Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring

Attention to addiction of women alone for fetus and infant's health has caused the possible role of father's status was less considered, while some developmental impairments including decrease of liter size, weight loss, congenital deficiencies, behavioral disorders, and learning and memory impairments in offspring with addicted father have been reported. In this study the effects of addiction of one or both parents to morphine on male and female offspring hippocampal long-term potentiation (LTP), were assessed. One hundred twenty female and 48 male rats (4-5 months, 250-270 g) were used. Forty females and 16 males were addicted by oral administration of morphine (32 mg/kg twice daily) for 5 days before mating. Then each two males with five females were housed (coupled) per cage as five groups for coupling: (A) addicted females+5% dextrose males (add.F); (B) addicted males+5% dextrose females (add.M); (C) addicted females+addicted males (add.MF); (D) 5% dextrose females+intact males (dex.F); (E) 5% dextrose males+intact females (dex.M). In puberty offspring LTP was induced in hippocampal dentate gyrus by stimulation of perforant path (pp). Changes of population spikes (PS) amplitude and LTP slope at 0, 5, 30, 60 and 120 min were evaluated. Slope of LTP at 30, 60 and 120 min, and amplitude of PS at 60 and 120 min in add.F and add.M offspring were significantly lower than dextrose groups (P<0.01). LTP slope and PS amplitude of male and female offspring did not different between add.F and add.M groups. Our results suggest that both parental and paternal addiction to morphine may cause memory deficiency through reduction of LTP in hippocampus.     

Analyzing biological rhythms in clinical trials

BackgroundThe human body exhibits a variety of biological rhythms. There are patterns that correspond, among others, to the daily wake / sleep cycle, a yearly seasonal cycle and, in women, the menstrual cycle. Sine/cosine functions are often used to model biological patterns for continuous data, but this model is not appropriate for analysis of biological rhythms in failure time data.MethodsWe consider a method appropriate for analysis of biological rhythms in clinical trials. We present a method to provide an estimate and confidence interval of the time when the minimum hazard is achieved. A motivating example from a clinical trial of adjuvant of pre-menopausal breast cancer patients provides an important illustration of the methodology in practice.ResultsAdapting the Cosinor method to the Weibull proportional hazards model is proposed as useful way of modeling the biological rhythm data. It presents a method to estimate the time that achieves the minimum hazard along with its associated confidence interval. The application of this technique to the breast cancer data revealed that the optimal day for pre-resection incisional or excisional biopsy of 28-day cycle (i.e. the day associated with the lowest recurrence rate) is day 8 with 95% CI 5–10. We found that older age, fewer positive nodes, smaller tumor size, and experimental treatment are important prognostic factors of longer relapse-free survival.ConclusionsThe analysis of biological/circadian rhythms is usually handled by Cosinor rhythmometry method. However, in FTD this is simply not possible. In this case, we propose to adapt the Cosinor method to the Weibull proportional hazard model. The advantage of the proposed method is its ability to model survival data. This method is not limited to breast cancer data, and may be applied to any biological rhythms linked to right censored data.     

Evaluation of coexistence of the Human Herpesvirus type 8 (HHV‐8) infection and pemphigus

Background Human Herpesvirus type 8 (HHV‐8) is a new member of the herpes virus family, first found in the tissue of acquired immune deficiency syndrome (AIDS)‐related Kaposi’s sarcoma. Environmental factors including viral infection may play a role in the onset and/or development of pemphigus. Some studies based on polymerase chain reaction findings suggest an association between HHV‐8 and pemphigus. The aim of this study is investigation of the association of pemphigus with HHV‐8 and the relationship between inflammatory and acantholytic cells with HHV‐8 infection. Methods Tissue‐extracted DNA from 41 paraffin‐embedded skin tissues from patients first presenting with pemphigus was tested using nested PCR for the presence of HHV‐8. A total of 37 cases had pemphigus vulgaris (PV) and 4 patients had pemphigus foliaceus (PF). For our control group, normal skin of 21 cosmetic surgery patients were included. Furthermore, microscopic slides with H&E staining were evaluated for the number of inflammatory and acantholytic cells per microscopic field. Results Skin lesions from 13 of 37 patients (35.1%) with PV and 2 of 4 cases (50%) with PF were positive for HHV‐8 DNA. All specimens in our control group were negative for this virus. Conclusion HHV‐8 infection might be a contributing factor in the initiation or development of pemphigus.     

Depression,anxiety, and fear of COVID-19 in patients with multiple sclerosis in pandemic era: a cross-sectional study

Neurological Sciences - Depression and anxiety are the two important factors determining quality of life of patients with multiple sclerosis (PWMS). In COVID-19 pandemic era, several factors can...     

Role of the vulnerable elders survey-13 screening tool in predicting treatment plan modification for older adults with cancer

Background: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7–10)have a higher likelihood of a change in treatment compared to low positive scores (3–6).Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality.Results: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7–10, 50.8% with scores 3–6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy.Conclusions: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.     

Impact of various culture conditions on ex vivo expansion of polyclonal T cells for adoptive immunotherapy

Currently, adoptive immunotherapy is considered as one of the leading treatments in cancer. Successful adoptive immunotherapy depends on producing large numbers of desired T cells ex vivo for infusion. This requires an effective protocol for maximum functional T‐cell expansion while keeping the time and costs to a minimum. Current T‐cell expansion protocols are diverse in their methodology, and a universal protocol of expansion is wanting. Also, new findings regarding T‐cell biology, signaling, and activation have reshaped the strategies of T‐cell propagation over the years, introducing new ways to expand T cells. Here, we reviewed different conditions for blood‐derived polyclonal T‐cell expansion so as to elucidate the influential factors of T‐cell expansion and their efficacy.