Interface Water Assists in Dimethyl Sulfoxide Crossing and Poration in Model Bilayer.

Understanding the mechanism of transport and pore formation by a commonly used cryoprotectant, dimethyl sulfoxide (DMSO), across cell membranes is fundamentally crucial for drug delivery and cryopreservation. To shed light on the mechanism and thermodynamics of pore formation and crossing behavior of DMSO, extensive all-atom molecular dynamics simulations of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) bilayers are performed at various concentrations of DMSO at a temperature above the physiological temperature. Our results unveil that DMSO partially depletes water from the interface and positions itself between lipid heads without full dehydration. This induces a larger area per headgroup, increased disorder, and enhanced fluidity without any disintegration even at the highest DMSO concentration studied. The enhanced disorder fosters local fluctuations at the interface that nucleate dynamic and transient pores. The potential of mean force (PMF) of DMSO crossing is derived from two types of biased simulations: a single DMSO pulling using the umbrella sampling technique and a cylindrical pore formation using the recently developed chain reaction coordinate method. In both cases, DMSO crossing encounters a barrier attributed to unfavorable polar nonpolar interactions between DMSO and lipid tails. As the DMSO concentration increases, the barrier height reduces along with the faster lateral and perpendicular diffusion of DMSO suggesting favorable permeation. Our findings suggest that the energy required for pore formation decreases when water assists in the formation of DMSO pores. Although DMSO displaces water from the interface toward the far interface region without complete dehydration, the presence of interface water diminishes pore formation free energy. The existence of interface water leads to the formation of a two-dimensional percolated water-DMSO structure at the interface, which is absent otherwise. Overall, these insights into the mechanism of DMSO crossing and pore formation in the bilayer will contribute to understanding cryoprotectant behavior under supercooled conditions in the future.

Thylakoid Composition Facilitates Chlorophyll a Dimerization through Stronger Interlipid Interactions.

Plant thylakoid membrane serves as a crucial matrix for the aggregation of chlororophyll a (CLA) pigments, essential for light harvesting. To understand the role of lipid compositions in the stability of CLA aggregates, dimerization of chlorophyll a molecules (CLA) is studied in the presence of the thylakoid and the bilayers comprising either the least or the highest unsaturated lipids by using coarse-grained molecular dynamics simulations. The thylakoid membrane enhances the stability of the CLA dimer compared with other membranes due to very strong lipid-lipid interactions. The thylakoid exhibits a distinct distribution of lipids around the CLA dimer. Less unsaturated lipids reside in close proximity to the dimer, promoting increased order and efficient packing. Conversely, higher unsaturated lipids are depleted from the dimer, imparting flexibility to the membrane. The combination of tight packing near the dimer and membrane flexibility away from the dimer enhances the stability of the dimer in the thylakoid membrane. Our results suggest that lipid mixing, rather than lipid unsaturation, plays a critical role in facilitating CLA dimerization by modulating the membrane microenvironment through stronger lipid-lipid interactions. These insights will be useful in understanding how lipid compositions affect efficient light absorption and energy transfer during photosynthesis in the future.

Aggregation of chlorophylls on plant thylakoid membranes using coarse-grained simulations.

Chlorophyll a (CLA) molecules in light-harvesting complexes are the most essential pigments for photosynthesis. Coarse-grained molecular dynamics simulations of CLA are carried out in plant thylakoid membranes at 293 K by varying the total lipid-to-CLA ratio using our previously derived coarse-grained model of CLA and MARTINI force fields for lipids. Our simulations show that CLA molecules dynamically form aggregates that break and reform. The lifetime of the dimer and the waiting time of the dimer formation follow bi-exponential distributions for the higher concentrations of CLA. The number of aggregates increases with an increasing concentration of CLA, where the aggregation is governed by van der Waals interactions. Our simulations suggest that selective lipids promote the formation of CLA aggregates in plant thylakoid membranes. As the concentration of CLA increases, diacylglycerol and phosphatidylglycerol lipids with palmitoyl tails prefer to reside near the CLA aggregates, and the lipids with linolenoyl tails with higher levels of unsaturation move away from the aggregates. Such preferential locations of lipids result in increasing lateral heterogeneity in the order parameter and density with increasing CLA concentration. This induces more undulations in membranes, resulting in a lower bending modulus and area compressibility. Our work unfolds the mechanism of the formation of CLA aggregates and their effect on the structure of thylakoid bilayers. The study provides the foundation for a better understanding of more complex biophysical phenomena, such as photosynthesis and non-photochemical quenching, in the future.

