Analysis of Cephalometric Differences of the Midface and Upper Face in Males and Females: A Radiographic Study.

Gender affirmation facial surgery (GAFS) is an important component in treating gender dysphoria among transgender individuals by addressing gender incongruence of the face. There is a paucity of literature describing objective characterizations of the anatomic differences between male and female faces. In this study, cephalometric measurements were taken on routine CT imaging performed on cisgender patients between 2017 and 2020. Specifically defined cephalometric landmarks of the upper and midface were measured and compared between male and female cohorts. Thirty-eight patients, 19 male and 19 female, were identified for this study. Significant differences were identified in the frontal prominence, orbital size, malar height, bizygomatic width, nose, and upper lip, with moderate rates of specificity for each gender. Some important ratios are also presented. Differences in the malar region and the orbit highlight the importance of these areas as a point of focus for GAFS. These cephalometric findings provide objective evidence and parameters for perceived anatomic differences in male and female faces. In addition, they help both corroborate current surgical techniques as well as guide future approaches to GAFS.

Feminization Rhinoplasty.

This article provides a brief cross-cultural history of transgender, nonbinary, and other diverse gender identities, before exploring the background of gender-affirming care and facial feminization surgery in the United States. A variety of techniques for feminization rhinoplasty are discussed in detail. The authors provide insight into assessment and counseling of this unique patient population, timing of surgery, functional nasal considerations, and performing rhinoplasty in the context of other facial feminization procedures. Finally, complications of feminization rhinoplasty are identified and methods to prevent and treat such complications are enumerated.

Activation of E-prostanoid4 and E-prostanoid2 receptors inhibits TNF-alpha release from human alveolar macrophages.

Prostaglandin (PG)E(2) has been shown to inhibit mediator release from human alveolar macrophages (AMs), but the prostanoid receptor(s) mediating this response have not yet been documented. To investigate this, the present authors conducted a range of pharmacological and expression-based studies in monocyte-derived macrophages (MDMs) and AMs. MDMs were obtained by in vitro differentiation of monocytes from the peripheral blood of healthy human volunteers. Human AMs were obtained by perfusion of lung tissue from carcinoma resection patients. In MDMs, PGE(2) potently inhibited lipopolysaccharide-induced tumour necrosis factor (TNF)-alpha release (p[A](50) 8.51+/-0.11, maximum inhibition 95.9+/-4.8%). In human AMs, PGE(2) also inhibited TNF-alpha release but the observed concentration-effect curve was very flat and inhibition was incomplete. The shape of the PGE(2) curve in AMs suggested that its effects were mediated by activation of a heterogeneous receptor population. Expression studies combined with the use of various E-prostanoid (EP) receptor agonists and a selective EP(4)-receptor antagonist (Ono-AE2-227) confirmed that the inhibitory effects of PGE(2) in both AMs and MDMs were mediated by activation of EP(4) and EP(2) receptors. These data indicate that both E-prostanoid(4) and E-prostanoid(2) selective agonists may have anti-inflammatory properties in lung diseases where macrophages play a role.

Protection from extinction in human fear conditioning.

Two experiments examined the ability of an added stimulus to interfere with extinction of a target excitatory fear stimulus (a predictor of shock) in human autonomic conditioning. Both experiments demonstrated disruption of extinction when the added stimulus was inhibitory (a predictor of no shock, or safety signal). Subjects showed a return of fear when the target stimulus was tested alone, on both self-reported shock expectancy and skin conductance measures. The second experiment also demonstrated disruption of extinction when the added stimulus was excitatory. This results suggests that protection from extinction may occur even when the added stimulus is not inhibitory. Additional factors that may contribute to protection from extinction include context-specificity, occasion-setting and external inhibition. The results highlight the role that concurrent stimuli play in extinction, and emphasise the need to keep concurrent stimuli as similar as possible to the desired transfer context in practical applications of extinction such as exposure therapy for anxiety.

Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex during motor tasks.

