Modified maxillomandibular advancement surgery for the treatment of obstructive sleep apnoea: a scoping review.

Modified maxillomandibular advancement (MMMA) has been proposed as an alternative to the classic maxillomandibular advancement (MMA) in East and Southeast Asian populations in which bimaxillary protrusion is a prevalent trait. The key difference between MMMA and MMA is the inclusion of anterior segmental osteotomies to reduce the protrusion of the perioral region. The aim of this scoping review was to identify the variations in MMMA and treatment outcomes. A search was conducted in the PubMed, Embase, and Cochrane electronic databases for articles published up to January 2023. Ten articles were included in this review. Three variations of MMMA have been reported in the literature. Treatment outcomes have mostly been favourable for all of these variations. Mandibular advancement of >10 mm and a greater than 50% reduction in the apnoea-hypopnoea index (AHI) have been well reported. Improvements in other outcome measures, such as enlargement of the airway dimension on computed tomography and the Epworth Sleepiness Scale score, have also been shown. Despite additional surgical procedures, complications have been uncommon and mostly minor in nature. It is necessary to be cognizant of MMMA and its variations when providing sleep surgery for East and Southeast Asian patients, tailoring this to the patient's profile and needs.

Improving vitamin D content in pork meat by UVB biofortification.

Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 µg/kg), 25(OH)D3 (2.09 vs. 1.65 µg/kg) and total vitamin D activity (22.88 vs. 14.50 µg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementation.

Bioavailability of vitamin D biofortified pork meat: results of an acute human crossover study in healthy adults.

Vitamin D intakes are concerningly low. Food-based strategies are urgently warranted to increase vitamin D intakes and subsequently improve 25-hydroxyvitamin D (25(OH)D) concentrations. This acute randomised three-way crossover study investigated the efficacy of vitamin D biofortified pork derived from pigs exposed to UVB light to increase serum 25(OH)D3 concentrations, compared to a dose-matched vitamin D3 supplement and control pork in adults (n = 14). Blood samples were obtained at baseline and then 1.5, 3, 6, 9 and 24 h postprandially. There was a significant effect of time (p < 0.01) and a significant treatment*time interaction (p < 0.05). UV pork and supplement significantly increased within-group serum 25(OH)D3 concentrations over timepoints (p < 0.05) (max. change 0.9 nmol/L (2.2%) UV pork, 1.5 nmol/L (3.5%) supplement, 0.7 nmol/L (1.9%) control). Vitamin D biofortified pork modestly increased 25(OH)D3 concentrations and produced a similar response pattern as a dose-matched vitamin D supplement, but biofortification protocols should be further optimised to ensure differentiation from standard pork.

Impact of cooking on vitamin D3 and 25(OH)D3 content of pork products.

Little is known regarding the impact of cooking on vitamin D content in pork, despite meat being a major contributor to vitamin D intakes. This paper investigated the effect of household cooking (pan-fry/roast/grill/sous-vide/sauté), on the vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) concentration/retention in pork loin, mince and sausages. We hypothesised that vitamin D concentrations would be higher in cooked vs raw pork, and retention would differ between products. Cooking significantly increased vitamin D3 (+49 %) and 25(OH)D3 (+33 %) concentrations. All cooked loin vitamin D3 concentrations were significantly lower than mince/sausage. Vitamin D3 retention was > 100 % for all samples (102-135 %), except sauté mince (99 %) which still did not differ significantly from 100 % retention. Sous-vide cooking resulted in the highest vitamin D3 retention (135 %). Likely owing to water/fat loss, household cooking of pork results in favourable retention of vitamin D3 and 25(OH)D3. The type of pork product has greater influence than cooking method.

Impact of molecular medicine on neuropsychiatry: the clinician's perspective.

Clinical neuropsychiatry has traditionally relied on individual practitioner experience or the apprentice-training model for formulating cases and choosing treatment. Scientifically-based diagnostic criteria and treatment algorithms have been lacking in the overlap area between psychiatry and neurology, owing largely to the complexity of this population population. However, the novel application of new molecular technologies is promising to change the care of neuropsychiatric patients. This review will highlight recent advances in molecular medicine pertaining to neuropsychiatry.Introduction

Pharmacologic therapy for behavioral symptoms of Alzheimer's disease.

