Chiroptical sensing of amino acids, amines, amino alcohols, alcohols and terpenes with π-extended acyclic cucurbiturils.

The efficiency and scope of two acyclic π-wall extended cucurbiturils, M2 and M3, exhibiting rapidly interconverting helical conformers for chiroptical sensing of amines, amino acids, alcohols, and terpenes at micromolar concentrations in water is evaluated. The formation of 1 : 1 host-guest complexes results in spontaneous induction of circular dichroism signals that can be used for accurate determination of the absolute configuration and enantiomeric composition of the analyte based on a simple mix-and-measure protocol.

Self Assembled Cages with Mechanically Interlocked Cucurbiturils.

We report preparation of (bis)aniline ligand 4 which contains a central viologen binding domain and its subcomponent self-assembly with aldehyde 5 and Fe(OTf)2 in CH3CN to yield tetrahedral assembly 6. Complexation of ligand 4 with CB[7] in the form of CB[7]•4•2PF6 allows the preparation of assembly 7 which contains an average of 1.95 (range 1-3) mechanically interlocked CB[7] units. Assemblies 6 and 7 are hydrolytically unstable in water due to their imine linkages. Redesign of our system with water stable 2,2'-bipyridine end groups was realized in the form of ligands 11 and 16 which also contain a central viologen binding domain. Self-assembly of 11 with Fe(NTf2)2 gave tetrahedral MOP 12 as evidenced by 1H NMR, DOSY, and mass spectrometric analysis. In contrast, isomeric ligand 16 underwent self-assembly with Fe(OTf)2 to give cubic assembly 17. Precomplexation of ligands 11 and 16 with CB[7] gave the acetonitrile soluble CB[7]•11•2PF6 and CB[7]•16•2PF6 complexes. Self-assembly of CB[7]•11•2PF6 with Fe(OTf)2 gave tetrahedron 13 which contains on average 1.8 mechanically interlocked CB[7] units as determined by 1H NMR, DOSY, and ESI-MS analysis. Self-assembly of CB[7]•16•2PF6 with Fe(OTf)2 gave cube 13 which contains 6.59 mechanically interlocked CB[7] units as determined by 1H NMR and DOSY measurements.

Conformationally Mobile Acyclic Cucurbit[n]uril-Type Receptors Derived from an S-shaped Methylene Bridged Glycoluril Pentamer.

We report the synthesis of the conformationally mobile S-shaped glycoluril pentamer building block 3a and two new acyclic CB[n]-type receptors P1 and P2. P1 (9 mM) and P2 (11 mM) have moderate aqueous solubility but their host•guest complexes are poorly soluble. Host P1 does not undergo intermolecular self-association whereas P2 does (Ks = 189±27 M-1). 1H NMR titrations show that P1 and P2 are poor hosts toward hydrophobic (di)cations 6 - 11 (P1: Ka = 375-1400 M-1; P2: Ka = 1950-19800 M-1) compared to Tet1 and Tet2 (Tet1: Ka = 3.09 × 106 to 4.69 × 108 M-1; Tet2: Ka = 4.59 × 108 to 1.30 × 1010 M-1). Molecular modelling shows that P1 and P2 exist as a mixture of three different conformers due to the two S-shaped methylene bridged glycoluril dimer subunits that each possess two different conformations. The lowest energy conformers of P1 and P2 do not feature a well-defined central cavity. In the presence of guests, P2 adapts its conformation to form 1:1 P2•guest complexes; the binding free energy pays the energetic price of conformer selection. This energetically unfavorable conformer selection results in significantly decreased Ka values of P1 and P2 compared to Tet1 and Tet2.

Sebaceous Carcinoma Treated With Mohs Micrographic Surgery.

