The Contribution of Macrophages in Old Mice to Periodontal Disease.

The prevalence of periodontal disease increases with age. Systemic inflammatory dysregulation also increases with age and has been reported to contribute to the myriad of diseases and conditions that become more prevalent with advanced age. As periodontal disease involves a dysregulated host inflammatory response, the age-related inflammatory dysregulation may contribute to the pathogenesis of periodontal disease in aging populations. However, our understanding of what drives the age-related inflammatory dysregulation is limited. Here, we investigate the macrophage and its contribution to periodontal disease in old and young mice using a ligature-induced periodontal disease model. We demonstrate that control old mice present with an aged periodontal phenotype, characterized by increased alveolar bone loss and increased local inflammatory cytokine expression compared to young mice. Macrophages were demonstrated to be present in the periodontium of old and young mice in equal numbers in controls, during disease induction, and during disease recovery. However, it appears age may have a detrimental effect on macrophage activity during disease recovery. Depletion of macrophages during disease recovery in old mice resulted in decreased inflammatory cytokines within the gingiva and decreased bone loss as measured by micro-computed tomography. In young mice, macrophage depletion during disease recovery had no beneficial or detrimental effect. Macrophage depletion during disease induction resulted in decreased disease severity similarly in young and old mice. Findings from this work support the diverse roles of macrophages in disease induction as well as the active roles of disease recovery, including the resolution of inflammation. Here, we conclude that age-related changes to the macrophage appear to be detrimental to the recovery from disease and may explain, in part, the age-related increase in prevalence of periodontal disease. Future studies examining the specific intrinsic age-related changes to the macrophage will help identify therapeutic targets.

Controlled obesity status: a rarely used concept, but with particular importance in the COVID-19 pandemic and beyond.

Obesity is a chronic disease that causes and aggravates several other diseases, and early reports suggest it is an important risk factor for COVID-19 severity. Although a deeper understanding of this relationship is vital, it is also important to inform the general public about the risks and, ideally, offer strategies to mitigate the risks. As "resolution" of obesity in the short-term is not feasible, it is indeed possible that smaller weight losses and increase in physical activity can actually reduce the risks. In this context, we propose that a term called "controlled obesity" be more often used and studied, in which those who have lost over 10% of their maximal weight and, ideally, are physically active are considered healthier. This context can have much broader usefulness, beyond the pandemics, as evidence points that weight loss over 10% can significant reduce overall health risks, irrespective of final BMI.

[Tumor boards: why they are necessary and which structure is needed]. / Tumorboards: Warum wir sie brauchen und welche Ausstattung nötig ist.

This review article gives a detailed overview regarding the growing importance of tumor boards in the daily clinical life. Improved diagnostic and therapeutic options for oncologic diseases lead to an increased complexity in patient management, which can only be handled optimally by a team of specialists. Within this process radiology as a specialty is of growing importance and constitutes the core in the diagnostic algorithm. Radiology is necessary for optimal tumor staging. In summary, there is a growing importance of tumor boards in the management of oncologic diseases and radiologists are a key factor in this process.

Bupropion/naltrexone fixed-dose combination for the treatment of obesity.

The combination of bupropion and naltrexone is one of the most promising new possibilities for the treatment of obesity in an era of increasing prevalence of this disease and decreasing options for its pharmacological management. Although approved by FDA panel members, it was temporally rejected by the FDA afterwards, who demanded more cardiovascular safety data for its commercialization. This monograph will focus on the physiology involved in its mechanisms of action and results of clinical trials.

Crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes.

Expert opinion was canvassed to identify crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes. Scientists that had published three or more papers on the effects of climate and environmental factors on reef fishes were invited to submit five questions that, if addressed, would improve our understanding of climate change effects on coral reef fishes. Thirty-three scientists provided 155 questions, and 32 scientists scored these questions in terms of: (i) identifying a knowledge gap, (ii) achievability, (iii) applicability to a broad spectrum of species and reef habitats, and (iv) priority. Forty-two per cent of the questions related to habitat associations and community dynamics of fish, reflecting the established effects and immediate concern relating to climate-induced coral loss and habitat degradation. However, there were also questions on fish demographics, physiology, behaviour and management, all of which could be potentially affected by climate change. Irrespective of their individual expertise and background, scientists scored questions from different topics similarly, suggesting limited bias and recognition of a need for greater interdisciplinary and collaborative research. Presented here are the 53 highest-scoring unique questions. These questions should act as a guide for future research, providing a basis for better assessment and management of climate change impacts on coral reefs and associated fish communities.

Performance of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography and integrated PET/CT in restaged breast cancer patients.

