Alterations of the Characteristics of the Circadian Rest‐Activity Rhythm of Cancer In‐Patients

The aim of the present study was to evaluate the characteristics of the circadian rest‐activity rhythm of cancer patients. Thirty‐one in‐patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest‐activity rhythm was studied non‐invasively by wrist actigraphy, and compared with 35 age‐matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4–7 consecutive days. Fifteen‐second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple‐range test, and t‐test. Dichotomy index (I<O) and autocorrelation coefficient (r24) were also computed. The results validated a statistically significant circadian rhythm in rest‐activity with a prominent period of 24 h for most cancer patients and control subjects. Results of this study further revealed that cancer patients do experience a drastic alteration in the circadian rest‐activity rhythm parameters. Both the dichotomy index and r24 declined in the group of cancer patients. The occurrence of the peak (acrophase, Ø) of the rest‐activity rhythm was earlier (p<0.001) in cancer patients than age‐ and gender‐matched control subjects. Results of sleep parameters revealed that cancer patients spent longer time in bed, had longer assumed and actual sleep durations, and a greater number of sleep and wake bouts compared to control subjects. Further, nap frequency, total nap duration, average nap, and total nap duration per 1 h awake span were statistically significantly higher in cancer patients than control subjects. In conclusion, the results of the present study document the disruption of the circadian rhythm in rest‐activity of cancer in‐patients, with a dampening of amplitude, lowering of mean level of activity, and phase advancement. These alterations of the circadian rhythm characteristics could be attributed to disease, irrespective of variability due to gender, sites of cancer, and timings of therapies. These results might help in designing patient‐specific chronotherapeutic protocols.     

The Route of Leishmania tropica Infection Determines Disease Outcome and Protection against Leishmania major in BALB/c Mice

Leishmania tropica is one of the causative agents of leishmaniasis in humans. Routes of infection have been reported to be an important variable for some species of Leishmania parasites. The role of this variable is not clear for L. tropica infection. The aim of this study was to explore the effects of route of L. tropica infection on the disease outcome and immunologic parameters in BALB/c mice. Two routes were used; subcutaneous in the footpad and intradermal in the ear. Mice were challenged by Leishmani major, after establishment of the L. tropica infection, to evaluate the level of protective immunity. Immune responses were assayed at week 1 and week 4 after challenge. The subcutaneous route in the footpad in comparison to the intradermal route in the ear induced significantly more protective immunity against L. major challenge, including higher delayed-type hypersensitivity responses, more rapid lesion resolution, lower parasite loads, and lower levels of IL-10. Our data showed that the route of infection in BALB/c model of L. tropica infection is an important variable and should be considered in developing an appropriate experimental model for L. tropica infections.     

Modeling the impact of early therapy for latent tuberculosis patients and its optimal control analysis

Effective tuberculosis (TB) control depends on case findings to discover infectious cases, investigation of contacts of those with TB, as well as appropriate treatment. Adherence and successful completion of the treatment are equally important. Unfortunately, due to a number of personal, psychosocial, economic, medical, and health service factors, a significant number of TB patients become irregular and default from treatment. In this paper, a mathematical model is developed to assess the impact of early therapy for latent TB and non-adherence on controlling TB transmission dynamics. Equilibrium states of the model are determined and their local stability is examined. With the aid of the center manifold theory, it is established that the model undergoes a backward bifurcation. Qualitative mathematical analysis of the model suggests that a high level of latent tuberculosis case findings, coupled with a decrease of defaulting rate, may be effective in controlling TB transmission dynamics in the community. Population-level effects of organized campaigns to improve early therapy and to guarantee successful completion of each treatment are evaluated through numerical simulations and presented in support of the analytical results.     

Interactions between climatic and production factors on returns of female pigs to service during summer in Japanese commercial breeding herds

