Effect of dietary lipids and other nutrients on milk odd- and branched-chain fatty acid composition in dairy ewes.

Milk odd- and branched-chain fatty acids (OBCFA) are largely derived from bacteria leaving the rumen, which has encouraged research on their use as biomarkers of rumen function. Targeted research has examined relationships between these fatty acids (FA) and dietary components, but interactions between the effects of lipids and other nutrients on milk OBCFA are not well characterized yet. Furthermore, factors controlling milk OBCFA in sheep are largely unknown. Thus, the present meta-analysis examined relationships between diet composition and milk OBCFA using a database compiled with lot observations from 14 trials in dairy ewes fed lipid supplements. A total of 47 lots received lipid supplements, whereas their respective controls (27 lots) were fed the same basal diets without lipid supplementation. Relationships between milk OBCFA and dietary components were first assessed through a principal component analysis (PCA) and a correlation analysis. Then, responses of milk OBCFA to variations in specific dietary components (selected on the basis of the PCA) were examined in more detail by regression analysis. According to the loading plot, dietary unsaturated C18 FA loaded opposite to major milk OBCFA (e.g., 15:0, 15:0 anteiso, and 17:0) and were strongly correlated with principal component 1, which described 46% of variability. Overall, regression equations supported this negative, and generally linear, relationship between unsaturated C18 FA levels and milk OBCFA. However, the influence of C20-22 n-3 polyunsaturated FA and saturated FA was more limited. The PCA also suggested that dietary crude protein is not a determinant of milk OBCFA profile in dairy ewes, but significant relationships were observed between some OBCFA and dietary fiber or starch, consistent with a potential role of these FA as biomarkers of rumen cellulolytic and amylolytic bacteria. In this regard, regression equations indicated that iso FA would show opposite responses to increasing levels of acid detergent fiber (positive linear coefficients) and starch (negative linear coefficients). Lipid supplementation would not largely affect these associations, supporting the potential of OBCFA as noninvasive markers of rumen function under different feeding conditions (i.e., with or without lipid supplementation). Because consumption of these FA may have nutritional benefits for humans, the use of high-fiber/low-starch rations might be recommended to maintain the highest possible content of milk OBCFA in dairy sheep.

Survival Rates of Stainless Steel Crowns and Multi-Surface Composite Restorations Placed by Dental Students in a Pediatric Clinic.

PURPOSE: This study examined survival rates of multi-surface composite restorations and stainless steel crowns (SSCs) placed by students in a pediatric dental clinic as well as the length of time it takes for restorations to be replaced with stainless steel crowns. STUDY DESIGN: Data from electronic dental records for all children with at least one 2-surface composite restorations or SSCs on a primary first or second molar from January 1, 2007 to September 30, 2015 were analyzed. The primary outcome was the time to a new restoration or SSC on the same tooth, with time to a crown as a secondary outcome. Descriptive statistics were obtained and the cumulative incidence of the event of interest was estimated using 95% confidence intervals and compared between groups using Fine-Gray regression. RESULTS: A total of 6,288 teeth from 2,044 children were analyzed. Three years after the initial procedure, 1.5% of SSCs and 21% of 2 and 3 surface composite restorations failed and needed a replacement (Hazard Ratio [HR]= 14; 95% Confidence interval [CI] 9-22, p<0.001). Also, 6.8% of composite restorations needed replacement with SSCs' (HR=4; 95% CI: 3-7). CONCLUSIONS: The study demonstrates that stainless steel crowns had a higher survival rate than multi-surface composite resins placed by students at a pediatric dental clinic in primary molars of children.

Huprine X and huperzine A improve cognition and regulate some neurochemical processes related with Alzheimer's disease in triple transgenic mice (3xTg-AD).

