Lithium-induced changes in the body mass index

A total of 117 manic-depressives who had been on lithium for a mean duration of 4.7 years were examined before lithium therapy and subsequently at intervals. Information relating to pre-lithium height and weight and current weight were determined and used to calculate the body mass index (BMI) for each individual. Other relevant variables such as age, sex, cumulative lithium dose, duration of therapy, thyroid profile and serum lithium levels were recorded. The results indicated that, although there was a nonsignificant increase in BMI for the whole population, lithium and sex were not significant predictors of any increase in BMI. In nearly 27% of patients BMI actually slightly decreased during lithium therapy. The overall conclusions from this study are that, in the population studied, lithium may not have exerted any pharmacological effects to increase BMI.     

Preemptive analgesia for postoperative pain relief in lumbosacral spine surgeries: a randomized controlled trial.

BACKGROUND CONTEXT: Administration of analgesic medication, before the actual onset of painful stimulus, is more effective than that after the onset of painful stimulus. This is the principle of preemptive analgesia. Although it is often considered superior to other forms of analgesia, its role in postoperative pain relief after lumbosacral spinal surgery has not been fully investigated. PURPOSE: To analyze the efficacy of preemptive analgesia with a single caudal epidural injection for patients undergoing surgeries on the lumbosacral spine by the posterior approach. STUDY DESIGN/SETTING: Randomized, double-blinded and controlled clinical trial. PATIENT SAMPLE: Eighty-two patients who underwent discectomy in the lumbosacral spine by the posterior approach, with or without instrumentation, were randomized to the control group (n=40) and to the study group (n=42). METHODS: Patients in control group received a single caudal epidural injection of 20 ml of normal saline. Patients in study group received a single caudal epidural injection of 20 ml containing bupivacaine and tramadol as the active agents. The time interval between this injection and the surgical incision was never less than 20 minutes in either of the groups. This facilitated enough time for the drug to get fixed to the nerve roots, leading to effective preemptive analgesia. OUTCOME MEASURES: Patients were monitored for postoperative pain immediately after surgery when they had completely recovered and regained consciousness from general anesthesia, and subsequently 4, 8, 12 and 24 hours thereafter. Pain was quantified using the visual analog scale (VAS) and the verbal rating scale (VRS). The time at which supplemental analgesic medication was first demanded in the postoperative period by the patient was also noted. RESULTS: The two groups were comparable for age, sex, body weight and the type of surgery they underwent. Because the data did not have a normal Gaussian distribution, the one-tailed Mann-Whitney test, being a nonparametric test, was adopted for statistical analysis. Accordingly, VAS and VRS values at all time intervals were significantly lower (p<.0001) in the study group as compared with the control group. This indicated significantly better pain relief in the study group. There was also a significant delay (p=.0041) in the first demand for supplemental analgesic medication in the postoperative period in the study group. No complication specific to the procedure was noted except for the development of postoperative urinary retention, which was transient and appropriately managed with urinary catheterization. CONCLUSIONS: Preemptive analgesia with a single caudal epidural injection of bupivacaine and tramadol is a safe, simple and effective method for postoperative pain relief.     

Comparison of two laboratory tests in the control of anticoagulant therapy

A prospective, randomized trial is described in which the usefulness of two tests in the control of anticoagulant therapy is compared. Fifty-two patients were controlled by the one-stage prothrombin time and 55 by the activated partial thromboplastin time. There was no significant difference in the incidence of bleeding between the two groups. When bleeding did occur, it was more often reflected by prolongation of the prothrombin time than of the activated partial thromboplastin time. The prothrombin time was found to have some practical advantages over the activated partial thromboplastin time.     

Signal transduction in human B cells initiated via Ig{beta} ligation

Ig and Igß heterodimers are non-covalently associatedwith Ig to compose the antigen receptor complexes on B cells.The demonstration that different sets of tyrosine kinases bindto the cytoplasmic tails of Ig and Igß suggests thatIg and Igß may activate distinct second messengerpathways. In this study, we examined the effects of mAbs againstan exposed epitope of human Igß on pre-B and B celltriggering. Cross-linkage of Igß on B cells leadsto activation of tyrosine kinases, hydrolysis of phosphatidylinositides,and elevation of intracellular Ca²⁺, effects qualitatively identicalto those of anti-_µ mAbs. Our observations thus indicatethat cross-linking of Igß does not segregate signaltransduction pathways connected with the cytoplasmic talls ofIg and Igß. Ig ligation has been reported to be moreeffective in triggering pre-B than B cells, whereas our resultsindicated that Igß ligation is more efficient in triggeringB than pre-B cells. In addition to their activation properties,the anti-Igß mAbs effectively modulated B cell receptorcomplexes and blocked terminal differentiation of all plasmacell isotypes. The findings support the idea that anti-Igßcould serve as a universal B cell immunosuppressant.     

