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Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.

Background: Muscle Tension Dysphonia is a relatively new clinical entity that, despite being one of the most frequent causes of functional dysphonia, is little-known by many otorhinolaryngologists. Objective: The objective of the current work is to describe the evolution of Muscle Tension Dysphonia—the concepts and the ways it has been diagnosed and treated—from its first descriptions to our current knowledge. Design: A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A search of three bibliographic databases was performed to identify original articles on Muscle Tension Dysphonia. Study selection and characterization was conducted by three independent reviewers and was further reviewed by a fourth individual. In case of relocating any of the studies, it was performed by agreement of two reviewers. We excluded articles not written in English or Spanish, letters to the editor, review articles, studies of the pediatric population, articles related to dysphagia, and other publications that were not relevant. Results: The search identified 1144 articles published from 1983 to December 2022. A total of 581 studies were repeated and another 462 were excluded because they were not written in English or Spanish, were not original articles, or were not relevant to the objective of the study. Finally, 101 articles were included in the review. The articles included in the review were divided into three groups considering the objective and conclusions of each study: 21 articles were classified as "Etiology and Physiopathology", 29 articles as "Diagnosis", and 51 articles were included in the "Treatment" group. Conclusions: The concept of Muscle Tension Dysphonia has been developed during the last forty years. For its diagnosis, endoscopic visualization of the larynx is crucial, but must be combined with the patient's clinical history and other methods can also be useful. This entity should be addressed in a multidisciplinary approach, with the active participation of speech therapists. Most therapeutic options include voice education, vocal hygiene, and rehabilitation of the voice. [ABSTRACT FROM AUTHOR]

In recent years, the direction associated with the study of maps from a finite set A to the set of all subsets of the set A, including the empty one, has been intensively developing. Such mappings are called multifunctions on A, as well as hyperfunctions on A, if an empty subset is excluded from the subsets under consideration. It is not difficult to see that the so-called undefined or undefined functions, which are studied in many works, are most directly related to this field of research. The power of the set A is called the rank of multifunction or hyperfunction. Obviously, multifunctions and hyperfunctions generalize well-known functions of k-valued logic, however, it should be noted that the usual superposition of functions of k-valued logic is not suitable for multifunctions and hyperfunctions. Two types of superpositions are most often considered here, one of them leads to sets closed relative to the superposition, which are called multiclones and hyperclones, and for the second type of superposition, closed sets are called ultraclones and partial ultraclones. In this article, the elements of the rank 2 ultraclone lattice are considered. By now, all the maximum and minimum elements of this lattice are known. For example, Panteleev V.I. described all maximal ultraclones in the predicate language, which allowed us to prove the completeness criterion of an arbitrary system of hyperfunctions of rank 2. We managed to prove the completeness criterion in the maximal ultraclone of linear hyperfunctions of rank 2. Thus, all submaximal ultraclones of linear hyperfunctions are described.

Background: Injecting botulinum neurotoxin (BoNT) into the salivary glands is a common treatment for certain diseases. Green tea's active compound, epigallocatechin-3-gallate (EGCG), has been linked to a variety of health benefits, including the reduction of free radicals and inflammation. This study compared the effects of BoNT and BoNT/EGCG on the submandibular salivary glands (SMG) histology and ultrastructure. Methods: Both BoNT and BoNT/EGCG nanoemulsions were injected into the submandibular salivary glands (SMGs) in adult male albino rats, which were then euthanized, and the right SMGs were thoroughly dissected and prepared for histological, immunohistochemical, and transmission electron microscopic analysis. Results: When compared to the BoNT group, the BoNT/EGCG nanoemulsion group significantly improved SMG acinar and ductal cells using both H&E and immunohistochemical stainings. Ultrastructural findings of the BoNT/EGCG nanoemulsion group revealed marked improvement in the SMG structure, almost normal acini, and striated ducts. Conclusion: Salivary gland histological structures are significantly altered after BoNT administration, but the addition of EGCG causes only minor alterations and can be used to treat hyperfunction.

Background: Muscle Tension Dysphonia is a relatively new clinical entity that, despite being one of the most frequent causes of functional dysphonia, is little-known by many otorhinolaryngologists. Objective: The objective of the current work is to describe the evolution of Muscle Tension Dysphonia—the concepts and the ways it has been diagnosed and treated—from its first descriptions to our current knowledge. Design: A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A search of three bibliographic databases was performed to identify original articles on Muscle Tension Dysphonia. Study selection and characterization was conducted by three independent reviewers and was further reviewed by a fourth individual. In case of relocating any of the studies, it was performed by agreement of two reviewers. We excluded articles not written in English or Spanish, letters to the editor, review articles, studies of the pediatric population, articles related to dysphagia, and other publications that were not relevant. Results: The search identified 1144 articles published from 1983 to December 2022. A total of 581 studies were repeated and another 462 were excluded because they were not written in English or Spanish, were not original articles, or were not relevant to the objective of the study. Finally, 101 articles were included in the review. The articles included in the review were divided into three groups considering the objective and conclusions of each study: 21 articles were classified as “Etiology and Physiopathology”, 29 articles as “Diagnosis”, and 51 articles were included in the “Treatment” group. Conclusions: The concept of Muscle Tension Dysphonia has been developed during the last forty years. For its diagnosis, endoscopic visualization of the larynx is crucial, but must be combined with the patient’s clinical history and other methods can also be useful. This entity should be addressed in a multidisciplinary approach, with the active participation of speech therapists. Most therapeutic options include voice education, vocal hygiene, and rehabilitation of the voice.

