Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

The Role of Wearable Sensors to Monitor Physical Activity and Sleep Patterns in Older Adult Inpatients: A Structured Review.

Low levels of physical activity (PA) and sleep disruption are commonly seen in older adult inpatients and are associated with poor health outcomes. Wearable sensors allow for objective continuous monitoring; however, there is no consensus as to how wearable sensors should be implemented. This review aimed to provide an overview of the use of wearable sensors in older adult inpatient populations, including models used, body placement and outcome measures. Five databases were searched; 89 articles met inclusion criteria. We found that studies used heterogenous methods, including a variety of sensor models, placement and outcome measures. Most studies reported the use of only one sensor, with either the wrist or thigh being the preferred location in PA studies and the wrist for sleep outcomes. The reported PA measures can be mostly characterised as the frequency and duration of PA (Volume) with fewer measures relating to intensity (rate of magnitude) and pattern of activity (distribution per day/week). Sleep and circadian rhythm measures were reported less frequently with a limited number of studies providing both physical activity and sleep/circadian rhythm outcomes concurrently. This review provides recommendations for future research in older adult inpatient populations. With protocols of best practice, wearable sensors could facilitate the monitoring of inpatient recovery and provide measures to inform participant stratification and establish common objective endpoints across clinical trials.

Evaluating the content and face validity of Arabic-translated Patient Measures of Safety survey PMOS-30.

BACKGROUND: The importance of patient perception of patient safety has been proven as an active role in promoting safety and predicting harm. Patients play a vital role in the healthcare sector and the impact of patient perception of patient safety has been repetitively proven in the literature to be for its effectiveness in predicting harm and promoting safety. Nonetheless, there is limited knowledge about the specific insights patients can provide concerning safety within Arab countries. Therefore, improving and strengthening active patient participation by including patients' perceptions of safety could offer novel contributions to the realm of patient safety. OBJECTIVE: This study aims to evaluate the validity of the Arabic version of the PMOS-30. METHOD: The forward-backward translation procedure was used to translate and validate the PMOS-30. Mix methods were used to assess the validity of the translated version. The expert raters evaluated the content validity and interviews were conducted with in-patients to assess the face validity. Test-retest approach was conducted to pilot the final Arabic version. RESULTS: Data of face validity from 13 participants for the first test and 5 participants for the re-test was collected and showed an improvement in the clarity rate (71.50% and 94.66% respectively). With respect to the content validity of the final version, the CVI was 0.92, indicating excellent relevant results. CONCLUSION: The final version of the revised was approved by the expert to be a valid tool to measure patient perceptions of patient safety in Arabic-speaking patients to be utilized on patient safety improvement initiatives.

Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining.

Effects of previous strength training can be long-lived, even after prolonged subsequent inactivity, and retraining is facilitated by a previous training episode. Traditionally, such "muscle memory" has been attributed to neural factors in the absence of any identified local memory mechanism in the muscle tissue. We have used in vivo imaging techniques to study live myonuclei belonging to distinct muscle fibers and observe that new myonuclei are added before any major increase in size during overload. The old and newly acquired nuclei are retained during severe atrophy caused by subsequent denervation lasting for a considerable period of the animal's lifespan. The myonuclei seem to be protected from the high apoptotic activity found in inactive muscle tissue. A hypertrophy episode leading to a lasting elevated number of myonuclei retarded disuse atrophy, and the nuclei could serve as a cell biological substrate for such memory. Because the ability to create myonuclei is impaired in the elderly, individuals may benefit from strength training at an early age, and because anabolic steroids facilitate more myonuclei, nuclear permanency may also have implications for exclusion periods after a doping offense.

Nanosponges - a completely new nano-horizon: pharmaceutical applications and recent advances.

