Growth, morbidity, and mortality in a cohort of institutionalized HIV-1-infected African children

OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors.     

<Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Ats1p interacts with Nap1p,a cytoplasmic protein that controls bud morphogenesis

Saccharomyces cerevisiae ATS1 (-tubulin suppressor 1) was originally identified as a high-copy suppressor of class two -tubulin mutations and was proposed to have a regulatory role in coordinating the microtubule state with the cell cycle. Here, we show that Ats1p interacts with Nap1p, a cytoplasmic protein that regulates the activity of the Cdc28p/Clb2p complex. Loss of Nap1p results in a delayed switch from polar to isotropic bud growth. The delayed switch results in elongated buds. Nap1p and Ats1p interact in two-hybrid and co-immunoprecipitation assays. Both nap1 and ats1 cells have a Clb2p-dependent elongated bud morphology. Deletion of ATS1 partially suppresses the elongated bud morphology and benomyl resistance of nap1 mutants. Our results suggest Ats1p might regulate coordination of the microtubule state with the cell cycle through an interaction with Nap1p.Communicated by S. Hohmann     

Continuous Glucose Monitoring Use in Clinical Trials for On-Market Diabetes Drugs

To the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacological agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 antihyperglycemic therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.

The availability of reliable continuous glucose monitoring (CGM) systems has proven to be a major innovation in diabetes management and research. Most current CGM systems are approved for 7- to 14-day use and use a wire-tipped glucose oxidase sensor inserted in subcutaneous tissue to monitor glucose concentrations in interstitial fluid. One implanted CGM system is approved for longer-term use (90–180 days); it operates with fluorescence-based technology. CGM sensors record a glucose data point every 1–15 minutes (depending on the system), collecting far more granular data and information on glycemic patterns than self-monitoring of blood glucose (SMBG) alone. Real-time CGM or intermittently scanned CGM systems send data continuously or intermittently to dedicated receivers or smartphones, whereas professional CGM systems provide retrospective data, either blinded or unblinded, for analysis and can be used to identify patterns of hypo- and hyperglycemia. Professional CGM can be helpful to evaluate patients when other CGM systems are not available to the patient or the patient prefers a blinded analysis or a shorter experience with unblinded data.In the 20 years since CGM systems first became available to people with diabetes, technological improvements, particularly pertaining to accuracy and form factor, have made CGM increasingly viable for both patient use and clinical investigation (1,2). Average sensor MARD (mean absolute relative difference; a summary accuracy statistic) has decreased from >20 to <10% (3–10), including two systems that do not require fingerstick calibrations and three that are approved to be used for insulin dosing (11). Concurrently, size, weight, and cost of CGM systems have all decreased, while user-friendliness and convenience have increased (12).To encourage use of CGM-derived data, researchers and clinicians have worked to develop a standard set of glycemic metrics beyond A1C. In 2017, two international groups of leading diabetes clinical and research organizations published consensus definitions for key metrics, including clinically relevant glycemic cut points for hypoglycemia (<70 and <54 mg/dL), hyperglycemia (>180 and >250 mg/dL), and time in range (TIR; 70–180 mg/dL) (13,14).CGM-derived metrics provide far greater precision and granularity than is possible with SMBG or A1C data alone (Table 1), enabling clinicians and investigators to better represent inter- and intraday glycemic differences with metrics such as TIR, glycemic variability, and time in hypoglycemia and hyperglycemia (15). Crucially, CGM also allows for the accurate measurement and detection of nocturnal glycemia (16). The use of these metrics enables a more comprehensive understanding of glycemic management that can facilitate individualized treatment for people with diabetes or prediabetes. Although A1C is a useful estimate of mean glucose over the previous 2–3 months, especially when evaluating population health, it is important to include other glycemic outcomes in clinical trials. Furthermore, there is emerging evidence suggesting that TIR predicts the development of microvascular complications at least as well as A1C (17,18).TABLE 1Benefits of CGM Compared With A1C Alone in Assessing Glycemia

Interferon-gamma receptor 1 promoter polymorphisms: population distribution and functional implications

Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polymorphisms (SNPs) were detected in the IFNGR1 MPR. The three ethnic groups showed different SNP distribution patterns, but no significant differences were detected between mycobacterial cases and controls. Two polymorphisms were found in all populations (G-611A, T-56C). We cloned the four allelic variants (var) of haplotype G-611A/T-56C into a luciferase reporter vector and determined their promoter activity. Polymorphisms at position -611 had a stronger effect on the promoter activity than those at position -56, and constructs carrying G-611 produced a stronger promoter activity than -611A constructs. The IFNGR1 MPR is a polymorphic region with at least two SNPs influencing its activity, but these are not associated with increased mycobacterial susceptibility.     