In this paper, we reformulate the quintic and sextic equations in the spaces of generalized functions. Using the pullbacks and the heat kernels, we investigate the approximate quintic and sextic mappings in the spaces of Schwartz tempered distributions and Fourier hyperfunctions. [ABSTRACT FROM AUTHOR]

Currently, concern about facial attractiveness is increasing, and this fact has led to orthodontics in adult patients being an increasingly demanded treatment, and with it, multi-disciplinary work. When it is caused by a vertical excess of the maxilla, the ideal solution is orthognathic surgery. However, in borderline cases and when the cause is hyperactivity of the upper lip levator muscle complex, alternative conservative solutions can be considered, such as the application of botulinum toxin A (BTX-A). Botulinum toxin is a protein produced by a bacterium and causes a reduction in the force of muscle contraction. The multi-factorial nature of the smile requires an individualized diagnosis in each patient, since there are multiple ways to treat the gummy smile (orthognathic surgery, gingivoplasty, orthodontic intrusion). In recent years, interest has grown in the simplest techniques that allow the patient to quickly return to their usual routine, such as lip replacement. However, this procedure shows recurrences in the first 6–8 post-operative weeks. The main objective of this systematic review and meta-analysis is to analyze the effectiveness of BTX-A in the treatment of gummy smile in the short term, to study its stability, and to evaluate potential complications. A thorough search of the PubMed, Scopus, Embase, Web of Science, and Cochrane databases and a grey literature search were conducted. The inclusion criteria were studies with a sample size greater than or equal to 10 patients with gingival exposure greater than 2 mm in smile, treated with BTX-A infiltration. Those patients whose exclusive etiology of their gummy smile was related to altered passive eruption, gingival thickening, or overeruption of upper incisors were excluded. In the qualitative analysis, the mean pre-treatment gingival exposure ranged between 3.5 and 7.2 mm, reaching a reduction of up to 6 mm after infiltration with botulinum toxin at 12 weeks. Although multiple muscles are involved in the facial expression, the muscles par excellence selected for blockade with BTX-A were levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor, infiltrating from 1.25 to 7.5 units per side. In the quantitative analysis, the difference in mean reduction between both groups was −2.51 mm at two weeks and −2.24 mm at three months. The benefit of BTX-A in terms of improvement of gummy smile is demonstrated, as a significant reduction in gummy smile is estimated by BTX-A therapy two weeks after its application. Its results gradually decrease over time, however, they stay satisfactory without returning to their initial values after 12 weeks. [ABSTRACT FROM AUTHOR]

Purpose: To assess the preliminary outcomes of inferior oblique (IO) disinsertion-distal myectomy and tucking combined with superior oblique (SO) full tendon advancement in patients with Knapp II or III superior oblique palsy. Methods: This single-centered retrospective study included 16 eyes from 13 patients with Knapp Class II or III SO palsy. All patients underwent IO disinsertion-distal myectomy and tucking combined with SO full tendon advancement while under general anesthesia. Pre- and post-operative levels of vertical deviation in the primary position, abnormal head position, IO hyperfunction and SO hypofunction, torsion, as well as the presence of diplopia, were all measured, and the differences were statistically compared. Results: Pre-operatively, 12 patients had abnormal head positions, and two had diplopia. The pre-and post-operative levels of IO hyperfunction and SO hypofunction, as well as a vertical deviation in the primary position and torsion, all differed statistically significantly (p < 0.01). Conclusions: Inferior oblique disinsertion distal myectomy and tucking combined with SO full tendon advancement surgery appears to be an effective procedure in patients with congenital and acquired Knapp Class II or III SO palsy. [ABSTRACT FROM AUTHOR]

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with progressive declines in biochemical and molecular processes resulting from damage accumulation, yet the role of continued developmental gene activation is less appreciated. Natural selection pressures are at their highest in youthful periods to modify gene expression towards maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene functions that were once beneficial for developmental growth but become pathogenic later in life. Due to this selective 'shadowing' in ageing, mechanisms to counter such hyper/hypofunctional genes are unlikely to evolve. Interventions aimed at targeting gene hyper/hypofunction during ageing might, therefore, represent an attractive therapeutic strategy. The nematode Caenorhabditis elegans offers a strong model for post-reproductive mechanistic and therapeutic investigations, yet studies examining the mechanisms of, and countermeasures against, ageing decline largely intervene from larval stages onwards. Importantly, however, lifespan extending conditions frequently impair early-life fitness and fail to correspondingly increase healthspan. Here, we consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in C. elegans , and how classical lifespan-extension mutations alter these dynamics. The relevance of such mutant models for exploring mechanisms of ageing are discussed, highlighting that post-reproductive gene optimisation represents a more translatable approach for C. elegans research that is not constrained by evolutionary trade-offs. Where some genetic mutations in C. elegans that promote late-life health map accordingly with healthy ageing in humans, other widely used genetic mutations that extend worm lifespan are associated with life-limiting pathologies in people. Lifespan has also become the gold standard for quantifying 'ageing', but we argue that gerospan compression (i.e., 'healthier' ageing) is an appropriate goal for anti-ageing research, the mechanisms of which appear distinct from those regulating lifespan alone. There is, therefore, an evident need to re-evaluate experimental approaches to study the role of hyper/hypofunctional genes in ageing in C. elegans. [Display omitted] • Views that ageing stems from molecular damage has narrowed our view that hyperactive wild-type genes drive physiological decline. • Systems biology will uncover hyperfunctional expression changes in ageing, enabling late-life gene optimisations to improve health. • Healthy phenotypes of long-lived Caenorhabditis elegans mutants are bound within evolutionary constraints. • There is an urgent need to employ pharmaco-genetic interventions commencing in post-reproductive animals to study healthy ageing. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to investigate the effect of fast speaking on pause duration, breath group duration, and fundamental frequency (F O ) in rote speech (counting)., Method: Twenty-eight healthy women (age 18-39) who had no experience of voice training, repeated a counting task in both a habitual and fast speaking rate. Pause duration, breath group duration, and mean fundamental frequency were measured from audio recordings. Differences in the study variables between habitual and fast speaking rates were analyzed and tested for statistical significance., Results: In fast speaking rate, mean pause duration was shorter and mean breath group duration longer as compared with habitual speaking rate, both with statistical significance at the group level. Surprisingly, mean fundamental frequency was significantly lower in the fast-speaking rate condition., Conclusion: The results overall supported the hypothesis that pause duration becomes shorter and breath group duration longer with a fast-speaking rate. This may have clinical relevance for voice therapy and supports the importance of speaking rate for the understanding and treatment of some hyperfunctional voice disorders. Notably, however, our findings indicated that counting as a speech task induces a specific pattern which may not be comparable to other speech tasks, nor representative of spontaneous speech in every-day-life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, concern about facial attractiveness is increasing, and this fact has led to orthodontics in adult patients being an increasingly demanded treatment, and with it, multi-disciplinary work. When it is caused by a vertical excess of the maxilla, the ideal solution is orthognathic surgery. However, in borderline cases and when the cause is hyperactivity of the upper lip levator muscle complex, alternative conservative solutions can be considered, such as the application of botulinum toxin A (BTX-A). Botulinum toxin is a protein produced by a bacterium and causes a reduction in the force of muscle contraction. The multi-factorial nature of the smile requires an individualized diagnosis in each patient, since there are multiple ways to treat the gummy smile (orthognathic surgery, gingivoplasty, orthodontic intrusion). In recent years, interest has grown in the simplest techniques that allow the patient to quickly return to their usual routine, such as lip replacement. However, this procedure shows recurrences in the first 6–8 post-operative weeks. The main objective of this systematic review and meta-analysis is to analyze the effectiveness of BTX-A in the treatment of gummy smile in the short term, to study its stability, and to evaluate potential complications. A thorough search of the PubMed, Scopus, Embase, Web of Science, and Cochrane databases and a grey literature search were conducted. The inclusion criteria were studies with a sample size greater than or equal to 10 patients with gingival exposure greater than 2 mm in smile, treated with BTX-A infiltration. Those patients whose exclusive etiology of their gummy smile was related to altered passive eruption, gingival thickening, or overeruption of upper incisors were excluded. In the qualitative analysis, the mean pre-treatment gingival exposure ranged between 3.5 and 7.2 mm, reaching a reduction of up to 6 mm after infiltration with botulinum toxin at 12 weeks. Although multiple muscles are involved in the facial expression, the muscles par excellence selected for blockade with BTX-A were levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor, infiltrating from 1.25 to 7.5 units per side. In the quantitative analysis, the difference in mean reduction between both groups was −2.51 mm at two weeks and −2.24 mm at three months. The benefit of BTX-A in terms of improvement of gummy smile is demonstrated, as a significant reduction in gummy smile is estimated by BTX-A therapy two weeks after its application. Its results gradually decrease over time, however, they stay satisfactory without returning to their initial values after 12 weeks.