Behavioral signs and symptoms in dementia are common, morbid, classifiable, and treatable. The current state-of-the-art approach is to evaluate carefully for social or environmental causes, intercurrent medical conditions, or other triggers of the behavior and attempt to deal with those directly. When these conservative steps fail, there may be a role for medication. A rational approach typically hinges on matching the most dominant behavioral target symptoms to the most relevant medication class, the key information of which is summarized.

Optimal pregnancy outcome in a minimal-stimulation in vitro fertilization program.

OBJECTIVE: We sought to provide a cost-beneficial approach to in vitro fertilization for infertile patients who could not afford the standard treatment with in vitro fertilization and to determine the optimal level of minimal ovarian stimulation to achieve acceptable pregnancy rates. STUDY DESIGN: We performed a retrospective cohort study of 216 patients who underwent "minimal stimulation" in vitro fertilization between January 1994 and December 1998. During the first half of this study, various minimal ovarian stimulation protocols were performed in our private, free-standing center for in vitro fertilization. More recently, more ovarian stimulation, including a 4-day protocol featuring gonadotropin-releasing hormone agonist flare (ultrashort flare), was used. Clinical pregnancy outcome, multiple gestation, complications, and maternal age were compared between the first and second halves of this study. RESULTS: The average ages of patients in the first half (phase 1) and the second half (phase 2) were similar, 32.4 +/- 0.3 versus 32.6 +/- 0.3 years, respectively. An average of 3.5 oocytes per retrieval was obtained in phase 1 versus 5.9 oocytes in phase 2. Failure to retrieve oocytes occurred in 3% of all cases. The mean number of embryos transferred per patient was 2.0 in phase 1 versus 2.4 in phase 2. In phase 1, 16.1% of patients failed to have viable embryos for transfer, in comparison with 9.7% in phase 2. The overall clinical pregnancy rate per retrieval was 16.9% in phase 1 versus 36. 6% in phase 2. Multiple gestation occurred in 5.0% of clinical pregnancies in phase 1 but increased to 33% in phase 2, with 9 sets of twins and 6 sets of triplets. The implantation rate was 9.3% for phase 1 versus 23.3% for phase 2. The clinical pregnancy rates per retrieval for phase 2 patients were 41.6% in women < or =34 years old and 25.6% for those > or =35 years old. No case of ovarian hyperstimulation syndrome was noted. CONCLUSIONS: Minimal ovarian stimulation in the setting of in vitro fertilization offers a cost-beneficial alternative to standard treatment with in vitro fertilization in infertile patients who are <35 years old and in women <40 years old who have adequate oocyte reserve. More stimulation improves outcome. Minimalstimulation in vitro fertilization provides an alternative for those patients who cannot afford standard in vitro fertilization or who are concerned with exposure to high dosages of fertility medications.

Prenatal availability of choline alters the development of acetylcholinesterase in the rat hippocampus.

Choline (Ch) supplementation during embryonic days (ED) 12-17 enhances spatial and temporal memory in adult and aged rats, whereas prenatal Ch deficiency impairs attention performance and accelerates age-related declines in temporal processing. To characterize the neurochemical and neuroanatomical mechanisms that may mediate these behavioral effects in rats, we studied the development [postnatal days (PD) 1, 3, 7, 17, 27, 35, 90, and 26 months postnatally] of acetylcholinesterase (AChE) activity in hippocampus, neocortex and striatum as a function of prenatal Ch availability. We further measured the density of AChE-positive laminae (PD27 and PD90) and interneurons (PD20) in the hippocampus as a function of prenatal Ch availability. During ED11-ED17 pregnant Sprague-Dawley rats received a Ch-deficient, control or Ch-supplemented diet (average Ch intake 0, 1.3 and 4.6 mmol/kg/day, respectively). Prenatal Ch deficiency increased hippocampal AChE activity as compared to control animals in both males and females from the 2nd to 5th week postnatally. Moreover, prenatal Ch supplementation reduced hippocampal AChE activity as compared to control animals over the same developmental period. There was no effect of prenatal Ch status on either cortical or striatal AChE activity at any age measured, and by PD90 the effect of Ch on hippocampal AChE was no longer observed. In order to localize the early changes in hippocampal AChE activity anatomically, frozen coronal brain sections (PD20, PD27, PD90) were stained histochemically for AChE. Consistent with biochemical results, the AChE staining intensity was reduced in PD27 hippocampal laminae in the Ch-supplemented group and increased in the Ch-deficient group compared to control animals. There was no effect of the diet on hippocampal AChE staining intensity on PD90. In addition, the prenatal Ch availability was found to alter the size and density of AChE-positive PD20 interneurons. These results show that prenatal Ch availability has long-term consequences on the development of the hippocampal cholinergic system.

