Mice lacking bi-1 gene show accelerated liver regeneration

The liver has enormous regenerative capacity such that, after partial hepatectomy, hepatocytes rapidly replicate to restore liver mass, thus providing a context for studying in vivo mechanisms of cell growth regulation. Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death. Interestingly, the BI-1 protein has been shown to regulate Ca(2+) handling by the ER similar to antiapoptotic Bcl-2 family proteins. Effects on cell cycle entry by Bcl-2 family proteins have been described, prompting us to explore whether bi-1-deficient mice display alterations in the in vivo regulation of cell cycle entry using a model of liver regeneration. Accordingly, we compared bi-1(+/+) and bi-1(-/-) mice subjected to partial hepatectomy with respect to the kinetics of liver regeneration and molecular events associated with hepatocyte proliferation. We found that bi-1 deficiency accelerates liver regeneration after partial hepatectomy. Regenerating hepatocytes in bi-1(-/-) mice enter cell cycle faster, as documented by more rapid incorporation of deoxynucleotides, associated with earlier increases in cyclin D1, cyclin D3, cyclin-dependent kinase (Cdk) 2, and Cdk4 protein levels, more rapid hyperphosphorylation of retinoblastoma protein, and faster degradation of p27(Kip1). Dephosphorylation and nuclear translocation of nuclear factor of activated T cells 1 (NFAT1), a substrate of the Ca(2+)-sensitive phosphatase calcineurin, were also accelerated following partial hepatectomy in BI-1-deficient hepatocytes. These findings therefore reveal additional similarities between BI-1 and Bcl-2 family proteins, showing a role for BI-1 in regulating cell proliferation in vivo, in addition to its previously described actions as a regulator of cell survival.     

Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience

Hydroxyurea (HU) is considered to be the most successful drug therapy for severe sickle cell disease (SCD). Nevertheless, questions remain regarding its benefits in very young children and its role in the prevention of cerebrovascular events. There were 127 SCD patients treated with no attempt to reach maximal tolerated doses who entered the Belgian Registry: 109 for standard criteria and 18 who were at risk of stroke only. During 426 patient-years of follow-up for patients with standard criteria, 3.3 acute chest syndromes, 1.3 cerebrovascular events, and 1.1 osteonecrosis per 100 patient-years were observed. A subgroup of 32 patients followed for 6 years experienced significant benefit over this period. In each subgroup of children (younger than 2 years, 2-5, 6-9, and 10-19 years) followed for 2 years, clinical and biologic changes were similar, except for children younger than 2 years who had no total hemoglobin increase and remained at risk of severe anemia. In 72 patients evaluated by transcranial Doppler studies (TCD), 34 patients were at risk of primary stroke and only 1 had a cerebrovascular event after a follow-up of 96 patient-years. These results confirm the benefit of HU, even in very young children, and its possible role in primary stroke prevention.     

Impact of a malaria-control project in Benin that included the integrated management of childhood illness strategy

Objectives. To estimate the impact of the Integrated Management of Childhood Illness (IMCI) strategy on early-childhood mortality, we evaluated a malaria-control project in Benin that implemented IMCI and promoted insecticide-treated nets (ITNs).Methods. We conducted a before-and-after intervention study that included a nonrandomized comparison group. We used the preceding birth technique to measure early-childhood mortality (risk of dying before age 30 months), and we used health facility surveys and household surveys to measure process indicators.Results. Most process indicators improved in the area covered by the intervention. Notably, because ITNs were also promoted in the comparison area children''s ITN use increased by about 20 percentage points in both areas. Regarding early-childhood mortality, the trend from baseline (1999–2001) to follow-up (2002–2004) for the intervention area (13.0% decrease; P < .001) was 14.1% (P < .001) lower than was the trend for the comparison area (1.3% increase; P = .46).Conclusions. Mortality decreased in the intervention area after IMCI and ITN promotion. ITN use increased similarly in both study areas, so the mortality impact of ITNs in the 2 areas might have canceled each other out. Thus, the mortality reduction could have been primarily attributable to IMCI''s effect on health care quality and care-seeking.In sub-Saharan Africa, malaria is a leading cause of child mortality.^1,2 These deaths can be prevented with insecticide-treated nets (ITNs), indoor insecticide spraying, prompt and effective treatment of malaria cases, and intermittent preventive treatment of malaria in pregnant women.²To improve children''s malaria treatment, the Roll Back Malaria partnership and the World Health Organization (WHO) recommend the Integrated Management of Childhood Illness (IMCI) strategy.^3–5 IMCI, which was developed by WHO and other partners, aims to prevent mortality from all leading causes of child deaths (e.g., pneumonia, diarrhea, and malaria). IMCI has 3 components: (1) improving case-management quality (especially in health facilities) by training health workers to use evidence-based clinical guidelines, (2) strengthening health systems, and (3) promoting community and family health practices.IMCI has been introduced in more than 100 developing countries,⁶ and studies have demonstrated that it can improve health care quality at health facilities.^7–10 With regard to its effect on mortality, however, the evidence is mixed. IMCI seems to have lowered child mortality in Tanzania,¹¹ but studies in Brazil¹² and Bangladesh⁸ did not find a statistically significant reduction. Thus, despite IMCI being one of the world''s most widely implemented child health strategies, its impact on mortality remains unclear.In 1998, before today''s billion-dollar malaria initiatives, the US Agency for International Development launched a subnational malaria demonstration project in Benin that included IMCI. Benin is a low-income country in West Africa with extreme poverty,¹³ endemic malaria, and high mortality for children younger than 5 years (160 deaths per 1000 live births when the project began¹⁴). We conducted this study to evaluate the project''s impact on early-childhood mortality, with an emphasis on IMCI''s impact.     

