Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States.

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA's Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted.

Herb formula enhances treatment of impotent patients after penile venous stripping: a randomised clinical trials.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P < 0.001). It appears that the combination of oral herbs and PVS treatment provides an enhanced outcome to impotent patients refractory to medicine and unsatisfied with PVS monotherapy alone.

Application of a long-lasting colloidal substrate with pH and hydrogen sulfide control capabilities to remediate TCE-contaminated groundwater.

A long-lasting emulsified colloidal substrate (LECS) was developed for continuous carbon and nanoscale zero-valent iron (nZVI) release to remediate trichloroethylene (TCE)-contaminated groundwater under reductive dechlorinating conditions. The developed LECS contained nZVI, vegetable oil, surfactants (Simple Green™ and lecithin), molasses, lactate, and minerals. An emulsification study was performed to evaluate the globule droplet size and stability of LECS. The results show that a stable oil-in-water emulsion with uniformly small droplets (0.7 µm) was produced, which could continuously release the primary substrates. The emulsified solution could serve as the dispensing agent, and nZVI particles (with diameter 100-200 nm) were distributed in the emulsion evenly without aggregation. Microcosm results showed that the LECS caused a rapid increase in the total organic carbon concentration (up to 488 mg/L), and reductive dechlorination of TCE was significantly enhanced. Up to 99% of TCE (with initial concentration of 7.4 mg/L) was removed after 130 days of operation. Acidification was prevented by the production of hydroxide ion by the oxidation of nZVI. The formation of iron sulfide reduced the odor from produced hydrogen sulfide. Microbial analyses reveal that dechlorinating bacteria existed in soils, which might contribute to TCE dechlorination.

FES for abnormal movement of upper limb during walking in post-stroke subjects.

BACKGROUND: Hemiplegia can cause accidental falls, as the patients place their arms in front of their chests or next to the hips when they walk. This is due to limitations in the ability to swing their arms during walking. OBJECTIVE: This study proposes a functional electrical stimulator approach in order to improve the foot drop and abnormal movement of the upper limbs during walking. The goal of this study is to verify the feasibility of improving the foot drop and arm swing problems of hemiplegic patients using electrical stimulators in a clinical trial. METHODS: The present study utilizes a functional electrical stimulator found on the market. The stimulator is controlling the gait and arm swing of the patient while the patient is walking. It can help him or her restore regular gait cycles and arm swings. The FES device can also train the patient to walk safely and regain control of his or her arm swing. After the four-week training, the subjects had to walk 10 meters without the FES system. The step length, step time, and joint goniograms were recorded in order to determine whether there was any improvement. RESULTS: After the four-week training was concluded, the three post-stroke patients showed an improvement in arm swing angle when walking. The improvement was found to be 7.16% in the first patient, 43.06% in the second, and 54.66% in the third. These results are all statistically significant. The t-test had a p-value 0.012 (p< 0.05), which demonstrated that the method used in the present study had the potential to significantly improve the arm swing of post-stroke patients. CONCLUSIONS: The present study showed that a traditional foot drop functional electrical stimulator providing stimulation also to the patient's upper limbs, while being triggered by a foot switch under his or her heel, can help the patient to swing the arms and reduce the foot drop. The method has significant effect on traditional foot drop therapy. The subjects' high degree of acceptance and willingness to commit to long-term use showed that the method is indeed worthy of further research.

Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension.

Glucocorticoids are administered to premature infants to accelerate pulmonary maturation. In experimental model, prenatal dexamethasone (DEX) results in reduced nephron number and adulthood hypertension. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), can cause oxidative stress and is involved in the development of hypertension. L-citrulline can be converted to l-arginine (the substrate for NOS) in the body. Thus we intended to determine if maternal L-citrulline therapy can prevent prenatal DEX-induced programmed hypertension by restoration ADMA/nitric oxide (NO) balance, alterations of renin-angiotensin system (RAS) and sodium transporters, and epigenetic regulation by histone deacetylases (HDACs). Male offspring were assigned to four groups: control, pregnancy rats received intraperitoneal DEX (0.2 mg/kg body weight) daily on gestational days 15 and 16 (DEX), pregnancy rats received 0.25% L-citrulline in drinking water during the entire pregnancy and lactation period (CIT), and DEX + CIT. We found DEX group developed hypertension at 16 weeks of age, which was prevented by maternal L-citrulline therapy. Prenatal DEX exposure increased plasma ADMA concentrations and reduced renal NO production. However, L-citrulline reduced plasma ADMA level and increased renal level of NO in DEX + CIT group. Next, prenatal DEX-induced programmed hypertension is related to increased mRNA expression of angiotensin and angiotensin II type 1 receptor, and class I HDACs in the kidney. Prenatal DEX exposure increased renal protein abundance of Na(+)/Cl(-) cotransporter (NCC), which was prevented by L-citrulline therapy. The beneficial effects of L-citrulline therapy include restoration of ADMA/NO balance and alteration of NCC, to prevent the prenatal DEX-induced programmed hypertension.

