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There is a great effort from numerous research groups in the development of materials and therapeutic strategies for the functional recovery of patients who have suffered peripheral nerve injuries (PNI). In an article in vivo, the formation of a nerve bridge was observed, reconnecting the distal and proximal stumps, in the sciatic nerve of rats, indicating the effective participation of the biomaterial in the recovery of peripheral nerve injuries. For the current pilot study, 15 cases of multiple fractures of the mandible, with involvement of the inferior alveolar nerve (IAN) were selected and studied: JC (control cases) n = 6 with conventional treatment, and JT (treated cases) n = 9, with the use of biomimetic biomaterial. The evaluation of the return to sensitivity was measured through a self-assessment, where the patients assigned scores from 0 to 10, where zero (0) represented the complete absence of sensitivity and ten (10) the normality of the perception of local sensitivity. Patients were evaluated from the preoperative period to the 360th day. The statistical results obtained by the t-Student, Shapiro-Wilk normality and non-parametric One-Way ANOVA tests indicated statistically significant differences (p

Blood nutritional indicators were measured on twenty-six prepubertal 8- mo-old buffalo heifers, weighing a mean of 134 kg to determine the effect of different feeding and management systems. Animals were randomly assigned to an intensive feeding (n=13; IF group) or to a pasture system plus hay (n=13; PS group), according to weight and age. Measurements of live weight and blood collection began on day 0 (=date of onset of trial).The heifers were weighed monthly, up to puberty, to evaluate the growth rate and blood samples were withdrawn every three months to assay the concentrations of blood metabolites. Significantly higher (P0.05).

Buffalo cows were submitted to three superovulatory treatments. T1 (n = 7): PRID for 10 days (d0-d9) plus decreasing doses of 500 IU FSH/LH (12 h-intervals d7‑d10); T2 (n = 8): PRID for 11 d (d0-d10) plus 2000 IU PMSG at d7; T3 (n = 9): PRID for 11 d plus 2000 IU PMSG at d7 and decreasing doses of 175 IU FSH/LH (12 h-intervals d10‑ d11). Overall plasma inhibin‑A (In-A) concentrations correlated with large follicles (LF, diameter >6mm, R=0.83, P10 mm at d12- 13 (T1=5.0+/-1.4, T2=1.2+/-0.9, T3=8.3+/-2.3). In-A concentrations significantly rised at d11-13 of T1 and T3. In-A seems a good indicator of the follicular development during superovulation in buffalo cows, while E2 is not. Furthermore T3 was followed by better ovarian follicular responses.

Twenty four weaned male buffalo calves where randomly divided in two groups: group 1 fed unifeed of corn silage, hay, maize meal and soybean meal until slaughter, and group 2 fed the same diet until they reached 325 kg of body weight, then fed alfalfa hay, maize meal, soybean meal and ruminal buffer. The animals were slaughtered once reached 420 kg of body weight. At the beginning of the trial the groups were homogeneous as for age and body weight as for somatic measures, while all along the study, group 1 proved to have higher body length and width of pelvis. Group 1, moreover, reached the slaughter weight at an earlier time (496 days) than Group 2 (516 days). Regarding the haematological profile, in the second period, group 1 evidenced higher blood cortisol and lower total protein and γ globulins levels.

During an oestrus synchronization trial on heifer and mixed-parity Mediterranean Italian buffaloes, some analyses on health parameters were performed to correlate them to reproductive performances (pregnancy rate and birth rate). Serum sampling were performed every year for two years to be used in serological techniques for the diagnosis of Chlamydia spp. (ELISA), Neospora (ELISA), BHV1 (ELISA gE glycoprotein) and BVDV (ELISA). On the total number of 465 observed buffaloes, the seroprevalence obtained for each disease has respectively been: 24 %, 25 %, 25 % and 22 %. Specific antibodies were not spread over the 13 farms in an homogeneous manner, farm prevalence differences are evidenced by high standard deviations in the mean farm seroprevalence: 42 ± 27.8, 26 ± 26.9, 20 ± 13.8, 9.8 ± 21.1. Among the buffaloes which resulted seropositive to Chlamydia, 33 % were pregnant, 32 % were those with Neospora, 32 % those with BHV1 and finally 29 % of the animals positive to BVDV resulted pregnant. Taking into account the animals that delivered normally, 41 % were positive to Chlamydia, 18 % to Neospora, 18 % to BHV1 and 19 % to BVDV.

