A continent-wide detailed geological map dataset of Antarctica.

A dataset to describe exposed bedrock and surficial geology of Antarctica has been constructed by the GeoMAP Action Group of the Scientific Committee on Antarctic Research (SCAR) and GNS Science. Our group captured existing geological map data into a geographic information system (GIS), refined its spatial reliability, harmonised classification, and improved representation of glacial sequences and geomorphology, thereby creating a comprehensive and coherent representation of Antarctic geology. A total of 99,080 polygons were unified for depicting geology at 1:250,000 scale, but locally there are some areas with higher spatial resolution. Geological unit definition is based on a mixed chronostratigraphic- and lithostratigraphic-based classification. Description of rock and moraine polygons employs the international Geoscience Markup Language (GeoSciML) data protocols to provide attribute-rich and queryable information, including bibliographic links to 589 source maps and scientific literature. GeoMAP is the first detailed geological map dataset covering all of Antarctica. It depicts 'known geology' of rock exposures rather than 'interpreted' sub-ice features and is suitable for continent-wide perspectives and cross-discipline interrogation.

Infant Exposure to Armodafinil Through Human Milk Following Maternal Use of Modafinil.

INTRODUCTION: Narcolepsy, a condition adversely affecting psychological, social, and cognitive function, is more prevalent in females of childbearing age than the general population. Modafinil and armodafinil are central nervous system stimulants approved for treatment of narcolepsy. Infant exposure to these agents through human milk has not been investigated. Poor quality medication safety information during lactation is associated with early cessation of breastfeeding and suboptimal healthcare for the breastfeeding family. MAIN ISSUE: In this case study, we measured the concentration of armodafinil (the most active form of modafinil) in human milk and infant plasma to quantify infant exposure. MANAGEMENT: The participant was a 30-year-old primipara with narcolepsy, taking modafinil (300 mg morning, 100 mg noon) while breastfeeding her 6-week-old infant despite the paucity of safety information. Armodafinil concentrations were measured in eight serial human milk samples collected over a 26-hr period and in single maternal and infant plasma samples using ultra performance liquid chromatography - tandem mass spectrometry. The average concentration of armodafinil in human milk was 1.96 mg/L; the relative infant dose was 4.85%; the theoretical infant dose was 0.294 mg/kg/day. Maternal and infant plasma concentrations of armodafinil were 12.02 mg/L and 0.19 mg/L, respectively. The participant continued to exclusively breastfeed the infant, who had normal growth and development. CONCLUSION: Based on these findings, relatively small amounts of armodafinil pass into human milk, with consequent limited infant exposure. Consideration can be given to the use of modafinil or armodafinil during breastfeeding, provided the infant is monitored. Further studies are needed to confirm these findings.

Soft and tissue repair of the hand and digital reconstruction.

This article summarizes the current views and proposed approaches to treating soft tissue defects of the hand. The article also outlines some key considerations of digital reconstruction. There are many options in treating soft tissue defects. For defects of the hand, local flaps are primarily considered if the defects are small or moderate in size. A vascularized free flap is only considered for a defect of large size (3 cm long or larger). Thumb reconstruction is of primary importance, while reconstruction of two fingers is necessary when all fingers are lost. Reconstructions of a missing distal part of a finger or reconstruction of an entire finger if only one finger is lost are cosmetic restorations; functionally these defects do not need reconstruction. Sensation is of great importance in repair or reconstruction of the tip of the thumb or finger. Therefore, sensory evaluation is a key factor in assessing and selecting the best options of surgery.

Telehealth for Cancer Care in Veterans: Opportunities and Challenges Revealed by COVID.

The Veterans Health Administration system is one of the largest integrated health care providers in the United States, delivering medical care to > 9 million veterans. Barriers to delivering efficient health care include geographical limitations as well as long wait times. Telehealth has been used as a solution by many different health care services. However, it has not been as widely used in cancer care. In 2018, the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System expanded the use of telehealth to provide antineoplastic therapies to rural patients by creating a clinical video telehealth clinic of the Virtual Cancer Care Network. This allows oncologists located at the tertiary center to virtually deliver care to remote sites. The recent COVID-19 pandemic forced oncologists across the VA system to adopt telehealth to provide continuity of care. On the basis of our review and personal experience, we have outlined opportunities for telehealth to play a role in every step of the cancer care journey from diagnosis to therapy to surveillance to clinical trials for medical, surgical, and radiation oncology. There are many advantages, such as decreased travel time and potential cost savings; however, there continues to be challenges with veterans having access to devices and the Internet as well as understanding how to use telehealth equipment. The lessons learned from this assessment of the VA telehealth system for cancer care can be adopted and integrated into other health systems. In the future, there needs to be evaluation of how telehealth can be further incorporated into oncology, satisfaction of veterans using telehealth services, overcoming telehealth barriers, and defining metrics of success.