Assisted cycling exercise improves fine manual dexterity in persons with Down's syndrome.

BACKGROUND: This study was aimed at investigating the impact of assisted cycling therapy (ACT) on fine manual dexterity in adults with Down's syndrome (DS). METHODS: Nine persons with DS completed four different interventions: voluntary exercise (VE), voluntary with music (VEM), assisted exercise (AE) and no exercise (NE). Fine manual dexterity (e.g., Purdue Pegboard) was tested pre and post interventions. RESULTS: The results showed dominant and bimanual hands were improved after AE but no evident in either subtest after VE. The assembly subtest, processed by spatial-temporal ability, was only improved after VEM and NE. CONCLUSIONS: It is speculated that AE stimulated more peripheral sensory input to the motor cortex and neurotransmitters than the other interventions. In addition, the involvement of music may enhance spatial intelligence during VEM. Even though the exact mechanisms are still unknown, the implication of our results showed that AE and VEM can improve fine manual dexterity in persons with DS.

Chronic intrathecal infusion of gabapentin prevents nerve ligation-induced pain in rats.

BACKGROUND: Gabapentin is an anticonvulsant and adjuvant analgesic. It is effective in several pain studies. Neuropathic pain is the most difficult type of pain to treat. In this study, we examined if intrathecal gabapentin could prevent nerve injury-induced pain. METHODS: Under isoflurane anaesthesia, male Sprague-Dawley rats (200-250 g) underwent right L5/6 spinal nerve ligation and placement of an intrathecal catheter connected to an infusion pump. After surgery, intrathecal saline or gabapentin (20 µg h(-1)) was given for 7 days (n=8 per group). The right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before (baseline) and once daily for 7 days after surgery. Haematoxylin and eosin and toluidine blue staining were used to evaluate the neurotoxicity of gabapentin (40 µg h(-1)). RESULTS: Seven days after nerve ligation, the affected paw withdrawal threshold and latency of saline-treated rats decreased from the baseline 11.7 (11.7-22.2) [median (inter-quartile range)] to 1.6 (0.9-3.2) g and 10.8 (10.5-11.2) to 4.3 (4.2-7) s, respectively. Rats receiving gabapentin (20 µg h(-1)) had higher withdrawal threshold [9.9 (9.9-19.3) g] and latency [11.5 (9.7-11.9) s] on day 7 after ligation. No obvious histopathological change or growth retardation was detected after intrathecal gabapentin (40 µg h(-1)) infusion. CONCLUSIONS: We showed a preventative effect of intrathecal gabapentin on the development of nerve injury-induced mechanical allodynia and thermal hyperalgesia. Our data suggest that continuous intrathecal gabapentin may be considered as an alternative for the prevention of nerve injury-induced pain.

2-Methoxystypandrone represses RANKL-mediated osteoclastogenesis by down-regulating formation of TRAF6-TAK1 signalling complexes.

BACKGROUND AND PURPOSE: 2-Methoxystypandrone (2-MS) is a naphthoquinone isolated from Polygonum cuspidatum, a Chinese herb used to treat bone diseases. Here we have determined whether 2-MS antagonised osteoclast development and bone resorption. EXPERIMENTAL APPROACH: RAW264.7 cells were treated with receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) to induce differentiation into osteoclasts. RT-PCR and Western blot were used to analyse osteoclast-associated gene expression and signalling pathways. KEY RESULTS: The number of multinuclear osteoclasts, actin rings and resorption pit formation were markedly inhibited by 2-MS, targeting osteoclast differentiation at an early stage and without significant cytotoxicity. The anti-resorption effect of 2-MS was accompanied by decreasing dendritic cell-specific transmembrane protein and matrix metalloproteinase-9 (MMP-9) mRNA expression. RANKL-increased MMP-9 gelatinolytic activity was also attenuated by concurrent, but not by subsequent addition of 2-MS. 2-MS markedly inhibited not only the RANKL-triggered nuclear translocations of NF-kappaB, c-Fos and nuclear factor of activated T cells c1 (NFATc1), but also the subsequent NFATc1 induction. Degradation of IkappaB and phosphorylation of mitogen-activated protein kinases were also suppressed. RANKL facilitated the formation of signaling complexes of tumour necrosis factor receptor-associated factor 6 and transforming growth factor beta-activated kinase 1 (TRAF6-TAK1), important for osteoclastogenesis and formation of such signalling complexes was prevented by 2-MS. CONCLUSIONS AND IMPLICATIONS: The anti-osteoclastogenic effects of 2-MS could reflect the block of RANKL-induced association of TRAF6-TAK1 complexes with consequent decrease of IkappaB-mediated NF-kappaB and mitogen-activated protein kinases-mediated c-Fos activation pathways and suppression of NFATc1 and other gene expression, essential for bone resorption.