Efficacy and outcome of bone marrow derived stem cells transplanted via intramedullary route in acute complete spinal cord injury - A randomized placebo controlled trial.

Due to lack of well-designed trials, there is no good evidence on the efficacy of stem cells in spinal cord injury. We aim to study the efficacy and outcome of bone marrow derived stem cells (BMSCs) in acute complete spinal cord injury (SCI). In this prospective study over a 3-year period, 27 patients with acute, complete SCI were randomized to receive BMSCs or placebo (intramedullary route) intraoperatively. Institutional ethics approval was taken and informed consent was taken from all patients. Functional outcome was assessed using ASIA scale, SCIM score and SSEP responses preoperatively, three and six months after surgery. Thirteen patients were available for final analysis of which six were in the stem cell group and seven received placebo. 6 patients had improvement by at least one grade in ASIA score in the stem cell group as compared to only one patient in the placebo group. However, no functional motor improvement in any of the patients. ASIA sensory score improved from a preoperative mean of 124 to 224 at 6 months compared to the static mean of 115 in the control group. Absent SSEP waveform converted to abnormal waveform at 6 months in 3 patients in the stem cell group and one patient in the control group. There was no significant difference in the SCIM scores between the groups at last follow-up. All patients in the stem cell group reported improved bladder sensation, decreased spasticity and improved posture control as compared to nine in the placebo group. BMSCs through intramedullary route are a potential therapy for acute complete SCI and more research is required in this area.

Safety and feasibility of intramedullary injected bone marrow-derived mesenchymal stem cells in acute complete spinal cord injury: phase 1 trial.

OBJECTIVE: The intramedullary route holds the potential to provide the most concentration of stem cells in cases of spinal cord injury (SCI). However, the safety and feasibility of this route need to be studied in human subjects. The aim of this study was to evaluate the safety and feasibility of intramedullary injected bone marrow-derived mesenchymal stem cells (BM-MSCs) in acute complete SCI. METHODS: In this prospective study conducted over a 2-year period, 27 patients with acute (defined as within 1 week of injury) and complete SCI were randomized to receive BM-MSC or placebo through an intramedullary route intraoperatively at the time of spinal decompression and fusion. Institutional ethics approval was obtained, and informed consent was obtained from all patients. Safety was assessed using laboratory and clinicoradiological parameters preoperatively and 3 and 6 months after surgery. RESULTS: A total of 180 patients were screened during the study period. Of these, 27 were enrolled in the study. Three patients withdrew, 3 patients were lost to follow-up, and 8 patients died, leaving a total of 13 patients for final analysis. Seven of these patients were in the stem cell group, and 6 were in the control group. Both groups were well matched in terms of sex, age, and weight. No adverse events related to stem cell injection were noted for laboratory and radiological parameters. Five patients in the control group and 3 patients in the stem cell group died during the follow-up period. CONCLUSIONS: Intramedullary injection of BM-MSCs was found to be safe and feasible for use in patients with acute complete SCI.

Fulminant necrotising amoebic colitis after corticosteroid therapy for severe COVID-19.

Acute fulminant necrotising colitis is an uncommon presentation of amoebiasis, which can be precipitated after corticosteroid therapy. Clinicians treating patients with COVID-19 with corticosteroid therapy should be familiar with this condition to avoid delay in diagnosis. The disease is associated with high mortality, and prompt diagnosis and management are essential for salvaging patients. We report successful management of a patient who developed this complication following administration of steroids for COVID-19.

Interactions Determining the Structural Integrity of the Trimer of Plant Light Harvesting Complex in Lipid Membranes.

