Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer's Disease Treated with Anti-Amyloid Beta Therapy.

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aß) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aß in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aß therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.

T cell-independent interleukin 15Ralpha signals are required for bystander proliferation.

Cytokine driven or "bystander" proliferation of T cells occurs in vivo independently of major histocompatibility complex-T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8(+) T cells. Surprisingly, IL-15Ralpha(-/-) CD8(+) T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8(+) T cells fail to proliferate in IL-15Ralpha(-/-) mice. Normal mice reconstituted with IL-15Ralpha(-/-) bone marrow cells also fail to exhibit bystander responses. Thus, CD8(+) T cell independent IL-15Ralpha signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8(+) T cells proliferate in IL-15Ralpha(-/-) mice after treatment with IL-15. Therefore, IL-15Ralpha signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Ralpha supports memory phenotype CD8(+) T cell proliferation, and suggest novel mechanisms by which memory CD8(+) T cells are maintained in vivo.

Hypoxia and auditory thresholds.

This paper reports the effects of hypoxia on hearing. Pure tone hearing and speech discrimination were tested at ground level and during hypoxic states at simulated altitudes of 4,600 m (15,000 ft) and 6,100 m (20,000 ft) in a high-altitude chamber. Pure tone hearing was not significantly altered during hypoxia produced by this method. Speech discrimination showed alterations, possibly due to central nervous system hypoxia. It was concluded that hypoxia does not cause significant deterioration of hearing for pure tones.

Poverty crisis in the Third World: the contradictions of World Bank policy.

Politicians, the mainstream media, and orthodox social science have all been telling us of a final victory of capitalism over socialism, suggesting that capitalism is the only viable option for solving the world's problems. Yet, the global capitalist system is itself entering the third decade of a profound structural crisis, the costs of which have been borne largely by the exploited and oppressed peoples of the underdeveloped periphery. While the World Bank's latest World Development Report recognizes the current poverty crisis in the third world, its "two-part strategy" for alleviating poverty is based on an inadequate analysis of how peripheral capitalist development marginalizes the basic needs of the third world poor. Hence, the World Bank's assertion that free-market policies are consistent with effective antipoverty programs does not confront the class structures and global capitalist interests bound up with the reproduction of mass poverty in the third world. The World Bank's subordination of the basic needs of the poor to free-market adjustments and reforms in fact suggests that the real purpose of its "two-part strategy" is to ensure continued extraction of surplus from third world countries by maintaining the basic structure of imperialist underdevelopment.

New law requires hazardous waste source-reduction plans.

For the first time, the state of California requires waste generators to be able to show official plans and reports for the source-reduction of hazardous waste.

Mucosal tattooing in oral cavity carcinoma.

Tattooing provides accurate localization for tumor surgery following radiation therapy. This paper describes studies done on tattooing technique and instruments available currently. Procedures tested included hypodermic needles and three types of surgical instruments. Chemical tested included india ink, iron oxide, and colored pigments. India ink and iron oxide used with the Spaulding-Rogers Outliner gave satisfactory tattoos.

Absence of neuropathic pelvic pain and favorable psychological profile in the surgical selection of patients with disabling interstitial cystitis.

PURPOSE: We evaluated the results among patients with disabling interstitial cystitis treated by cystectomy, urethrectomy and creation of a continent colonic urinary reservoir (the Florida pouch). The value of psychological evaluation and pain localization techniques, as well as the use of a team approach in the evaluation of these patients were assessed. MATERIALS AND METHODS: The 20 women and 2 men who underwent surgery for disabling interstitial cystitis ranged from 31 to 75 years old (mean age 48). The duration of symptoms ranged from 2 to 14 years (mean 7). All patients had undergone multiple prior therapies, including vesical hydrodistension, instillations, laser treatments, and use of tranquilizers and a variety of pain medications. Patients underwent a clinical, cystoscopic (with bladder biopsies) and urodynamic evaluation as well as examination by a gynecologist with expertise in vaginal ultrasonography. The last 5 patients underwent psychological evaluation and pain localization techniques. RESULTS: Among the clinical parameters, the presence of a small capacity bladder with the patient under anesthesia (less than 400 cc) was associated with the best surgical results. Among 11 patients evaluated only clinically success was achieved in 64%, while all 5 (100%) who also underwent pain localization techniques and psychological evaluation had a successful outcome postoperatively. The overall surgical success rate in the 22 patients was 73%. Two patients undergoing psychological evaluation and pain localization techniques were not considered to be surgical candidates. Among 7 surgical failures 4 patients underwent postoperative psychological evaluation and pain localization techniques, and they would not have been considered candidates for surgery with the new parameters. CONCLUSIONS: A team approach is essential in the evaluation of these patients. Following the initial selection of patients who had a small bladder capacity while under anesthesia, psychological evaluation and pain localizing techniques may assist surgeons in selecting those who would benefit from a radical operation.

Increasing handwashing in an intensive care unit.

The present study provides the first systematic evaluation of strategies for increasing handwashing of hospital staff. Nursing staff on two intensive care units (ICUs) were observed over a 3-month period. After baseline observations, two interventions were implemented on the experimental unit: changing to an emollient handwashing agent, and providing feedback to staff about the frequency of handwashing. Feedback focused on the previous day's handwashing following completed patient contacts, interrupted patient contacts, and critical procedures. No increase in handwashing was observed following introduction of the emollient soap. However, when feedback was provided on the experimental ICU, handwashing following completed patient contacts (the major dependent measure) increased to 92%, and was significantly higher than handwashing on the control unit. Follow-up observations suggested that compliance on the experimental unit appeared to return to baseline levels.