms in Grade 3 or Grade 2 toxicities: ≥ Grade 3 – MHF 8%, UHF 2% (p=0.235); ≥ Grade 2 MHF 36%, UHF 24% (p=0.235). There are also no significant differences in percentages of patients with a “minimal important change” of QOL in the Incontinence (MHF 36%, UHF 33% p =0.746), Irritative/Obstructive (MHF 56%, UHF 74% p=0.074) or Bowel domains (MHF 58%, UHF 52% p=0.508) on the EPIC questionnaire.

CONCLUSIONS: UHF radiotherapy for prostate cancer is well tolerated and there were no significant differences in toxicities and quality of life changes between UHF and MHF up to six months after treatment in the current trial.

PMID:35417763 | DOI:10.1016/j.ijrobp.2022.04.006

J Anim Sci. 2022 Apr 13:skac125. doi: 10.1093/jas/skac125. Online ahead of print.

ABSTRACT

This study determined the energy requirement for maintenance of purebred Nellore cattle and its crossbreds using data from a comparative slaughter trial in which animals were raised under the same plane of nutrition from birth through slaughter and born from a single commercial Nellore cow herd. Seventy-nine castrated steers (361 ± 54 kg initial BW) were used in a completely randomized design by age (22 months ± 23 days of age) with four genetic groups (GG): Nellore (NL), ½ Angus x ½ Nellore (AN), ½ Canchim x ½ Nellore (CN), and ½ Simmental x ½ Nellore (SN). The experimental design provided ranges in ME intake, BW, and ADG needed to develop regression equations to predict NEm requirements. Four steers of each GG were slaughtered to determine the initial body composition. The remaining 63 steers were assigned to different nutritional treatments (NT) by GG; ad libitum or limit-fed treatments (receiving 70% of the daily feed of the ad libitum treatment of the same GG). Full BW was recorded at birth, weaning, 12, 18, and 22 months. In the feedlot, steers were fed for 101 days a diet containing (DM basis) 60% corn silage and 40% concentrate. No difference of age at weaning (P = 0.534) and slaughter (P = 0.179 and P = 0.896, for GG and NT, respectively) were observed. AN steers were heavier at weaning weight, yearling weight and had higher EBW (P = 0.007, P = 0.014 and P < 0.001, respectively) in comparison to NL, CN, and SN. There were no interactions (P > 0.05) between GG and NT for any variable evaluated. When fed ad libitum, AN steers had higher daily MEI (Mcal/d; P < 0.001) in comparison to NL, CN, and SN. On a constant age basis, differences were observed on body composition (P < 0.05) between GG. The slope (P = 0.600) and intercept (P = 0.702) of the regression of log HP on MEI were similar among GG. Evaluating at the same age and the same frame size, there were no differences in NEm requirement between Nellore and AN (P = 0.528), CN (P = 0.671), and SN (P = 0.706). The combined data indicated a NEm requirement of 86.8 kcal/d/kg 0.75 EBW and a MEm requirement had a common value of 137.53 kcal/d/kg 0.75 EBW. The km and kg values were similar among GG (P > 0.05 and P > 0.05, respectively) and were on average 63.2 and 26.0%, respectively. However, although not statistically different, the NEm values from NL showed a decrease in NEm of 5.76% compared to AN steers.

PMID:35417561 | DOI:10.1093/jas/skac125

Biostatistics. 2022 Apr 13;23(2):380-396. doi: 10.1093/biostatistics/kxaa030.

ABSTRACT

Multi-state models for event history analysis most commonly assume the process is Markov. This article considers tests of the Markov assumption that are applicable to general multi-state models. Two approaches using existing methodology are considered; a simple method based on including time of entry into each state as a covariate in Cox models for the transition intensities and a method involving detecting a shared frailty through a stratified Commenges-Andersen test. In addition, using the principle that under a Markov process the future rate of transitions of the process at times $t > s$ should not be influenced by the state occupied at time $s$, a new class of general tests is developed by considering summaries from families of log-rank statistics where patients are grouped by the state occupied at varying initial time $s$. An extended form of the test applicable to models that are Markov conditional on observed covariates is also derived. The null distribution of the proposed test statistics are approximated by using wild bootstrap sampling. The approaches are compared in simulation and applied to a dataset on sleeping behavior. The most powerful test depends on the particular departure from a Markov process, although the Cox-based method maintained good power in a wide range of scenarios. The proposed class of log-rank statistic based tests are most useful in situations where the non-Markov behavior does not persist, or is not uniform in nature across patient time.