We investigated the basal ganglia, motor cortex area 4, and supplementary motor area (SMA) using functional magnetic resonance imaging (fMRI) and five motor tasks: switching between finger and toe movements, writing, finger tapping, pronation/supination, and saccadic eye movements. We found reliable activation in the caudate nucleus and putamen in single subjects without the need for inter-subject averaging. Percent signal changes in basal ganglia were smaller by a factor of three than those in SMA or motor cortex (1% vs. 2.5-3%). There was a definite foot-dorsal, hand-ventral basal ganglia somatotopy, similar to prior data from primates. Saccadic eye movements activated the caudate nucleus significantly more than the other tasks did. Unilateral movements produced bilateral activation in the striatum even when motor cortex activation was unilateral. Surprisingly, bilateral performance of the tasks led, on average, to consistently smaller basal ganglia activation than did unilateral performance (P<0.001), suggesting less inhibition of contralateral movements during bilateral tasks. Moreover, there was a striking dominance pattern in basal ganglia motor activation: the left basal ganglia were more active than the right for right handers, regardless of the hand used. This lateralization appears much stronger than that previously reported for motor cortex. Comparisons of inter-subject and intra-subject reproducibility indicated a much larger variability in basal ganglia and SMA compared to motor cortex, in spite of similar percent signal changes in the latter two structures.

The aza-

The inclusion of a C-2 trialkylsilyl substituent into allylic amine precursors allows the base-induced aza-[2,3]-Wittig sigmatropic rearrangement to proceed in excellent yield and diastereoselectivity. The rearrangement precursors require a carbonyl-based nitrogen protecting group that must be stable to the excess of strong base required for the reaction. The N-Boc and N-benzoyl group are very good at stabilizing the product anion and initiating deprotonation. The migrating groups (G) need to stabilize the intial anion by resonance and require G-CH(3)() pK(a) > 22 in order for the initial anion to be reactive enough for rearrangement. Products 7, 20b-d,f,g, and 23 are formed with high (10-20:1) anti diastereoselectivity. Product 23 containing the morpholine amide group is useful for preparing other carbonyl derivatives.

Motor and somatosensory corticostriatal projection magnifications in the squirrel monkey.

1. Motor and somatosensory cortex project massively to the primate striatal matrix, terminating in distributed sets of overlapping projection zones (matrisomes) within the putamen. To study this system quantitatively, we have developed a computer-assisted estimation of the changes in magnification that occur as motor and somatosensory cortical body representations are projected onto the putamen. 2. Cortical and striatal body maps were assessed in squirrel monkeys by injecting anterograde tract tracers into electrophysiologically identified body-part representations in cortical areas 4, 3a, 3b, and 1. Relative projection magnification was defined as the ratio of the cortical injection site volume to the striatal projection site volume. 3. Magnification comparisons indicate that the tracers wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and 35S-methionine have similar sensitivities. 4. The relative proportions of body-part representations in the striatal maps were not significantly different from those in cortical maps. Both had large representations of hand, foot, and mouth, and smaller representations of trunk. 5. The relative magnification of the motor cortex projection to the striatum was roughly twice as large as those of projections from individual somatosensory areas. 6. These findings suggest that, in the sensorimotor striatum, motor and somatosensory inputs may undergo different proportions of local processing at the borders of their distribution zones (striosomes and matrisomes).

The basal ganglia and adaptive motor control.

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Input-output organization of the sensorimotor striatum in the squirrel monkey.

The basal ganglia receive massive inputs from the neocortex and send outputs that exert both inhibitory and disinhibitory control over parts of the frontal cortex and brainstem. Between these basal ganglia inputs and outputs lies the striatum, which receives most of the cortical afferents and projects to the basal ganglia output nuclei--the globus pallidus and substantia nigra. To analyze this system we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the striatum and striatal outputs to the globus pallidus. Anterograde tracers were injected into the motor (MI) and somatosensory (SI) cortical body maps, at sites determined by electrophysiological stimulation and recording. Retrograde tracers were stereotaxically injected into the external and internal pallidal segments (GPe and GPi). We found that multiple dispersed modules ("matrisomes") in the putamen that all received inputs from single body-part representations in sensorimotor cortex could, in turn, send convergent outputs to single sites in the pallidum. This divergence-reconvergence pattern was found for both GPe and GPi sites, and for inputs from both SI and MI cortex. Thus, information from a single functional region in the cortex can be split up at the striatal stage only to be brought back together in the pallidum. The temporary divergence may increase lateral interactions between sensorimotor matrisomes, as well as between matrisomes and striosomes. One function of striatal modularity may thus be to set up an associative network in the striatum, which might contribute to sensorimotor learning. We also found that some sets of matrisomes did not receive strong sensorimotor inputs, even though they projected to regions of GPe and GPi that are near the sensorimotor-recipient zones described above. Thus, the matrisomal system may sort MI/SI inputs and other inputs before transfer to paired regions of GPe and GPi.