PURPOSE: This study was conducted to compare the clinical stage derived from 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET) to that of integrated PET/computed tomography (CT) in restaged breast cancer patients. PROCEDURES: Fifty-eight female patients (age range 29-80 years, mean age +/-SD, 53.3 +/- 11.7 years) underwent PET/CT restaging for breast cancer. Two experienced nuclear medicine physicians interpreted PET images. A radiologist was added for reading PET/CT studies. A patient-based analysis was performed. Histopathological findings, correlative imaging studies, changes in number, size, and hypermetabolic activity of suspicious lesions and/or patient outcome served as standard of reference for determining the diagnostic accuracy of both modalities. RESULTS: PET staged 79.3% (46/58) of the patients correctly, overstaged seven (12.1%), and understaged five patients (8.6%). Integrated PET/CT staged 89.7% (52/58) of the patients correctly, overstaged four (6.9%), and understaged two patients (3.4%). The staging accuracy of PET/CT was not significantly better than that of PET alone (p = 0.059). Lesions exhibiting mild hypermetabolic activity, benign inflammatory lesions, and physiological variants largely explained incorrect PET findings. CONCLUSION: Integrated PET/CT only marginally improves the restaging accuracy over PET alone (p = 0.059) in breast cancer patients.

The effect of microgravity and space flight on the chemical senses.

The effect of space flight and microgravity on the chemical senses is reviewed. Skylab-4 and Soyuz 30-31 studies revealed changes in taste thresholds while no effect was found in a Canadian investigation (41-G) and conflicting results were obtained on another Soyuz mission. Two simulated microgravity studies found no effect on taste or smell sensitivity; while 5 other studies found an effect. Microgravity induces physiological changes including an upward shift of body fluids toward the head, which may lead to an attenuation of the olfactory component in the flavor of foods. Chemosensory changes may also relate to space sickness, Shuttle atmosphere, stress, radiation, and psychological factors.

Spondylolysis.

Spondylolysis is a relatively common incidental radiographic finding that, most frequently, is asymptomatic. Isthmic spondylolysis with a lesion in the pars interarticularis may be a significant cause of pain in a given individual, particularly in adolescent athletes involved in sports with repetitive spinal motions. The pars lesion likely represents a stress fracture of the bone caused by the cumulative effect of repetitive stress imposed by physical activity. The lesion frequently presents as focal LBP and can often be identified on plain radiography. Advanced imaging with SPECT, CT, and MR imaging may be needed to ascertain the acuity of the lesion, assist in identifying a particular pars lesion as potentially symptomatic, and to exclude other spinal pathology that may be present. Conservative treatment is usually successful in controlling symptoms and restoring function; only a small percentage of patients require surgical intervention for pain or progressive spondylolisthesis. Based on current evidence, treatment requires activity restriction (i.e., temporary discontinuation of the aggravating sport or activity) and may require bracing to achieve treatment goals, although healing, pain relief or both may occur without brace application. A full understanding of spinal biomechanics and pathophysiology, the role of diagnostic imaging, and treatment options is needed to care for these patients.

Sensory coding, decoding, and representations. Unnecessary and troublesome constructs?

Reception of certain environmental energy patterns can allow organisms to successfully respond to present or future environmental conditions. Sensory systems are the means by which this reception occurs. The bioelectric components of this process are typically characterized as "sensory coding." "Coding" logically requires subsequent "decoding," and implies that the decoder has a special, commanding role. In contrast, the term "transformation," which is sometimes applied to the prebioelectric components of sensory systems, can connote a series of changes in the medium, form, or content of sensory processes. Neither coding nor decoding are implied, no notions of "representation" or "reconstruction" of the world are introduced, and distributed, parallel processing is a natural corollary of transformations. It is proposed that the problematic construct of sensory coding, with its concomitant decoding, be replaced with the more neutral and physical concept of transformations. Elimination of the notions of representation or reconstruction of the world in some special nervous system locus is also suggested.

Glutamate and the flavor of foods.

Investigations of the effects of glutamic acid or its salts on the flavor, hedonic characteristics or acceptance of foods have emphasized a sodium salt of L-glutamic acid, monosodium glutamate (MSG). Food palatability increased with appropriate concentrations of MSG, and could be represented f(MSG and NaCl) as points on the surface of an elliptic paraboloid. Hedonic effects differed between foods, were a function of concentrations of MSG and other ingredients and did not necessarily become positive when only MSG was added. For example, with boiled or fried rice, ratings were neutral or negative with MSG alone, positive for fried rice with MSG and NaCl, but positive for boiled rice only if soy sauce was also added. A one-dish meal, Chinese noodle, became positive with an appropriate concentration of NaCl plus a MSG-5'ribonucleotide mixture, but not with NaCl alone. Flavor of meat, fish or vegetable stocks containing natural glutamates differed from that of quinine, sucrose, NaCl or acid solutions. Glutamates and free amino acids plus nucleotides were necessary for full boiled potato flavor. Overall, the effects of MSG on foods were different from those of NaCl but often interacted with NaCl, and positive effects were facilitated by low concentrations of 5'-ribonucleotides.