Physiologic and neuroendocrine responses to intravenous naloxone in subjects with Alzheimer's disease and age-matched controls.

BACKGROUND: Prior work showed that administration of naloxone HCl had different behavioral effects in patients with Alzheimer's disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous naloxone of patients with probable Alzheimer's disease to aged-matched controls. METHODS: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin were obtained at regular intervals. RESULTS: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p < .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. CONCLUSIONS: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.

Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats.

The effects of choline supplementation during two time-frames of early development on radial-arm maze performance and the morphology of basal forebrain neurons immunoreactive for the P75 neurotrophin receptor (NTR) in male and female Sprague-Dawley rats were examined. In the first experiment, rats were supplemented with choline chloride from conception until weaning. At 80 days of age, subjects were trained once a day on a 12-arm radial maze for 30 days. Compared to control littermates, supplemented rats made fewer working and reference memory errors; however, the memory enhancing effects of choline supplementation were greater in males than females. A morphometric analysis of NTR-immunoreactive cell bodies at three levels through the medial septum/diagonal band (MS/DBv) of these rats revealed that perinatal choline supplementation caused the somata of cells in the MS/DBv to be larger by 8-15%. In a second experiment, choline supplementation was restricted to embryonic days 12-17. A developmental profile of NTR immunoreactive cell bodies in the MS/DBv of 0-, 8-, 16-, 30- and 90-day old male and female rats again revealed that cell bodies were larger in choline-supplemented rats than controls. As in the behavioral studies, the effect of choline supplementation was greater in male than female rats. These data are consistent with the hypothesis that supplementation with choline chloride during early development leads to an increase in the size of cell bodies of NTR-immunoreactive cells in the basal forebrain and that this change may contribute to long-term improvement in spatial memory.

Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells.

Treatment of rats with choline during critical periods in brain development results in long-lasting enhancement of spatial memory in their offspring. Apoptosis is a normal process during brain development, and, in some tissues, is modulated by the availability of the nutrient choline. In these studies, we examined whether availability of choline influences apoptosis in fetal brain and in the PC12 cell line derived from a rat pheochromocytoma. Timed-bred Sprague Dawley rats were fed a choline-deficient (CD), choline-control, or choline-supplemented (CS) diet for 6 days and, on embryonic day 18, fetal brain slices were prepared and apoptosis was assessed using terminal dUTP nucleotide end labeling (TUNEL) to detect DNA strand breaks and by counting of apoptotic bodies. TUNEL-positive cells were detected in 15.9% (P < 0.01), 8.7% and 7.2% of hippocampal cells from fetuses of dams fed the CD, control or CS diets, respectively. A similar inverse relationship between dietary intake of choline and TUNEL positive cells was detected in an area of cerebral cortex from these fetal brain slices. Counts of apoptotic bodies in fetal brain slices correlated inversely with choline intake of the mothers (6.2% (P < 0.01), 2.5% and 1.9% of hippocampal cells had apoptotic bodies in fetuses of dams fed the CD, control and CS diets, respectively). PC12 cells were grown in DMEM/F12 media supplemented with 70 microM choline or with 0 microM choline. The number of apoptotic bodies in PC12 cells increased when cells were grown in 0 microM choline medium (1.5%; P < 0.05) compared to 70 microM choline medium (0.55%). In PC12 cells, TUNEL labeling (DNA strand breaks) increased in choline deficient (13.5%, P < 0.05) compared to sufficient medium (5.0%). In addition, cleavage of genomic DNA-into 200 bp internucleosomal fragments was detected in choline-deficient cells. These results show that choline deficiency induces-apoptotic cell death in neuronal-type cells and in whole brain. We suggest that variations in choline availability to brain modulate apoptosis rates during development.

Retrograde axonal transport and lesion-induced upregulation of the TrkA high-affinity NGF receptor.