Let P be a minimal parabolic subgroup of a real reductive Lie group G and H a closed subgroup of G. Then it is proved by Kobayashi and Oshima that the regular representation C ∞ (G / H) contains each irreducible representation of G at most finitely many times if the number of H -orbits on G / P is finite. Moreover, they also proved that the multiplicities are uniformly bounded if the number of H ℂ -orbits on G ℂ / B is finite, where G ℂ , H ℂ are complexifications of G , H , respectively, and B is a Borel subgroup of G ℂ . In this paper, we prove that the multiplicities of the representations of G induced from a parabolic subgroup Q in the regular representation on G / H are uniformly bounded if the number of H ℂ -orbits on G ℂ / Q ℂ is finite. For the proof of this claim, we also show the uniform boundedness of the dimensions of the spaces of group invariant hyperfunctions using the theory of holonomic X -modules. [ABSTRACT FROM AUTHOR]

Abstract Classical theory maintains that ageing evolves via energy trade‐offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late‐life hyper‐function of reproduction‐promoting genes leading to excessive biosynthesis in late‐life. The hyper‐function theory uniquely predicts that optimizing nutrient‐sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF‐1 nutrient‐sensing signaling via daf‐2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long‐lived daf‐2 RNAi parents showed normal fecundity as self‐fertilizing hermaphrodites and improved late‐life reproduction when mated to males. Remarkably, the offspring of daf‐2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient‐sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late‐life lies at the heart of ageing.

The research of multifunctions is a one of the directions in discrete function’s investigations. Multifunction is a discrete function from a finite set A to all subsets of A. The set of hyperfunctions is a subset of set of multifunctions. Hyperfunction is a discrete function from a finite set A to all nonempty subsets of A. The subset relation of hyperfunctions to maximal multiclones is a relation of equivalence and according it all hyperfunctions are divided into equivalence classes. Based on this equivalence it is possible to estimate the cardinality of all possible bases, calculate the number of different types of bases of the same cardinality, and construct some intervals of the clone lattice. Knowing the number of maximal clones, we can obtain upper-bound estimate of the number of such classes as the cardinality of the set of all subsets of the set of maximal clones. It possible to lower this estimate by using properties of the hyperfunctions . A lower-bound estimate for the number of classes can be obtained by constructing the corresponding classes. It is noteworthy that the complexity of the problem of describing all equivalence classes increases essentially with the cardinality of the set of maximal clones increasing. This paper considers multifunctions on a two-element set. The number of maximal multiclones equals to 15 (Panteleyev V.I., 2009). The primary purpose of this research is describing the classification of the set of hyperfunctions into equivalence classes. As Kazimirov A.S. and Panteleyev V.I. showed there are 18 equivalence classes on the set of Boolean functions, which is a subset of the set of hyperfunctions. In this paper were obtained special properties of hyperfunctions and were described all the equivalence classes generated by functions of 3 arguments having applied a computer experiment. The obtained results made it possible to show that the subset relation of hyperfunctions to maximal multiclones splits the set of all hyperfunctions into 67 equivalence classes.

Classical theory maintains that ageing evolves via energy trade‐offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late‐life hyper‐function of reproduction‐promoting genes leading to excessive biosynthesis in late‐life. The hyper‐function theory uniquely predicts that optimizing nutrient‐sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF‐1 nutrient‐sensing signaling via daf‐2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long‐lived daf‐2 RNAi parents showed normal fecundity as self‐fertilizing hermaphrodites and improved late‐life reproduction when mated to males. Remarkably, the offspring of daf‐2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient‐sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late‐life lies at the heart of ageing. [ABSTRACT FROM AUTHOR]

