Disposable masks can be used more than once, but it's important to make sure the mask isn't carrying coronavirus.

Cryptocurrency profits from sextortion spam funneled into wallets tied to other cybercrime and dark web market activity.

Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)⁺ compared with AAb^– relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb⁺ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb⁺ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

Background: ⁶⁸Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (P < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease.

Objectives: Lutetium-177 (¹⁷⁷Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies.

Background: Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following ¹⁷⁷Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods: Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes: 1) response: ≥30% decline, 2) progression: ≥25% increase and 3) stable: <30% decline and <25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A ≥30% decline in PSA at 6 wk was associated with longer overall survival (median 16.7 mo; 95%CI 14.4–19.0) compared with patients with stable PSA (median: 11.8 mo; 95%CI 8.6–15.1; P = 0.007) and progression (median: 6.5 mo; 95%CI 5.2–7.8; p<0.001). Patients with ≥30% decline in PSA at 6 wk also had a reduced risk of imaging-based progression compared with patients with stable PSA (HR: 0.60; 95%CI 0.38–0.94; P = 0.02), while patients with PSA progression had a higher risk of imaging-based progression compared with those showing stable PSA (HR: 3.18; 95%CI 1.95–5.21; p<0.001). The percentage changes of PSA at 6 wk and 12 wk were highly associated (r=0.90; p<0.001). 29 of 31 (94%) patients who experienced early PSA progression at 6 wk achieved biochemical progression at 12 wk. Overall, only 1 of 36 (3%) patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). Limitations of the study included its retrospective nature and the single center experience. Conclusion: PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA.

1 November 2008 , Number 8

Ghana’s President John Kufuor has successfully promoted his country as a haven of political and economic stability, but as he comes to the end of his two terms in office, the cracks are beginning to appear. Can Ghana escape the election traumas that have been so destructive in Kenya and Zimbabwe?

If your business key column is a name literal, like " business key "n, a syntax error occurs when that variable name does not follow standard SAS naming conventions.

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4⁺Foxp3⁺ regulatory T cells (T_regs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded T_regs in T1D and solid-organ transplant recipients are limited by poor T_reg engraftment without host manipulation. We showed that T_reg engraftment and therapeutic benefit in nonautoimmune models required ablative host conditioning. Here, we evaluated T_reg engraftment and therapeutic efficacy in the nonobese diabetic (NOD) mouse model of autoimmune diabetes using nonablative, combinatorial regimens involving the anti-CD3 (αCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6–1) antibody complex. We demonstrate that αCD3 alone induced substantial T-cell depletion, impacting both conventional T cells (T_conv) and T_regs, subsequently followed by more rapid rebound of T_regs. Despite robust depletion of host T_conv and host T_regs, donor T_regs failed to engraft even with interleukin-2 (IL-2) support. A single dose of CyP after αCD3 depleted rebounding host T_regs and resulted in a 43-fold increase in donor T_reg engraftment, yet polyclonal donor T_regs failed to reverse diabetes. However, infusion of autoantigen-specific T_regs after αCD3 alone resulted in robust T_reg engraftment within the islets and induced remission in all mice. This novel combinatorial therapy promotes engraftment of autoantigen-specific donor T_regs and controls islet autoimmunity without long-term immunosuppression.

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

OBJECTIVE

To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group
May 1, 2016; 39:686-693
Cardiovascular Disease and Diabetes

The ADA is urging dentists to be cautious about using novel coronavirus diagnostic tests before they have been properly evaluated and made available for dentists.

A 29 years old female presented to us in the metabolic clinic of the University of Port Harcourt Teaching Hospital (UPTH) on account of a week history of easy fatigability, weakness, and lower extremity muscle cramps associated with numbness and tingling sensation in the peri-oral area, fingers and toes. Two weeks prior to the onset of her presenting symptoms, she had visited a local pharmaceutical shop on account of a distressing epigastric discomfort and was subsequently placed on daily oral omeprazole 20mg daily for a month by a pharmacist. She had been on the omeprazole medication for two weeks before her present symptoms manifested. Her past medical history was not suggestive of hypoparathyroidism nor pancreatitis. She was married with three children and has an uneventful family, social and obstetric histories. On examination, she was a healthy well-oriented young female with positive Trousseau’s, Chvostek’s and epigastric tenderness signs. Further Laboratory evaluation revealed she had low plasma magnesium, low plasma albumin-corrected calcium, and low serum parathyroid hormone levels, while other laboratory parameters were essentially normal. A diagnosis of omeprazole-induced electrolyte disorders (hypomagnesaemia and hypocalcaemia) associated with hypoparathyroidism was made following the review of her clinical examination and laboratory findings. She was subsequently managed with oral magnesium supplements following the withdrawal of the omeprazole medication (replaced with oral ranitidine), monitored weekly, and full recovery was achieved after three weeks.