Long-term physiological responses of nerve growth factor (NGF) and other neurotrophins require gene regulation and likely depend on retrograde axonal transport of NGF or a signaling molecule activated by ligand-receptor interaction. The low-affinity neurotrophin receptor p75LANR is retrogradely transported, but this receptor is not sufficient for NGF-dependent cell survival or differentiation. In this study we examined the distribution and transport of the TrkA NGF receptor using two anti-peptide polyclonal antibodies and a monoclonal antibody, all of which are TrkA specific. We find that (1) in the adult rat brain TrkA-like immunoreactivity is similar with all antibodies in striatal and basal forebrain neurons, (2) TrkA is upregulated in neuronal and nonneuronal cells near the sites of injury, and (3) TrkA immunoreactivity builds up within the proximal and distal segments of transected fimbrial axons, which is consistent with its transport in the anterograde and retrograde directions. Thus, TrkA may itself be, or be a component of, the neurotrophic intraaxonal messenger by which NGF regulates gene expression in sensitive neurons.

Regional CNS uptake of blood-borne nerve growth factor.

Nerve growth factor (NGF), in addition to being a neurotrophic substance, has effects on the endocrine and immune systems. For example, intravenous injection of NGF results in a cascade of events leading to an increase in glucocorticoid secretion. While this response appears to be mediated centrally, there has been no evidence that circulating NGF has access to the CNS. Using intravenous injections of 125I-NGF, we find specific uptake at 1 hr but none at 6 hr, into homogenates of the basal forebrain, cerebellum, frontal cortex, hippocampus, and olfactory bulb. By autoradiography, uptake is localized to circumventricular organs, deep layers of the cerebellum, and all layers of the hippocampal region CA1, but not the dentate gyrus. Thus, uptake of blood-borne NGF could affect the hypothalamic-pituitary-adrenal axis via binding to NGF receptors present in the hippocampus. However, the sources of endogenous NGF, the mechanism of access through the blood-brain barrier, the eventual fate of NGF entering from the blood, and the physiological significance of this uptake remain to be elucidated.

The pharmacology and the potential applications of GnRH antagonists.

Gonadotropin-releasing hormone (GnRH) antagonists are potent analogs of native GnRH. As biochemical probes, these recently developed compounds have allowed for profound insights into the physiology of the pituitary-ovarian and pituitary-testicular axes; as therapeutic alternatives, the GnRH antagonists hold great promise for various clinical applications, including contraception, ovulation induction, precocious puberty, and gonadal steroid-dependent neoplasia. Indeed, because of intrinsic mechanistic differences, the antagonists hold certain practical advantages over the GnRH agonists.

Relationship of APP mRNA transcripts and levels of NGF and low-affinity NGF receptors to behavioral measures of age-related cognitive dysfunction.

This study was designed to examine the relationship between cognitive function and endogenous levels of NGF, low-affinity NGF receptor (LNGFR), and amyloid precursor protein (APP) mRNAs. Using 3 month (n = 5), 18 month (n = 40), and 29 month (n = 17) Fischer-344 male rats, cognitive function was assessed with the Morris water maze, reverse transcription and polymerase chain reaction were used to quantify APP mRNAs, and NGF and LNGFR levels were determined with an ELISA. Cognitive function declined progressively with age from 3 months to 18 months, and from 18 months to 29 months, but only RNA content in the tissue declined significantly from 3 months to 18 months. Between 18 month and 29 month rats were small but statistically significant decreases only for Kunitz protease inhibitor (KPI)-inclusive mRNAs and cortical NGF levels. There was a small but statistically significant correlation between cognitive function and %KPI (the amount of KPI APP mRNAs relative to the total amount of APP mRNA), with lower %KPI related to more impaired spatial learning. No other statistically significant correlation or linear relationship could be detected between cognitive function and any of the other neurological measures or any combination of these measures (i.e., hippocampal levels of APP 695 mRNA, cortical and hippocampal levels of NGF, and cortical, hippocampal, and basal forebrain levels of LNGFR).(ABSTRACT TRUNCATED AT 250 WORDS)

Reproductive performance following a second ectopic gestation.