Patients harboring adrenal tumors are characterized by higher prevalence of metabolic syndrome (MetS) components and a higher incidence of cardiovascular complications, especially in cases of subclinical or overt hormonal hypersecretion. Early detection and referral of those patients in tertiary centers could prevent unfavorable outcomes. In this cross-sectional, retrospective study, we evaluated 111 consecutive patients with adrenal incidentalomas and 14 patients with known hypersecretory adrenal lesions (autonomous cortisol secretion, primary aldosteronism, and pheochromocytoma), who were investigated in our clinic. Based on the different distribution of MetS components in patients with non-functional and functional adrenal lesions we introduced a predictive model of hormonal hypersecretion using those components. We performed multivariate discriminant analysis and compared predictive results with conventional multiple logistic regression analysis. Diabetes, impaired glucose tolerance, impaired fasting glucose, hypertension, body mass index, HDL-cholesterol levels, triglyceride levels, drug treatment for lipid disorder (statins, fenofibrate, and fish oils, alone or in combination), and maximal adrenal lesion diameter were used as discriminating covariates. Multivariate discriminant function exhibited a sensitivity of 77.27 % and specificity of 73.08 % in predicting adrenal hormonal hypersecretion. Receiver operating characteristic curve of discriminant predictive function had an area under the curve value of 0.785, S.E. 0.04. Logistic function delivered comparable results. MetS components exhibit a good predictive feature of hormonal hypersecretion in patients with adrenal tumors. Predictive functions may help in the search for an easy and generally available algorithm to validly predict the functional activity of adrenal masses. [ABSTRACT FROM AUTHOR]

One of the direction in discrete function's investigations is research of functional systems: the sets of functions and the sets of operators defined on this functions. The modern line of inquiry of functional systems deals with generalization of many-valued functions such as partial functions, multifunctions or hyperfunctions. Hyperfunctions are discrete functions from a finite set $A$ to all nonempty subsets of $A$ which closed with respect to the superposition operator. In addition of the superposition operator its interesting to exam more stronger operators which given nontrivial function's classifications. For example, the criterion of completeness for the closure operator with the equality predicate branching on the set of hyperfunctions on two-element set was found. Another well-known strong operator is the parametric closure operator. Twenty five closed classes of Boolean functions is known for this operator. In this work we precise the definition of the parametric closure operator for the set of hyperfunctions and consider this operator on set of hyperfunctions on two-element set. With respect to this operator thirteen closed classes of hyperfunctions are founded. Two of them $S^-$ and $L^-$ are parametric precomplete. The lattice of parametric closed classes of hyperfunctions on two-element set are obtained and parametric bases of this classes are defined.

Background: Noncarious cervical lesions (NCCLs) are rarely described in the periodontal literature, perhaps because no direct link between NCCLs and periodontal lesions has been demonstrated. Aim: The aim of this study is to determine the stress and displacement produced in the tooth at different bone levels under different occlusal load using finite element model (FEM) study. Materials and Methods: Four FEMs of maxillary incisor were designed consisting of the tooth, pulp, periodontal ligament, and alveolar bone at the various level of bone height (25%, 50%, and 75%). Different occlusal load (5 kg, 15 kg, 24 kg, and 29 kg) at an angle of 50° to the long axis of the tooth was applied on the palatal surface at the level of middle third of the crown. All the models were assumed to be isotropic, linear and elastic, and the analysis was performed on a Pentium IV processor computer using the ANSYS software. Results: The maximum stress in the tooth was seen in the cervical region and to a greater extent at the apex for all models. The maximum tooth displacement for all the occlusal loads applied in this study was at the incisal edge with the minimum tooth displacement at the cervical third of the root which shifted apically with the reduction of alveolar bone support. Conclusion: The cumulative effect of increased stress and displacement at the cervical region of the tooth would result in abfraction as the age advances along with other wasting diseases.

Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.

In this work we consider the closure operator with the equality predicate branching (E-operator) on the set of hyperfunctions on two-element set. With respect to this operator closed classes of hyperfunctions are generated. We show that there are four submaximal classes and prove the criterion of functional completeness. The relation of equivalence is considered on the set of hyperfunctions obtained by their membership in E-submaximal classes. All hyperfunctions are divided into 14 equivalence classes. In closed sets the minimal closed subsets named basis are derived. We show that basis of hyperfunctions can have cardinality from 1 to 3 and there is no basis with cardinality more than 3. There is only one kind of basis with cardinality 1. The function from that basis does not belong to any of four E-submaximal classes. We obtain 23 kind of basis with cardinality 2 and 11 with cardinality 3.

Let D'L∞(R2n) and A'L∞(R2n) be the spaces of bounded distributions and bounded hyperfunctions respectively. In this paper we consider the Ulam's stability of the sine-cosine functional equation u ...T - u ⊗ v + v ⊗ u ∈ D'L∞(R2n) [resp. A'L∞(R2n)], where u, v are Gelfand hyperfunctions, T : R2n → Rn such that T(x, y) = x - y for all x, y ∈ Rn, and ... ⊗ denote pullback and tensor product of generalized functions respectively. [ABSTRACT FROM AUTHOR]

In this paper, we propose an application of hyperfunction theory to numerical integration. Hyperfunction theory is a generalized version of function theory where functions with singularities such as poles, discontinuities and delta impulses are expressed in terms of complex analytic functions. This feature of hyperfunction theory allows us to construct a numerical integration method for analytic functions. Theoretical error estimates show that our method converges geometrically, and numerical examples show that our method is very efficient especially for integrals with strong end-point singularities. In addition, we present an automatic integration method based on our hyperfunction method. [ABSTRACT FROM AUTHOR]

Background: Noncarious cervical lesions (NCCLs) are rarely described in the periodontal literature, perhaps because no direct link between NCCLs and periodontal lesions has been demonstrated. Aim: The aim of this study is to determine the stress and displacement produced in the tooth at different bone levels under different occlusal load using finite element model (FEM) study. Materials and Methods: Four FEMs of maxillary incisor were designed consisting of the tooth, pulp, periodontal ligament, and alveolar bone at the various level of bone height (25%, 50%, and 75%). Different occlusal load (5 kg, 15 kg, 24 kg, and 29 kg) at an angle of 50° to the long axis of the tooth was applied on the palatal surface at the level of middle third of the crown. All the models were assumed to be isotropic, linear and elastic, and the analysis was performed on a Pentium IV processor computer using the ANSYS software. Results: The maximum stress in the tooth was seen in the cervical region and to a greater extent at the apex for all models. The maximum tooth displacement for all the occlusal loads applied in this study was at the incisal edge with the minimum tooth displacement at the cervical third of the root which shifted apically with the reduction of alveolar bone support. Conclusion: The cumulative effect of increased stress and displacement at the cervical region of the tooth would result in abfraction as the age advances along with other wasting diseases. [ABSTRACT FROM AUTHOR]

Botox has been primarily used in cosmetic treatment for lines and wrinkles on the face, but the botulinum toxin that Botox is derived from has a long history of medically therapeutic uses. For nearly 13 years, until the introduction of Botox Cosmetic in 2002, the only FDAapproved uses of Botox were for crossed eyes (strabismus) and abnormal muscle spasms of the eyelids (blepharospasm). Since then botulinum A, and the seven other forms of the botulinum toxin, have been continuously researched and tested. Botox is a neurotoxin derived from bacterium clostridium botulinm. The toxin inhibits the release of acetylcholine (ACH), a neurotransmitter responsible for the activation of muscle contraction and glandular secretion, and its administration results in reduction of tone in the injected muscle. The use of Botox is a minimally invasive procedure and is showing quite promising results in management of muscle-generated dental diseases like Temporomandibular disorders, bruxism, clenching, masseter hypertrophy and used to treat functional or esthetic dental conditions like deep nasolabial folds, radial lip lines, high lip line and black triangles between teeth.