BACKGROUND: Different studies have established that cholinergic neurodegeneration could be a major pathological feature of Alzheimer's disease (AD). Thus, enhancement of the central cholinergic neurotransmission has been regarded as one of the most promising strategies for the symptomatic treatment of AD, mainly by means of reversible acetylcholinesterase inhibitors (AChEIs). The cognitive-enhancing properties of both huprine X, a new AChEI, and the structurally related huperzine A, as well as their effects on the regulation of several neurochemical processes related to AD have been studied in triple transgenic mice (3xTg-AD). METHODS: Seven-month-old homozygous 3xTg-AD male mice, which received chronic intraperitoneal treatment with either saline, huprine X (0.12 µmol·kg(-1)) or huperzine A (0.8 µmol·kg(-1)) were subjected to a battery of behavioural tests after 3 weeks of treatment and thereafter the brains were dissected to study the neurochemical effects induced by the two AChEIs. RESULTS: Treatments with huprine X and huperzine A improved learning and memory in the Morris water maze and some indicators of emotionality without inducing important adverse effects. Moreover, huprine X and huperzine A activate protein kinase C/mitogen-activated protein kinase pathway signalling, α-secretases (ADAM 10 and TACE) and increase the fraction of phospho-glycogen synthase kinase 3-ß. CONCLUSION: Results obtained herein using a sample of 3xTg-AD animals strongly suggest that the treatment with the two AChEIs not only improves the cognitive performance of the animals but also induces some neurochemical changes that could contribute to the beneficial effects observed.

Acetylcholinesterase as an amyloid enhancing factor in PrP82-146 aggregation process.

Acetylcholinesterase (AChE) triggers beta amyloid plaques formation and is associated with amyloid plaques in the brain. Recent studies have demonstrated that AChE promotes the aggregation of PrP106-126, a peptide deduced from the prion protein sequence. In the present study we show that AChE triggers also the fibrillization of the main component of the amyloid plaques -the peptide spanning residues 82-146 (PrP82-146)- found in patients with Gerstmann-Sträussler-Scheinker disease (GSS). The kinetics of PrP82-146 aggregate formation was directly correlated with AChE concentration and mature fibrils showed the tinctorial and optical properties of amyloid. Atomic force microscopy analysis showed that oligomer and amyloid fibril formation were significantly accelerated by AChE. This effect was mediated by the peripheral site of the enzyme since propidium iodide inhibited the fibrillization process. Present results strongly support the role of AChE in triggering amyloidogenesis and the potential therapeutic relevance of peripheral site blocker compounds.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia.

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

Blindness in a bladder cancer patient.

Blindness is an unusual symptom in the clinical course of cancer. When it appears it is necessary to differentiate between benign and malign causes. Brain metastases in bladder cancer are extremely rare. MRI is the best diagnostic option. We present a deaf-and-dumb male with subacute blindness, 12 months after the diagnosis of a metastatic bladder cancer. Computerised tomography scan and MRI revealed a mass into the pituitary gland and sella, probably of metastatic origin.

Implications of quenching in efficiency, spectrum shape and alpha/beta separation.

Liquid scintillation spectrometry (LSS) is a meaningful technique for the determination of alpha and beta emitters. However, this technique is highly affected by quenching phenomena, which reduce the counting efficiency, shift the spectra to low energies and cause misclassification problems. In this paper, a selection of chemical and colour quench agents was evaluated to study the influence of alpha and beta energy and the quenching effect on the detection efficiency, the shape of the spectra and the α/ß misclassification.

Effect of acetylcholinesterase inhibitors on AChE-induced PrP106-126 aggregation.

Transmissible spongiform encephalopaties are caused by an extracellular surface protein, the scrapie prion protein (PrPsc), which is an aberrant form of normal and functional cellular PrP (PrPc). The pathological hallmarks of these diseases are the accumulation and deposition of PrPsc in the form of amyloid fibrils in the central nervous system (Tateishi et al., 1988), similar to amyloid-beta (Abeta) protein in Alzheimer's disease (AD). In some patients, Abeta and prion pathology can coexist (Hainfellner et al., 1998), and a common spatial pattern of protein deposition has been described (Armstrong et al., 2001). In addition, it is well-known that acetylcholinesterase (AChE) colocalizes with Abeta deposits of brains in AD patients and accelerates assembly of Abeta peptides through the peripheral site of the enzyme (Inestrosa et al., 1996). The aim of the present study was to analyze time course and concentration dependence of the AChE proaggregating effect on synthetic peptide-spanning residues 106-126 of human PrP (PrP106-126) and the reversion of this effect by different AChE inhibitors (AChEIs).