In recent years, nanosponges (NS) have gained tremendous impetus in drug delivery through nanotechnology. Nanosponges are capable of providing solutions for several formulation related problems. Through this review, scientists working in the field of nanotechnology can have an insight into the techniques of preparation, characterization and applications of NS. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability. They can be crafted for targeting drugs to specific sites, prevent drug and protein degradation and prolong drug release in a controlled manner. This review attempts to elaborate different schemes of synthesis of NS and their characterization. Factors affecting drug loading and release have been enumerated. Due to their advantages, NS have not only been explored for their pharmaceutical applications but also have large popularity in allied sciences, especially in water purification.

Osteoid Osteoma of the Calcaneus in a Young Patient Treated With Radiofrequency Ablation: A Case Report.

Osteoid osteoma (OO) is a common benign tumor that tends to affect children and young adults. Patients typically present with nocturnal pain that is relieved with non-steroidal anti-inflammatory drugs (NSAIDs) and a unique round or oval radiolucent area with surrounding sclerotic bone on X-ray. The cortex of the diaphysis or metaphysis of long bones is the usual anatomical location, with only 4% of cases localizing to the foot and ankle. Treatment options include medical management, surgical excision, and less invasive techniques such as radiofrequency ablation (RFA). We present a case report of a 21-year-old female with an osteoid osteoma of the calcaneus, a rare presentation for this type of tumor. She was successfully treated with RFA and had an excellent functional outcome.

An Unusual Presentation of Candidal Onychomycosis: A Case Report.

Onychomycosis can present with various manifestations such as subungual hyperkeratosis, onycholysis, and nail plate destruction. Here we present a case of a 61-year-old African male with a known case of type 2 diabetes mellitus on insulin. He worked as a mechanic and presented with nail changes that started four months prior to presentation and worsened over time, mainly affecting the fingernails of bilateral hands. On examination, there was yellowish to greenish discoloration with very extensive hyperkeratosis of skin around the fingers and nails that caused avulsion of nails. Swab and culture showed Candida albicans +3. Nail and skin biopsy showed bacterial colony with fungal hypha. The patient showed marked improvement after receiving oral fluconazole 300 mg weekly for three months.

Immunohistochemical Expression of BRCA1 Protein, ER, PR and Her2/neu in Breast Cancer: A Clinicopathological Study.

Breast cancer is a heterogeneous hormone-dependent disease. Potential prognosis depends on the clinicopathological evaluation and assessment of other prognostic indicators. The detection of the oestrogen Receptor (ER), Progesterone Receptor (PR), Human epidermal growth factor receptor 2 (Her2/neu) and BRCA1 oncoprotein is pivotal for prognostic evaluation and to choose the appropriate post-surgical adjuvant therapy beside selecting the proper candidate for genetic counselling. OBJECTIVES: To detect the immunoexpression of the BRCA1 oncoprotein in mammary invasive ducal carcinoma and its association with the prognostic markers (ER, PR and Her2/neu hormonal receptors) and other clinicopathological parameters to improve the patients' treatment plans. METHODS: A cross-sectional study design including 83 paraffin blocks and histological slides collected from Al-Jumhoori Medical City Teaching Hospital Laboratory in Mosul and the Central Public Health Laboratory in Baghdad between the 1st of January 2010 to the 13th of March 2012 for patients diagnosed with primary invasive ductal breast carcinomas. Immunohistochemistry (IHC) using monoclonal antibodies against ER, PR, Her2/neu receptors and BRCA1 protein was performed via the fully automated immunostaining instrument 'Ventana Benchmark'. RESULTS: BRCA1 protein immunoexpression was detected in 20.5% of cases. It was significantly high with increasing tumour grade and stage. Although there was a trend of BRCA1 negativity toward negative ER, PR and Her2 receptors, no significant associations were observed with any of these parameters and the patients' age. CONCLUSION: Altered BRCA1 expression is significantly associated with advanced tumour grade and stage. High number of cases with negative BRCA1 expression showed negative ER, PR and Her2/neu expression.

The reactions of para-halo diaryl diselenides with halogens. A structural investigation of the CT compound (p-FC6H4)2Se2I2, and the first reported "RSeI3" compound, (p-ClC6H4)SeI·I2, which contains a covalent Se-I bond.