Let $G$ be a commutative group and $\mathbb{C}$ the field of complex numbers, $\mathbb{R}^{+}$ the set of positive real numbers and $f,g,h,k:G\times \mathbb{R}^{+}\rightarrow \mathbb{C}$. In this paper, we first consider the Levi-Civitá functional inequality $$\begin{eqnarray}\displaystyle f(x+y,t+s)-g(x,t)h(y,s)-k(y,s)\leq {\rm\Phi}(t,s),\quad x,y\in G,t,s>0, & & \displaystyle \nonumber\end{eqnarray}$$ where ${\rm\Phi}:\mathbb{R}^{+}\times \mathbb{R}^{+}\rightarrow \mathbb{R}^{+}$ is a symmetric decreasing function in the sense that ${\rm\Phi}(t_{2},s_{2})\leq {\rm\Phi}(t_{1},s_{1})$ for all $0

In the framework of Clifford analysis, a chain of harmonic and monogenic potentials in the upper half of Euclidean space $${\mathbb{R}^{m+1}_+}$$ was recently constructed, including a higher dimensional analogue of the logarithmic function in the complex plane, and their distributional boundary values were computed. In this paper we determine these potentials in lower half-space $${\mathbb{R}^{m+1}_-}$$ and investigate whether they can be extended through the boundary $${\mathbb{R}^m}$$ . This is a stepping stone to the representation of a doubly infinite sequence of distributions in $${\mathbb{R}^m}$$ , consisting of positive and negative integer powers of the Dirac and the Hilbert-Dirac operator, as the jump across $${\mathbb{R}^m}$$ of monogenic functions in the upper and lower half-spaces, in this way providing a sequence of interesting examples of Clifford hyperfunctions. [ABSTRACT FROM AUTHOR]

Botox has been primarily used in cosmetic treatment for lines and wrinkles on the face, but the botulinum toxin that Botox is derived from has a long history of medically therapeutic uses. For nearly 13 years, until the introduction of Botox Cosmetic in 2002, the only FDAapproved uses of Botox were for crossed eyes (strabismus) and abnormal muscle spasms of the eyelids (blepharospasm). Since then botulinum A, and the seven other forms of the botulinum toxin, have been continuously researched and tested. Botox is a neurotoxin derived from bacterium clostridium botulinm. The toxin inhibits the release of acetylcholine (ACH), a neurotransmitter responsible for the activation of muscle contraction and glandular secretion, and its administration results in reduction of tone in the injected muscle. The use of Botox is a minimally invasive procedure and is showing quite promising results in management of muscle-generated dental diseases like Temporomandibular disorders, bruxism, clenching, masseter hypertrophy and used to treat functional or esthetic dental conditions like deep nasolabial folds, radial lip lines, high lip line and black triangles between teeth. [ABSTRACT FROM AUTHOR]

Abstract: We find upper and lower bounds of the multiplicities of irreducible admissible representations π of a semisimple Lie group G occurring in the induced representations from irreducible representations τ of a closed subgroup H. As corollaries, we establish geometric criteria for finiteness of the dimension of (induction) and of (restriction) by means of the real flag variety , and discover that uniform boundedness property of these multiplicities is independent of real forms and characterized by means of the complex flag variety. [Copyright &y& Elsevier]

Summary: High vertical laryngeal position (VLP), pharyngeal constriction, and laryngeal compression are common features associated with hyperfunctional voice disorders. The present study aimed to observe the effect on these variables of different semioccluded vocal tract postures in 20 subjects diagnosed with hyperfunctional dysphonia. During observation with flexible endoscope, each participant was asked to produce eight different semioccluded exercises: lip trills, hand-over-mouth technique, phonation into four different tubes, and tube phonation into water using two different depth levels. Participants were required to produce each exercise at three loudness levels: habitual, soft, and loud. To determine the VLP, anterior-to-posterior (A-P) compression, and pharyngeal width, a human evaluation test with three blinded laryngologists was conducted. Judges rated the three endoscopic variables using a five-point Likert scale. An intraclass correlation coefficient to assess intrarater and interrater agreement was performed. A multivariate linear regression model considering VLP, pharyngeal width, and A-P laryngeal compression as outcomes and phonatory tasks and intensity levels as predictive variables were carried out. Correlation analysis between variables was also conducted. Results indicate that all variables differ significantly. Therefore, VLP, A-P constriction, and pharyngeal width changed differently throughout the eight semioccluded postures. All semioccluded techniques produced a lower VLP, narrower aryepiglottic opening, and a wider pharynx than resting position. More prominent changes were obtained with a tube into the water and narrow tube into the air. VLP significantly correlated with pharyngeal width and A-P laryngeal compression. Moreover, pharyngeal width significantly correlated with A-P laryngeal compression. [Copyright &y& Elsevier]