Emergency general surgery in Rwandan district hospitals: a cross-sectional study of spectrum,management, and patient outcomes

Background

Management of emergency general surgical conditions remains a challenge in rural sub-Saharan Africa due to issues such as insufficient human capacity and infrastructure. This study describes the burden of emergency general surgical conditions and the ability to provide care for these conditions at three rural district hospitals in Rwanda.

Methods

This retrospective cross-sectional study included all patients presenting to Butaro, Kirehe and Rwinkwavu District Hospitals between January 1st 2015 and December 31st 2015 with emergency general surgical conditions, defined as non-traumatic, non-obstetric acute care surgical conditions. We describe patient demographics, clinical characteristics, management and outcomes.

Results

In 2015, 356 patients presented with emergency general surgical conditions. The majority were male (57.2%) and adults aged 15–60 years (54.5%). The most common diagnostic group was soft tissue infections (71.6%), followed by acute abdominal conditions (14.3%). The median length of symptoms prior to diagnosis differed significantly by diagnosis type (p?<?0.001), with the shortest being urological emergencies at 1.5 days (interquartile range (IQR):1, 6) and the longest being complicated hernia at 17.5 days (IQR: 1, 208). Of all patients, 54% were operated on at the district hospital, either by a general surgeon or general practitioner. Patients were more likely to receive surgery if they presented to a hospital with a general surgeon compared to a hospital with only general practitioners (75% vs 43%, p?<?0.001). In addition, the general surgeon was more likely to treat patients with complex diagnoses such as acute abdominal conditions (33.3% vs 4.1%, p?<?0.001) compared to general practitioners. For patients who received surgery, 73.3% had no postoperative complications and 3.2% died.

Conclusion

While acute abdominal conditions are often considered the most common emergency general surgical condition in sub-Saharan Africa, soft tissue infections were the most common in our setting. This could represent a true difference in epidemiology in rural settings compared to referral facilities in urban settings. Patients were more likely to receive an operation in a hospital with a general surgeon as opposed to a general practitioner. This provides evidence to support increasing the surgical workforce in district hospitals in order to increase surgical availability for patients.

     

Barriers to and facilitators of adherence to pediatric antiretroviral therapy in a sub-Saharan setting: insights from a qualitative study

Despite the need for HIV-positive children to adhere effectively to antiretroviral treatment (ART), a guiding theory for pediatric ART in resource-limited settings is still missing. Understanding factors that influence pediatric ART adherence is critical to developing adequate strategies. In-depth qualitative interviews were undertaken in Kinshasa, Democratic Republic of the Congo, with 20 sets of HIV disclosed and nondisclosed children along with respective caregivers to better characterize barriers, facilitators, and adherence experiences in children taking ART. Commonly cited barriers included lack of food or nutritional support, lack of assistance or supervision for children, lack of assistance for caregivers, and being unable to remember to take medicines on a consistent basis. Facilitators included having a strong caregiver-child relationship and support system along with strategies for maintaining adherence. Similar themes arose within the child-caregiver sets, but were often characterized differently between the two. Children who were aware of their HIV status displayed fewer instances of frustration and conflict concerning taking medicines and within the child-caregiver relationship. Continued study on pediatric ART adherence should account for differing perspectives of children and caregivers, as well as between status disclosed and nondisclosed children. Areas of future intervention should focus on child-caregiver relationships, disclosure of HIV status, and available nutritional and psychosocial support for children and their caregivers.     

Posterior dislocation in a voluntary subluxator: a case report

PURPOSE: Posterior instability of the shoulder is an uncommon occurrence. Its etiology has been classified as traumatic or atraumatic and its type as voluntary (individual can subluxate the shoulder posteriorly) or involuntary. Typically, patients with posterior voluntary instability do not have a history of trauma, can be treated successfully with physical therapy; and undergo surgery if the instability becomes symptomatic or develops an involuntary component. We present a patient with voluntary posterior subluxation who developed a symptomatic posterior instability after a traumatic event. PATIENT PRESENTATION: This patient was unable to return to his preinjury function despite nonoperative interventions, including rehabilitation, and required operative treatment of his posterior labrum lesion. This patient had a rare combination of voluntary, atraumatic instability that coexisted with traumatic posterior shoulder instability. CONCLUSION: This case emphasizes the importance of recognizing this constellation of instability patterns and documents that traumatic posterior instability, even in the presence of preexisting voluntary posterior subluxations, may require operative intervention in young, active individuals.