UNVEILING THE COMPLEX ROLE OF NF-ΚB IN ALZHEIMER'S DISEASE: INSIGHTS INTO BRAIN INFLAMMATION AND POTENTIAL THERAPEUTIC TARGETS.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and dementia. One of the major pathologies underlying AD is chronic neuroinflammation mediated by microglia and astrocytes in the brain. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathway is a key regulator of inflammation and has been implicated in the neuroinflammatory processes associated with AD. This review comprehensively summarizes current findings on the complex role of NF-κB signalling in AD pathogenesis. The canonical and non-canonical NF-κB activation pathways are described, along with evidence from human studies and animal models demonstrating increased NF-κB activity in AD brains. The deleterious effects of NF-κB-mediated neuroinflammation are discussed, including the upregulation of inflammatory cytokines, chemokines, and enzymes that exacerbate neuronal damage over time. Targeting the NF-κB pathway is proposed as a promising therapeutic approach to dampen neuroinflammation in AD. Preclinical studies utilizing genetic or pharmacological inhibition of NF-κB are reviewed, and key challenges in translating these findings to clinical applications are analyzed. Overall, this review unveils the multifaceted contributions of NF-κB signalling to AD neuropathology and highlights anti-neuroinflammatory NF-κB modulation as a potential avenue for future AD treatments. Further research is warranted to fully elucidate the complex interactions between NF-κB and AD pathogenesis.

Public health investigation of infection prevention and control complaints in Ontario, 2015-2018.

BACKGROUND: Following an update to the provincial Infection Prevention and Control Complaint Protocol in 2015, Ontario public health units have been mandated to investigate infection prevention and control (IPAC) complaints in various settings, including those where regulated health professionals work. No surveillance system exists for IPAC complaints; therefore, little is known about their occurrence. Anecdotal evidence suggests a recent increase in IPAC complaints resulting in increased demand on public health resources. OBJECTIVES: To describe the occurrence of IPAC complaints and lapses in Ontario in 2015-2018 and the public health response to these. METHODS: Ontario public health units were surveyed about the occurrence and key challenges of IPAC complaint investigations through closed- and open-ended questions. The survey was disseminated through the Council of Ontario Medical Officers of Health listserv. Data collection spanned February 4-28, 2019. Descriptive statistical analyses and thematic analysis of free-text responses were performed. RESULTS: Twenty-one public health units responded for a 60% response rate; fewer responding health units had a population size of less than 100,000. A nearly six-fold increase in IPAC complaints was found, from a total of 79 complaints in 2015 to 451 in 2018. IPAC lapses nearly tripled, with 61 identified in 2015 and 168 in 2018. Whereas variation in the number of IPAC complaints and lapses among public health units was noted, the most common IPAC lapse involved inadequate reprocessing of reusable equipment. Key challenges in investigating IPAC complaints included lack of staff expertise/training, increased workload and costs, interjurisdictional inconsistencies and lack of guidance. CONCLUSION: IPAC complaints and lapses have increased in Ontario since 2015 when the Ministry of Health and Long-Term Care changed the IPAC complaint protocol. Public health units identified lack of expertise, increased workload, interjurisdictional inconsistencies and lack of guidance as challenges. Further research to confirm these findings, identify best practices to address these challenges as well as interventions to prevent IPAC lapses would be useful. Prospective surveillance of IPAC complaints, like for reportable diseases, would also be useful.

Community outbreak of hepatitis A disproportionately affecting men who have sex with men in Toronto, Canada, January 2017-November 2018.