The process of senescence (aging) is predominantly determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function that senescence serves, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood's disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is assessed. • Evolutionary (ultimate) and mechanistic (proximate) factors together cause aging. • The disposable soma theory is one integrated ultimate/proximate account of aging. • Recently new ultimate/proximate theories of aging have emerged. • They view programmatic mechanisms as more important to aging than damage. • Here the hyperfunction, developmental and ontogenetic theories are reviewed. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to vocally assess a group of rock singers who use growl voice and reinforced falsetto. Method: A group of 21 rock singers and a control group of 18 pop singers were included. Singing and speaking voice was assessed through acoustic, perceptual, functional and laryngoscopic analysis. Results: No significant differences were observed between groups in most of the analyses. Acoustic and perceptual analysis of the experimental group demonstrated normality of speaking voice. Endoscopic evaluation showed that most rock singers presented during singing voice a high vertical laryngeal position, pharyngeal compression and laryngeal supraglottic compression. Supraglottic activity during speaking voice tasks was also observed. However, overall vocal fold integrity was demonstrated in most of the participants. Slightly abnormal observations were demonstrated in few of them. Singing voice handicap index revealed that the most affected variable was the physical sphere, followed by the social and emotional spheres. Conclusions: Although growl voice and reinforced falsetto represent laryngeal and pharyngeal hyperfunctional activity, they did not seem to contribute to the presence of any major vocal fold disorder in our subjects. Nevertheless, we cannot rule out the possibility that more evident vocal fold disorders could be found in singers who use these techniques more often and during a longer period of time. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Discovering the biological basis of aging is one of the greatest remaining challenges for science. Work on the biology of aging has discovered a range of interventions and pathways that control aging rate. A picture is emerging of a signaling network that is sensitive to nutritional status and that controls growth, stress resistance, and aging. This network includes the insulin/IGF-1 and target of rapamycin (TOR) pathways and likely mediates the effects of dietary restriction on aging. Yet the biological processes upon which these pathways act to control life span remain unclear. A long-standing guiding assumption about aging is that it is caused by wear and tear, particularly dam-age at the molecular level. One view is that reactive oxygen species (ROS), including free radicals, generated as by-products of cellular metabolism, are a major contributor to this damage. Yet many recent tests of the oxidative damage theory have come up negative. Such tests have opened an exciting new phase in biogerontology in which fundamental assumptions about aging are being reexamined and revolutionary concepts are emerging. Among these concepts is the hyperfunction theory, which postulates that processes contributing to growth and reproduction run on in later life, leading to hypertrophic and hyperplastic pathologies. Here we reexamine central concepts about the nature of aging. [ABSTRACT FROM AUTHOR]

Context: While clinical successes and descriptions have been reported in a few texts, no data exist to define the utility of flow phonation to improve voice quality in patients with laryngeal hyperfunction. Aims: To provide pilot data regarding the utility of three exercises (gargling, cup bubble blowing, and stretch-and-flow) to improve phonatory airflow during voicing in patients with laryngeal hyperfunction. Settings and Design: Outpatient Voice and Swallowing Center in a University Medical Center. Materials and Methods: Participants received five treatment sessions and were evaluated prior to treatment and after each session using a Phonatory Aerodynamic System to measure airflow during voicing tasks. Noise-to-harmonic ratio and perceptual voice measures were also obtained, as was self-perception of voice handicap. Statistical Analysis Used: Repeated All increased airflow and decreased laryngeal airway resistance over five sessions. Measures Analysis of Variance. Results: Six participants completed the protocol. All participants decreased self-perception of voice handicap and improved on noise-to-harmonic ratio and perceptual ratings of vocal quality. Conclusions: Data derived on a small sample of patients in an exploratory investigation suggest further research into the use of these three exercises to improve airflow with voicing and improve vocal quality in patients with laryngeal hyperfunction is warranted. [ABSTRACT FROM AUTHOR]

New C. elegans studies imply that lipases and lipid desaturases can mediate signaling effects on aging. But why might fat homeostasis be critical to aging? Could problems with fat handling compromise health in nematodes as they do in mammals? The study of signaling pathways that control longevity could provide the key to one of the great unsolved mysteries of biology: the mechanism of aging. But as our view of the regulatory pathways that control aging grows ever clearer, the nature of aging itself has, if anything, grown more obscure. In particular, focused investigations of the oxidative damage theory have raised questions about an old assumption: that a fundamental cause of aging is accumulation of molecular damage. Could fat dyshomeostasis instead be critical? [ABSTRACT FROM AUTHOR]

In this era the demands of esthetics and treatment which involves minimal surgical procedures is preferred. There are many medical and dental conditions which do not have complete treatment modalities in conventional ways. The botulinum toxin can be used as an alternative treatment modality working through chemo denervation method in many medical and dental conditions. Botox is a safe, conservative, non surgical, reversible, minimally invasive treatment modality to achieve better patient satisfaction. [ABSTRACT FROM AUTHOR]

This article reviews current literature on vocal fatigue and considers its potential relationship to vocal hyperfunction. Vocal fatigue is defined by its symptoms. Specifically, the voice user perceives an increase in phonatory effort over time that may be accompanied by decreased phonatory function. Vocal fatigue can present as a pure condition, such that no specific aetiology is apparent, or as a component of other voice disorders. The underlying bases of vocal fatigue appear to include the neurophysiological and biomechanical effects of extended periods of phonation. It can also be a function of strategies used to adapt to extended periods of phonation, such as the use of excessive muscular tension and suboptimal vocal fold posturing. Studies that have attempted to identify observable responses that are reliably associated with vocal fatigue have met with limited success, but recent advances in research methodology are promising. This review addresses current approaches to the study of vocal fatigue, especially regarding subject selection, design variables, and measurement variables. Future studies should address the relationship between vocal fatigue and other voice disorders, differences in individual responses to vocal-loading tasks, and differential evaluation and management of the neuromuscular, biomechanical, and central processes involved in vocal fatigue. [ABSTRACT FROM AUTHOR]

The aim was to investigate how female patients with vocal nodules use their voices when trying to make themselves heard over background noise. Ten patients with bilateral vocal fold nodules and 23 female controls were recorded reading a text in four conditions, one without noise and three with noise from cafés/pubs, played over loudspeakers at 69, 77 and 85 dBA. The noise was separated from the voice signal using a high-resolution channel estimation technique. Both patients and controls increased voice sound pressure level (SPL), fundamental frequency (F0), subglottal pressure (Ps) and their subjective ratings of strain significantly as a main effect of the increased background noise. The patients used significantly higher Ps in all four conditions. Despite this they did not differ significantly from the controls in voice SPL, F0 or perceived strain. It was concluded that speaking in background noise is a risk factor for vocal loading. Vocal loading tests in clinical settings are important and further development of assessment methods is needed. [ABSTRACT FROM AUTHOR]