Patient-driven loop control for ambulation function restoration in a non-invasive functional electrical stimulation system.

PURPOSE: In this study, a patient-driven loop control in a non-invasive functional electrical stimulation (FES) system was designed to restore ambulation function of patients with stroke with their residual capabilities. METHOD: With this patient-driven loop control, patients use the electromyographic (EMG) signals from their voluntary controlled muscles in affected extremity to adjust stimulus parameters of the system. A special designed FES system generated electrical stimuli to excite the paralysed muscles through surface electrodes on the basis of the control command from the residual myoelectric signals. The EMG signals were also served as the trigger and the adjustment of stimulus parameters and thereby adding versatility of the FES system. One patient with hemiplegia was recruited to conduct clinical evaluation and treated by using the new closed-loop FES system. RESULTS: The experimental results showed that hemiplegic could successfully control the system to restore their lost ambulation functions with the strategy of patient-driven loop control. It is revealed that the mean velocity, cadence, stride length, active ankle motion range and functional ambulation category have improved significantly from 0.22 + or - 0.17 m/s, 37.3 + or - 15.5 steps/min, 0.32 + or - 0.11 m, 10 degrees , level 2 to 0.46 + or - 0.23 m/s, 58.2 + or - 19.1 steps/min, 0.73 + or - 0.22 m, 35 degrees , level 4 respectively for the patient. A paired t-test indicated that differences in the EMG of the tibialis anterior and the gastrocnemius muscles between patient's disabled (affected-side) foot and normal (unaffected-side) foot are not significant (p > 0.05) after 12 weeks of training. CONCLUSIONS: According to the experiment results, this patient-driven loop control can be beneficial for patient with hemiplegia to restore their ambulation functions such as dorsi-flexion and plantar-flexion. The control strategy of this study has the potential to be employed not only in the FES system but also in other assistive devices.

The synthesis and characterization of [(124)I]IMPY, a thioflavin-S derivative, in transgenic mouse models of Alzheimer's disease.

6-[(124)I]iodo-2-(4'-N,N-dimethylamino)-phenylimidazo[1,2-a]pyridine ([(124)I]IMPY) was synthesized and characterized as a positron-emitting probe to identify Alzheimer's disease in transgenic mouse models. A significant reduction in radioactivity retention in the hippocampus and frontal cortex by co-incubation with nonradioactive IMPY was observed. Highly specific retention of radioactivity in beta-amyloid-rich regions of brain sections was also noted. This study demonstrated that [(124)I]IMPY was a promising probe for the mouse model and may be useful for positron emission tomography to image beta-amyloid plaques in the human brain.

The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease.

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications.

Regulation of steroidogenesis by Cordyceps sinensis mycelium extracted fractions with (hCG) treatment in mouse Leydig cells.

The in vitro effect of extracted fractions of Cordyceps sinensis (CS) mycelium on hCG-treated testosterone production from purified normal mouse Leydig cells was examined. Different fractions extracted from CS (F1-water soluble polysaccharide, F2- water soluble protein and F3- poorly water soluble polysaccharide, and protein) were added to Leydig cells with hCG, and the production of testosterone was determined by radioimmunoassay (RIA). Testosterone productions stimulated by hCG in mouse Leydig cells were suppressed by F2 at 10 mg/ml and F3 at doses from 3 to 10 mg/ml, respectively. F2 and F3 at 10 mg/ml did inhibit dbcAMP-stimulated testosterone productions which indicated that F2 and F3 might affect steroidogenesis at the site after the formation of cyclic AMP. Finally, cycloheximide inhibited F2- and F3-treated mouse Leydig cell testosterone production.

