Genome Profiling of SARS-CoV-2 in Indonesia,ASEAN and the Neighbouring East Asian Countries: Features,Challenges and Achievements

Whole-genome sequencing (WGS) has played a significant role in understanding the epidemiology and biology of SARS-CoV-2 virus. Here, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asian countries as a genomic surveillance during the COVID-19 pandemic. Nottingham–Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in the Research Center for Biotechnology, National Research and Innovation Agency (BRIN), to carry out a small number of SARS-CoV-2 WGS in Indonesia using Oxford Nanopore Technology (ONT). Analyses of SARS- CoV-2 genomes deposited on GISAID reveal the importance of clinical and demographic metadata collection and the importance of open access and data sharing. Lineage and phylogenetic analyses of two periods defined by the Delta variant outbreak reveal that: (1) B.1.466.2 variants were the most predominant in Indonesia before the Delta variant outbreak, having a unique spike gene mutation N439K at more than 98% frequency, (2) Delta variants AY.23 sub-lineage took over after June 2021, and (3) the highest rate of virus transmissions between Indonesia and other countries was through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.     

Acute management and outcome of multiple trauma patients with pelvic disruptions

ABSTRACT: INTRODUCTION: Data on pre-hospital and trauma room fluid management of multiple trauma patients with pelvic disruptions are rarely reported. Present trauma algorithms recommend early haemorrhage control and massive fluid resuscitation. By matching the German Pelvic Injury Register (PIR) with the TraumaRegister DGU(R) (TR) for the first time, we attempt to assess the initial fluid management for different Tile/OTA types of pelvic ring fractures. Special attention was given to the patient's post traumatic course, particularly ICU data and patient outcome. METHODS: A specific match code was applied to identify certain patients with pelvic disruptions from both PIR and TR anonymous trauma databases, admitted between 2004 and 2009. From the resulting intersection set, a retrospective analysis was done of pre-hospital and trauma room data, length of ICU stay, days of ventilation, incidence of multiple organ dysfunction syndrome (MODS), sepsis, and mortality. RESULTS: In total 402 patients were identified. Mean ISS was 25.9 points and the mean ratio of patients with ISS [greater than or equal to]16 was 85.6%. The fracture distribution was as follows: 19.7% type A, 29.4% type B, 36.6% type C, and 14.3% isolated acetabular and/or sacrum fractures. The type B/C, compared with type A fractures, were related to constantly worse vital signs that necessitated a higher volume of fluid and blood administration in the pre-hospital and/or the trauma room setting. This group of B/C fractures were also related to a significantly higher presence of concomitant injuries and related with increased ISS. This was related to increased ventilation and ICU stay, increased rate of MODS, sepsis and increased rate of mortality at least for the type C fractures. Approximately 80% of the deceased had sustained type B/C fractures. CONCLUSIONS: The present study confirms the actuality of traditional trauma algorithms with initial massive fluid resuscitation in the recent therapy of multiple trauma patients with pelvic disruptions. Low volume resuscitation seems not yet accepted in practice in managing this special patient entity. Mechanically unstable pelvic ring fractures type B/C (according Tile's/OTA classification) form a distinct entity that has to be considered notably in future trauma algorithms.     

Dermatological manifestations of tuberous sclerosis complex (TSC)

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement that frequently occurs in early childhood. Dermatologic manifestations include facial angiofibromas, hypomelanotic macules, fibrous cephalic plaques, shagreen patches, and ungual fibromas. The International TSC Consensus Conference in 2012 provided guidelines for standardized baseline evaluation and follow‐up. Detailed clinical dermatological evaluation at the time of diagnosis and annual skin examination is recommended for both pediatric and adult populations. The onset of dermatological manifestations is clearly age‐related. However, dermatologists also have to assess for clinical manifestations beyond their own specialty. With advances in genetics and the advent of mTORC1 inhibitors, new specific therapeutic options have become available for TSC patients with skin manifestations. Early intervention is commonly recommended for symptomatic, rapidly evolving, disfiguring, or debilitating lesions. The consensus guidelines recommend “treatment as appropriate for the lesion and clinical context” and suggest the use of surgical excision, laser therapy, or topical mTORC1 inhibitors. Topical mTORC1 inhibitors present a useful option for TSC‐associated skin lesions, particularly in medically complex patients. They may prevent or reduce the risks of subsequent surgeries and permanent scarring.     