[Arthroscopy of the trapeziometacarpal and metacarpophalangeal joints]. / Arthroscopie des articulations trapézometacarpienne et métacarpophalangienne: installation, voie d'abord et exploration.

Indications for small joint arthroscopy in the hand remain poorly understood. This is due to a paucity of papers discussing this technique in the literature, as well as inadequate hands on training in the pearls and pitfalls regarding this application within the commonly used "scope" of arthroscopy. Despite the fact that small joint arthroscopes have been available for over a decade, hand surgeons have been slow to adopt this technique within their treatment armamentarium for the treatment of both traumatic and degenerative conditions involving the thumb and the digital metacarpophalangeal joints. A proposed arthroscopic classification for basal joint osteoarthritis provides additional clinical information and can direct further treatment depending on the stage of disease. This chapter will also review the brief history of trapeziometacarpal arthroscopy and provide insight as to how this technique can be incorporated into a treatment algorithm in managing this common affliction. Metacarpophalangeal joint arthroscopy is even less commonly used, while traumatic and overuse injuries are frequently seen in the thumb, and present an ideal indication in certain scenarios. Painful conditions affecting the metacarpophalangeal joints of the fingers are less commonly seen, yet the small joint arthroscope presents a much clearer picture of the present pathology compared to other imaging techniques or even open, and potentially deleterious, surgery. The application of this technology to the smaller joints will soon make the treating surgeon realize that a myriad of pathologies are readily visible and can augment treatment, as well as diagnosis. Similar to the wrist, small joint arthroscopy may one day supplant imaging techniques such as MRI or CT in establishing an accurate diagnosis.

[Surgical diagnosis of pleural disease]. / Le diagnostic chirurgical en pathologie pleurale.

Videothoracoscopy is a minimally invasive techinique providing a direct view of the pleural cavity. It enables complete exploration of the cavity with biopsies of pathological zones. The indication, based on clinical or radiographic findings, is retained when less invasive methods have been unable to establish the diagnosis and a specific pleural disease (tumor or other) is suspected. Depending on the observations at videothoracoscopy and the suspected disease, deep biopsies to the subpleural fat can be made with a forceps if nodules have been identified. If the pleura is uniformly thin, a small flap can be detached for the biopsy. Several pleura sites are biopsied and a direct pathology examination can be performed on certain specimens. Videothoracoscopy enables careful hemostasis of biopsied zones and symphysis (generally with talc) if needed. The perioperative mortality is low (<0.5%) with good sensitivity greater than 90% and excellent specificity at 100%. The presence of complete pleural symphysis counterindicates videothoracoscopy. In such patients, direct access via an intercostal incision is needed to obtain localized biopsies.

[Evolution of species: Lung cancer evolution over one third of a century]. / De l'évolution des espèces : évolution du cancer du poumon en un tiers de siècle.