Prolonged contact with blood alters surgical gown permeability.

INTRODUCTION: Surgical gowns are designed to prevent or minimize transmission of blood and pathogens between patients and hospital personnel. During prolonged procedures, a gown will probably be presented with repeated challenges of blood and other liquids. These multiple insults may alter the fabric's permeability to subsequent blood contact. METHODS: In this study, a pressing-leaning simulator was used to quantify changes in fabric permeability to blood after surgical gowns were prewetted with anticoagulated or coagulating blood. RESULTS: Of the five commercially available gowns tested, contact with blood for 1 hr before application of an external pressure increased permeability for two gowns, decreased permeability for two gowns, and did not alter the permeability of one gown (as compared with test conditions in which the fabrics were not prewetted with blood). These data indicate that at least in some cases prolonged contact with blood increases the amount of blood penetration on application of an external pressure, such as may occur during a pressing or leaning motion. CONCLUSION: Because increased fabric permeability results in an increased risk of skin contact with liquid-borne pathogens for gown users, a major criterion in the design and selection of a gown should be its ability to resist blood penetration for prolonged periods.

Output architecture of the primate putamen.

The basal ganglia act through direct and indirect striatopallidal output pathways that have different effects on cortical activity. This division has been proposed to underlie the fundamental distinction between hyperkinetic and hypokinetic movement disorders such as Parkinson's disease and Huntington's disease. Evidence to date does not favor a relationship between this dual organization and the division of the striatum into striosome and matrix compartments. However, the possibility has been raised that the division of striatopallidal output paths reflects a compartmentalization of the matrix itself into clusters of different striatopallidal projection neurons. We directly tested this hypothesis in squirrel monkeys by comparing the distributions of striatal output neurons retrogradely labeled from the two pallidal segments. Striatopallidal neurons labeled by small injections confined to either the external pallidum (GPe) or the internal pallidum (GPi) formed small clusters ("matrisomes") in the matrix compartment of the putamen. However, contrary to previous predictions, labeled matrisomes projecting to GPe were not systematically separated from those projecting to GPi. They could overlap extensively, and within individual matrisomes GPe-projecting neurons and GPi-projecting neurons were extensively intermixed. Double-retrograde labeling analysis in single sections demonstrated that only 2.1 +/- 2.7% of labeled striatal neurons were doubly labeled from both GPe and GPi--a number not significantly different from zero. GPe-projecting and GPi-projecting neurons in the putamen also differed sharply in their expression of enkephalin-like immunoreactivity: 71.3 +/- 7.6% of the neurons labeled by GPe injections were enkephalin positive, in contrast to 10.0 +/- 3.6% of the neurons labeled by GPi injections. These results suggest that in the primate, populations of striatopallidal output neurons are grouped in clusters in the matrix, but that individual neurons in any given cluster project either to GPe or to GPi. Matrisomal clustering may thus coordinate signals sent into the direct and indirect pathways of the basal ganglia from distributed populations of projection neurons in the striatum.

Two input systems for body representations in the primate striatal matrix: experimental evidence in the squirrel monkey.