The use of chimeric musculocutaneous posterior interosseous artery flaps for treatment of osteomyelitis and soft tissue defect in hand.

INTRODUCTION: There is growing evidence of the superior ability of muscular tissue to clear bacterial bone infection. Unfortunately, in the hand, there are almost no small local muscular flaps, and muscular transfers to the hand are mainly microsurgical free transfers. In this report, we present the results of the use of a chimeric posterior interosseous flap including part(s) of the forearm muscles to treat osteomyelitis and soft tissue defect of hand from a series of patients. PATIENTS AND METHODS: Four male patients with an average age of 32 years (range 20-46 years), were affected by acute osteomyelitis in hand. Previous fracture fixation with percutaneous K-wires was the cause of bone infection in three case. In one case, the osteomyelitis was a consequence of an open fracture. The bones affected were four metacarpals and one proximal phalanx, all with a minimal cortical defect (from the K-wire) obscuring a larger medullary infection, which required extensive bone and overlying soft tissue debridement, leaving a soft tissue defect to be reconstructed of size ranging from 2 x 4 cm to 5 x 7 cm. The soft tissue defects were due to concomitant superficial infection and consequent debridement. All patients were treated with bone debridement and a chimeric posterior interosseous flap, which included part of the extensor digiti minimi and/or extensor carpi ulnaris to fill the intramedullary canal of the bones. No fixation of bone was necessary. RESULTS: The skin paddle of the flaps ranged from 2 x 5 cm to 5 x 6 cm, replicating the defect area, plus a teardrop tail of skin circa 1.5 cm wide and as long as the pedicle of the flap. The muscular components of the flaps used to fill the intramedullary canals ranged from 1 x 1 x 1.5 cm to 1.5 x 1.5 x 4 cm. All flaps survived and osteomyelitis resolved in all cases without major complications. At the final follow-up at 16 months (range 12-26 months), assessment of the hands using TAM, Power Grip and Key Pinch Strength measurements and, where appropriate, Kapandji scores, demonstrated satisfactory hand function. CONCLUSION: The chimeric posterior interosseous flap including part of the muscles of the forearm may be a robust solution for augmenting the flap bulk and may be used in cases of severe osteomyelitis of the hand.

A Pilot Investigation of Repetitive Transcranial Magnetic Stimulation for Post-Traumatic Brain Injury Depression: Safety, Tolerability, and Efficacy.

Depression following a traumatic brain injury (TBI) is common and difficult to treat using standard approaches. The current study investigated, for the first time, transcranial magnetic stimulation (TMS) for the treatment of post TBI depression. We specifically assessed the safety, tolerability, and efficacy of TMS in this patient population. We also explored cognitive outcomes. Twenty-one patients with a current episode of major depression subsequent to a TBI participated in a randomized double-blind placebo-controlled trial of repetitive TMS (rTMS). Sequential bilateral rTMS (to the left and right dorsolateral prefrontal cortex) was provided in 20 treatments over a period of 4 weeks. Patients were randomly allocated to receive either active or sham stimulation. There were no adverse effects and treatment was well tolerated. There was no significant effect of rTMS on post-TBI depression, with all patients showing a significant improvement in depressive symptoms irrespective of their treatment group (p = 0.002). There were significant improvements in cognition following active rTMS in the areas of working memory (p = 0.021) and executive function (p = 0.029). rTMS was shown to be safe and well tolerated in patients who had developed depression after a TBI. We did not find a therapeutic effect for post-TBI depression; however, this approach may have some utility in improving cognitive function. Future research should focus on alternative rTMS treatment approaches for post-TBI depression and the direct investigation of rTMS as a treatment for cognitive impairment in TBI.

Small molecule inhibition of DDAH1 significantly attenuates triple negative breast cancer cell vasculogenic mimicry in vitro.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a key enzyme involved in the metabolism of the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA). Increased DDAH1 expression and subsequent increased NO production have been recently linked to cancer. Specifically, DDAH1 is implicated in establishment of a vascular network by tumour cells, vasculogenic mimicry (VM), which is strongly associated with tumour progression and poor patient prognosis. The use of DDAH1 inhibitors as potential therapeutic agents thus represents a growing field of interest. Here we describe a UPLC-MS assay to quantify stability and intracellular concentration of two small molecule DDAH1 inhibitors synthesised by our group, ZST316 and ZST152, following incubation with MDA-MB-231 breast cancer cells. In an in vitro assay of VM, both DDAH1 inhibitors significantly attenuated formation of capillary-like tube structures in a dose-dependent fashion. This was not due to cell toxicity or altered cell proliferation, but may be due in part to inhibition of cell migration. Mechanistically, we demonstrate significant modulation of the endogenous DDAH/ADMA/NO pathway following exposure of 100 µM ZST316 or ZST152: a 40% increase in the DDAH1 substrate ADMA, and a 38% decrease in the DDAH1 product l-citrulline. This study represents the first evidence for therapeutic inhibition of DDAH1 by small molecules in breast cancer.

Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis of <12 months. Even with bans on the use of asbestos in most Western countries, the incidence is still increasing due to the long latency periods between exposure and development of the disease. Diagnosis is often delayed due to invasive biopsies and lack of distinguishable markers. Patients frequently present with pleural effusions months to years before a radiologically detectable mass appears. This study aimed to investigate the proteome of pleural effusions taken from patients with MPM, adenocarcinoma and benign conditions in an attempt to identify a biomarker for early diagnosis. We identified several proteins that may be possible targets and warrant further investigation. Due to the predominance of up regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM.

The Combination of Metformin and Valproic Acid Has a Greater Anti-tumoral Effect on Prostate Cancer Growth In Vivo than Either Drug Alone.

BACKGROUND/AIM: The hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA) have individually shown anti-tumor effects in prostate cancer in vitro. The present study intended to investigate the efficacy of the combination of MET and VPA in prostate cancer treatment in a pre-clinical xenograft model. MATERIALS AND METHODS: Prostate cancer cell lines (LNCaP and PC-3) were inoculated under the skin of BALB/c nude mice. The mice were treated with 200 µl/ml MET and/or 0.4% (w/v) VPA diluted in drinking water, or with vehicle control, and were monitored until the tumor volume reached 2,000 mm3 Evaluation of toxicity of the drug combination was determined in liver and kidney by histology. RESULTS: In both LNCaP and PC-3 xenografts, MET combined with VPA significantly reduced tumor growth during the first 4 weeks following treatment, and delayed the time-to-tumor volume of 2,000 mm3 by 90 days, as compared to MET or to VPA alone, and to vehicle control. There was no significant difference in total mouse weight, liver or kidney morphology in response to combination treatment (MET+VPA) compared to MET or VPA alone and vehicle control. CONCLUSION: The combination treatment of MET with VPA is more effective at slowing prostate tumor growth in vivo compared to either drug alone, in mouse xenografts. These pre-clinical results support previous in vitro data and also demonstrate the low toxicity of the combination of these drugs, suggesting that this may be a potential new therapy to be investigated in clinical trials for prostate cancer.

Development of an LC⁻Tandem Mass Spectrometry Method for the Quantitative Analysis of Hercynine in Human Whole Blood.

Given that the peculiar redox behavior of ergothioneine involves a rapid regeneration process, the measurement of its precursor and redox metabolite hercynine could be particularly useful in assessing its role in oxidative stress or other biological processes. Thus, a LC-MS/MS method for the determination of hercynine concentrations in whole blood was developed. After lysis of red blood cells by cold water, samples were filtered on micro concentrators at a controlled temperature of 4 °C. The clear filtered fluid was then treated with diethylpyrocarbonate to derivatize hercynine for the analysis by LC-MS/MS. The derivatized analyte was isocratically separated as a carbethoxy derivative on a C18 column with a mobile phase of an aqueous 0.1% v/v formic acid and acetonitrile (95:5). Effluents were monitored by MRM transitions at m/z 270.28→95 and 273.21→95 for hercynine and its deuterated counterpart, respectively. No cross-talk between MRM transitions was observed and a good linearity was found within a range of 35⁻1120 nmol/L. The LOD and LOQ were, respectively, 10.30 and 31.21 nmol/L with an intraday and intermediate precision below 7%. The average hercynine concentration in whole blood from 30 healthy male volunteers (aged 77 ± 12 years) was 178.5 ± 118.1 nmol/L. Overall, the method is easy to perform, allowing a rapid and accurate assessment of whole blood concentrations of hercynine.

Repair of soft tissue defects in finger, thumb and forearm: less invasive methods with similar outcomes.

We review recent developments in using occlusive dressings, dermal templates, and venous flaps for less invasive approaches to treat soft tissue defects of the forearm and fingers. Occlusive dressings can be used for thumb tip or fingertip trauma with soft tissue defects of small or moderate sizes. They permit skin regeneration without use of skin graft or a flap transfer. This is currently a popular way to treat tip soft tissue defects in European countries. Extensive soft tissue defects in the thumb, fingers, hand and forearm require flap transfers traditionally, but in recent years, surgeons use dermal templates to cover the defect site to allow regeneration of subcutaneous tissues, over which a skin graft is used in lieu of a flap. Transfer of a venous flap is currently a reliable procedure and is less invasive compared with conventional flaps, which usually damage a named artery in the donor. We advocate that less invasive methods should be considered for soft tissue defects in the hand and forearm.