BACKGROUND: In late 2016 and early 2017, a number of countries began reporting hepatitis A virus (HAV) outbreaks involving person-to-person transmission among men who have sex with men (MSM), people using illicit drugs and homeless or underhoused persons. OBJECTIVE: To describe the epidemiology and public health response to an outbreak of HAV disproportionately affecting MSM in Toronto, Canada from January 2017 to November 2018. METHODS: Following an increase in the number of cases of HAV in MSM being reported in other countries, enhanced surveillance was performed for all non-travel-related cases of HAV reported from June 1, 2017 to November 1, 2018, including a retrospective analysis of cases reported from January 2017 to June 2017. Descriptive analysis and viral sequencing were performed to describe person-to-person transmission patterns and target interventions. Control strategies included interventions to promote the uptake of preexposure HAV vaccination, including social media campaigns geared to MSM, messaging to healthcare providers and vaccine clinics. RESULTS: Based on the outbreak case definitions, 52 confirmed and probable cases of HAV were identified. Over 80% of outbreak cases were male (n=43/52) and, among those for whom data were available, 64% (n=25/39) reported an MSM exposure. Data on hospitalization was available for 51 cases; 56% of confirmed cases (n=23/41) and 40% of probable cases (n=4/10) required hospitalization. Of the cases with serum samples that had HAV sequencing, 83% (n=30/36) had one of the three strains seen circulating in outbreaks among MSM internationally; 72% (n=26/36) were VRD_521_2016, which had been detected in recently reported European outbreaks among MSM. Targeted promotion of publicly-funded vaccination using social media platforms popular with MSM and targeted vaccine clinics were developed to promote HAV awareness and vaccine uptake among MSM. CONCLUSION: Outbreaks of HAV, attributed to person-to-person transmission of strains of HAV that disproportionately affected MSM and were likely to have been imported from international MSM outbreaks, have now occurred in Canada. Genetic sequencing of HAV, risk factor analysis of cases, monitoring trends of vaccine coverage in high-risk groups and initiation of vaccination campaigns that address barriers to HAV preexposure vaccine coverage in the MSM population may prevent future outbreaks.

Rare yeasts causing fungemia in immunocompromised and haematology patients: Case series from Delhi.

Systemic fungal infection related to fluconazole-resistant yeasts are emerging in immunocompromised patients. In this case-series, we report eight cases of fungemia caused by Trichosporon spp. (2), Stephanoascus ceferrii (1), Kodamaea ohmeri (1), Pichia kutrawersi (2), Candida rugosa (1) and Candida lusitianae (1) in immunocompromised patients. All the yeasts except (Trichosporon asahii) were sequenced. As these rare species are inherently resistant to antifungal agents and they may lead to the development of nosocomial outbreaks, therefore, accurate identification followed by antifungal susceptibility testing is crucial for proper treatment and management.

Antileishmanial efficacy of Boerhaavia diffusa L. and Ocimum sanctum L. against experimental visceral leishmaniasis.

The chemotherapy of visceral leishmaniasis (VL) has several limitations including resistance and toxicity of the existing drugs. Down regulation of immune system further aggravates the problems. To combat this situation we evaluated the leishmanicidal efficacy of Boerhaavia diffusa and Ocimum sanctum through oral route in L. donovani infection in BALB/c mice. Results have demonstrated maximum clearance of the parasites from infected animals treated with combination of B. diffusa and O. sanctum (@ 100 and 400 mg/kg body wt., respectively 5 days) as depicted through Leishman Donovan Units in liver. Up-regulation of cell-mediated immunity was also observed in animals of this group as heightened delayed type hypersensitivity responses and increased IgG2a levels were observed. Moreover, increased levels of SGOT, SGPT, serum urea, blood urea nitrogen and serum creatinine were brought down to normal levels. Since VL is associated immunosuppression, the above treatment is a good option as it helps in the up-regulation of Th1 responses and reduction in parasite load in L. donovani infected mice. These findings suggest a new option for antileishmanial chemotherapy at lower cost and nil toxicity.

Amebic peritonitis.

A total of 18 patients with amebic peritonitis were studied. Fourteen of these cases were due to rupture of amebic liver abscess into the peritoneum and the remaining cases were due to perforation of amebic colitis. No initial suspicion of amebic etiology was made in more than half of the cases. In the group of ruptured liver abscesses, nearly half of the patients showed right lower lung syndrome. The diagnosis in 13 of 14 cases of rupture of liver abscess was confirmed on aspiration. Patients with ruptured amebic liver abcess were of two types: 1. Diffuse type with diffuse signs, shorter duration of illness and poor prognosis. 2. Localized type with longer duration of illness, marked signs of peritonitis and better prognosis. Once the diagnosis of peritonitis was made, the management was surgical. Conservative treatment was tried only in cases with signs of localization. The mortality rate had been 33% in amebic liver abscess rupturing into the peritoneum and 75% in perforation of the intestine. A high index of suspicion of amebiasis in patients with an acute abdomen and institution of early treatment are recommended to help in reducing this mortality. Amebic liver abscess and amebic dysentery should be treated energetically to avoid this fatal complication and surgical intervention whenever indicated should not be delayed.

Agenesis of the gallbladder: report of two cases.

Two cases of agenesis of the gallbladder are presented. In one patient there was a remnant of cystic duct, the other had no cystic duct. A brief review of the literature is included.