The striatum is important in basal ganglia motor control and movement disorders. In this study we demonstrate the existence of two distinct sensorimotor cortical input systems to the striatum of the squirrel monkey. The first is a group of discrete zones in the extrastriosomal matrix of the putamen ("matrisomes") that receive somatotopically organized projections from both the body map in ipsilateral primary motor cortex (MI) and maps in ipsilateral primary somatosensory cortex (SI). The second system is a group of matrisomes in largely different locations that receive somatotopically organized inputs from contralateral MI but not SI. Intracortical microstimulation and multiunit recording were used to guide deposits of multiple anterograde tracers in MI and SI. Striosome/matrix architecture was demonstrated by enkephalin immunohistochemistry. We found that inputs from regions of ipsilateral MI and SI that represented the same body parts sent projections to the same matrisomes of the ipsilateral putamen. Contralateral MI sent its strongest inputs to matrisomes that tended to interdigitate with those receiving inputs from ipsilateral SI and MI, except the contralateral MI face region, which sent projections that overlapped those from the ipsilateral MI face region. MI regions representing axial body parts (trunk and face) sent stronger representations to the contralateral putamen than did those representing distal parts (hand and foot). SI sent no contralateral projection. Thus, with the exception of the face representation, inputs from contralateral and ipsilateral body representations may alternate in the primate striatal matrix, an arrangement reminiscent of the alternating ocular dominance columns in visual cortex. Ipsilateral SI and MI and contralateral MI all innervated matrisomes intermingled with striosomes and with matrisomes not receiving sensorimotor cortical input. The patchiness of these maps is thus unlike the smoother somatotopic maps of sensorimotor cortex, and is also unlike the fractured somatotopy reported for the cerebellum.

Blood pressure effects of tranylcypromine when prescribed singly and in combination with amitriptyline.

Data on blood pressure was extracted from the findings of a 6-week double-blind study that was carried out to evaluate the efficacy and safety of prescribing tranylcypromine (TCP) singly and in combination with amitriptyline (AMI). The effect of TCP on blood pressure was one of the methods used to evaluate its safety. Target daily doses of medication for the final 2 weeks of the study were: TCP 30 mg, AMI 150 mg, or the two in combination. Because of side effects, mean daily doses actually achieved were lower: single TCP 18.5 mg; single AMI 114.3 mg; combined TCP/AMI: TCP 19.7 mg, AMI 108.7 mg. When TCP alone was prescribed, a significant fall in diastolic blood pressure in the standing position was noted and orthostatic hypotension was more frequently observed. Dizziness was complained of on at least one occasion in over three quarters of patients on TCP/AMI. No correlation between blood pressure effects and dizziness was detected and there were no other troublesome side effects from this antidepressant combination. The study concluded that although TCP's overall effect on mean blood pressure readings when prescribed alone or in combination was small, its orthostatic effect is noteworthy and should be borne in mind by the prescribing clinician.

Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations.

1. The basal ganglia of primates receive somatosensory input carried largely by corticostriatal fibers. To determine whether map-transformations occur in this corticostriatal system, we investigated how electrophysiologically defined regions of the primary somatosensory cortex (SI) project to the striatum in the squirrel monkey (Saimiri sciureus). Receptive fields in the hand, mouth, and foot representations of cortical areas 3a, 3b, and 1 were mapped by multiunit recording; and small volumes of distinguishable anterograde tracers were injected into different body-part representations in single SI areas. 2. Analysis of labeled projections established that at least four types of systematic remapping occur in the primate corticostriatal system. 1) An area of cortex representing a single body part sends fibers that diverge to innervate multiple regions in the putamen, forming branching, patchy fields that are densest in the lateral putamen. The fields do not form elongated cylindrical forms; rather, they are nearly as extended mediolaterally as they are rostrocaudally. 2) Cortical regions representing hand, mouth, and foot send globally somatotopic, nonoverlapping projections to the putamen, but regions with closely related representations (such as those of the thumb and 5th finger in area 3b) send convergent, overlapping corticostriatal projections. The overlap is fairly precise in the caudal putamen, but in the rostral putamen the densest zones of the projections do not overlap. 3) Regions representing homologous body parts in different SI cortical areas send projections that converge in the putamen. This was true of paired projections from areas 3a and 3b, and from areas 3b and 1. Thus corticostriatal inputs representing distinct somatosensory submodalities can project to the same local regions within the striatum. Convergence is not always complete, however: in the rostral putamen of two cases comparing projections from areas 3a and 1, the densest zones of the projections did not overlap. 4) All projections from SI avoid striosomes and innervate discrete zones within the matrix. 3. These experiments demonstrate that the somatosensory representations of the body are reorganized as they are projected from SI to the somatosensory sector of the primate putamen. This remapping suggests that the striatal representation of the body may be functionally distinct from that of each area of SI. The patchy projections may provide a basis for redistribution of somatosensory information to discrete output systems in the basal ganglia. Transformations in the corticostriatal system could thus be designed for modulating different movement-related programs.