OBJECTIVES: Our purpose was to determine the obstetric outcome following a second ectopic gestation in women actively trying to conceive, with a review of the literature. METHODS: Charts of 37 patients coded for having at least two ectopic pregnancies between 1986 and 1989 were reviewed. Duration of follow-up ranged from 7 months to 7 years with a mean follow-up time of 25 months. RESULTS: We report a 45.4% intrauterine pregnancy rate, 27.3% live birth rate, and 36.4% recurrent ectopic pregnancy rate. Review of the literature shows an intrauterine pregnancy rate of 26-50%, live birth rate of 25-31.2%, and recurrent ectopic pregnancy rate of 7.7-40%. CONCLUSIONS: Four of five studies report the risk of a third ectopic gestation is less than an intrauterine gestation. This may prove helpful in counseling patients with a history of recurrent ectopic gestation in choosing IVF or attempting conception naturally.

Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease, cholinergic basal forebrain neurons, which have receptors for nerve growth factor (NGF), degenerate, while NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are elevated in urine of patients with peripheral neuropathies and in animals with peripheral-nerve injury, but it has not been determined whether urine levels of NGF-Rt are altered by the presence and/or progression of dementia-related neuropathologic changes in patients with Alzheimer's disease. In this study, we developed an enzyme-linked immunosorbent assay to determine whether urine levels of NGF-Rt are altered in patients with Alzheimer's disease. DESIGN: Survey of urine NGF-Rt levels in neurologically normal (n = 19), mildly demented (n = 31), and moderately to severely demented (n = 31) patients. SETTING: Subjects were participants in the Rochester Alzheimer's Disease Project and mildly demented patients about to begin a clinical drug study. PATIENTS: All patients met established criteria for a clinical diagnosis of probable Alzheimer's disease. Aged, nondemented, neurologically normal controls were selected from the families of the demented subjects. RESULTS: Urine NGF-Rt levels were substantially elevated in mildly demented patients relative to those of nondemented controls. CONCLUSIONS: These results suggest that an enzyme-linked immunosorbent assay on urine samples may provide an antemortem measure of dementia-related neuropathologic changes, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demented patients.

Ventilatory work and oxygen consumption during exercise and hyperventilation.

The work of breathing (WB), and thus the energy requirement of the respiratory muscles, is increased any time minute ventilation (VE) is elevated, by either exercise or voluntary hyperventilation. Respiratory muscle O2 consumption (VRMO2) in humans has generally been estimated by having subjects breathe at a level comparable to that during exercise while the change in O2 consumption (VO2) is measured. The difference between VO2 at rest and during hyperventilation is attributed to the respiratory muscles and is assumed to be similar to VRMO2 during exercise at the same VE. However, it has been suggested that WB differs between exercise and hyperventilation and that WB during exercise is lower than during hyperventilation at the same VE. In this study we measured WB during exercise and hyperventilation and from these measurements estimated VRMO2. WB, VE, and VO2 were measured in five male subjects during rest and during exercise or hyperventilation at levels of VE ranging from 30 to 130 l/min. VE/WB relationship was determined for both hyperventilation and exercise. Multiple regression analysis showed that the shape of the two curves was different (P < 0.0001), with WB at high levels of VE being < or = 25% higher in hyperventilation than in exercise. In a second study in which frequency, tidal volume, and duty cycle were controlled as well as VE, there was no difference in WB between exercise and hyperventilation. VO2 was significantly correlated with WB, and the estimated VRMO2 did not increase as a fraction of total VO2 as exercise intensity rose.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary function changes following exercise.

Many studies have documented differing changes in forced vital capacity (FVC) following various intensities and durations of exercise. This investigation used three different intensities and durations of treadmill running, with subjects who were active runners, with the intent of finding an intensity or duration that might elicit changes in FVC and if these changes are related to respiratory muscle fatigue. Intensities and durations included a graded maximal test to exhaustion (7-14 min); a 7-min test at 90% of maximal VO2, and a 30-min test at 60% of maximal VO2 (intensity). Maximal inspiratory pressures (MIP), maximal expiratory pressures (MEP), forced expiratory volume in 1 s (FEV1.0) and FVC were measured pretest, and 5, 10, and 30 min post-test (time). MIP was not different across time or intensities. The decrease in MEP approached significance at 10-min post-exercise compared to pretest values (P = 0.0569), with no differences found between intensities. FVC was different between times (P = 0.0117) but not between intensities. FVC was decreased at 5 and 10 min post-test compared with pre and 30 min. FEV1.0 was significantly reduced at 5 and 10 min post-test compared with pretest. These data suggest that a combination of duration and intensity may be necessary to elicit pulmonary function changes after exercise and that expiratory muscle fatigue may be a factor that results in a reduced FVC.