BACKGROUND: Sebaceous carcinoma is a rare and potentially aggressive adnexal neoplasm with historic data indicating high rates of recurrence, metastasis, and cancer-specific mortality. OBJECTIVE: To evaluate the incidence of local recurrence, metastasis, disease-specific mortality, and all-cause mortality and to identify work-up approaches. PATIENTS AND METHODS/MATERIALS: Retrospective review of patients with sebaceous carcinoma treated with Mohs micrographic surgery between 2001 and 2013 at one institution. RESULTS: Thirty-seven patients had 45 sebaceous carcinomas located on the periocular region (13%), non-periocular face (47%), scalp (7%), neck (4%), trunk (9%), and extremities (20%). The mean age was 66.1 years, and 24 (65%) patients were male. Five patients had Muir-Torre syndrome (MTS) or Lynch syndrome. Seven of 12 tumors showed loss of expression of ≥1 mismatch repair gene. The most common work-up involved taking a detailed personal and family medical history. No local recurrences, metastases, or disease-specific deaths occurred during an average follow-up of 3.6 years. CONCLUSION: Mohs micrographic surgery is an effective treatment for sebaceous carcinoma. Detailed history taking, age-appropriate cancer screening, and immunohistochemical staining with MLH1, MSH2, or MSH6 is helpful in identifying which patients should be referred to a geneticist for work-up of MTS.

Sebaceous carcinoma: review of the literature.

BACKGROUND: Sebaceous carcinoma is an uncommon adnexal neoplasm with a documented capability for regional and distant metastasis. Traditionally, sebaceous carcinoma has been associated with high rates of recurrence after excision. OBJECTIVE: To review the current literature on sebaceous carcinoma and detail its epidemiology, pathogenesis, clinical presentation, histopathology, diagnostic workup, treatment, and prognosis. MATERIALS AND METHODS: Literature review using PubMed search for articles related to sebaceous carcinoma. RESULTS: Sebaceous carcinoma typically presents as a painless pink or yellow nodule. Diagnosis requires histopathologic examination, and immunohistochemical analysis often assists in the differentiation of sebaceous carcinoma from other benign and malignant skin neoplasms. Sebaceous carcinoma should prompt a workup for Muir-Torre syndrome. Periorbital sebaceous carcinoma has an increased tendency for regional metastasis, although cancer-specific mortality rates are similar among all anatomic locations. CONCLUSION: Surgery is the preferred treatment for local disease. Limited data suggest that Mohs micrographic surgery may provide superior clinical outcomes, but more research is needed regarding the long-term outcomes. Radiation and systemic chemotherapy are reserved for recurrent or metastatic disease.

Vulvar dermatitis from allergy to moist flushable wipes.

Methylchloroisothiazolinone/methylisothiazolinone is a preservative found in cosmetic and industrial products, and is a common ingredient in moist toilet paper. It is a well-known allergen and is capable of causing allergic contact dermatitis.We present the case of a 58-year-old white woman with a cutaneous vulvar eruption with associated discomfort and pruritus of 6 months in duration. She had been treated with antibiotic and antifungal agents without improvement of symptoms. Careful history taking revealed that the patient was using moist toilet paper. Patch testing confirmed an allergy to methylchloroisothiazolinone, a preservative in the moist toilet paper. After discontinuation of the product and treatment with potent topical steroids, the eruption completely cleared.With the growing use of moist toilet paper among adults, the risk of exposure and potential sensitization is increasing. Health care providers should be aware of the risks of moist toilet paper containing potential allergens because perianal and perineal dermatitis caused by these products may be unrecognized or misdiagnosed. After proper treatment, patients must be educated about alternatives and the importance of label reading.

Cutaneous metastasis from penile squamous cell carcinoma resembling carcinoma en cuirasse.

Penile squamous cell carcinoma is a rare malignancy seen more frequently in developing nations. Metastasis occurs in a predictable manner, with superficial lymph node involvement occurring first, followed by deep lymph node involvement, and then distant spread. Brain, lung, liver, and bone are the typical sites of distant metastasis. We present the unusual case of an 81-year-old man with penile squamous cell carcinoma requiring total penectomy who developed a confluent red to violaceous, indurated suprapubic plaque with satellite papules and bulky inguinal lymphadenopathy. The shield-like clinical presentation and infiltrating strands and cords on histology resembled carcinoma en cuirasse, a rare form of cutaneous metastasis frequently associated with breast cancer but not reported with penile squamous cell carcinoma.

Novel imaging techniques for tumor margin detection in basal cell carcinoma: a systematic scoping review of FDA and EMA-approved imaging modalities.

Mohs micrographic surgery (MMS) is the gold standard for removing basal cell carcinomas (BCCs) due to its ability to guarantee 100% margin evaluation through frozen section histopathology, offering the highest cure rate among current treatments. However, noninvasive imaging technologies have emerged as promising alternatives to clinical assessment for defining presurgical margins. This systematic scoping review examines the efficacy of these imaging modalities, focusing on those approved for clinical use by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A systematic search of EMBASE, Scopus, PubMed, and the Cochrane Public Library databases identified 11 relevant studies out of 2123 records, encompassing 644 lesions across five imaging techniques. The findings suggest that dermoscopy, high-frequency ultrasound (HFUS), optical coherence tomography (OCT), line-field optical coherence tomography (LC-OCT), and reflectance confocal microscopy (RCM) show potential in detecting BCC margins, which could enhance MMS by providing better preoperative planning, informing patients of expected defect size, aiding in reconstruction decisions, and reducing overall procedure costs. This review discusses the benefits and limitations of each technique, offering insights into how these innovations could influence the future of BCC management. Emerging imaging techniques could enhance MMS by improving BCC margin assessment and reducing costs. Their adoption will depend on price and ease of use.

Malignant tumors of the penis.

BACKGROUND: Although penile cancer is rare in developed countries, it occurs more frequently in other parts of the world and causes significant morbidity and mortality. OBJECTIVE: To review the current literature on the pathogenesis, risk factors, clinical presentation, staging, and treatment of premalignant and malignant tumors of the penis. MATERIALS AND METHODS: A literature review using PubMed was conducted searching for articles on penile malignancies. RESULTS: The majority of penile cancers are in situ or invasive squamous cell carcinomas, although other rare tumors of the penis occur, such as melanoma, basal cell carcinoma, extramammary Paget's disease, and soft tissue sarcomas. CONCLUSION: Physicians should be aware of the risk factors and clinical presentation of penile malignancies because early diagnosis is essential in effective management and cure. Accurate staging is imperative for risk stratification and treatment planning. Depending on the type of tumor, size of tumor, location, staging, and grading, treatment modalities vary and may include topical chemotherapy, surgical excision, Mohs micrographic surgery, laser excision or ablation, systemic chemotherapy, and radiotherapy.

Anthracene-Walled Acyclic CB[n] Receptors: in†vitro and in†vivo Binding Properties toward Drugs of Abuse.

We report studies of the interaction of six acyclic CB[n]-type receptors toward a panel of drugs of abuse by a combination of isothermal titration calorimetry and 1 H NMR spectroscopy. Anthracene walled acyclic CB[n] host (M3) displays highest binding affinity toward methamphetamine (Kd =15 nM) and fentanyl (Kd =4 nM). Host M3 is well tolerated by Hep G2 and HEK 293 cells up to 100 µM according to MTS metabolic and adenylate kinase release assays. An in vivo maximum tolerated dose study with Swiss Webster mice showed no adverse effects at the highest dose studied (44.7 mg kg-1 ). Host M3 is not mutagenic based on the Ames fluctuation test and does not inhibit the hERG ion channel. In vivo efficacy studies showed that pretreatment of mice with M3 significantly reduces the hyperlocomotion after treatment with methamphetamine, but M3 does not function similarly when administered 30 seconds after methamphetamine.

Ultraviolet imaging in dermatology.

Visual examination plays a central role in the diagnosis of skin diseases. Many dermatologists use magnification, or dermoscopy, to improve diagnostic certainty when assessing the skin under visible light. In addition to magnification, other technological advances have been made over the last century to improve our visual assessment of the skin. Examination of skin under ultraviolet (UV) radiation, with Wood's light, gained traction for its utility in assessing superficial cutaneous infections and pigmentary changes. During Wood's light examination, UV light is directed at the skin and fluorescence is detected by our eyes. The variable fluorescent characteristics of endogenous and exogenous cutaneous chromophores help us better diagnose skin disease. UV fluorescent photography is based on the same concept as the Wood's light, but also allows image analysis and documentation of the captured image. In addition to UV-induced fluorescence, the differential reflection and absorption of UV light captured in the UV spectral range can also provide a new contrast for diagnosing skin diseases during UV reflectance photography. This review discusses the most widely used UV imaging techniques and provides an overview of the role of UV imaging in dermatology.

Self-assembly of cucurbit[7]uril based triangular [4]molecular necklaces and their fluorescence properties.

Self-assembly of rigid-rod dipyridine ligand 1 with M(en)(NO3)2 (M = Pd, Pt) affords triangular (3, 5) and square (4, 6) supramolecular coordination complexes (SCCs). The binding affinity of 1 toward CB[n]-type containers results in the formation of triangular [4]molecular necklaces ([4]MNs, 7-10) by either one-pot or post complexation approaches as evidenced by 1H NMR, diffusion ordered spectroscopy, and ESI-MS.

Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation.

Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. We previously reported the discovery of 2 (NEU-617), a small molecule with activity against T. brucei bloodstream proliferation. Further optimization of 2 to improve the physicochemical properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants 9i and 9j, and the linker variant 18. Although these 3 compounds had reduced potency compared to 2, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered 9o with potent activity towards T. brucei, T. cruzi and L. major, while four others compounds (17, 18, 21, 26) showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics.

Noninvasive treatments for pediatric complex regional pain syndrome: a focused review.

This is a review of current literature of noninvasive treatments for pediatric complex regional pain syndrome (CRPS). There are a variety of noninvasive approaches to the treatment of pain, but few pediatric-focused studies have been published in regard to CRPS. In comparison with adult CRPS, there is a greater need for behavioral approaches in children to enable coping with difficult symptoms. Current gaps in knowledge include mechanisms triggering CRPS, pediatric-focused diagnostic criteria, validated tests that are diagnostically specific, definitive treatment protocols, age-based medication recommendations, and validation of specific noninvasive treatments in pediatric populations. Intensive multidisciplinary treatment is supported by high recovery rates and a family-centered approach that allows continuation of goals into the community environment.

Secondary cervical dystonia associated with structural lesions of the central nervous system.

We tested the hypothesis that structural lesions of the central nervous system (CNS) associated with cervical dystonia more commonly involve the cerebellum and its primary afferent pathways than basal ganglia structures. Cervical dystonia is the most common focal dystonia, the majority of cases are idiopathic, and only a small percentage of patients have a family history of dystonia or other movement disorders. Pathophysiological mechanisms operative in solely or predominantly appendicular dystonias such as writer's cramp and Oppenheim's dystonia, respectively, may not be directly applicable to axial dystonias. The localization of structural lesions of the CNS associated with secondary cervical dystonia may provide some insight into the neural structures potentially involved in primary cervical dystonia. The National Library of Medicine Gateway (from 1960) and a clinical database maintained by the senior author (from 1999) were searched for cases of secondary cervical dystonia associated with structural lesions of the CNS. Search terms included one or more of the following: dystonia, torticollis, cervical, secondary, and symptomatic. Lesion localization and type, patient age, patient gender, head position, occurrence of sensory tricks, and associated neurological findings were tabulated for each case. Structural lesions associated with cervical dystonia were most commonly localized to the brainstem and cerebellum. The remaining cases were equally divided between the cervical spinal cord and basal ganglia. Although inconsistent, head rotation tended to be contralateral to lesion localization. Additional neurological abnormalities were present in the majority of patients with secondary cervical dystonia. The relative paucity of basal ganglia pathology and concentration of lesions in the brainstem, cerebellum, and cervical spinal cord in patients with secondary cervical dystonia suggests that dysfunction of cerebellar afferent pathways may be important to the pathophysiology of primary cervical dystonia.