Amphiphilic bonder improves adhesion at the acrylic bone cement–bone interface of cemented acetabular components in total hip arthroplasty: in vivo tests in an ovine model

INTRODUCTION: Even following the introduction of the "third generation" cementing technique, an improvement of the fixation of the acetabular component similar to that of the femoral has not been shown in clinical studies. The goal of the present study was to achieve a better stability with the use of an amphiphilic bonder while preserving the mechanically important subchondral sclerosis. MATERIALS AND METHODS: In a total of 20 sheep, a cemented total hip replacement was implanted. In the treatment group (n = 10), the implantation was carried out following surface conditioning of the acetabular bed with an amphiphilic bonder. All the sheep were followed for 9 months. To assess the biocompatibility, the osseous ingrowth at the cement-bone interface was depicted with the help of an in vivo fluorescent marking of the osteoblasts. Additionally, conventional radiographs were obtained over the course of treatment. Finally, the ovine pelvic regions were split following a standardized technique allowing for histological evaluation of the cement-bone interfaces. RESULTS: The acetabular components of the treatment group revealed a stable cement-bone compound. In the control group, the implants were easily dislodged from their beds. This finding was consistent with the radiological and histological results, which had revealed increased, progressive lytic radiolucent lines and the interposition of fibrous tissue at the cement-bone interface in the control group compared to the treatment group. The bonder was biocompatible. CONCLUSION: Following the application of the bonder, the cemented acetabular components revealed an improved stability without signs of inflammation or neoplasia in a viable acetabular osseous bed. With the help of this technique, the in vivo longevities of cemented acetabular components can be increased in the clinical setting without sacrificing the biomechanical relevant subchondral sclerosis.     

Mouse models for the study of fate and function of innate lymphoid cells

Natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were discovered more than 40 and 20 years ago, respectively. These two cell types were initially studied for their unique functions in the elimination of infected or transformed cells, and in the development of lymphoid tissues. It took an additional 10 years to realize that NK cells and LTi cells were members of a larger family of innate lymphoid cells (ILCs), whose phenotypes and functions mirror those of T cells. Many mouse models have since been developed to identify and isolate ILCs, map their developmental pathways and characterize their functions. Because of the similarity between ILCs and T cells, this exploration remains a challenge. In spite of this, a broad range of mouse models available to researchers has lead to significant progress in untangling the unique roles of ILCs early in defense, regulation of adaptive immunity and homeostasis. Here, we review these mouse models, and discuss their strengths and limitations.     

Oligoclonal bands predict multiple sclerosis in children with optic neuritis

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow‐up of 4.0 years. Multiple Cox proportional‐hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39–10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32–5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02–1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84‐fold higher HR for developing MS compared to double negativity (95% CI = 12.26−58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON. Ann Neurol 2015;77:1076–1082     

Ultrasound-induced microbubble coalescence

We studied the interaction of ultrasound contrast agent bubbles coated with a layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the submicrosecond timescale reveals that some bubbles bounce off each other, while others show very fast coalescence during bubble expansion. This fast coalescence cannot be explained by dissipation-limited film drainage rates. We conclude that the lipid shell ruptures upon expansion, exposing clean free bubble interfaces that support plug flow profiles in the film and inertia-limited drainage whose time scales match those of the observed coalescence.     

Synthesis and Characterization of Defined Branched Poly(propylene)s with Different Microstructures by Copolymerization of Propylene and Linear Ethylene Oligomers (Cn = 26–28) with Metallocenes/MAO Catalysts

Summary: Copolymers of propylene and hexacosene (C_n = 26–28) were synthesized in the presence of three different metallocene catalysts activated by methylaluminoxane. The poly(propylene) copolymers were prepared with iso‐, syndio‐, and atactic backbone microstructures by using different symmetric metallocenes such as rac‐{Me₂Si[2‐Me‐4‐(1‐Naph)Ind]₂}ZrCl₂ ( 1 ), [Ph₂C(Cp)(Flu)]ZrCl₂ ( 2 ), and [(H₃C)₂Si(9‐Flu)₂]ZrCl₂ ( 3 ) and up to 46.6 mol‐% comonomer content in the feed. The influence of the incorporated linear, ethylene‐based side chains into the poly(propylene) backbone were investigated by DSC, GPC, and ¹³C NMR. Generally, a decreasing content of comonomer in the feed enhances the activity of metallocene based catalysts. The determination of the branched microstructure by ¹³C NMR of the copolymers allows a smart identification of the amount of inserted hexacosene because of the separated backbone and side chain signals. Moreover, the relationship between the population of the side chains and the melting behavior of resulting copolymers were discussed. The melting point of the syndiotactic and isotactic poly(propylene) backbone decreases with increasing hexacosene content. When the inserted comonomer content exceeds 2 mol‐%, a second melting point of the crystallized ethylene based side chains can be observed which increases with an increasing amount of hexacosene.

Thermal behavior of isospecific hexacosene/propylene copolymers in dependence on the incorporation of hexacosene.