INTRODUCTION: Management of non-small cell lung cancer (NSCLC) is getting better and results on long-term survival have improved. We reviewed the modifications observed in surgery over a 32-year time period. PATIENTS AND METHOD: Data of 6105 patients who underwent surgery from 1979 to 2010 were analyzed over three equal time-periods: gender, age, type of surgery, histology, pTNM, tobacco addiction, comorbidity and time periods. RESULTS: Age, number of females and high-risk patients with comorbidity (including the history of a previous cancer) increased with time periods. Number of exploratory thoracotomy (7.7 % to 1.6 %) and pneumonectomy (48 % to 18 %) decreased. Number of wedge resection (0.5 % to 6 %) and lobectomy (42 % to 64 %) increased. Rates of the other types of resection were unchanged. Neoadjuvant treatments accounted for more than 20 % of patients in the last time period. Postoperative mortality (4 %) did not vary but non-lethal complication rates increased (16.9 % to 27.7 %). Global 5-year survival rates dramatically increased with time going from 37.4 % to 49.8 % (P<10(-6)). Survival improvement was observed in the different components of the pTNM and whatever the type of treatment. However, survival was affected by increasing age and multiplication of comorbidities but without impairing the general better outcome trend. CONCLUSION: NSCLC itself, its diagnostic and therapeutic management, and patient's characteristics evolved with time. Survival improved in most studied prognosis factors. Time period factor was of paramount importance and might be included in research dealing with NSCLC.

[Lung cancer measuring 1cm or less: A miniature subset requiring surgery]. / Cancers du poumon de 1 à 10millimètres : des cancers miniatures à opérer.

INTRODUCTION: Lung cancer measuring 1cm or less has an apparently very good outcome. However, the characteristics permitting their oncological management are unappreciated. PATIENT AND METHOD: We reviewed 187 patients with such a cancer (145 men and 42 women, mean age 60.2years) and studied the type of surgery performed, the pTNM, and the histological features. RESULTS: Surgery (19 wedge-resections, 12 segmentectomies, 136 lobectomies, 20 pneumonectomies) was complete (R0) in 97.3%. The tumors, each precisely defined among 98 adenocarcinomas (52.4%), 83 squamous cell carcinomas (44.4%), and 6 others, measured 1mm to 10mm:<5mm (n=41), 6 to 9mm (n=43), and 10mm (n=103). There were 161 pT1 (86.1%), 22 pT2 (11.8%) and 4 pT3; 148 pN0 (79.6%), 18 pN1 (9.7%) and 20 pN2 (10.7%). pN1 and pN2 were present in tumors<5mm (12/41, 29.3%) as well as in the others (26/146, 17.8% P=0.11). Histological examination frequently discovered visceral pleura involvement (tumors:<5mm 12.2% (5/41), 6 to 9mm 7% (3/43), 10mm 13.6% (14/103), P=0.53) and lympho-vascular invasion (12.9%). Five-year survival rate (66.4%) was adversely influenced by age, type of resection, pN and histological features. The survival rate was not better in tumor<5mm. CONCLUSION: Surgical resection allows the local control of lung cancers<1cm and their complete histological study, a key issue in the therapy of the future, which renders surgery an absolute must even in very small tumors.

Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer.

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m(2) intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P =.04 for survival and P =.01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.

Nicotinic-receptor potentiator drugs, huprine X and galantamine, increase ACh release by blocking AChE activity but not acting on nicotinic receptors.

The main goal of the present study was to analyse the effects of (+/-)-huprine X ((+/-)-HX) and galantamine (GAL), with potentiating action on nicotinic receptors, and huperzine A (HPA), devoid of nicotinic activity, on [3H]-acetylcholine ([3H]-ACh) release in striatal slices of rat brain. All compounds are non-covalent and reversible inhibitors of AChE. Addition of (+/-)-HX (0.01 microM), GAL (10 microM) and HPA (0.1 microM) to the superfusion medium decreased the release of the ACh neurotransmitter to a similar extent: 36%, 30% and 34%, respectively (P<0.01). This effect was reverted in the presence of atropine (ATR; 0.1 microM), which blocks the pre-synaptic muscarinic M2 receptor. After that, a wide range of concentrations of drugs, concomitantly with ATR (0.1 microM), was studied in the presence of haloperidol (HAL; 0.01 microM), a dopamine D2 antagonist. In these conditions, a dose-dependent increase of [3H]-ACh release was observed in the presence of (+/-)-HX, GAL and HPA. To test the role of nicotinic receptors in the drugs' effects on [3H]-ACh release, mecamylamine (MEC) 100 microM was used to block such receptors. MEC alone significantly decreased neurotransmitter release by 18% (P<0.05), but no change was obtained in the presence of both ATR and MEC. Under these conditions, (+/-)-HX, GAL and HPA increased the release of [3H]-ACh by 37%, 25% and 38%, respectively (P<0.01). Taking into account all of these data, the present results suggest that the effects induced by (+/-)-HX and GAL nicotinic-receptor potentiators seem to be mainly due to their ability in inhibiting acetylcholinesterase activity, but not by interaction on the nicotinic receptors.