A few clinical investigations of children's voices have suggested a relation between voice deviation and oral motor and sensory dysfunction. This motivated the present retrospective study of the occurrence of voice disorders in a group of children with oral motor problems. A further aim was to evaluate the effect of an oral motor and articulatory treatment programme upon voice function in this patient group. Subjects were 38 children with oral motor deficits who had received and finished therapy at the clinic. The recordings of a picture naming task, before onset of therapy and at therapy ending, were selected. The voices were presented in random order on a test tape and perceptually evaluated by an expert panel of speech pathologists. Eleven perceptual parameters were selected, based on previous investigations of children's voices. Ten of these parameters were represented by a 100 mm visual analogue scale. Register was represented by a categorical scale with the options chest, falsetto, and child voice register. The results were compared with previous investigations of child voice function. Results indicated: 1) The occurrence of voice disorders in the present group of children with oral motor difficulties was somewhat lower than in children with normal articulation. 2) Oral motor treatment also influenced and improved the perceptual impression of voice quality in this group. [ABSTRACT FROM AUTHOR]

Let M be a CR manifold. The main results of this paper are the following:(A)When M is real analytic, a semi-global Hartogs extension phenomenon occurs for real analytic CR functions if and only if M is nowhere strictly pseudoconvex and dimRM&ges;3.(B)When M is a standard manifold, the Hartogs–Bochner extension phenomenon occurs for non-CR-confined domains if and only if M is nowhere strictly pseudoconvex and dimCRM&ges;2.(C)If M is a smooth submanifold of Cn foliated by complex curves, a semi-global Hartogs–Bochner extension phenomenon occurs for smooth non-CR-confined domains if and only if dimCRM&ges;2.(D)If M is a real analytic nowhere strictly pseudoconvex manifold and if Ω is a sufficiently small domain in M, a hyperfunction which is real analytic in a neighborhood of bΩ and CR in a neighborhood of Ω is in fact real analytic on Ω. [Copyright &y& Elsevier]

Objective This report aims to study the prevalence of features of laryngeal muscle tension in a population of patients with functional dysphonia (FD) and nondysphonic control subjects. Study Design Prospective control-blinded, cross-sectional study. Methods We reported on a prospective control-blinded, cross-sectional study of the prevalence of the six features described by Van Lawrence and the six features incorporated in the Morrison-Rammage classification. A senior laryngologist and senior speech pathologist independently rated sound-free, random-sequence video laryngoscopies of 51 patients with FD and 52 nondysphonic control subjects. Assessments were made of the presence or absence of the 12 laryngoscopic features of laryngeal dysfunction, and an overall rating made of the vocal technique as 'normal' or 'abnormal.' Results More than 60% of the control population demonstrated 1 or more of the 12 features of hyperfunction. There was no significant difference in the prevalence of the six Van Lawrence features, the six Morrison-Rammage features, or the total number of abnormal features between patients with FD and control subjects. On overall assessment, both assessors noted a high prevalence (50% and 36%, respectively) of abnormal vocal technique in the control population. There was no statistical difference in the total number of abnormal features observed between patients with FD and control subjects. Positive predictive value calculations showed that the presence of a clinical feature, at best, presented a 75% chance of correctly identifying a patient with FD and, at worst, a 50% chance. Conclusion The laryngoscopy features commonly associated with FD are frequently prevalent in the nondysphonic population and fail to distinguish patients with FD from normal subjects. [ABSTRACT FROM AUTHOR]

In this work we study microlocal regularity of hyperfunctions defining in this context a class of generalized FBI transforms first introduced for distributions by Berhanu and Hounie. Using a microlocal decomposition of a hyperfunction and the generalized FBI transforms we were able to characterize the wave-front set of hyperfunctions according to several types of regularity. The microlocal decomposition allowed us to recover and generalize both classical and recent results and, in particular, we proved for differential operators with real-analytic coefficients that if the elliptic regularity theorem regarding any reasonable regularity holds for distributions, then it is automatically true for hyperfunctions. [ABSTRACT FROM AUTHOR]

In this paper, we propose a numerical method for calculating Fourier transforms based on hyperfunction theory, a theory of generalized functions based on complex function theory. In the proposed method, we first obtain analytic functions giving the desired Fourier transform as a hyperfunction, and, then, we compute the Fourier transform by using continued fractions to determine the analytic continuation of these analytic functions onto the real axis. Using the proposed method, we can evaluate Fourier transforms that are difficult to evaluate using the conventional numerical integration rules. In addition, we can use the proposed method to evaluate Fourier transforms of hyperfunctions. Numerical examples show the efficiency of the presented method compared to previous methods. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnONPs) have been widely used in food storage containers and food additives in daily life. However, the impact of oral intake of ZnONPs on nervous system is extremely limited, especially on children and adolescents. In this study, four weeks old mice were treated with either vehicle or ZnONPs suspension solution at 26 mg/kg by intragastric administration for 30 days. Our results demonstrated that oral ZnONPs exposure could induce pathological changes in gut and abnormal excitement of enteric neurons. Interestingly, we found that ZnONPs caused enhancement of 5-hydroxytryptamine (5-HT) in gut by activation of its biosynthesis, transport and receptors, and subsequently resulting in increased level of 5-HT in brain via gut-brain communication by blood. Our data also showed that there were no apparent changes on the expressions of interleukin (Il)-6 , Il-1β , C–C motif chemokine ligand 2 (Ccl2), tumor necrosis factor (Tnf) in gut and zinc chelator Mt2 in gut and cortex. Meanwhile, no significant changes were observed on the expressions of tryptophan hydroxylase type 1, 5-HT receptor 3A (Htr3a) and Htr4 in hippocampus and cortex. Our study indicate that oral ZnONPs exposure causes hyperfunction of 5-HT in gut in young mice which may further spread to brain via gut-brain communication. • ZnONPs caused pathological changes and impaired endothelial tight junctions in gut. • ZnONPs caused abnormal excitement of enteric neurons and enhancement of 5-HT in gut. • ZnONPs caused activation of biosynthesis, transport and receptors of 5-HT in gut. • ZnONPs caused enhancement of 5-HT in brain via gut-brain communication by blood. [ABSTRACT FROM AUTHOR]