Effect of thiol manipulation on chemopotentiation by nitroimidazoles.

Highly electron affinic compounds such as the nitroimidazole misonidazole (MISO) have been shown both in vitro and in vivo to be effective potentiators of certain conventional chemotherapeutic agents. Mechanistically, the observation that nitroheterocyclics reduce intra-cellular thiols by enhancing the oxidation of glutathione (GSH), has suggested that thiol depletion by MISO may be a key factor in this enhancement. The present investigations were undertaken to determine whether the use of buthionine sulfoximine (BSO) to affect GSH metabolism may lead to more effective potentiation of chemotherapeutic agents by sensitizers. KHT/iv cells were treated in exponential phase under hypoxic conditions with variable doses of the activated form of cyclophosphamide (4-hydroxy-cyclo-phosphamide, 4OH-CY) administered concomitantly with or without MISO (2.5 mM) for an exposure time of 4 hr. Inclusion of the sensitizer in the treatment protocol resulted in a dose modifying factor of approximately 2.4. Exposing cells to 1.0 mM BSO for 2 hr prior to treatment reduced intracellular GSH levels to 70-80% of control and increased the efficacy of 40H-CY approximately 1.2-fold. If BSO was administered prior to the 4OH-CY + MISO combination, severe tumor cell toxicity resulted. For example, when combined with 4OH-CY, similar cell kill could be achieved with 5 to 6-fold lower MISO doses in the presence of BSO as in the absence of BSO. Ultrastructural evaluations revealed that in the three agent combination, membrane damage, as reflected by the formation of surface blebs, may play a key role in the mechanism of the observed enhanced cytotoxicity.

Day hospital as an alternative to inpatient care for cancer patients: a random assignment trial.

A stratified, random-assignment trial of 442 cancer patients was conducted to evaluate medical, psychosocial, and financial outcomes of day hospital treatment as an alternative to inpatient care for certain cancer patients. Eligible patients required: a 4- to 8-hour treatment plan, including chemotherapy and other long-term intravenous (i.v.) treatment; a stable cardiovascular status; mental competence; no skilled overnight nursing; and a helper to assist with home care. Patients were ineligible if standard outpatient treatment was possible. No statistically significant (p less than 0.05) differences were found between the Adult Day Hospital (ADH) and Inpatient care in medical or psychosocial outcomes over the 60-day study period. The major difference was in medical costs--approximately one-third lower for ADH patients (p less than 0.001) than for the Inpatient group. The study demonstrates that day hospital care of medical oncology patients is clinically equivalent to Inpatient care, causes no negative psychosocial effects, and costs less than Inpatient care. Findings support the trend toward dehospitalization of medical treatment.

Postweaning social experience and adult aggression in rats.

One group of male rats was reared continuously in small, stable colonies of three animals each during a ten-week period beginning when they were 46 days old. A second group of animals was also reared in small groups of three animals each but membership within these colonies was randomly changed at weekly intervals. Thereafter, all subjects were housed in individual cages. A 24 hr test of the subjects' aggression toward an unfamiliar male conspecific at 130-133 days of age indicated that only the heaviest animal in each of the stable colonies was aggressive. In contrast, all animals in the random-composition group were aggressive toward intruders. Scores on a second test of intruder-directed aggression administered when the subjects were nine months old were significantly related to scores on the first aggression test. Subtle variations in social experience during development are critical in establishing long-term patterns of aggression toward conspecifics in laboratory rats.