The structural basis for the stability of the trimeric form of the light harvesting complex (LHCII), a pigmented protein from green plants pivotal for photosynthesis, remains elusive till date. The protein embedded in a dipalmitoylphosphatidylcholine (DPPC) lipid membrane is investigated using all-atom molecular dynamics simulations to find out the interactions responsible for the structural integrity of the trimer and its relation to antenna function. Central association of chlorophyll a (CLA) molecules near the LHCII chains is attributed to a conserved coordination between the Mg of CLA and the oxygen of a specific residue of the first helix of a chain. The residue forms a salt-bridge with the fourth helix of the same chain of the trimer, not of the monomer. In an earlier experiment, three residues (WYR) at each chain of the trimer have been found indispensable for the trimerization and referred to as trimerization motif. We find that the residues of the trimerization motif are connected to the lipids or pigments by a chain of interactions rather than a direct contact. Synergistic effects of sequentially located hydrogen bonds and salt-bridges within monomers of the trimer keep the trimer conformation stable in association with the pigments or the lipids. These interactions are exclusively present in the pigmented trimer and not present in the monomer or in the unpigmented trimer. Thus, our results provide a molecular basis for the inherent stability of the LHCII trimer in a lipid membrane and explain many pre-existing experimental data.

Unilateral facial edema after filler injection of the lower eyelid.

The use of hyaluronic acid (HA) gel fillers for rejuvenation of the face has been increasing in popularity over the years. This nonsurgical, temporary technique is commonly used in the periocular region to restore volume. The aim of this study was creating awareness in the potential causes of edema after hyaluronic acid gel filler injections under the eyes. A 32-year-old woman presented for a cosmetic consultation to address unilateral swelling of the left check. She states she had an HA filler injected in the tear trough on both sides. Extensive evaluation and ultrasound were performed by physicians of different specialties. Intra-oral and radiological examination revealed a tooth-related cause known as apical periodontitis. Removal of this tooth resulted in complete resolution of the patient's presenting symptoms. Familiarity with all the potential causes of adverse events after injections with hyaluronic acid gel fillers accelerates the treatment and healing of the patient with complications. Reporting this case should raise awareness about possible teeth-related complications.

Bedside computed tomography in traumatic brain injury: Experience of 10,000 consecutive cases in neurosurgery at a level 1 trauma center in India.

INTRODUCTION: Patients with traumatic brain injury (TBI) need frequent computed tomography (CT) of the head for assessment and management. In view of the associated polytrauma, hemodynamic instability, and various in-dwelling catheters and tubes, shifting of patients for CT scans may be difficult. AIMS AND OBJECTIVES: To assess the role of mobile CT (Ceretom®; NeuroLogica Corporation, Boston, MA, USA) in a trauma center with respect to patient management. MATERIALS AND METHODS: In this retrospective study over 67 months (June 2009 to January 2015), the number of CT scans done, the time taken for CT and downtime were evaluated. Also, for the first 1000 mobile CT scans, the clinical and radiological records of all patients with TBI who underwent imaging using the mobile CT scanner in the intensive care units (ICUs) were analyzed. OBSERVATIONS AND RESULTS: A total of 10,000 mobile CT scans were done on the mobile CT scanner till January 5, 2015. Of the first 1000 patients evaluated, 75.3% had severe TBI, 15.1% had moderate TBI, and 9.6% had mild TBI. 78.1% patients were on ventilator, with 80.2% requiring sedation and 8.4%, an inotropic support. An in situ intracranial pressure monitoring was present in 21.1% of patients. In all, 12.4% of patients had long-bone fractures requiring skeletal traction; and, the tube thoracostomy was in-situ in 7.4%. No adverse events related to line malfunction/pullout occurred. The mean time for the performance of imaging using the mobile CT scan was 11.6 minutes compared with 47.8 minutes when patients were shifted to a conventional CT scan suite. The machine was nonfunctional 94 times, with an average downtime of 4.2 hours (range 2-72 hours). The life-cycle cost per mobile CT scan was Rs. 1340. CONCLUSIONS: A mobile CT has considerably changed the management response time in the neurosurgical intensive care unit (ICU) setup and decreased patient transfer times and the associated complications. Inclusion of a mobile CT scanner in the armamentarium of a neurosurgeon as a "bedside tool" can dramatically change decision making and the response time. It should be considered as the standard of care in any large-volume emergency department or neurosurgical facility.