Refractive error consequences of reversed-optic AMO SI-40NB intraocular lens.

OBJECTIVE: To evaluate the refractive consequences of inadvertently implanting a reversed-optic AMO SI-40NB posterior chamber intraocular lens (IOL). DESIGN: Retrospective case series. METHODS: One surgeon (BLH) implanted 457 SI-40NB IOLs over a 2-year period beginning on January 1, 1996, and ending on December 31, 1997. Six of these IOLs (1.3%) were noted to have been implanted with a reversed optic. The authors retrospectively reviewed the target spherical equivalent refractive errors (SEREs) and actual postoperative SEREs for all 457 eyes. MAIN OUTCOME MEASURES: The SRK-II formula was used to predict target SEREs. Actual postoperative SEREs were determined at 1 month after surgery using either a manifest or an automated refraction. Target postoperative SEREs were subtracted from actual postoperative SEREs to calculate diopter surprises, or the degree to which the actual SEREs differed from the target SEREs. RESULTS: The mean (+/-standard deviation) diopter surprise for reversed-optic SI-40NB IOLs was 0.01 (+/-0.89) diopter (D) more myopic than predicted; diopter surprises ranged from -1.39 D to +1.42 D. The mean diopter surprise for nonreversed SI-40NB IOLs was 0.18 (+/-0.81) D more hyperopic than predicted; diopter surprises ranged from -1.88 D to +2.56 D. The difference between the mean diopter surprises (0.19 D) was not statistically significant (t = 0.56, P = 0.57). CONCLUSIONS: A reversed-optic SI-40NB IOL is as likely to produce a satisfactory refractive result as a nonreversed IOL. Therefore, the refractive consequences of a reversed-optic SI-40NB IOL do not warrant the risks associated with repositioning the lens.

Anion size of sodium salts and simple taste reaction times.

Simple taste reaction times (RT) and taste intensities were measured in adult humans for 100-mM aqueous solutions of sodium chloride, acetate, glutamate, ascorbate, and gluconate flowed over the anterodorsal tongue with a closed liquid delivery system. Results from 12 subjects showed a significant increase in RT with molecular weight of the tastant, and a correlation of 0.941 between RT and the square roots of anionic weights. A multiple regression analysis controlling for perceived taste intensity indicated that RT increased linearly with the square root of the anionic weight. These findings support a model that includes both the permeability of ions through the tight junctions between the taste receptor cells of fungiform papillae taste buds and the effects of ions at apical portions of the receptor cells. They also suggest that gustatory transduction of sodium salts in humans normally involves intercellular spaces of taste buds as part of the functional sensory structures, in addition to individual taste receptor cells.

Amiloride and vertebrate gustatory responses to NaCl.

Amiloride at < or = 1 microM may block epithelial Na+ channels without affecting other cellular mechanisms, and attenuates gustatory responses to lingual NaCl from the chorda tympani nerves (CT) of gerbil, hamster, rhesus monkey, and several strains of laboratory rat and mouse, and from glossopharyngeally innervated frog taste-receptor cells; at 5 microM to 50 microM, also from Wistar rat and mongrel dog CT. Affected units responded more to NaCl than to KCl. Suppression of CT responses to KCl, HCl, NH4Cl, or saccharides also occurred in some mammals, but amiloride did not elicit responses. Taste-dependent behaviors towards NaCl or KCl were altered. DBA and 129/J laboratory mice, and mudpuppy, were unaffected by amiloride. In humans, 10 microM amiloride both produced taste reports and reduced total intensity of NaCl and LiCl by 15-20%. NaCl and LiCl sourness, and KCl and QHCl bitterness declined, but saltiness generally did not change. Effects on sweetness were inconsistent. Amiloride-sensitive gustatory mechanisms were prominent in some mammals, were not necessary for responses to NaCl, and were of minor importance for human taste.

Effects of amiloride on gustatory quality descriptions and temporal patterns produced by NaCl.

The amiloride-sensitivity of perceived taste qualities and time-intensity patterns for NaCl, and interactions between amiloride and NaCl as taste stimuli, were explored using caffeine as the control treatment. NaCl at 100, 250 and 500 mM, dissolved in 10 or 100 microM amiloride, or in caffeine concentrations matched to the amiloride taste, was flowed over 39.3 mm2 of the anterodorsal tongue for 4 s using a closed stimulus delivery system. Amiloride, caffeine and NaCl in H2O were also presented. It was found that NaCl-amiloride mixtures were most frequently described as salty, with the incidence of salty descriptions directly associated with NaCl concentration but not significantly associated with the presence or concentration of amiloride. Amiloride in H2O was called 'bitter', and the incidence of bitter descriptions was significantly associated with the presence of amiloride. The perceived temporal patterns varied with NaCl concentration but did not change with the presence of amiloride, except for an increase in perceived duration. No evidence was found for a dependence upon specific amiloride-sensitive mechanisms of human description of NaCl as salty or of gustatory temporal patterns evoked by NaCl.