Administering Fixed Oral Doses of Curcumin to Rats through Voluntary Consumption.

Curcumin, a polyphenol derived from turmeric, has a wide variety of therapeutic benefits including antiinflammatory, antioxidative, and chemopreventative effects. Oral gavage is widely performed to administer curcumin in laboratory rodents in several experimental models. Although effective, this method can increase stress in the animal, potentially influencing experimental results. Moreover, oral gavage can result in mortality due to accidental instillation of fluid into the lungs, serious mechanical damage, and gavage-related reflux. Here we describe a method for the administration of fixed dosages of curcumin to rats through voluntary consumption of peanut butter, to reduce gavage-related morbidity and distress to animals and to provide environmental enrichment. Fischer 344 (n = 6) rats received 1100 mg/kg of a commercial curcumin product (equivalent to approximately 200 mg/kg of curcumin) in 8 g/kg of peanut butter daily for 5 wk. Curcumin concentrations in rat plasma were measured by using UPLC-MS at 2 to 4 h after administration. All rats voluntarily consumed the peanut butter-curcumin mixture consistently over the 5-wk period. Total curcumin concentrations in plasma samples collected 2 to 4 h after curcumin consumption were 171 ± 48.4 ng/mL (mean ± 1 SD; range, 103 to 240 ng/mL). This noninvasive curcumin delivery method was effective, eliminated the stress caused by daily oral gavage, and added environmental enrichment.

Accelerated repetitive transcranial magnetic stimulation in the treatment of depression.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used clinically in the treatment of patients with major depressive disorder (MDD). However, rTMS treatment response can be slow. Early research suggests that accelerated forms of rTMS may be effective but no research has directly evaluated a schedule of accelerated rTMS compared to standard rTMS. To assess the efficacy of accelerated rTMS compared to standard daily rTMS., 115 outpatients with MDD received either accelerated rTMS (n = 58) (i.e., 63,000 high frequency rTMS pulses delivered as 3 treatments per day over 3 days in week 1, 3 treatments over 2 days in week 2 and 3 treatments on a single day in week 3) or standard rTMS (n = 57) (i.e., 63,000 total high frequency rTMS pulses delivered over 5 days per week for 4 weeks) following randomization. There were no significant differences in remission or response rates (p > 0.05 for all analyses) or reduction in depression scores (Time by group interaction (F (5, 489.452) = 1.711, p = 0.130) between the accelerated and standard rTMS treatment groups. Accelerated treatment was associated with a higher rate of reported treatment discomfort. It is feasible to provide accelerated rTMS treatment for outpatients with depression and this is likely to produce meaningful antidepressant effects.

Exploring alternative rTMS strategies in non-responders to standard high frequency left-sided treatment: A switching study.

BACKGROUND: High-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) is now commonly used treatment for patients with depression. However, there are several other forms of rTMS (low-frequency right-sided and sequential bilateral rTMS) which have also been shown to be effective. No information has been systematically gathered on the likelihood of response to alternative forms of rTMS in patients who do not improve after an initial course of left-sided treatment. OBJECTIVE: To evaluate whether there are differences in antidepressant response between switching to either low-frequency right sided or sequential bilateral stimulation or continuing high-frequency left-sided TMS following non-response to an initial course of high-frequency left-sided rTMS. METHODS: 113 rTMS naïve patients were provided with an initial three-week course of high-frequency left-sided rTMS. Non-responders were then randomised to receive another three weeks of left-sided treatment (n = 21), right-sided low frequency stimulation (n = 18) or sequential bilateral rTMS (n = 20). RESULTS: Although there was an overall improvement in depressive symptoms in the randomised phase of the study, no significant differences in response was seen between the three treatment groups on Montgomery Asberg Depression Rating Scale or Hamilton Depression Rating Scale scores. LIMITATIONS: The main limitation of the study was the duration of treatment provided in both the lead in and random treatment phases. CONCLUSION: This study does not provide evidence for differences in response to different forms of rTMS in initial non-responders to left-sided stimulation. However, further studies with longer periods of treatment and a larger sample size are required to definitively establish or exclude between group differences in rTMS response in initial non-responders to treatment.

A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and electroconvulsive therapy in persistent depression.

BACKGROUND: Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. METHODS: Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. RESULTS: No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. CONCLUSIONS: MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials.