Mechanical Design Optimization of Prosthetic Hand's Fingers: Novel Solutions towards Weight Reduction.

From the mechanical function of grabbing objects to the emotional aspect of gesturing, the functionality of human hands is fundamental for both physical and social survival. Therefore, the loss of one or both hands represents a devastating issue, exacerbated by long rehabilitation times and psychological treatments. Prosthetic arms represent an effective solution to provide concrete functional and esthetical support.

Discovery and structure-activity relationships of a novel oxazolidinone class of bacterial type II topoisomerase inhibitors.

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile.

Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress.

Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may be involved in SAT dysfunction during obesity.

BCRP expression in schwannoma, plexiform neurofibroma and MPNST.

Background: peripheral nerve sheath tumors comprise a broad spectrum of neoplasms. Vestibular schwannomas and plexiform neurofibromas are symptomatic albeit benign, but a subset of the latter pre-malignant lesions will transform to malignant peripheral nerve sheath tumors (MPNST). Surgery and radiotherapy are the primary strategies to treat these tumors.

Total synthesis of (-)-blepharocalyxin D and analogues.

An efficient strategy for the total synthesis of (-)-blepharocalyxin D and an analogue is described. The key step involves an acid-mediated cascade process in which reaction of methyl 3,3-dimethoxypropanoate with γ,δ-unsaturated alcohols possessing diastereotopic styrenyl groups gives trans-fused bicyclic lactones with the creation of two rings and four stereocenters in one pot.

Bicyclic oxygen heterocycles from γ,δ-unsaturated alcohols: synthetic targets inspired by blepharocalyxin D.

trans-2,8-Dioxabicyclodecanes were prepared in high yield with the creation of up to three stereocenters in a single pot by the acid-mediated reaction of γ,δ-unsaturated alcohols with aldehydes (see scheme, Bn=benzyl). This versatile reaction enables the stereoselective introduction of substituents at the C3, C4, C7, and C9 positions of the bicyclic framework.

Use of ambulatory blood pressure monitoring to compare antihypertensive efficacy and safety of two angiotensin II receptor antagonists, losartan and valsartan. Losartan Trial Investigators.

The efficacy and safety of losartan and valsartan were evaluated in a multicenter, double-blind, randomized trial in patients with mild to moderate essential hypertension. Blood pressure responses to once-daily treatment with either losartan 50 mg (n = 93) or valsartan 80 mg (n = 94) for 6 weeks were assessed through measurements taken in the clinic and by 24-hour ambulatory blood pressure monitoring (ABPM). Both drugs significantly reduced clinic sitting systolic (SiSBP) and diastolic blood pressure (SiDBP) at 2, 4, and 6 weeks.

Angiotensin II antagonists for hypertension: are there differences in efficacy?

We compared the antihypertensive efficacy of available drugs in the new angiotensin-II-antagonist (AIIA) class. The antihypertensive efficacy of losartan, valsartan, irbesartan, and candesartan was evaluated from randomized controlled trials (RCT) by performing a metaanalysis of 43 published RCT. These trials involved AIIA compared with placebo, other antihypertensive classes, and direct comparisons between AIIA.

Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer.

Purpose: In the tumor-node-metastasis (TNM) staging system, no recommendations are provided on what lymph node retrieval technique is to be used to determine lymph node status, which leads to variability in nodal status assessment and TNM staging.

Patient And Methods: Lymph node retrieval was quantitated using data from 237 curatively resected gastric cancer patients, from a prospective, randomized trial that compared the Western resection with limited (D1) and the Japanese resection with extended lymphadenectomy (D2), and compared data from the literature. Moreover, the efficacy of different lymph node retrieval techniques was determined.

Lymph node staging standards in gastric cancer.

Purpose: In tumor-node-metastasis (TNM) staging, no recommendations are provided on the number of lymph nodes to examine per N level. We investigated the relationship between number of nodes examined and probability of detecting metastases, and ultimately staging accuracy.

Patients And Methods: Data from 473 curatively resected gastric cancer patients, from a randomized trial that compared the Western resection with limited and the Japanese resection with extended lymphadenectomy, were used.

Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries.

Purpose: Possible causes underlying the substantial differences in gastric cancer survival rates observed between Japan and the West were examined in a randomized trial comparing the Western R1 resection with limited lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy.

Patients And Methods: The effect of four factors associated with lymphadenectomy on microscopic tumor-node-metastasis (TNM) staging, and on stage-specific survival rates was assessed in 473 curatively resected patients.

Results: After application of extended lymphadenectomy, additional information on N status was available, only in R2 resections with up-staging to N2 status in 30% of patients.

Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer.

Purpose: In the context of a prospective, randomized trial of gastric cancer treatment, comparing Western surgical resection with limited lymphadenectomy (R1) versus Japanese surgical resection with extended lymphadenectomy (R2), we analyzed adherence to the specified surgical-pathologic guidelines.

Patients And Methods: Following evaluation of 389 patients, we quantified noncompliance (ie, performance of less dissection than specified) and contamination (ie, performance of more extensive dissection than specified). Of 389 patients, pathologic data permitted identification of 237 eligible patients treated with curative intent.

Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials.

Purpose: An overview is presented of reports published since 1980, in which postoperative adjuvant chemotherapy is compared with surgery alone for patients with gastric cancer. A MEDLINE literature review yielded 123 reports, 14 of which were relevant randomized trials; data from 11 of these trials were (or became) available for analysis of crude mortality odds. These 11 trials included 2,096 patients.

Anomalous optic discs in a patient with a Dandy-Walker cyst.

A 19-month-old female infant with a Dandy-Walker cyst had anomalous optic discs, each of which appeared to divide to form an accessory optic nerve. The discs probably lie within the spectrum of anomalous discs including optic nerve aplasia and hypoplasia, megallopapillae, morning glory disc, optic disc dysplasia, and optic nerve colobomas. The association of anomalous optic discs with a Dandy-Walker cyst has not been previously recognized.

The ultrastructure of isolated glial (Müller) cells from the turtle retina.

Sarthy and Lam (1978) described a method for isolation of glial (Müller) cells from turtle retina which involves papain treatment, mechanical dissociation of the retinae, and subsequent separation of the dispersed cells by velocity sedimentation at unit gravity. In order to establish the cytologic integrity and the extent of contamination, we have carried out ultrastructural studies on the isolated cells using scanning and transmission electron microscopy. During the course of these studies we have also examined the effect of papain on the morphology of the retina.

Fucosylated protein of retinal cone photoreceptor outer segments: morphological and biochemical analyses.

Cone outer segments (OS) of the goldfish retina are diffusely labeled after intravitreal injection of [(3)H]fucose while rod OS remain unlabeled. By electron microscopic radioautography, the OS of red- and blue-sensitive cones are heavily labeled while green- sensitive cone OS are lightly labeled. The time-course and pattern of OS labeling in all cone types from 30 min to 24 h resemble that of incorporation of other sugars into rhodopsin in rod OS.

Alveolar soft-part sarcoma of the orbit.

An 11-month-old white female with a three-month history of swelling of soft tissue around the right eye presented with a proptotic globe and marked limitation of motility. A CT scan showed a soft-tissue mass in the orbit, which was biopsied and examined by light and electron microscopy. The specimen consisted of large polygonal and cuboidal cells of uniform appearance arranged in pseudo-alveoli around capillaries.

Multifocal choroidal melanoma in ocular melanocytosis.

A 29-year-old white women had ocular melanocytosis with scleral pigmentation and a diffuse choroidal nevus. The eye was enucleated because of two choroidal tumors. Light and electron microscopy showed two separate choroidal melanomas with differential cytologic characteristics.

Feulgen-positive deposits in retinoblastoma. Incidence, composition, and ultrastructure.

The incidence of hematoxyphilic extracellular deposits in 159 cases of retinoblastoma was found to be 18%. Six other features of these tumors also were examined. In the majority of eyes with these deposits, the tumors were composed solely of anaplastic cells.

Preparation and retrograde axonal transport of an antiviral drug/horseradish peroxidase conjugate.

Recurrent Herpes simplex virus infections of the cornea are currently treated with antiviral drugs administered locally during periods of active infection. We have examined the feasibility of an alternate approach to treating recurrent infection, that of delivering an antiviral drug by axonal transport to cell somata in the trigeminal ganglion where the latent virus is thought to reside. We have coupled an antiviral drug to horseradish peroxidase (HRP), a protein which is readily transported retrogradely in corneal sensory axons to ganglion cell somata in the trigeminal ganglion.

Fine structure and radioautography of retinal cone outer segments in goldfish and carp.

Cone but not rod outer segments (OSs) in the retinas of goldfish and carp are diffusely labeled after intravitreal injection of 3H-fucose. Among the different cone types, the OSs are heavily labeled in the long double, short single, and some long single cones. The OSs of short double and the remaining long single cones are consistently more lightly labeled.

Endocytosis and compartmentation of peroxidases and cationized ferritin in neuroblastoma cells.

To investigate further the selectivity of retrograde axonal transport of horseradish peroxidase (HRP) isoenzymes previously observed in the rat central visual pathways, cultured mouse neuroblastoma cells (clone N18) were examined for selectivity of endocytosis of peroxidases and cationized ferritin in vitro. Differentiating N18 cells were incubated with proteins in various timing and pulse-chase experiments, and examined for the ultrastructural localization of endocytosed protein using cytochemical techniques. Semi-quantitative morphometry was performed on some of the samples.

Ultrastructural and histochemical studies of conjunctival concretions.

Ultrastructural and histochemical studies were performed on conjunctival concretions (yellow spots in the tarsal conjunctiva) from two patients who had associated atopic keratoconjunctivitis and posttrachomatous degeneration. By electron microscopy, these concretions were composed of finely granular material and membranous debris accumulating in the conjunctival subepithelium. Histochemically, concretions stained strongly positive for phospholipid and elastin, weakly positive for neutral polysaccharides and lipid, and were negative for amyloid, collagen, glycogen, iron, mucopolysaccharides, RNA, and DNA.