Sensitivity and behavioral responses to the pheromone androstenone are not mediated by the vomeronasal organ in domestic pigs.

Based largely on results of studies of laboratory rodents, the vomeronasal or accessory olfactory system is believed to function mainly in social communication, mediating the effects of stimuli such as urine or glandular secretions on the behavior or endocrine response of conspecifics. In the domestic pig (Sus scrofa), the steroid androstenone has been identified as a pheromone that facilitates expression of both attraction to the male and a receptive mating stance in estrous females. Though the domestic pig is one of the few vertebrate species in which the identity of a compound that functions as a pheromone is known, the role of the vomeronasal system in domestic pigs has never been investigated. We have examined the role of the vomeronasal organ in mediating the pheromonal effects of androstenone in pigs. In addition, we have examined the structure of the vomeronasal organ at the gross and light-microscopic levels. The vomeronasal organ appears functional, with sensory epithelium lining the medial wall, and has access to stimuli from both the oral and nasal cavities. To determine whether the vomeronasal organ is necessary for androstenone detection or attraction or receptive behavior in female pigs, access to the vomeronasal organ was blocked with surgical cement, and androstenone detection threshold and sexual behavior were measured. Experimental animals did not differ significantly in androstenone sensitivity, measured behaviorally, from untreated controls. Vomeronasal organ-blocked animals also did not differ from untreated controls in either androstenone-mediated receptive standing behavior or attraction to the odor of androstenone. We conclude that in the domestic pig, the vomeronasal organ is not necessary for androstenone detection or androstenone-mediated sexual behavior in estrous females.

Orthonasal and retronasal odorant identification based upon vapor phase input from common substances.

Subjects were trained to identify by assigned number common substances presented as vapor phase stimuli via an orthonasal or a retronasal route. Following training, odorant identification learning was evaluated by measuring ability to correctly identify to a criterion. Those who met the criterion were then tested first with the stimuli presented to the nares that differed in location from the nares used in training, and second to the nares that corresponded in location to the nares used in training. It was found that, under conditions of natural retronasal breathing, orthonasally trained subjects made correct identifications on approximately 80% of the trials upon retronasal testing, but for the following orthonasal testing identifications were significantly more frequent, approaching 100% correct. After subsequent retronasal training, the same subjects' orthonasal identifications remained significantly higher, although identifications improved to approximately 92% correct on retronasal trials. Other subjects were instructed in a breathing technique designed to enhance retronasal stimulation. After orthonasal training, retronasal testing of these subjects still gave significantly fewer correct identifications than orthonasal testing, notwithstanding the modified retronasal breathing, but after subsequent retronasal training correct identifications by these subjects no longer differed significantly between orthonasal and retronasal testing. Efficacy of modified retronasal breathing was confirmed in two subsequent experiments. The observed substantial positive transfers between retronasal and orthonasal odorant identification training and testing loci demonstrate that these odorant pathways do not subserve completely independent olfactory systems, while the less accurate identifications via the retronasal route, unless instruction in retronasal breathing was given, suggest a difference in the efficiency with which odorants are normally delivered to the olfactory mucosa.

The incidence of atonic pupil following cataract surgery.

OBJECTIVE: To determine and compare the incidence of atonic pupil following modern extracapsular cataract extraction and small-incision phacoemulsification with lens implantation in a large series of consecutive patients. PATIENTS AND DESIGN: A retrospective review was undertaken of 1283 consecutive cases of cataract surgery with posterior chamber intraocular lens implantation (919 extracapsular and 364 small-incision phacoemulsification) performed by two surgeons between October 30, 1991, and June 30, 1993. Postoperative atonic pupil was defined as a pupil that, following cataract surgery, was 6 mm or more in diameter and minimally or nonreactive to light, accommodation, or 1% pilocarpine hydrochloride. RESULTS: Postoperatively, 25 (1.95%) of 1283 eyes developed an atonic pupil following cataract extraction with posterior chamber intraocular lens implantation (21 [2.29%] of 919 extracapsular and four [1.10%] of 364 phacoemulsification procedures). When an atonic pupil was present following surgery, disturbing glare often resulted, despite a well-centered intraocular lens. CONCLUSIONS: To our knowledge, this is the first large, consecutive study of the incidence of atonic pupil following modern cataract surgery and the first study to compare the incidence of atonic pupil following extracapsular surgery vs small-incision phacoemulsification. Although the incidence of atonic pupil may be lower following phacoemulsification, caution is advised in the implantation of ever-smaller optic lenses.