Effects of (+/-)-huprine Y and (+/-)-huprine Z, two new anticholinesterasic drugs, on muscarinic receptors.

The cholinergic profile of (+/-)-huprine Y and (+/-)-huprine Z on muscarinic receptors has been determined. Displacement of [3H]-pirenzepine and [3H]-QNB plus pirenzepine was performed in rat hippocampus. Both compounds showed a higher degree of affinity to M1 muscarinic receptors (P < 0.01) than to M2 muscarinic receptors. To determine the M1 agonist or antagonist role of the two huprines, studies of inositol phosphates (IP) production were performed. Both huprines significantly stimulated IP accumulation in a concentration-dependent manner. The reversion of this effect by different antagonists showed that M1 muscarinic receptors were activated by (+/-)-huprine Y and (+/-)-huprine Z, but some other mechanisms, such as alpha1-adrenoceptors or nicotinic receptors, were involved.

[Pleural endometriosis: an unusual presentation]. / Endométriose pleurale: une présentation inhabituelle.

INTRODUCTION: Numerous conditions can produce chronic exudative pleural effusions. Pleural endometriosis is a rare cause of unilateral effusion with diffuse pleural thickening. CLINICAL CASE: We report the case of chronic pleural effusion in a thirty year old African woman, where pleural endometriosis was diagnosed only following pleuro-pulmonary decortication, with the diagnosis being confirmed by immunohistochemistry. CONCLUSION: Pleural endometriosis must be considered as a possible diagnosis in women with pleural effusions of unknown aetiology. The presence of endometrial glands or of chorionic cells within the pleura is characteristic. Immunohistochemistry is an important diagnostic tool.

[Lung cancer surgery in a single-lung]. / Chirurgie du cancer bronchique sur poumon unique.

INTRODUCTION: The diagnosis of a second lung cancer in a patient with a previous medical history of lung cancer is no longer a rarity. Also, it is possible to observe a new location in a patient who underwent pneumonectomy in the past. Surgery remains the best treatment. Our objective was to overview this subject. PATIENTS AND METHODS: Among 5611 patients operated in our institution, 186 (3.3%) had metachronous cancer and 17 had previous pneumonectomy (0.7% of pneumonectomies and 0.2% of NSCLC treated in our department). The procedure was diagnostic and therapeutic in 88% of cases (n=15). RESULTS: There were 16 males and 1 female, mean age was 62.5-years. All were smokers (11 were former smokers) and 6 had other medical history. Mean FEV was 52% (range 35-95%). Types of resection were 2 lobectomies, 4 segmentectomies, and 11 wedge resections. There were no postoperative deaths, but two complications. Histological subtype of the first and second cancer was the same in 11 patients. All patients were pN0 after second surgery. The long-term survival (median 33 months) was 35.3% at 5-years and 14.1% at 10-years. Two patients treated with pneumonectomy for their first cancer were pN2. Patients who underwent upper right lobectomy for treatment of their second cancer survived longer than 5-years. CONCLUSION: Surgical resection for lung cancer on single-lung is associated with acceptable morbidity and mortality. Prolonged survival can be achieved in selected patients.

[Pneumonectomy for benign disease: indication and factors affecting the postoperative course]. / Pneumonectomie pour lésions bénignes: indications et facteurs affectant les suites opératoires.