Sixteen pluriparous lactating buffaloes were divided in two groups homogeneous for parity, lactation stage, milk yield and weight. The diets assigned to two groups, based on maize silage (M group) and sorghum silage (S group), had the same energy-protein level (0.90 Milk FU/kg DM and 155 g/kg DM of crude protein). Five records of milk yield and quality during lactation were carried out. The physical-chemical characteristics (pH, fat, protein, lactose and urea), somatic cell count, coagulation properties and nutritional parameters (cholesterol, alfa tocopherol, 13 cis and trans retinol and 13 cis/trans retinol ratio) were analysed. Statistical analysis was performed using a factorial model. The average daily milk yield during experimental period was similar: 9.29 and 9.55 kg respectively in M and S groups. Fat and protein content were not different, while the urea content was significantly different varying from 39.13 mg/dl in M group to 45.55 mg/dl in S group. The coagulation properties, the estimated Mozzarella yield, somatic cell count and the nutritional parameters analysed were not different between the two groups. These results indicate that the sorghum silage diet utilised did not affect the milk yield and quality, then it could be adopted in lactating buffaloes.

Thirty adult buffaloes were used for this study. The animals were synchronized by PRID+PMSG+PGF2α and artificially inseminated. The ovaries were ultrasonografically examined to study the preovulatory follicle (PF) and the successive corpus luteum (CL). At the same time, blood sample were collected for P4 determination carried out by RIA. On the basis of echogenic appearance, the corpora lutea (CLs) were classified as belonging to grade 1, 2 or 3. Significant difference was found in the diameter of PF and in that of CL in relation to the CL echogenic appearance. Well defined granular CL, distinguishable from the ovarian stroma and dark grey in colour (grade 3) resulted to have a bigger diameter compared with CLs belonging to a grade 1 or 2, and resulted to derive from a larger PF. Positive correlation was found between plasma P4 concentration and CL diameter. The PF diameter was larger in buffaloes become pregnant after AI respect to the non-pregnant. The CL diameter, also, was significantly larger in the pregnant buffalo compared to the non-pregnant since the first observation at day 7, while significant difference in P4 value was found starting from day 21 after AI.

4 cannulated buffalo milking cows were administered two different diets with the same energy and protein content based on maize silage (diet G1) and sorghum silage (diet G2). Total viable bacteria, cellulolytic and xilanolytic bacteria, fungi, protozoa and pH were determined on whole rumen content samples. Total viable bacteria, xilanolytic bacteria, fungi, protozoa counts and pH values did not show any significant difference between the two diets. Only the values regarding cellulolytic bacteria showed the tendency (P≤0,10) to be higher in diet G2 in comparison with diet G1. This fact was probably due to a lower content of indigestible fiber in diet G2 with respect to diet G1 (ADF 15.6 vs. 22.4 respectively).

Since oestrus behaviour in buffalo is frequently scarcely clear and the oestrus signs, even when showed, are not reliable, ovulation can not be predicted. Furthermore high individual variability of the oestrus signs – LH peak interval was observed both in spontaneous and hormonal induced oestrus (Moioli et al., 1998; Barile et al, 1998).

Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary for growth and proliferation. In fact, cancer cells are characterized by an increased "de novo" synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes of purine metabolism are the targets of drugs as antineoplastic agents, and a better knowledge of the mechanisms underlying their regulation would be of great help in finding new therapeutic approaches. The mammalian target of the rapamycin (mTOR) signaling pathway, which is often activated in cancer cells, promotes anabolic processes and is a major regulator of cell growth and division. Among the numerous effects exerted by mTOR, noteworthy is its empowerment of the "de novo" synthesis of nucleotides, accomplished by supporting the formation of purinosomes, and by increasing the availability of necessary precursors, such as one-carbon formyl group, bicarbonate and 5-phosphoribosyl-1-pyrophosphate. In this review, we highlight the connection between purine and mitochondrial metabolism, and the bidirectional relation between mTOR signaling and purine synthesis pathways.