What do you think is more dangerous? Terrorists getting their hands on a biological weapon that can be smuggled into the country or another hurricane like Katrina? Which is the smarter way to keep Social Security solvent? Raise the retirement age or raise taxes? How can the current economic crisi...

By winding down DACA over six months, President Trump may have addressed a short-term political dilemma. But this action ensures debate will rage on in search of a lasting solution, as many in Congress and beyond recognize the loss of work authorization and deportation relief will affect not only DACA recipients and their families, but also employers, universities, and communities alike, as this commentary explores.

A home schooling advocacy group was concerned when a state legislator proposed requiring home schoolers to follow the Common Core State Standards.

Paris (rue de la Vannerie a l'image St. Michel) : Dupuis graveur du Roy, [1721]

Rockville, Maryland : National Institute on Drug Abuse, 1978.

Rockville, Maryland : National Institute on Drug Abuse, 1978.

WT Newsome
Jun 1, 1988; 8:2201-2211
Articles

We took a look around and put together a list of  Twitter accounts to keep you informed about what is happening in the world of soils.  Here are, in alphabetical order, ten voices on twitter you should follow for the latest on soils: @agriculturesnet The AgriCultures Network shares knowledge on small-scale family farming and agroecology. With agroecology we can build soils for life! http://t.co/pN62odtLt9 [...]

From a media bed unit start-up in Bangkok to a fully developed 120 households deep water culture (DWC) unit in Ethiopia, aquaponics is showcasing its true potential to produce sustainable food anytime, anywhere. A marriage between aquaculture (raising aquatic animals such as fish, snails or prawns in tanks) and hydroponics (cultivating plants in water), aquaponics is a ‘clean and green’ [...]

The purplish-blue pigment, derived from a Portuguese fruit, fell out of use by the 19th century

This rapid and efficient method to prepare highly purified recombinant adeno-associated viruses (rAAVs) is based on binding of negatively charged rAAV capsids to an anion-exchange resin that is pH dependent.

When we find something particularly beautiful or impressive, we literally get big eyes: Our pupils dilate. The pupil controls how much light enters the eye and falls on the retina.

Karina LeBlanc was returning home from her second hospital visit after giving birth to her first child, only this time she would have to spend 14 days in self-isolation after doctors feared she contracted COVID-19 during her stay.

OPP are investigating a fatal crash that took place in Lakeshore Thursday night.

Prime Minister Justin Trudeau said Sunday that NHL players would — at a minimum — need to follow quarantine protocols if they were to arrive in Canada while the border remains closed due to the pandemic.

OMer Gyöngyi served around the world, then the Riverboat led her back home to Hungary.

In a largely unreached nation, where Christians often face persecution, OM comes alongside local churches to see more vibrant communities of Jesus followers established.

AN SNP MP has been accused of capitalising on the virus crisis to undermine Nicola Sturgeon and boost their own profile following a series of remarks made in an online party meeting.

Two high school basketball coaches and an assistant principal/athletic director are facing criminal charges stemming from an alleged hazing incident that resulted in the hospitalization of a 15-year-old boy.

FOOTBALLERS are performers, we all know that. But can they tackle a film script? Can they find the head space to turn out a tricky line on a crowded set? And what of football managers? Can they take to acting? We’ve long believed them to have the ego of an oligarch and to make the demands of a dictator. Does any of this suggest those born to kick balls around a park can turn their hand to thespianism?

Although follow-up examinations are recommended for suspected victims of sexual abuse or assault, little is known about the potential benefits of a second examination with regard to diagnosing trauma or sexually transmitted infections.

In ~23% of pediatric patients evaluated for sexual abuse or assault, a second examination by a specialist changed the interpretation of trauma likelihood or results in the detection of a sexually transmitted infection. (Read the full article)

Adolescence is a time of risk taking, with poor inner-city youth at greater risk than the general population for drug use, school failure, adjudication, and teen parenthood. Little is known regarding these youths’ perceptions and intentions in early childhood.

Poor inner-city children were surprisingly idealistic regarding their future. Despite this, by late adolescence most experienced 1 or more trajectory-altering events. Early childhood experiences, exposure to violence and poor home environment, were factors most strongly associated with these outcomes. (Read the full article)

Youth violence and alcohol misuse are a preventable public health problem. Previous studies have demonstrated the efficacy of brief interventions in the emergency department (ED) in reducing alcohol misuse and related consequences among older adolescents and adults.

This study supports the efficacy of brief interventions in the ED in reducing peer aggression and victimization 12 months after ED visit. The previous reductions in alcohol consequences noted at 6 months follow-up were not sustained at 12 months. (Read the full article)