Miracle-dz/UniFAR-FTUs huggingface dataset:
The regulation of the energy output of the heart

EXPERIMENTS carried out in this Laboratory have shown that in an isolated heart, beating at a constant rhythm and well supplied with blood, the larger the diastolic volume of the heart (within physiological limits) the greater is the energy of its contraction. It is this property which accounts for the marvellous adaptability of the heart, completely separated from the central nervous system, to varying load, to which attention was first called by Cohnheim. So important is this property of the heart for the processes of adaptation and compensation in the healthy and diseased organ that it was called by one of us "the law of the heart"(1) and regarded as a special instance of the law connecting energy of the contractile process with the initial length of muscular fibre (Blix(2), A. V. Hill(3)). The law as stated above applies only so long as the physiological state of the cardiac muscle can be regarded as unimpaired. As the heart tires it has to dilate continuously in order to maintain its mechanical performance constant, so that the heart in situ becomes inefficient, i.e. unable to carry on the circulation at the previous output and arterial pressure, so soon as further dilatation is prevented by the heart, during diastole, coming up against the pericardium(4). In such a case freeing the heart from the pericardium will allow it to continue its function and to carry on the circulation as efficiently as before for a certain further period of time. It was shown by Lovatt Evans() and his fellow-workers that any increase in the work thrown upon the heart in the heart-lung preparation, whether by increasing the arterial resistance or by augmenting the inflow into the heart, caused a corresponding increase in the gaseous metabolism of the organ, whether measured by oxygen intake or by C02 output. It was therefore assumed that the increased energy of contraction incident on greater diastolic volume was attended by and due to increased chemical change. Thus
Genetic algorithms vs. Tabu search in timetable scheduling

In a timetabling problem, exam subjects must be slotted to certain times that satisfy several of constraints. They are NP-completeness problems, which usually lead to satisfactory but sub-optimal solutions. This paper investigates and compares Genetic Algorithm and Tabu Search approaches to solve these kinds of problem. The experiment shows that TS approach can produce better timetables than those of GA approach can. Further, the search time spent in TS is less than that of GA. However, GA can produce several different near optimal solutions simultaneously.
The entrepreneurial growth of firms located in clusters: a cross-case study

The notion of regional clusters of firms has been the subject of research for over a century. Recent research has increasingly reported evidence of cluster firms’ growth, contrasting with the general assumption that being embedded in a cluster restrains the possibility for firm growth in terms of attitude, opportunities and resources. However, despite the recent research interest on those firms that have experienced growth, detaching from the cluster cliche of being small, local and homogeneous, little is known on the antecedents of such growth. In this paper, we use the lenses of firm-level entrepreneurship as a framework for analysing, comparing and generalising the empirical results of four case studies (Alessi, Illycaffe, Luxottica and Geox). We argue that local and non-local resources and competencies, together with firm capabilities of acquisition and recombination, are the main antecedents of the continuous process of opportunity recognition and exploitation, i.e., growth of cluster firms.
Magnetic Resonance Imaging Functional Activation of Left Frontal Cortex During Covert Word Production

Six normal volunteers underwent 4‐T functional magnetic resonance imaging while performing a covert letter fluency task. An echo planar imaging sequence was utilized to detect activation based on deoxyhemoglobin contrast. All 6 subjects showed consistent activation in the frontal operculum and premotor and primary motor cortices. Activation was also detected in the supramarginal gyrus and the posterior part of the superior temporal gyrus. These results show that magnetic resonance functional neuroimaging can be used to investigate cerebral activity noninvasively during performance of complex cognitive tasks.
History of Sudden Unexpected Loss Is Associated With Elevated Interleukin-6 and Decreased Insulin-Like Growth Factor-1 in Women in an Urban Primary Care Setting

Objective: To investigate the hypothesis that a history of sudden unexpected loss including number of losses and type of loss (death due to unnatural versus natural causes) would be associated with the magnitude of dysregulation. The sudden unexpected death of a loved one confers risk of morbidity and mortality, perhaps due to dysregulation in the immune/inflammatory and endocrine systems. Methods: Female primary care patients aged ≥40 years (n = 75) completed questionnaires, a clinical interview, and a blood draw. Interleukin (IL)-6 and insulin-like growth factor (IGF)-1 were assayed, using standard enzyme-linked immunosorbent assay protocols and anticytokine antibody pairs. Results: History of sudden loss was positively associated with IL-6 (mean = 4.07 pg/mL; log10 values, B = 0.314, p = .009) and negatively associated with IGF-1 (mean = 97.05 ng/mL; B = −0.277, p = .023). A linear relationship parsimoniously captured the association between ordered categories of lifetime loss (0, 1, 2–5, 5+) and increases in log10 IL-6 (B = 0.107, p = .005) and decreases in IGF-1 (B = −0.116, p = .005). Adjusting for illness burden, depressive symptom severity, and obesity did not change the observed associations. The hypothesized effect of type of loss was not supported. Conclusions: These preliminary findings encourage further investigations to elucidate pathways from sudden unexpected loss to biomarker changes that increase risk for morbidity and mortality. IL-6 = interleukin-6; IGF = insulin-like growth factor.
Prognostic Value of Cyclin D1 and P53 Protein in Colorectal Carcinoma

The multistep carcinogenic process of colorectal cancer involves a series of events as oncogenes, inactivation of suppressor genes and abnormalities in cell cycle regulating proteins. This study concerns altered expression and prognostic role of cyclin D1 and p53 in colorectal cancer patients. We evaluate nuclear accumulation of cyclin D1 and p53 immunohistochemically in archival tissue specimens from 41 primary colorectal adenocarcinomas. They had undergone surgery with a median follow up of 23 months (range 1-85 months). Survival time was analyzed using Kaplan-Meier survival estimates and Cox proportional hazards model for nuclear accumulation of cyclin D1 and p53 with adjustments for other confounding demographic and clinical variables. The expression of cyclin D1 was identified in 41.5% while p53 was expressed in 58.5% of our cases. Cyclin D1 was statistically associated with p53, Dukes' stage, nodal state, histologic grade and vascular invasion, but not with age, gender, location, size, gross picture, tumor type, bilharziasis or stromal reaction. p53 was significantly related to male gender and to mucinous and signet ring tumor types but not to either age, location, size gross picture, Dukes' stage, nodal state, histologic grade, bilharziasis, stromal reaction or vascular invasion. Using Kaplan-Meier survival curve, cyclin D1, p53, size, Dukes' stage, nodal state and tumor type were significantly correlated with poor survival. By Cox multivariate regression analysis, p53 (relative risk 3.33, 95% confidence interval 1.39-7.95; p = 0.006), nodal state (relative risk 3.17, 95% confidence interval 1.31-7.68; p = 0.01) and Dukes' stage (relative risk 1.83, 95% confidence interval 1.06-3.15; p = 0.027) were independent prognostic indicators in our colorectal adenocarcinoma cases. Our data suggest that cyclin D1/p53 pathway represent a frequent target of the multistep evolution of colorectal carcinoma. Nuclear p53 accumulation combined with nodal state and Dukes' stage can predict the clinical behavior of a tumor and high risk colorectal cancer patients. Hence p53 might help to define, a subset of biologically unfavorable neoplasms and improve the prognostic accuracy for colorectal cancer.
Intranasal delivery of stem cells to the brain

Introduction: Stem cell-based therapy has proved to be a promising treatment option for neurological disorders. However, there are difficulties in successfully administrating these stem cells. For example, the brain–blood barrier impedes the entrance of stem cells into the CNS after systemic administration. Direct transplantation or injection may result in brain injury, and these strategies are clinically less feasible. Intranasal administration is a non-invasive and effective alternative for the delivery of drugs, vector-encoded viruses or even phages to the CNS. Recent studies have in fact demonstrated that stem cells may enter the CNS after intranasal administration. These results suggest that intranasal delivery may provide an alternative strategy for stem cell-based therapy. Areas covered: This review summarizes current studies that have applied the intranasal delivery of stem cells into the brain. In addition, the distribution and fate of stem cells in the brain and the potential opportunities as well as challenges of intranasal stem cell delivery are also discussed. Expert opinion: Intranasal delivery of stem cells is a new method with great potential for the transplantation of stem cells into the brain, and it may provide an extraordinary approach to overcoming the existing barriers of stem cell delivery for the treatment of many neurological disorders. This potential benefit emphasizes the importance of future research into intranasal delivery of stem cells.
The expression of megalin ( gp 330 ) and LRP diverges during F 9 cell differentiation

The receptor-associated protein, RAP, is a chaperonin-like molecule that binds to two members of the low density lipoprotein receptor (LDLR) superfamily – megalin (gp330) and the LDL receptor-related protein (LRP). In F9 embryonal carcinoma cells, expression of RAP mRNA increases when differentiation is induced with retinoic acid and dibutyryl-cyclic AMP. We have investigated the expression of megalin and LRP and their interaction with RAP in F9 cells using biochemical and immunocytochemical methods. Both receptors are expressed in uninduced F9 cells, but only megalin co-precipitates with RAP. When F9 cells were induced to differentiate into parietal endoderm, the expression of megalin was dramatically increased. The expression of megalin exceeded that of LRP and RAP by an order of magnitude and both receptors co-precipitated with RAP. By immunoelectron microscopy, megalin and LRP were localized to clathrin-coated pits at the cell surface in both undifferentiated and differentiated F9 cells, whereas RAP was found mainly in the ER. A sizeable pool of LRP was also detected in the ER. When F9 cells were grown in suspension in the presence of RA and induced to develop into embryoid bodies, the expression of megalin and LRP segregated into different cell types: megalin was found in the outer epithelial layer and LRP in the stem cells of the inner core. Our results demonstrate that F9 cells induced to differentiate in monolayer culture express megalin, LRP and RAP, and RAP is capable of interacting simultaneously with both receptors. In embryoid bodies the expression of megalin and LRP diverges, and only megalin is expressed in the outer epithelial layer. The high levels of expression and cell specificity of megalin and LRP suggest important roles for these receptors in early embryonic development.
Placental blood collection: effects on newborns.

Human placental blood (PB) is increasingly used as a source of hematopoietic stem cells for transplantation. Since the first successful transplant in 1988, more than 50 pediatric patients have been engrafted by means of PB collected at the birth of full-term newborns. ’ and large PB banking programs are arising both in the United States and in Europe. ’ In this regard, concern has been raised about risks for the newborn associated to PB collection procedures because clamping of the umbilical cord “too early’’ could “deprive the baby of blood”. ’-5 To clarify this issue, we evaluated hemoglobin and bilirubin values during the first 4 days of life in 131 full-term newborns who had their PB collected and stored in our PB bank, established in Milan, Italy in 1993. The procedure was performed after vaginal delivery or cesarean section by an on-call staff from the blood bank. PB was collected by gravity in a blood collection bag containing 18 mL citrate-phosphate-dextrose by venepuncturing the free end of the umbilical cord. On 59 occasions, the umbilical cord was clamped within 30 seconds after delivery, and 76 2 22 mL PB was collected. When the umbilical cord clamping was delayed (35180 seconds, n = 72). 39 2 17 mL PB was collected. As a control, hemoglobin and bilirubin values were evaluated in 75 full-term newborns who did not undergo PB collection. In the latter cases, the umbilical cord was clamped 20 to 120 seconds after collection. As shown in Table I , hemoglobin values were 17.4 t 1.3 g/dL in newborns who had the PB collected after delayed clamping and 17.2 2 I . S g/dL in control subjects who had no PB collected. When the umbilical cord was clamped within 30 seconds and the PB collected, the hemoglobin value was 16.0 f 1.1 g/dL ( P < .01 versus controls and newborns who had a delayed clamping of the cord. determined by unpaired Student’s t-test). A weak negative relationship was found between the volume of PB collected and the newborn’s hemoglobin value ( r = -.42, P = .01). Length of hospital
Enteropathogenic Escherichia coli markedly decreases the resting membrane potential of Caco-2 and HeLa human epithelial cells

It is presumed, but not proven, that enteropathogenic Escherichia coli (EPEC) causes secretory diarrhea by altering ion transport in enterocytes. In this study we used the whole-cell, current clamp variant of the patch clamp technique to demonstrate that EPEC infection of HeLa and Caco-2 human epithelial cells reduces cell resting membrane potential. The observed reduction of resting membrane potential in HeLa cells results from EPEC-mediated signal transduction to the host cell but is not dependent upon EPEC-mediated elevation of levels of intracellular free calcium. These findings indicate that EPEC can directly alter the relative distribution of ions across epithelial host cell membranes. This may be relevant to the etiology of diarrhea caused by EPEC infection.
Audiological Assessment in Ramsay Hunt Syndrome

Ramsay Hunt syndrome is known to cause symptoms and signs of vestibulocochlear dysfunction, including sensorineural hearing loss. The present study investigates the audiological features of a group of 15 patients with this syndrome. A complete otolaryngological, neurologic, and audiological workup was performed in every patient, including auditory brain stem response measurements and recording of transiently evoked otoacoustic emissions. In most patients, some degree of hearing loss was evident, and abnormal latencies and interpeak latencies of the auditory brain stem response, or even absence of the waves, were observed. Transiently evoked otoacoustic emissions were present in only 6 cases, and caloric tests showed unilateral weakness in the majority of the patients. In all of the performed tests, abnormalities were present only on the affected side. The audiological data suggested cochlear or retrocochlear involvement or involvement at more than one site along the auditory pathway.
Evaluation of Safety and Tolerability of Amlodipine and Cilnidipine-A Comparative Study

Amlodipine and Cilnidipine are found equally efficacious in terms of blood pressure control but very few studies have been conducted on safety and tolerability profile of both the drugs except regarding ankle oedema. Cilnidipine has a slow-onset but the long-lasting antihypertensive action action like Amlodipine. It had get approval in June 2007 and introduced in the market and claimed to be superior over Amlodipine. The aim of this study is to assessment of safety and tolerability of both calcium antagonists i. e Amlodipine and Cilnidipine. The Objectives are to evaluate the incidence of adverse drug reactions of Amlodipine and Cilnidipine and to compare the incidence of ADRs between Amlodipine and Cilnidipine. Patients with hypertension (n= 326) meeting the inclusion and exclusion criteria, reporting in the department of medicine between December 14 to November 15 for their treatment were enrolled in the study. The enrolled patients were then divided as (1) Hypertensive patient the study group received Cilnidipine and control group receiving Amlodipine. (2) Hypertensive with controlled diabetic patients are also grouped separately as study or control group receiving Cilnidipine or Amlodipine respectively. All patients were examined periodically at 1, 3, 6, and 12 months intervals. Dose of Amlodipine and Cilnidipine were titrated according to their BP goal. We exclude the data of drop out participants, those who withdraw consentand any protocol violation like those patients for whom additional anti hypertensive were added other than ARB or ACEI for inadequate BP control.After exclusion of dropouts, the study was continued in 258 participants. All values were expressed as means ± SEM (n = 6 in each group). The comparison between Amlodipine and Cilnidipine in both diabetic as well as non diabetic hypertensive patients was done by Fischer exact test. Significance is set at P ≤ 0.05. It is evident from the present study that incidence of ankle edema, palpitations and weight gain was significantly more in Amlodipine than cilnidipine. Incidence of other adverse drug reactions were noted to be more frequent in Amlodipine treated patients but no significant difference was found. It can be concluded that Cilnidipine has a better tolerability profile than Amlodipine, though having equal potency in equivalent doses as the incidence of ADRs were more associated with Amlodipine than Cilnidipine in both diabetic and non diabetic hypertensive patients.
The Impact of Gender, Depression, and Personality on Cravings

Abstract Craving plays an important role in the addictive behavior process. The impact of gender, emotional state and personality on craving, however, has been understudied. Craving plays an important role in the addictive behavior process. The impact of gender, emotional state and personality on craving, however, has been understudied. Recency of substance use and impulsivity were significantly associated with craving intensity for both women and men. Regression analyses revealed that depression best predicted craving for women, but not for men. These results suggest that while recent substance use and impulsivity can be important predictors of craving across gender, depression plays a critical role in craving among women. This finding underscores the need for vigorous assessment and treatment of comorbid symptomatology in women entering addiction treatment.
Laparoscopic renal and adrenal surgery in obese patients: comparison to open surgery.

