The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.

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Apoptosis: A Review of Programmed Cell Death

A precise definition of the basic reproduction number, Ro, is presented for a general compartmental disease transmission model based on a system of ordinary dierential equations. It is shown that, if Ro 1, then it is unstable. Thus,Ro is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for Ro near one. This criterion, together with the definition of Ro, is illustrated by treatment, multigroup, staged progression, multistrain and vectorhost models and can be applied to more complex models. The results are significant for disease control.

/pdf/reproduction-numbers-and-sub-threshold-endemic-equilibria-4b4f32pm0g.pdf

Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission

Many models for the spread of infectious diseases in populations have been analyzed mathematically and applied to specific diseases. Threshold theorems involving the basic reproduction number $R_{0}$, the contact number $\sigma$, and the replacement number $R$ are reviewed for the classic SIR epidemic and endemic models. Similar results with new expressions for $R_{0}$ are obtained for MSEIR and SEIR endemic models with either continuous age or age groups. Values of $R_{0}$ and $\sigma$ are estimated for various diseases including measles in Niger and pertussis in the United States. Previous models with age structure, heterogeneity, and spatial structure are surveyed.

https://epubs.siam.org/doi/pdf/10.1137/S0036144500371907

The Mathematics of Infectious Diseases

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Anemia is a complication of severe burn injury. Burn patients who refuse blood transfusions, such as Jehovah's Witnesses, present difficult challenges, and treatment paradigms need to be altered to reduce blood loss and increase red cell restoration. In this report the authors present a case of a 36-year-old Jehovah's Witness who suffered a 35% TBSA burn injury. In addition to standard burn injury treatment, the authors attempted to reduce blood loss with a combination of intraoperative (tranexamic acid) and perioperative (erythropoietin, intravenous iron) strategies.

Reducing postburn injury anemia in a Jehovah's Witness patient.

Despite continued efforts to increase safety, burns associated with motor vehicles have accounted for as much as 10% of all burn admissions. Our objective was to characterize the mechanism of these burn types. We undertook a retrospective review of all patients admitted to a regional burn center from 1997 through 2003. A total of 2745 patients were admitted; 8.0% (n = 220) had automobile-associated injuries. Their mean age was 29.6 +/- 18.1 years, and 83.6% (n = 184) were men. Mean burn size was 14 +/- 15.6% TBSA, 7.5 +/- 15.2% full-thickness. Inhalation injury occurred in 25 patients, and 25 patients had associated nonburn injuries. Mean length of stay was 14.8 +/- 23.6 days. Those patients undergoing procedures (n = 108) had an average of 2.1 operations, with a mean area grafted of 2780 cm. There were two deaths in this group of patients. Hospital charges amounted to $53,200 +/- 78,000 per patient. Automobile burns still account for a significant portion of burn unit admissions. The most severe injuries appear to be from the regular use and maintenance of vehicles. The most common burn injuries are from radiators and carburetors. Simple prevention should be adequate to avoid these injuries. Current efforts appear to have made minimal headway. Language: en

Burn injury caused by motor vehicle use and repair.

Envelope (env) proteins of certain endogenous retroviruses (ERVs) participate in various pathophysiological processes. In this study, we characterized pathophysiologic properties of two murine leukemia virus-type ERV (MuLV-ERV) env genes cloned from the ovary of C57BL/6J mice. The two env genes (named ENV(OV1) and ENV(OV2)), with 1,926 bp coding region, originated from two MuLV-ERV loci on chromosomes 8 and 18, respectively. ENV(OV1) and ENV(OV2) were ~75 kDa and predominantly expressed on the cell membrane. They were capable of producing pseudotype murine leukemia virus virions. Tropism trait and infectivity of ENV(OV2) were similar to the polytropic env; however, ENV(OV1) had very low level of infectivity. Overexpression of ENV(OV2), but not ENV(OV1), exerted cytotoxic effects and induced expression of COX-2, IL-1β, IL-6, and iNOS. These findings suggest that the ENV(OV1) and ENV(OV2) are capable of serving as an env protein for virion assembly, and they exert differential cytotoxicity and modulation of inflammatory mediators.

/pdf/tropism-cytotoxicity-and-inflammatory-properties-of-two-5awxqabc0a.pdf

Tropism, Cytotoxicity, and Inflammatory Properties of Two Envelope Genes of Murine Leukemia Virus Type-Endogenous Retroviruses of C57BL/6J Mice

Not all burn centers are quiet during the COVID-19 crisis "Trends in Burn Injuries in Northern Israel during the COVID-19 Lockdown"

The case studies reported in this article strive to illustrate the clinical value of multiplex polymerase chain reaction (PCR)-based pathogen detection in patients with burn sepsis. Adult (age ≥18 years) burn patients (≥20% TBSA) presenting with signs and symptoms of burn sepsis were enrolled into a prospective, observational trial. Patients received PCR testing in parallel to routine blood cultures. The authors report two cases in which PCR was used to rapidly detect pathogens in whole blood from burn patients with suspected septicemia. PCR identified Escherichia coli in 5.8 hours in case 1. Blood and sputum cultures required 17 hours for Gram stain results. Empiric ceftriaxone therapy was initiated. Blood cultures required an additional 18 hours to identify the same pathogen detected by PCR. Ceftriaxone was replaced with ciprofloxacin for improved coverage. Follow-up antimicrobial susceptibility results revealed intermediate ciprofloxacin resistance. Meropenam therapy was initiated. In case 2, PCR detected Pseudomonas aeruginosa in 5.45 hours while blood cultures remained negative. Respiratory cultures became positive for P. aeruginosa 2 days later. Serial PCR samples continued detecting P. aeruginosa despite negative blood cultures and appropriate antimicrobial therapy. The patient later became hypotensive and coagulopathic and expired. For both patient cases, PCR identified high-risk pathogens faster than culture methods. In the second patient case, PCR identified the presence of pathogen DNA despite negative cultures before the onset of septic shock and presumptive disseminated intravascular coagulation. These results warrant further investigation to determine the clinical significance of pathogen DNA in burn sepsis.

David G. Greenhalgh

Papers

Reducing postburn injury anemia in a Jehovah's Witness patient.

Burn injury caused by motor vehicle use and repair.

Tropism, Cytotoxicity, and Inflammatory Properties of Two Envelope Genes of Murine Leukemia Virus Type-Endogenous Retroviruses of C57BL/6J Mice

Not all burn centers are quiet during the COVID-19 crisis "Trends in Burn Injuries in Northern Israel during the COVID-19 Lockdown"

Multiplex PCR pathogen detection in two severely burned patients with suspected septicemia.