Muscle tension dysphonia (MTD) is generally diagnosed through clinical history and physical examination. Several diagnostic or classification systems exist, such as those of Van Lawrence, Morrison-Rammage, and Koufman, that delineate MTD and distinguish subtypes on the basis of laryngoscopic features. The aim of this study is to determine which of the clinical features included in these classifications are most related to the aerodynamic profile of MTD. This is an analytic retrospective study. This study evaluates a series of 30 consecutive patients, all over 18 years old, who attended the voice clinic consult of our department and were diagnosed with MTD. All subjects underwent fiberoptic nasal endoscopy, acoustic voice assessment, and aerodynamic voice assessment. The study only includes patients with a pathological aerodynamic profile. Presence or absence of each laryngoscopic feature in the full range of features in the Van Lawrence, Morrison-Rammage, and Koufman classification systems was evaluated independently by three experts. Cohen's kappa coefficient was calculated to indicate the degree of concordance between the experts. The chi-squared test was used to determine the degree of association between clinical features and mean value of the subglottic pressure peak (mmH 2 O). Clinical parameters that were found to have a statistically significant association (P < 0.05) with an alteration in mean subglottic pressure peak were those related to anteroposterior and lateral compression of the larynx in Van Lawrence, Morrison-Rammage, and Koufman classification systems. While several studies have sought to clarify the laryngoscopic features of MTD, the current study is the first to evaluate these features in subjects who have been objectively diagnosed by means of aerodynamic voice assessment. The laryngoscopic features most strongly related to an aerodynamic profile of MTD were anteroposterior compression of the larynx, lateral compression of the larynx, and vestibular fold contribution to phonation. [ABSTRACT FROM AUTHOR]

Objective: The aim of our work was to investigate the peculiarities of the functioning circadian organization the ion-regulating function of pineal gland hyperfunction of the influence nitrogen monoxide synthesis blockade., Patients and Methods: Materials and methods: The experiments were conducted on 72 mature non-linear albino male rats with their body mass 0,15-0,18 kg. The control group included animals (n=36) kept under conditions of usual light regimen (12.00L:12.00D) during 7 days. The experimental group included animals (n=36) injected with N-nitro-L-arginine (L-NNA) in the dose of 20 mg/kg during 7 days under conditions of continuous absolute darkness (12.00D:12.00D). On the 8th day the animals were exposed to 5% water load with heated to room temperature water supplied and the parameters of the kidney ion-regulating function under conditions of forced diuresis were investigated., Results: Results and conclusions: The obtained results of the performed blockade nitrogen monoxide (NO) synthesis in conditions of hyperfunction of the brain epiphysis allow to conclude that the daily mean of the rate of excretion of sodium ions decreases in comparison with the animals that were kept under pineal gland (PG) hyperfunction of the filtration fraction and reabsorption of sodium ions are reduced compared to the control animals and rats which were kept under conditions of PG hyperfunction and accompanied by stable indicators of the concentration the specified cation in the blood plasma during the observation period. The action of the blockade NO synthesis in conditions of PG hyperfunction leads to a decrease in the distal transport bridge of sodium ions with a maximum in the day and night intervals of the day the position of the acro- and batiphase of the rhythm changes as compared with the control animals.

Objective: Introduction: In recent decades chronobiology - a science that studies the regularities of the functioning of the organism, especially biological rhythms is developing rapidly. Biorhythms are stable nonstopper lifetime fluctuations with individual amplitude-frequency characteristics. Kidneys are characterized by a clear time organization of functions too, however, the peculiarities of circadian organization and the mechanisms of the participation of intracellular messengers in particular nitrogen monoxide (NО) in biorhythmic regulation of renal functions, remain insufficiently studied The aim of our work was to investigate the peculiairities of the influence nitrogen monoxide synthesis blockade on circadian organization of kidney acid-regulating function under conditions of pineal gland hyperfunction., Patients and Methods: Materials and methods: The experiments were conducted on 72 mature non-linear albino male rats with their body mass 0,15-0,18 kg. The animals were kept under vivarium conditions at a stable temperature and air humidity fed on a standard dietary intake. The control group included animals (n=36) kept under conditions of usual light regimen (12.00L:12.00D) during 7 days. The experimental group included animals (n=36) injected with N-nitro-L-arginine (L-NNA) in the dose of 20 mg/kg during 7 days under conditions of continuous absolute darkness (12.00D:12.00D). On the 8th day the animals were exposed to 5& water load with heated to room temperature water supplied and the parameters of the kidney acid-regulating function under conditions of forced diuresis were investigated., Results: Results: The inhibition of the monoxide synthesis (NО) in conditions of pineal gland (PG) hyperfunction violated the structures of chronorhythms acid-regulating function of the kidneys. The decrease in urine pH at daytime intervals was due to a decrease in the level of hydrogen ion excretion during this period of the day. The introduction of the NО blocker against the background of the PG hyperfunction violated the structure of the acid esterification chronorhythms that are titrated. The maximum level of this indicator was recorded at 20.00 a.m. a day. The blockade of the synthesis NО on the background of the PG hyperfunction significantly reduced the level of excretion of ammonia., Conclusion: Conclusions: The maximum level of excretion was 12.00 a.m., bathyphase - at 24.00 a.m. The average daily level was 1.5 mcmol/100 mcl GF and was lower relative to the control animals and animals that were in the conditions of PG hyperfunction.

Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on the older theory of antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on of processes that in early life promote fitness. Here we apply this idea to investigate the etiology of senescent pathologies in the reproductive system of Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration. Hermaphrodite germ cells frequently undergo "physiological" (non-damage-induced) apoptosis (PA) to provision growing oocytes. Run-on of such PA is a potential cause of age-related gonad degeneration. We document the continuation of germline apoptosis in later life, and report that genetically blocking or increasing PA retards or accelerates degeneration, respectively. In wild-type males, which lack germ line apoptosis, gonad disintegration does not occur. However, mutational induction of PA in males does not lead to gonad disintegration. These results suggest that as germ-cell proliferation rate declines markedly in aging hermaphrodites (but not males), run-on of PA becomes a pathogenic mechanism that promotes gonad degeneration. This illustrates how hyperfunction, or non-adaptive run-on in later life of a process that promotes fitness in early life, can promote atrophic senescent pathology in C. elegans., Competing Interests: There are no conflicts of interest.