The objectives of this study were to determine the associations between climatic factors and production factors for returns to service of female pigs during summer and to quantify the associations between these factors and occurrences of returns to service. The factors that were assessed were as follows: maximum temperature (HT), relative humidity, age of gilts at first mating, parity, weaning-to-first-mating interval (WMI), and lactation length. The study analyzed records of 18,307 gilts in 99 herds and 78,135 parity records of 56,322 sows in 103 herds; all the females were first-serviced between June and September, 2007 to 2009. Average daily HT and relative humidity for 15 days post-service of a female were obtained from 21 local weather stations and coordinated with the performance data of the respective local herds. The returns to service were categorized into three groups: regular returns (RRs: 18–24 days), irregular returns (IRs: 25–38 days), and late returns to service (LRs: 39 days or later). Two-level mixed-effects models were applied to the data by using a herd at level 2 and an individual record at level 1. In mated gilts, the occurrences (%) of RRs, IRs, and LRs were 4.8%, 1.8%, and 5.3%, respectively. In mated sows, the respective occurrences were 3.3%, 1.8%, and 4.2%. Mean values (ranges) of HT and relative humidity were 28.4 °C (13.6 °C–39.8 °C) and 73.4% (35.0%–98.0%), respectively. In gilts, as HT increased from 25 °C to 30 °C, the occurrence of RR increased from 3.7% to 4.4% (P < 0.05). However, there was no association between the occurrence of RR and either relative humidity (P = 0.17) or age at first mating (P = 0.23). In addition, there were no associations between the occurrences of either gilt IR or LR and HT (P ≥ 0.05), relative humidity (P ≥ 0.46), or age at first mating (P ≥ 0.32). In sows, greater occurrences of RRs, IRs, and LRs were associated with higher HT, lower parity, and a WMI of 7 days or longer (P < 0.05), but they were not associated with relative humidity (P ≥ 0.62) or lactation length (P ≥ 0.13). The occurrence of RRs in sows of all WMI groups increased 1.22 (1.04⁵) times for each 5 °C increase in HT. For sows with WMI 0 to 6 days, each 5 °C rise in HT increased the occurrence of IRs and LRs by 1.36 (1.06⁵) and 1.27 (1.05⁵) times, respectively. However, there was no association between increased HT and occurrences of IRs or LRs for sows with WMI 7 days or longer (P ≥ 0.38). Therefore, in order to prevent returns to service, it is recommended that producers apply cooling management for females during the post-service periods in summer.     

Prognostic value of leptin: 6-Month outcome in patients with intracerebral hemorrhage

Leptin has recently been discussed as a novel biomarker for the clinical outcome of critical illness. This study aims to investigate the prognostic value of leptin with regard to long-term clinical outcomes in patients with intracerebral hemorrhage. In 50 healthy controls and 92 patients with acute spontaneous basal ganglia hemorrhage presenting to the emergency department of a large primary care hospital, we measured plasma leptin levels using an enzyme-linked immunosorbent assay in a blinded fashion. Plasma leptin levels on admission were considerably higher in patients than healthy controls. A significant correlation emerged between plasma leptin level and National Institutes of Health Stroke Scale score. A multivariate analysis identified plasma leptin level as an independent predictor for 6-month clinical outcomes including 6-month mortality and unfavorable outcome (Modified Rankin Scale score > 2). Using receiver operating characteristic curves, we calculated areas under the curve for 6-month clinical outcomes. The predictive performance of leptin was similar to, but did not obviously improve that of National Institutes of Health Stroke Scale scores. Thus, leptin may help in the prediction of 6-month mortality and unfavorable outcome after intracerebral hemorrhage.     

妊娠合并甲状腺功能减退症26例妊娠结局分析

目的：对妊娠合并甲状腺功能减退症进行分析,探讨其对母儿的影响,及孕期筛查甲状腺功能有无意义。方法：对我院26例妊娠合并甲减的临床资料进行回顾性统计分析。结果：26例妊娠合并甲减病例中有1例早产（孕33周）,其余25例患者维持至足月妊娠,其中剖宫产17例（65.38%）,合并妊娠期高血压疾病5例（19.23%）,妊娠期糖尿病3例（11.53%）,羊水胎粪污染3例（11.54%）,新生儿无先天性甲减。经过治疗后甲状腺功能减退孕妇的剖宫产率,糖尿病发生率、高血压疾病发生率、羊水粪染的发生率较对照组增加;但两组妊娠结局差异无统计学意义（P〉0.05）。结论：妊娠合并甲状腺功能减退症孕妇多种妊娠并发症的发病率高于正常孕妇,应加强对妊娠甲减的早期筛查及治疗,可有效降低不良妊娠结局,减少先天性甲低的出生。     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

淋巴结转移阴性的胃癌患者临床病理特征及生存探讨

目的:探讨淋巴结转移阴性胃癌患者的临床病理特征以及预后影响因素。方法:收集2000年1月至2009年1月我院收治的胃癌患者325例,其中经病理检查显示淋巴结转移阴性的105例患者作为阴性组(LN-组),另229例阳性患者作为阳性组(LN+组),比较两组的临床病理特征及临床预后。结果:LN-组的肿瘤直径、浸润深度及术后化疗与LN+组比较差异显著(P0.05);LN-组的5年生存率为76.2%,显著高于LN+组的43.2%(P0.05)。未透浆膜的LN-患者3年、5年生存率显著高于浸透浆膜者,术后化疗的LN-患者5年生存率显著高于未化疗者(P0.05),肿瘤直径5 cm的LN-患者3、5年生存率显著高于≥5 cm者(P0.05)。单因素分析显示浸润深度、肿瘤大小及术后化疗与LN-胃癌患者的预后具有密切关系(P0.05)。COX多因素分析显示浸润深度是影响LN-胃癌患者临床预后的独立因素(P0.05)。结论:淋巴结转移阴性胃癌患者的病灶多位于中下部,男性多于女性,发病年龄多在60岁以内,肿瘤直径多不超过5 cm,浸润深度多未浸透浆膜,临床预后优于淋巴结转移阳性胃癌患者,浸润深度是影响淋巴结转移阴性胃癌患者临床预后的独立因素。