The reactions of the diaryl-diselenides (p-FC(6)H(4))(2)Se(2) and (p-ClC(6)H(4))(2)Se(2) with diiodine have been investigated. Species of stoichiometry "RSeI" are formed when the ratio employed is 1:1. The solid-state structure of "(p-FC(6)H(4))SeI" has been determined, and shown to be a charge-transfer (CT) adduct, (p-FC(6)H(4))(2)Se(2)I(2), where the Se-Se bond is retained and the diiodine molecule interacts with only one of the selenium atoms. The Se-I bond in (p-FC(6)H(4))(2)Se(2)I(2) is 2.9835(12) Å, which is typical for a (10-I-2) Se-I-I CT system. When diiodine is reacted in a 3:1 ratio with (p-XC(6)H(4))(2)Se(2) (X = F, Cl) species of stoichiometry "RSeI(3)" are formed. The structure of "(p-ClC(6)H(4))SeI(3)" reveals that this is not a selenium(IV) compound, but is better represented as a selenium(II) CT adduct, (p-ClC(6)H(4))SeI·I(2). The Se-I bond to the diiodine molecule is typical in magnitude for a CT adduct, Se-I: 2.8672(5) Å, whereas the other Se-I bond is much shorter, Se-I: 2.5590(6) Å, and is a genuine example of a rarely observed covalent Se-I bond, which appears to be stabilised by a weak Se···I interaction from a neighbouring iodine atom. The reaction of (p-ClC(6)H(4))SeI with Ph(3)P results in the formation of a CT adduct, Ph(3)PSe(p-ClC(6)H(4))I, which has a T-shaped geometry at selenium (10-Se-3). By contrast, the reaction of (p-FC(6)H(4))SeI with Ph(3)P does not form an adduct, but results in the formation of Ph(3)PI(2) and (p-FC(6)H(4))(2)Se(2).

Structural isomerism in (p-XC6H4)SeCl3 and (p-XC6H4)SeBr3 (X = F, Cl) compounds. Co-crystallisation of cis- and trans-dimeric forms of (p-ClC6H4)SeCl2(µ-Cl)2(p-ClC6H4)SeCl2. A new structural modification for the "PhSeBr" reagent, Ph2Se2Br2, containing an elongated Se-Se bond.

A series of di(para-halophenyl)diselenides, (p-XC(6)H(4))(2)Se(2) (X = F, Cl) have been reacted with three equivalents of SO(2)Cl(2) or Br(2), leading to the formation of selenium(iv) RSeX(3) compounds. The structures of (p-FC(6)H(4))SeX(3) (X = Cl, Br) have been determined, and both exhibit a dimeric RSeX(2)(µ-X)(2)RSeX(2) structure consisting of two "saw-horse" (p-FC(6)H(4))SeX(3) units linked by two halide bridges, with an overall square pyramidal geometry at selenium. In both structures all the selenium and halogen atoms are planar, with both aryl rings located on the same side of the Se(2)X(6) plane (cis-isomer). The structure of (p-ClC(6)H(4))SeCl(3) also adopts a planar dimeric structure, however both cis- and trans-dimeric molecules are co-crystallised in the unit cell. In contrast, the structure of (p-ClC(6)H(4))SeBr(3) adopts a folded cis-dimeric structure due to steric constraints. Secondary Se···X interactions to the "vacant" sixth coordination site at selenium are a feature of most of these structures, but are most prominent in the folded structure of (p-ClC(6)H(4))SeBr(3). A re-examination of the PhSeBr/PhSeBr(3) system resulted in the isolation of crystals of a second structural form of "PhSeBr". The structure of Ph(2)Se(2)Br(2) consists of two PhSeBr units linked by an elongated Se-Se bond of 2.832(4) Å, and longer secondary Se···Br interactions of 3.333(4) Å to form a chain structure. Further weak Se···Br and Br···Br interactions are present, which form loosely linked rippled sheets of selenium and bromine atoms, similar to the sheets observed for the tetrameric form, Ph(4)Se(4)Br(4).