PMID:35417532 | DOI:10.1093/biostatistics/kxaa030

Arq Bras Oftalmol. 2022 Mar 7:S0004-27492022005004208. doi: 10.5935/0004-2749.20230025. Online ahead of print.

ABSTRACT

PURPOSE: To investigate ocular surface and meibomian glands in patients with treatment-naive acne vulgaris.

METHODS: The Ocular Surface Disease Index (OSDI) questionnaire, invasive tear film breakup time, fluorescein staining of the ocular surface, and Schirmer II test were performed for all subjects. Total eyelid and meibomian gland secretion scores were assessed. Non-contact meibography was performed with the Sirius corneal topographic device.

RESULTS: The right eyes of 35 patients with acne vulgaris and 35 healthy volunteers were included the study. While the OSDI and staining scores were significantly higher in the acne group than in the control group (p=0.01 and p=0.003, respectively), the invasive tear film breakup time and Schirmer measurements were significantly lower in the acne group (p=0.000 and p=0.003, respectively). The total eyelid and meibomian gland secretion scores were also higher in the acne group than in the control group (p=0.003 and p=0.000, respectively). On the morphological evaluation of the meibomian glands, the thickening, thinning, tortuosity, and presence of ghost areas were statistically significantly more common in the acne vulgaris group than in the control group (p=0.000, p=0.001, p=0.05, and p=0.006, respectively). The percentage of the meibomian gland loss area was significantly high in the acne vulgaris group on both upper and lower meibography. The meibomian gland loss area positively correlated with total eyelid and meibomian gland secretion scores.

CONCLUSION: Acne vulgaris may have a predisposition to meibomian gland dysfunction and ocular surface damage. Early recognition of meibomian gland and ocular surface alterations seems important, especially in acne vulgaris cases for which oral isotretinoin treatment is planned.

PMID:35417517 | DOI:10.5935/0004-2749.20230025

Arq Bras Oftalmol. 2022 Mar 7:S0004-27492022005004206. doi: 10.5935/0004-2749.20230023. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the impact of social isolation due to the COVID-19 pandemic on the number of new cases and therapeutic approaches at the Ocular Oncology division from the Universidade Federal de São Paulo (UNIFESP).

METHODS: A retrospective study was conducted by medical records review of new patients treated before the pandemic from March 2019 to September 2019 (pre-pandemic group) and during the pandemic from March 2020 to September 2020 (pandemic group). Data regarding age, sex, ethnicity, place of origin, clinical diagnosis, time since referral, and proposed therapy were analyzed.

RESULTS: We analyzed 186 new cases, 122 from the pre-pandemic group and 64 from the pandemic group, representing a decrease of 47.54% in new cases. There was no statistically significant change in sex, race, state of origin, history of cancer, age, or time with suspected cancer (p>0.05). A higher frequency of malignancies was observed in the pandemic group (68%) when compared to the pre-pandemic group (48.48%). Benign tumors were the most common diagnosis in the pre-pandemic group (41.80%), while conjunctival squamous cell carcinoma was the modal diagnosis in the pandemic group (31.25%). There was a decreasing trend (p=0.097) in the number of surgeries (-7.63%) and an increase in topical treatment (+10.68%). There was also a tendency to perform fewer surgeries in benign tumors and decreased follow-up visits.

CONCLUSION: Our findings showed a significant decrease in the number of new cases referred to the Ocular Oncology service. Moreover, the pandemic led to a switch in the therapeutic approach with preference to non-invasive treatments that would demand operating rooms. A drastic increase of cases perhaps in advanced stages might be expected because of the decrease observed in the first six months of quarantine.

PMID:35417515 | DOI:10.5935/0004-2749.20230023