There is a great effort from numerous research groups in the development of materials and therapeutic strategies for the functional recovery of patients who have suffered peripheral nerve injuries (PNI). In an article in vivo , the formation of a nerve bridge was observed, reconnecting the distal and proximal stumps, in the sciatic nerve of rats, indicating the effective participation of the biomaterial in the recovery of peripheral nerve injuries. For the current pilot study, 15 cases of multiple fractures of the mandible, with involvement of the inferior alveolar nerve (IAN) were selected and studied: JC (control cases) n = 6 with conventional treatment, and JT (treated cases) n = 9, with the use of biomimetic biomaterial. The evaluation of the return to sensitivity was measured through a self-assessment, where the patients assigned scores from 0 to 10, where zero (0) represented the complete absence of sensitivity and ten (10) the normality of the perception of local sensitivity. Patients were evaluated from the preoperative period to the 360th day. The statistical results obtained by the t-Student, Shapiro-Wilk normality and non-parametric One-Way ANOVA tests indicated statistically significant differences ( p  < 0.005; 0.005 e 0.5 respectively), between the two treatments, which were reflected in the clinical results observed, we also calculate the size of the effect represented by ϵ , calculated by Cohen's 2 , calculated by Cohen's d . The results indicate a great difference between the treatments performed , ϵ 2  = 1.00. In the 6 cases followed up in the JC group, four remained with a significant deficit until the end of the evaluations and two indicated the remission of the lack of sensitivity in this period. In the JT group, in 28 days, all cases indicated complete remission of the lack of sensitivity with healing concentration. In one of the cases where there was a complete rupture of the mental nerve, the (score-10) was observed in 60 days. The observed results indicate the existence of a statistical significance between the groups and an important relationship when using the biomimetic biomaterial during the recovery of the perception of sensitivity in polytraumatized patients, compatible with the results observed in laboratory animals, which may indicate its clinical feasibility in the reduction of sequelae in PNI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Cellular purine nucleotides derive mainly from de novo synthesis or nucleic acid turnover and, only marginally, from dietary intake. They are subjected to catabolism, eventually forming uric acid in humans, while bases and nucleosides may be converted back to nucleotides through the salvage pathways. Inborn errors of the purine salvage pathway and catabolism have been described by several researchers and are usually referred to as rare diseases. Since purine compounds play a fundamental role, it is not surprising that their dysmetabolism is accompanied by devastating symptoms. Nevertheless, some of these manifestations are unexpected and, so far, have no explanation or therapy. Herein, we describe several known inborn errors of purine metabolism, highlighting their unexplained pathological aspects. Our intent is to offer new points of view on this topic and suggest diagnostic tools that may possibly indicate to clinicians that the inborn errors of purine metabolism may not be very rare diseases after all.

Uric acid is the final product of purine catabolism in man and apes. The serum concentration of uric acid is sex-, age- and diet-dependent and is maintained close to its maximal solubility, indicating that it plays some important role. Indeed, it has been demonstrated that, at physiological concentrations, uric acid is a powerful antioxidant, while at high intracellular concentrations, it is a pro-oxidant molecule. In this review, we describe the possible causes of uric acid accumulation or depletion and some of the metabolic and regulatory pathways it may impact. Particular attention has been given to fructose, which, because of the complex correlation between carbohydrate and nucleotide metabolism, causes uric acid accumulation. We also present recent results on the positive and negative effects played by uric acid in cancer and some new findings and hypotheses about the implication of this metabolite in a variety of signaling pathways, which can play a role in the pathogenesis of diseases such as metabolic syndrome, diabetes, and inflammation, thus favoring the development of cancer. The loss of uricase in Homo sapiens and great apes, although exposing these species to the potentially adverse effects of uric acid, appears to be associated with evolutionary advantages.