Complex mosaic structural variations in human fetal brains

Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions, and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200–400 mosaic SNVs per cell in three human fetal brains (15–21 wk postconception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones, and we timed its origin to ∼14 wk postconception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extrachromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs and present in ∼10% of neurons, SVs in developing human brain affect a comparable number of bases in the genome (∼6200 vs. ∼4000 bp), implying that they may have similar functional consequences.

Somatic mosaicism, the presence of more than one genotype in the somatic cells of an individual, is a prominent phenomenon in the human central nervous system. Forms of mosaicism include aneuploidies and smaller copy number variants (CNVs), structural variants (SVs), mobile element insertions, indels, and single nucleotide variants (SNVs). The developing human brain exhibits high levels of aneuploidy compared to other tissues, generating genetic diversity in neurons (Pack et al. 2005; Yurov et al. 2007; Bushman and Chun 2013). Such aneuploidy was suggested to be a natural feature of neurons, rather than a distinctive feature of neurodegeneration. However, the frequency of aneuploidy in neurons has been debated, with a separate study suggesting that aneuploidies occur in only about 2.2% of mature adult neurons (Knouse et al. 2014). They hence infer that such aneuploidy could have adverse effects at the cellular and organismal levels. Additionally, analysis of single cells from normal and pathological human brains identified large, private, and likely clonal somatic CNVs in both normal and diseased brains (Gole et al. 2013; McConnell et al. 2013; Cai et al. 2014; Knouse et al. 2016; Chronister et al. 2019; Perez-Rodriguez et al. 2019), with 3%–25% of human cerebral cortical nuclei carrying megabase-scale CNVs (Chronister et al. 2019) and deletions being twice as common as duplications (McConnell et al. 2013). Given that CNVs often arise from nonhomologous recombination and replication errors, their likely time of origin is during brain development. However, when CNVs first arise in human brain development has not yet been investigated. The present work is the first to examine this question using clonal populations of neuronal progenitor cells (NPCs) obtained from fetal human brains.Detection of CNVs in single neurons is challenging, given the need to amplify DNA. Such amplification may introduce artifacts that could, in turn, be misinterpreted as CNVs. In order to address this technical limitation, Hazen et al. reprogrammed adult postmitotic neurons using somatic cell nuclear transfer (SCNT) of neuronal nuclei into enucleated oocytes (Hazen et al. 2016). These oocytes then made sufficient copies of the neuronal genome allowing for whole-genome sequencing (WGS), thus eliminating the need for amplification in vitro. Using this method, they identified a total of nine structural variants in six neurons from mice, three of which were complex rearrangements. However, it is not possible to extend such studies to humans, given the ethical issues involved, besides the technical challenges in obtaining and cloning adult neurons. To circumvent the need of single-cell DNA amplification or nuclear cloning, we examined clonal cell populations obtained from neural progenitor cells from the frontal region of the cerebral cortex (FR), parietal cortex (PA) and basal ganglia (BG) and describe here the discovery and analysis of mosaic SVs in these NPCs (Bae et al. 2018). These clones were sequenced at 30× coverage (much higher than most previous single-cell studies), allowing identification of SVs other than large deletions and duplications as well as precise breakpoint resolution.     

Dengue disease spectrum among infants in the 2001 dengue epidemic in Chennai,Tamil Nadu,India

An investigation in a referral pediatric hospital has indicated that during a recent dengue outbreak in Chennai, Tamil Nadu, India, dengue in infancy constituted 20% of total dengue virus infections with low mortality rates in this hospital. In developing countries, strengthening of dengue management capabilities at hospitals can prevent dengue-related deaths in infants.     

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

Background  

CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART.     

Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

5-Benzoyl-5-deacetylwilforidine: a new sesquiterpene nicotinoyl alkaloid from Maytenus buchananii

A new sesquiterpene nicotinoyl alkaloid has been isolated from Maytenus buchananii (Loes.) R. Wilczek and identified as 5-benzoyl-5-deacetylwilforidine (1). This appears to be the first sesquiterpene nicotinoyl alkaloid based on hydroxywilfordic acid with a benzoyl group at C-5.     

New 5-Factor Modified Frailty Index Predicts Morbidity and Mortality in Primary Hip and Knee Arthroplasty

Background

While the 11-factor modified frailty index (mFI) has been shown to predict adverse outcomes in patients undergoing total joint arthroplasty, the 5-factor index has not been evaluated in this patient population. The goal of this study was to evaluate the utility of the mFI-5 as a predictor of morbidity and mortality in patients undergoing primary total hip and knee arthroplasty.