Pneumonectomy for benign disease is rare but may generate more postoperative morbimortality than when performed for lung cancer. We questioned this assessment and retrospectively reviewed 1436 pneumonectomies and 54 completions of which 82 and 10 performed for benign disease (5.7% and 18.5%, respectively): left n=65 and right n=27. Indications were: post-tuberculosis destroyed lung (n=37), aspergilloma (n=18), bronchiectasis (n=19), infection (n=5), congenital malformations (n=5), inflammatory pseudotumor (n=3), trauma (n=2), post-radiation (n=2) and mucormycosis (n=1). Pneumonectomy consisted of 48 standard and 44 pleuro-pneumonectomies. Stump coverage by flaps was performed in 66.3% (61/92). Complications occurred in 21.7% (20/92) and postoperative deaths in 7.6% (7/92, of which 5 with fungal infections), which was not different than what was observed in lung cancer. There was no difference in fistula formation and mortality regarding the side, the type of resection and the protective role of stump coverage. Considering patients with fungal infections versus others, mortality was 26.3% (n=5/19) and 2.7% (n=2/74), respectively (P=0.0028). Pneumonectomy for benign disease achieves cure with acceptable mortality and morbidity. However, presence of fungal infection should raise the attention for possibility of increased postoperative risks.

[Clinical and paraclinical prognostic factors in non-small cell lung cancer surgery]. / Facteurs pronostiques cliniques et paracliniques dans la chirurgie du cancer du poumon non à petites cellules.

INTRODUCTION: Lung cancer prognosis is mainly based on the TNM, histology and molecular biology. Our aim was to analyze the prognostic value of certain clinical and paraclinical variables. PATIENTS AND METHODS: We studied among 6105 patients operated on, divided during 3 time-periods (1979 to 2010), the following prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history, clinical presentation, and paraclinical variables. RESULTS: Postoperative mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5-year overall survival was 43.2% and 10-year was 27%. Best survival was observed after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(-6)). All these factors were confirmed by multivariate analysis, except gender. Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became significant in the multivariate one (P=0.013). CONCLUSION: Medical and human factors, and the general physiological state, play an important role in prognosis after surgery. We do not know their exact meaning and, like studies on chemotherapy, they justify special research.

AVCRI104P3, a novel multitarget compound with cognition-enhancing and anxiolytic activities: studies in cognitively poor middle-aged mice.

The present work describes, for the first time, the in vivo effects of the multitarget compound AVCRI104P3, a new anticholinesterasic drug with potent inhibitory effects on human AChE, human BuChE and BACE-1 activities as well as on the AChE-induced and self-induced Aß aggregation. We characterized the behavioral effects of chronic treatment with AVCRI104P3 (0.6 µmol kg(-1), i.p., 21 days) in a sample of middle aged (12-month-old) male 129/Sv×C57BL/6 mice with poor cognitive performance, as shown by the slow acquisition curves of saline-treated animals. Besides, a comparative assessment of cognitive and non-cognitive actions was done using its in vitro equipotent doses of huprine X (0.12 µmol kg(-1)), a huperzine A-tacrine hybrid. The screening assessed locomotor activity, anxiety-like behaviors, cognitive function and side effects. The results on the 'acquisition' of spatial learning and memory show that AVCRI104P3 exerted pro-cognitive effects improving both short- and long-term processes, resulting in a fast and efficient acquisition of the place task in the Morris water maze. On the other hand, a removal test and a perceptual visual learning task indicated that both AChEIs improved short-term 'memory' as compared to saline treated mice. Both drugs elicited the same response in the corner test, but only AVCRI104P3 exhibited anxiolytic-like actions in the dark/light box test. These cognitive-enhancement and anxiolytic-like effects demostrated herein using a sample of middle-aged animals and the lack of adverse effects, strongly encourage further studies on AVCRI104P3 as a promising multitarget therapeutic agent for the treatment of cholinergic dysfunction underlying natural aging and/or dementias.