Dental surgeons need in-depth knowledge of the bone tissue status and gingival morphology of atrophic maxillae. The aim of this study is to describe preoperative virtual planning of placement of 5 implants and to compare the plan with the actual surgical results. Three-dimensional (3D) planning of rehabilitation using software programs enables surgical guides to be specially designed for the implant site and manufactured using 3D printing. A patient with 5 teeth missing was selected for this study. The patient's maxillary region was scanned with cone-beam computed tomography (CBCT), and a cast model was produced. After virtual planning using ImplantViewer, 5 implants were placed using a printed surgical guide. Two weeks after the surgical procedure, the patient underwent another CBCT scan of the maxilla. Statistically significant differences were detected between the virtually planned positions and the actual positions of the implants, with a mean deviation of 0.36 mm in the cervical region and 0.7 mm in the apical region. The surgical technique used enables more accurate procedures compared with the conventional technique. Implants can be better positioned, with a high level of predictability, reducing both operating time and patient discomfort.

Cytosolic 5'-nucleotidase II (cN-II) is an allosteric catabolic enzyme that hydrolyzes IMP, GMP, and AMP. The enzyme can assume at least two different structures, being the more active conformation stabilized by ATP and the less active by inorganic phosphate. Therefore, the variation in ATP concentration can control both structure and activity of cN-II. In this paper, using a capillary electrophoresis technique, we demonstrated that a partial silencing of cN-II in a pulmonary carcinoma cell line (NCI-H292) is accompanied by a decrease in adenylate pool, without affecting the energy charge. We also found that cN-II silencing decreased proliferation and increased oxidative metabolism, as indicated by the decreased production of lactate. These effects, as demonstrated by Western blotting, appear to be mediated by both p53 and AMP-activated protein kinase, as most of them are prevented by pifithrin-α, a known p53 inhibitor. These results are in line with our previous observations of a shift towards a more oxidative and less proliferative phenotype of tumoral cells with a low expression of cN-II, thus supporting the search for specific inhibitors of this enzyme as a therapeutic tool for the treatment of tumors.

Introduction: This study aimed to test the accuracy of a new automatic deep learning-based approach on the basis of convolutional neural networks (CNN) for fully automatic segmentation of the sinonasal cavity and the pharyngeal airway from cone-beam computed tomography (CBCT) scans., Methods: Forty CBCT scans from healthy patients (20 women and 20 men; mean age, 23.37 ± 3.34 years) were collected, and manual segmentation of the sinonasal cavity and pharyngeal subregions were carried out by using Mimics software (version 20.0; Materialise, Leuven, Belgium). Twenty CBCT scans from the total sample were randomly selected and used for training the artificial intelligence model file. The remaining 20 CBCT segmentation masks were used to test the accuracy of the CNN fully automatic method by comparing the segmentation volumes of the 3-dimensional models obtained with automatic and manual segmentations. The accuracy of the CNN-based method was also assessed by using the Dice score coefficient and by the surface-to-surface matching technique. The intraclass correlation coefficient and Dahlberg's formula were used to test the intraobserver reliability and method error, respectively. Independent Student t test was used for between-groups volumetric comparison., Results: Measurements were highly correlated with an intraclass correlation coefficient value of 0.921, whereas the method error was 0.31 mm 3 . A mean difference of 1.93 ± 0.73 cm 3 was found between the methodologies, but it was not statistically significant (P >0.05). The mean matching percentage detected was 85.35 ± 2.59 (tolerance 0.5 mm) and 93.44 ± 2.54 (tolerance 1.0 mm). The differences, measured as the Dice score coefficient in percentage, between the assessments done with both methods were 3.3% and 5.8%, respectively., Conclusions: The new deep learning-based method for automated segmentation of the sinonasal cavity and the pharyngeal airway in CBCT scans is accurate and performs equally well as an experienced image reader., (Copyright © 2021. Published by Elsevier Inc.)

Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5'-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington's disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garcia-Gil, Camici, Allegrini, Pesi and Tozzi.)

Objectives: To compare volume and shape changes of pulp chamber of maxillary posterior teeth between tooth-borne and bone-borne maxillary expansions in adolescents., Materials and Methods: This study included 36 adolescents with bilateral maxillary crossbite who received tooth-borne rapid maxillary expansion (TB group, average age 14.4 years) or bone-borne rapid maxillary expansion (BB group, average age 14.7 years). Cone beam computed tomography (CBCT) was taken before treatment (T1) and after a 6-month retention period (T2). Volumetric and shape changes of pulp chamber of maxillary first molars and premolars were detected by referring to a specific 3D digital technology involving deviation analysis of T1/T2 CBCT-derived models of pulp chamber. Student's t tests were used to (1) compare T1 and T2 volumes of pulp chambers in TB and BB groups and (2) assess differences between the two groups in the post-treatment volumetric changes and in the percentage of matching of 3D pulp models., Results: All investigated teeth showed a reduction of pulp volume, being this difference significant in both TB (p < 0.0001) and BB (p < 0.0001) groups. The volumetric reduction was greater in the TB group; also, subjects in the TB group showed a lower percentage of matching between T1 and T2 pulp models (p < 0.0001). The area most affected by shape change was that of pulp horns., Conclusions: TB expander could induce a higher volumetric reduction of pulp chamber of posterior teeth compared with BB expander, in the short term., Clinical Relevance: The present findings add new information concerning the effects of RME protocols on pulp tissue.

Cytosolic 5'-nucleotidase II (NT5C2) is a highly regulated enzyme involved in the maintenance of intracellular purine and the pyrimidine compound pool. It dephosphorylates mainly IMP and GMP but is also active on AMP. This enzyme is highly expressed in tumors, and its activity correlates with a high rate of proliferation. In this paper, we show that the recombinant purified NT5C2, in the presence of a physiological concentration of the inhibitor inorganic phosphate, is very sensitive to changes in the adenylate energy charge, especially from 0.4 to 0.9. The enzyme appears to be very sensitive to pro-oxidant conditions; in this regard, the possible involvement of a disulphide bridge (C175-C547) was investigated by using a C547A mutant NT5C2. Two cultured cell models were used to further assess the sensitivity of the enzyme to oxidative stress conditions. NT5C2, differently from other enzyme activities, was inactivated and not rescued by dithiothreitol in a astrocytoma cell line (ADF) incubated with hydrogen peroxide. The incubation of a human lung carcinoma cell line (A549) with 2-deoxyglucose lowered the cell energy charge and impaired the interaction of NT5C2 with the ice protease-activating factor (IPAF), a protein involved in innate immunity and inflammation.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: Premature loss of a tooth element causes extensive local bone atrophy. Block biomaterials are used in patients with an atrophic maxilla to reshape the premaxilla bone. This study aimed to evaluate the responses to xenogeneic bone blocks at cellular and tissue levels., Materials and Methods: Viability of human periodontal ligament stem cells (hPDLSCs) submitted to culture medium-containing substances leached from a xenogeneic block biomaterial (Orthogen) was assessed by the MTT assay. Cells grown in a fresh medium were used as the control. Cell viability was measured at 24, 48, and 72 hours. The results were statistically compared (α ≤ .05). Tissue response to the biomaterial was evaluated by the placement of xenogeneic blocks anchored with miniscrews in six patients with atrophic maxillae and a remaining cortical bone tissue thickness of 2.0 to 3.0 mm. After 8 months, specimens were collected from the grafted areas and analyzed under a light microscope for evaluating the types of collagen fibers and amount of newly formed bone tissue, using the Image-Pro Plus software program., Results: The number of viable cells was similar in both groups. The histologic sections revealed remaining biomaterial in 10.12% of the patients and newly formed bone in 21.57%., Conclusion: The xenogeneic block biomaterial tested proved to be biocompatible in vitro, and the porosity of the block favored the in vivo formation of new bone matrix deposits.