Orbital period change of Dimorphos due to the DART kinetic impact.

The Double Asteroid Redirection Test (DART) spacecraft successfully performed the first test of a kinetic impactor for asteroid deflection by impacting Dimorphos, the secondary of near-Earth binary asteroid (65803) Didymos, and changing the orbital period of Dimorphos. A change in orbital period of approximately 7 min was expected if the incident momentum from the DART spacecraft was directly transferred to the asteroid target in a perfectly inelastic collision1, but studies of the probable impact conditions and asteroid properties indicated that a considerable momentum enhancement (ß) was possible2,3. In the years before impact, we used lightcurve observations to accurately determine the pre-impact orbit parameters of Dimorphos with respect to Didymos4-6. Here we report the change in the orbital period of Dimorphos as a result of the DART kinetic impact to be -33.0 ± 1.0 (3σ) min. Using new Earth-based lightcurve and radar observations, two independent approaches determined identical values for the change in the orbital period. This large orbit period change suggests that ejecta contributed a substantial amount of momentum to the asteroid beyond what the DART spacecraft carried.

Linear trichilemmomas on the ankle of a 28-year-old female.

Trichilemmomas are benign cutaneous proliferations derived from the outer root sheath of the hair follicle. They most often occur on the head and neck region and show a female predominance. When multiple, they are associated with Cowden syndrome (CS), a rare disorder due to an autosomal dominant germline mutation in PTEN (phosphatase and tensin homolog on chromosome 10), a tumor suppressor gene. Trichilemmomas outside of the head and neck region are rare, and as such, the association with CS is not clear. A 28-year-old healthy female with no significant family history of cancer presented to her dermatologist with multiple erythematous papules on the left anterior ankle, starting at birth. A shave biopsy confirmed the diagnosis of trichilemmoma with focal desmoplastic features (or desmoplastic trichilemmoma). A PTEN immunohistochemical study showed patchy (but not complete) loss of staining of the lesional cells. After shave removal, the trichilemmomas recurred 1-2 months later.

Therapy for Alopecia Areata in Mice by Stimulating the Hair Cycle with Parathyroid Hormone Agonists Linked to a Collagen-Binding Domain.

UNLABELLED: Alopecia areata is a common disorder in which autoimmune destruction of hair follicles results in patchy hair loss. Currently there is no adequate therapy, although immune modulator therapies are currently in development. Parathyroid hormone (PTH) is a hair cycle stimulator which shows promise in treating various forms of alopecia, although its short half-life limits its clinical use. PTH-CBD is a PTH analog which binds collagen, prolonging retention in skin. We tested effects of PTH-CBD in C3H/HeJ-engrafted mice, the animal model for alopecia areata, on hair growth and found that a significant proportion of animals had reduced hair loss (PTH-CBD: 13/21, 62% vs. CONTROL: 3/10, 30%; P<0.01). Histological analysis showed no change in immune response, but there was increased number of anagen hair follicles and increased production of beta-catenin, a factor which initiates the anagen phase of the hair cycle. PTH-CBD thus shows promise as a therapy for alopecia areata, either alone or in conjunction with immune modulation therapy.

Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.

Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia.

Therapy for alopecia areata in mice using parathyroid hormone agonists and antagonists, linked to a collagen-binding domain.

Alopecia areata is a common form of hair loss in which autoimmune-mediated destruction of hair follicles causes patchy hair loss, for which there is no adequate therapy. Parathyroid hormone (PTH) induces the hair cycle and promotes hair growth. PTH-CBD is a fusion protein of PTH and a bacterial collagen-binding domain (CBD), leading to targeted delivery to and retention in the skin collagen. We tested the effects of a single dose of PTH-CBD (low or high dose) on an animal model for alopecia areata, the C3H/HeJ engrafted mouse. In all the treated animals, there was a rapid (1-4 days) increase in hair growth, with sustained effects observed over a 2-month period (7/10 total treated mice<40% hair loss based on gray scale analysis, vs. 2/5 in vehicle control animals). Histological examination revealed massive stimulation of anagen VI hair follicles in treated animals despite an ongoing immune response. PTH-CBD thus shows promise as a therapy for alopecia areata, likely in conjunction with a mild immune suppressant, such as hydrocortisone cream.

Cytologic features of microcystic adnexal carcinoma.

Microcystic adnexal carcinoma (MAC) is an uncommon skin neoplasm with a predilection location around the lips. It is characterized by cords and nests of neoplastic cells forming ductular or glandular structures that are embedded in dense collagenous stroma. An eighty-seven year old Caucasian female patient presented with a painless, slowly enlarging mass measuring 3.3 × 2.7 × 1.0 cm on the lower lip for approximately 6 months. The patient underwent 2 fine needle aspiration biopsies (FNAs). Smears made from both FNAs demonstrated similar features including low cellular smears, three dimensional cell clusters forming a glandular structure, round to oval cells with high N:C ratio, occasional cytoplasmic lumens, without distinct hyperchromasia, focal inconspicuous nucleoli, smooth regular nuclear membranes, abundant naked nuclei, occasional squamoid cells and focal acellular stromal fragments in the background. The cytologic differential diagnosis included skin adnexal carcinoma and low grade mucoepidermoid carcinoma arising in the minor salivary gland. The mass was subsequently excised. The diagnosis of microcystic adnexal carcinoma was made. We report cytologic features of MAC and also suggest that MAC can possibly be diagnosed by FNA with the appropriate clinical vignette and immunohistochemical profile..

Presynaptic G-protein-coupled receptors dynamically modify vesicle fusion, synaptic cleft glutamate concentrations, and motor behavior.

Understanding how neuromodulators regulate behavior requires investigating their effects on functional neural systems, but also their underlying cellular mechanisms. Utilizing extensively characterized lamprey motor circuits, and the unique access to reticulospinal presynaptic terminals in the intact spinal cord that initiate these behaviors, we investigated effects of presynaptic G-protein-coupled receptors on locomotion from the systems level, to the molecular control of vesicle fusion. 5-HT inhibits neurotransmitter release via a Gbetagamma interaction with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that promotes kiss-and-run vesicle fusion. In the lamprey spinal cord, we demonstrate that, although presynaptic 5-HT receptors inhibit evoked neurotransmitter release from reticulospinal command neurons, their activation does not abolish locomotion but rather modulates locomotor rhythms. Liberation of presynaptic Gbetagamma causes substantial inhibition of AMPA receptor-mediated synaptic responses but leaves NMDA receptor-mediated components of neurotransmission mostly intact. Because Gbetagamma binding to the SNARE complex is displaced by Ca(2+)-synaptotagmin binding, 5-HT-mediated inhibition displays Ca(2+) sensitivity. We show that, as Ca(2+) accumulates presynaptically during physiological bouts of activity, 5-HT/Gbetagamma-mediated presynaptic inhibition is relieved, leading to a frequency-dependent increase in synaptic concentrations of glutamate. This frequency-dependent phenomenon mirrors a shift in the vesicle fusion mode and a recovery of AMPA receptor-mediated EPSCs from inhibition without a modification of NMDA receptor EPSCs. We conclude that activation of presynaptic 5-HT G-protein-coupled receptors state-dependently alters vesicle fusion properties to shift the weight of NMDA versus AMPA receptor-mediated responses at excitatory synapses. We have therefore identified a novel mechanism in which modification of vesicle fusion modes may profoundly alter locomotor behavior.

Fine needle aspiration of urethral recurrence of urothelial carcinoma after radical cystectomy presenting as a perineal mass: a case report.