Structural isomerism in tris-tolyl halo-phosphonium and halo-arsonium tri-halides, [(CH3C6H4)3EX][X3], (E = P, As; X = Br, I).

The group 15 ligands (o-CH(3)C(6)H(4))(3)P, (m-CH(3)C(6)H(4))(3)P, (p-CH(3)C(6)H(4))(3)P, Ph(3)As, (o-CH(3)C(6)H(4))(3)As and (p-CH(3)C(6)H(4))(3)As have been reacted with two equivalents of di-iodine or di-bromine to yield complexes of formula R(3)EX(4) (E = P, As; X = I, Br). These halogenated group 15 compounds are ionic, [R(3)EX][X(3)] consisting of halo-phosphonium or halo-arsonium cations and trihalide anions. These adducts exhibit structural isomerism and may exist either as simple 1:1 ion pairs, [R(3)EX][X(3)], isomer (A), which display a weak XX interaction between cation and anion, or as a 2:1 complex, which consists of a [{R(3)EX}(2)X(3)](+) cationic species made up of two [R(3)EX](+) cations interacting with one [X(3)](-) anion. The overall charge is balanced by a second [X(3)](-) anion. These 2:1 species also exhibit structural isomerism due to subtle differences in the connectivity of the [{R(3)EX}(2)X(3)](+) fragment, as the {R(3)EX}(+) units may either interact at the same end of the [X(3)](-) ion, to give a Y-shaped motif, isomer (B), or at opposite ends, giving a Z-shaped motif, isomer (C). The type of structural isomer formed is related to the way in which [Ar(3)EX](+) cations pack together via aryl embraces. Isomer (A) and (C) structures form chains of side-to-side, anti-parallel embracing cations. In (A) and (C) structures a square-like stacking motif of cations is observed. In contrast, isomer (B) structures feature side-to-side, parallel embracing cations, and do not exhibit the square motif.

Pituitary apoplexy after stimulation tests.

Pituitary apoplexy occurs after infarction of a non-neoplastic pituitary or sudden expansion of an adenoma following haemorrhage or infarction. It usually occurs spontaneously but can follow a number of causes including pituitary stimulation tests. Since this complication is potentially life-threatening, the benefits of subjecting patients who might have pituitary tumours to such tests should be considered.

A large transmural thoracic lipoma easily mistaken for pulmonary malignancy.

Lipomas in the thorax are very rare. Most such lesions are asymptomatic and discovered by accident on a chest radiograph. However, radiographic features are non-specific and can mimic malignancy. We describe the case of an 82-year-old woman whose history and chest radiograph suggest a malignant lung tumour. A computed tomography scan of the chest eventually determined the fatty nature of her chest lesion.

Coexpression after electroporation of plasmid mixtures into muscle in vivo.

AIM: Muscle is perhaps the most frequently considered tissue for non-viral gene therapy, in particular after gene transfer by electroporation. Expression in muscle is stable, but since the cell turnover is so slow incorporation in the host genome is not required. This raises interesting practical and theoretical questions related to the behaviour of the transgenic DNA under such conditions. METHODS: We have investigated expression of reporter genes from plasmid mixtures electroporated into the extensor digitorum longus (EDL) muscle in mice in order to assess the degree of coexpression. RESULTS: Under conditions where the reporter is easily identified the coexpression rate was 100%, as none of 287 fibres from five different muscles expressing blue fluorescent protein (BFP) failed to express green fluorescent protein (GFP). With other reporter combinations the rate was lower, but this we attribute to marginal sensitivity for fluorescent proteins, or from reporter protein degradation for beta-galactosidase. CONCLUSIONS: The high degree of coexpression suggests that a large copy number takes part in the final transcription with this system. The finding also enhances the usefulness of muscle and electroporation for gene therapy and experimental biology.