PURPOSE The efficacy and morbidity of laparoscopic renal and adrenal surgery in comparison to open surgery in obese patients are unknown. This retrospective study was performed to compare the outcome of laparoscopic versus open renal and adrenal surgery in the markedly and morbidly obese patient (body mass index 30 or greater). MATERIALS AND METHODS The study group comprised all obese patients undergoing laparoscopic renal and adrenal surgery (laparoscopic group) from August 1997 to February 1998 at our institution. The majority of procedures were performed using a retroperitoneoscopic approach via the flank. These patients were compared with all obese patients undergoing open renal and adrenal surgery (open group) from 1994 to 1998. Open group patients with factors precluding laparoscopic surgery were excluded from the study (mass greater than 10 cm., renal vein and/or inferior vena caval thrombus and extension outside Gerota's fascia). RESULTS There were 21 obese patients in each group and baseline parameters were comparable between groups. Median body mass index in the laparoscopic and open groups was 34 and 31, respectively. Median surgical time between the laparoscopic (210 minutes) and open (185) groups was comparable (p = 0.16). However, the laparoscopic group had decreased blood loss (100 versus 350 ml., p<0.001), quicker resumption of oral intake and ambulation (less than 1 versus 5 days, p<0.001), decreased narcotic analgesic requirements (12 versus 279 mg., p<0.001), shorter median hospital stay (less than 1 versus 5 days, p<0.001) and quicker convalescence (3 versus 9 weeks, p<0.001). There were 6 complications in 4 laparoscopic cases and 14 in 9 open surgery cases (p = 0.16). CONCLUSIONS Markedly obese patients have an increased risk of complications from surgery, regardless of the approach. Our data suggest that laparoscopic renal and adrenal surgery is technically feasible in the markedly and morbidly obese patient, and compared with open surgery results in significantly decreased blood loss, quicker return of bowel function, less analgesic requirement, shorter convalescence and reduced hospital stay.
N,O‐di and N,N,O‐tri [3H] acetyl α‐bungarotoxins as specific labelling agents of cholinergic receptors

1 α‐Bungarotoxin isolated from the venom of Bungarus multicinctus was acetylated with [3H] acetic anhydride and N‐[3H] acetyl imidazole. Tri‐N‐acetyl and hexa‐N‐acetyl derivatives were obtained from the former, and N,O‐di, N,N,O‐tri and N,N,N,O‐tetraacetyl derivatives from the latter reaction, respectively. 2 There were parallel decreases in both neuromuscular blocking action in the phrenic nerve—diaphragm preparation of rats and depression of acetylcholine response of the rectus abdominis muscle of frogs with increased acetylation. Also, a parallel but greater decrease of toxicity in mice was found. 3 N,O‐Di and N,N,O‐triacetyl toxins were localized mostly in the motor endplate region of the rat diaphragm, whereas a slight nonspecific binding along the whole muscle fibre in addition to the peak in the endplate region was observed with N,N,N,O‐tetraacetyl and tri‐N‐acetyl toxins. In contrast, there was a marked nonspecific binding with hexa‐N‐acetyl toxin and no peak was observed at the endplate zone. 4 The specific binding was saturable and irreversible. The number of toxin‐receptive sites in one endplate was 1·9–2·2 × 107 for all of the labelled toxins irrespective of their potency. 5 (+)‐Tubocurarine protected effectively against the binding as well as the irreversible neuromuscular blocking effect of the toxins. 6 Denervation of the rat diaphragm caused an increase of toxin‐receptive sites beginning from the endplate zone at 1–2 days and then along the whole muscle fibre, reaching the maximum at about 18 days. The total receptive sites increased by about 30‐fold. 7 The significance of the findings is discussed and it is concluded that N,O‐di and N,N,O‐tri‐[3H] acetyl α‐bungarotoxins are specific and irreversible labelling agents for the cholinergic receptors of skeletal muscle.