Increased Contact Time and Strength Deficits in Runners With Exercise-Related Lower Leg Pain

ContextExercise-related lower leg pain (ERLLP) is common in runners.ObjectiveTo compare biomechanical (kinematic, kinetic, and spatiotemporal) measures obtained from wearable sensors as well as lower extremity alignment, range of motion, and strength during running between runners with and those without ERLLP.DesignCase-control study.SettingField and laboratory.Patients or Other ParticipantsOf 32 young adults who had been running regularly (>10 mi [16 km] per week) for ≥3 months, 16 had ERLLP for ≥2 weeks and 16 were healthy control participants.Main Outcome Measure(s)Both field and laboratory measures were collected at the initial visit. The laboratory measures consisted of alignment (arch height index, foot posture index, navicular drop, tibial torsion, Q-angle, and hip anteversion), range of motion (great toe, ankle, knee, and hip), and strength. Participants then completed a 1.67-mi (2.69-km) run along a predetermined route to calibrate the RunScribe devices. The RunScribe wearable sensors collected kinematic (pronation excursion and maximum pronation velocity), kinetic (impact g and braking g), and spatiotemporal (stride length, step length, contact time, stride pace, and flight ratio) measures. Participants then wore the sensors during at least 3 training runs in the next week.ResultsThe ERLLP group had a slower stride pace than the healthy group, which was accounted for as a covariate in subsequent analyses. The ERLLP group had a longer contact time during the stance phase of running (mean difference [MD] = 18.00 ± 8.27 milliseconds) and decreased stride length (MD = −0.11 ± 0.05 m) than the control group. For the clinical measures, the ERLLP group demonstrated increased range of motion for great-toe flexion (MD = 13.9 ± 4.6°) and ankle eversion (MD = 6.3 ± 2.7°) and decreased strength for ankle inversion (MD = −0.49 ± 0.23 N/kg), ankle eversion (MD = −0.57 ± 0.27 N/kg), and hip flexion (MD = −0.99 ± 0.39 N/kg).ConclusionsThe ERLLP group exhibited a longer contact time and decreased stride length during running as well as strength deficits at the ankle and hip. Gait retraining and lower extremity strengthening may be warranted as clinical interventions in runners with ERLLP.     

Health-related quality-of-life measures for children with asthma: reliability and validity of the Children's Health Survey for Asthma and the Pediatric Quality of Life Inventory 3.0 Asthma Module.

BACKGROUND: Economically disadvantaged African American youth are especially vulnerable to the effects of pediatric asthma and are at increased risk for difficulties in daily functioning. Measures of health-related quality of life (HRQoL) yield important information regarding the impact of pediatric chronic illness on daily functioning. It is essential to develop and validate measures of HRQoL to detect the impact of asthma on this vulnerable population. OBJECTIVE: To examine the psychometric properties of 2 asthma-specific measures of pediatric HRQoL in a sample of economically disadvantaged African American children diagnosed as having asthma. METHODS: One hundred twenty-seven caregivers completed questionnaires regarding their child's HRQoL, asthma symptoms, health care utilization, and school absences and regarding caregiver emotional distress. The severity of the child's asthma was measured via spirometry. RESULTS: The Children's Health Survey for Asthma and the Pediatric Quality of Life Inventory 3.0 Asthma Module demonstrated adequate internal consistency reliability and validity for the present sample. Lower HRQoL was associated with poorer adherence and more health care utilization, asthma symptom days, school absences, and caregiver distress. Only the Children's Health Survey for Asthma was significantly associated with severity, when defined as airway obstruction. CONCLUSIONS: This study supports the psychometric equivalence of 2 condition-specific measures of HRQoL in a population at high risk for asthma and asthma-related problems. The utility of each measure will depend on the needs of the researcher or physician. Both measures can inform the treatment course, help identify and address barriers to treatment adherence, and inform treatment interventions.     

A screening study of antidepressant treatment rates and mood symptoms in pregnancy

Summary Study design: As part of a large screening study of perinatal depression, pregnant women were screened for demographic, depression and treatment variables in obstetrics clinics. Women taking antidepressant medication prior to conception were included in the sample as the study aimed to document rates of antidepressant medication use, and relationship to depressive symptomatology.Results: Among women who reported using antidepressant medications within 2 years prior to screening (n = 390, or 11% of all women), 22% reported current use of these medications. Women who reported using antidepressant medications (52%) and those who discontinued them (49%) evidenced elevated depressive symptoms during pregnancy.Conclusions: Both women who discontinue and some who continue antidepressants during pregnancy demonstrate depressive symptoms, suggesting sub-optimal management of both groups. Future studies should carefully assess the adequacy of treatments prescribed as well as the monitoring and adherence of recommended treatments. Full symptom remission should be the goal for antenatal and postnatal depression in order to minimize risk to mother and baby.