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway.

Epimedium brevicornum Maxim (EbM) has been reputed to have sexual stimulation effects on males. The study is aimed to test the hypothesis that EbM extracts relaxed the corpus cavernosum (CC) smooth muscle through activation of multitargets on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Water extract of EbM and its subfraction (EP-20) were prepared and standardized by high-performance liquid chromatography. Isolated rabbit CC strips were mounted in organ baths and isometric tension was recorded in the presence or absence of specific inhibitors related to NO/cGMP signaling such as L-N(G)-nitro-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor) or phosphodiesterase 5 (PDE 5) inhibitors. cGMP level was determined in EP-20-treated CC strips. The results showed that EP-20 enriched the content of L-arginine in the process of purification and relaxed the CC smooth muscle precontracted with phenylephrine (PE, 1 microM) in a concentration-dependent manner. Besides, EP-20 increased the amount of cGMP production in rabbit CC tissues. Coincubation with EP-20 and L-NAME or ODQ significantly decreased EP-20-induced relaxation whereas EP-20 increased sodium nitroprusside-induced relaxation in PE-precontracted CC strips. Besides, EP-20 increased the potency and the duration of the relaxation effects caused by electrical field stimulation. Finally, EP-20 could potentiate PDE 5 inhibitors in relaxation of PE-precontracted CC strips. We concluded that extract of EbM relax the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and might bring into perspective the treatment strategy for those patients with erectile dysfunction.

Two phenanthraquinones from Dendrobium moniliforme.

Two phenanthraquinones were isolated from the stems of Dendrobium moniliforme. They were identified by interpretation of spectral data as 2,6-dimethoxy-1,4,5,8-phenanthradiquinone and 5-hydroxy-3,7-dimethoxy-1,4-phenanthraquinone, named moniliformin (1) and denbinobin (2), respectively. This is the first report of compound 1, which possesses a novel 1,4,5,8-diquinone moiety in the phenanthraquinone skeleton. Compound 2 showed potent antiinflammatory effects in vitro.

Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb.

To evaluate the anti-leukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb., cytotoxicity tests with an XTT-based colorimetric assay were used. Five leukemic cell lines, namely L1210, U937, K562, Raji and P3HR1, were cultured with hot water extracts of B. pilosa var. minor or H. cordata. Hot water extracts of B. pilosa var. minor inhibited these five leukemic cells with IC50s between 145 microg/ml and 586 microg/ml. The effect was greatest on four cell lines, namely L1210, P3MR1, Raji and K562, with IC50s below 200 microg/ml and a selective index of more than 5. Hot water extract of H. cordata inhibited these five leukemic cells with IC50s between 478 microg/ml and 662 microg/ml. The selective index was between 1.5 and 2.1. B. pilosa var. minor was more effective than H. cordata in inhibiting most of the leukemic cells in our study. We suggest that B. pilosa L. var. minor (Blume) Sherff may prove to be a useful medicinal plant for treating leukemia.

Three xanthones and a benzophenone from Garcinia mangostana.

Investigation of the constituents of Garcinia mangostana has led to the isolation of four new compounds: three minor xanthones, garcimangosone A (1), garcimangosone B (2), and garcimangosone C (3), and a benzophenone glucoside, garcimangosone D (4). The structures of these four compounds were established by spectral (NMR and MS) and chemical methods.

Water-soluble glycosides from Ruta graveolens.

An EtOH extract of the dried aerial parts of Ruta graveolens was suspended in water and then partitioned with EtOAc. Three new glycosides, 3'-sinapoyl-6-feruloylsucrose (4), methylcnidioside A (5), and methylpicraquassioside A (6), together with four known glycosides, 3',6-disinapoylsucrose (1), cnidioside A (2), rutin, and picraquassioside A (3), were isolated from the water-soluble part. Their structures were elucidated by interpretation of IR, MS, and 1D and 2D NMR spectra and comparison with literature data.

Isolation of Haemophilus parahaemolyticus in a patient with cryptogenic brain abscess.

Haemophilus parahaemolyticus rarely causes disease in humans. We present the case of a 68-y-old man who suffered from a brain abscess over the right-side thalamus and midbrain. Stereotactic aspirates grew H. parahaemolyticus. No portal of entry for the microorganism was identified in this case. The patient made a good recovery after treatment.