BACKGROUND: Recurrence of urothelial (transitional cell) carcinoma in the urethra after cystectomy for invasive urothelial carcinoma is relatively uncommon. It is also uncommon for the recurring urethral tumor to present as a painful perineal mass. Fine needle aspiration (FNA) can be used to evaluate such perineal lesions and confirm tumor recurrence. CASE: A 5-cm-diameter mass was found in the perineum of a 63-year-old man 1 year after radical cystoprostatectomy for invasive urothelial carcinoma of the urinary bladder. The mass was detected on pelvic computed tomographic scanning. FNA cytology showed numerous urothelial carcinoma cells of high grade displaying squamous cell differentiation mimicking the histopathologic findings of the primary tumor found on cystectomy. Diagnosis of recurrent urothelial carcinoma was rendered. The FNA in this case spared the patient an open biopsy. CONCLUSION: Mass lesions arising in the perineum of patients who underwent cystectomy for urothelial carcinoma should raise the suspicion of urothelial carcinoma recurrence. Evaluation of perineal masses for recurrence of urothelial carcinoma can be made on FNA without the need for open biopsy.

The Application of Molecular Diagnostics to Stained Cytology Smears.

Detection of mutational alterations is important for guiding treatment decisions of lung non-small-cell carcinomas and thyroid nodules with atypical cytologic findings. Inoperable lung tumors requiring further testing for staging and thyroid lesions often are diagnosed using only cytology material. Molecular diagnostic tests of these samples typically are performed on cell blocks; however, insufficient cellularity of cell blocks is a limitation for test performance. In addition, some of the fixatives used while preparing cell blocks often introduces artifacts for mutation detection. Here, we applied qClamp xenonucleic technology and quantitative RT-PCR to cells microdissected directly from stained cytology smears to detect common alterations including mutations and translocations in non-small-cell carcinomas and thyroid lesions. By using this approach, we achieved a 1% molecular alteration detection rate from as few as 50 cells. Ultrasensitive methods of molecular alteration detection similar to the one described here will be increasingly important for the evaluation of molecular alterations in clinical scenarios when only tissue samples that are small are available.

Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats.

Neuronal death due to ischemic stroke results in permanent deficits in sensory, language, and motor functions. The growth-restrictive environment of the adult central nervous system (CNS) is an obstacle to functional recovery after stroke and other CNS injuries. In this regard, Nogo-A is a potent neurite growth-inhibitory protein known to restrict neuronal plasticity in adults. Previously, we have found that treatment with monoclonal antibody (mAb) IN-1 to neutralize Nogo-A immediately after stroke enhanced motor cortico-efferent plasticity and recovery of skilled forelimb function in rats. However, immediate treatment for stroke is often not clinically feasible. Thus, the present study was undertaken to determine whether cortico-efferent plasticity and functional recovery would occur if treatment with mAb IN-1 was delayed 1 week after stroke. Adult rats were trained on a forelimb-reaching task, and the middle cerebral artery was occluded to induce focal cerebral ischemia to the forelimb sensorimotor cortex. After 1 week, animals received mAb IN-1 treatment, control antibody, or no treatment, and were tested for 9 more weeks. To assess cortico-efferent plasticity, the sensorimotor cortex opposite the stroke lesion was injected with an anterograde neuroanatomical tracer. Behavioral analysis demonstrated a recovery of skilled forelimb function, and anatomical studies revealed neuroplasticity at the level of the red nucleus in animals treated with mAb IN-1, thus demonstrating the efficacy of this treatment even if administered 1 week after stroke.

Femtosecond optical parametric oscillator based on periodically poled stoichiometric LiTaO3 crystal.

Efficient optical parametric oscillation is demonstrated in periodically poled stoichiometric lithium tantalate crystal pumped by a mode-locked Ti:sapphire laser. The optical parametric oscillator (OPO) delivers a maximum average power of more than 345 mW in signal and 180 mW in idler beams. The OPO is continuously tunable across the 940-1350 nm wavelength range in its signal branch, delivering nearly transform-limited 160-180 fs pulses. Despite the onset of high absorption loss in the crystal in the mid-IR, more than 40 mW of power is obtained for the idler beam tunable within the 4.3-4.6 microm wavelength range. The high parametric gain in the crystal allows tunable OPO operation at a repetition rate as high as 760 MHz with 50 mW of output power.