Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeutic approach.

We previously demonstrated that most diseases display a form of anabolism due to mitochondrial impairment: in cancer, a daughter cell is formed; in Alzheimer's disease, amyloid plaques; in inflammation cytokines and lymphokines. The infection by Covid-19 follows a similar pattern. Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction. This unrelenting anabolism leads to the cytokine storm, chronic fatigue, chronic inflammation or neurodegenerative diseases. Drugs such as Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism. Similarly, coMeBining Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism.

Post-thaw quality of ram sperm frozen with different concentrations of low-density lipoproteins associated with non-enzymatic antioxidants.

The cryopreservation reduces ram sperm quality, decreasing the pregnancy rate of ewes inseminated with thawed sperm. Hence, we aimed to improve the post-thaw quality of ram sperm replacing egg yolk on Tris-Glucose extender with different concentrations of LDL (2 or 8%), associated with the addition of 10 mM non-enzymatic antioxidants (ascorbic acid, hydroxytoluene butylate, ascorbyl palmitate, and trehalose). Semen samples were collected from six rams, split into different treatments, and frozen. After thawing, kinematic (CASA), structural (propidium iodide and carboxyfluorescein diacetate) and functional (hypoosmotic test) sperm membrane integrity was assessed. Total motility, VCL, and LIN were also assessed in thawed samples during 3 h of incubation (38 °C). The results showed that hydroxytoluene butylate at 10 mM in Tris-Glucose extender with 8% LDL improved velocity parameters immediately post-thaw compared with Tris-Glucose egg yolk extender, as well as prevented the reduction of total motility and VCL after incubation. There was no benefit of adding ascorbic acid and trehalose. Moreover, for the first time, it was shown the motility impairment promoted by ascorbyl palmitate to ram sperm.

Genomic medicine in Africa: a need for molecular genetics and pharmacogenomics experts.

The large-scale implementation of genomic medicine in Africa has not been actualized. This overview describes how routine molecular genetics and advanced protein engineering/structural biotechnology could accelerate the implementation of genomic medicine. By using data-mining and analysis approaches, we analyzed relevant information obtained from public genomic databases on pharmacogenomics biomarkers and reviewed published studies to discuss the ideas. The results showed that only 68 very important pharmacogenes currently exist, while 867 drug label annotations, 201 curated functional pathways, and 746 annotated drugs have been catalogued on the largest pharmacogenomics database (PharmGKB). Only about 5009 variants of the reported ∼25,000 have been clinically annotated. Predominantly, the genetic variants were derived from 43 genes that contribute to 2318 clinically relevant variations in 57 diseases. Majority (∼60%) of the clinically relevant genetic variations in the pharmacogenes are missense variants (1390). The enrichment analysis showed that 15 pharmacogenes are connected biologically and are involved in the metabolism of cardiovascular and cancer drugs. The review of studies showed that cardiovascular diseases are the most frequent non-communicable diseases responsible for approximately 13% of all deaths in Africa. Also, warfarin pharmacogenomics is the most studied drug on the continent, while CYP2D6, CYP2C9, DPD, and TPMT are the most investigated pharmacogenes with allele activities indicated in African and considered to be intermediate metaboliser for DPD and TPMT (8.4% and 11%). In summary, we highlighted a framework for implementing genomic medicine starting from the available resources on ground.

An Alternate [2×2] Grid Constructed Around TiO4 N2 Units.

The formation of a tetranuclear self-assembled species constructed around a TiO4 N2 motif is reported. This aggregate is generated from Ti(Oi Pr)4 , 2,2'-bipyrimidine (bpym) and a bis-biphenol strand (L2 H4 ) where two 2,2'-biphenol units are connected with a biphenyl spacer. The solid-state structure of the [Ti4 (L2 )4 (bpym)4 ] architecture reveals the formation of an unprecedented chiral alternate [2×2] grid. In addition to the structural characterization of the [Ti4 (L2 )4 (bpym)4 ] architecture, geometry optimisation on various possible isomeric tetrameric assemblies ([2×2] grid, alternate [2×2] grid, circular helicate or cyclic hemihelicate) is performed using DFT calculations. These results confirm the higher stability of the alternate [2×2] grid over the other possible tetranuclear isomers and allow examining the replacement of the bpym ligands by two novel diimine chelates within the tetranuclear assembly (2,2'-bipyridine=bipy and 2,2'-bipyrazine=bipyraz). From this initial theoretical investigation, the competition between these three nitrogen ligands in the course of the self-assembly process is next evaluated. Overall, this investigation shows that the exclusive formation of the alternate [2×2] grid is driven by CH⋅⋅⋅N interactions.

Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity.

A hyper-specialization characterizes modern medicine with the consequence of classifying the various diseases of the body into unrelated categories. Such a broad diversification of medicine goes in the opposite direction of physics, which eagerly looks for unification. We argue that unification should also apply to medicine. In accordance with the second principle of thermodynamics, the cell must release its entropy either in the form of heat (catabolism) or biomass (anabolism). There is a decreased flow of entropy outside the body due to an age-related reduction in mitochondrial entropy yield resulting in increased release of entropy in the form of biomass. This shift toward anabolism has been known in oncology as Warburg-effect. The shift toward anabolism has been reported in most diseases. This quest for a single framework is reinforced by the fact that inflammation (also called the immune response) is involved in nearly every disease. This strongly suggests that despite their apparent disparity, there is an underlying unity in the diseases. This also offers guidelines for the repurposing of old drugs.

Verification of Nuclear Magnetic Resonance Characterization of Traditional Homeopathically Manufactured Metal (Cuprum metallicum) and Plant (Gelsemium sempervirens) Medicines and Controls.

BACKGROUND: Nuclear magnetic resonance (NMR) proton relaxation is sensitive to the dynamics of the water molecule, H2O, through the interaction of the spin of the proton (1H) with external magnetic and electromagnetic fields. NMR relaxation times describe how quickly the spin of 1H, forced in a direction by an external electromagnetic field, returns to a normal resting position. As a result, such measurements allow us potentially to describe higher structuring of water in homeopathic medicines. OBJECTIVE: The purpose of the present study was to verify whether specific NMR relaxation times could be measured in full lines of cH dynamizations of a metal (copper) and of a plant substance (Gelsemium sempervirens), compared with a solvent control, a potentized lactose control and a control prepared by simple dilution, in three production lines. It is aimed at verification of a previous publication (2017) on two new manufacturing lines of the same starting material and controls. MATERIALS AND METHODS: To monitor dilution and potentization processes, measurements of 1H spin-lattice T1 and spin-spin T2 relaxation times were used. T1 and T2 relaxation times were measured at 25°C with a spin analyser working at a frequency of 20 MHz. To account for its possible role as a confounding factor, free oxygen was also measured in all samples, using a MicroOptode meter. RESULTS: When the values of the three production lines were pooled, a statistically significant discrimination of NMR relaxation times between the medicines and their controls was confirmed. We found for copper cH and Gelsemium sempervirens cH a highly significant influence of the starting material (p = 0.008), a highly significant influence of level of dilution (p < 0.001), and a significant influence of the O2 concentration (p = 0.04). CONCLUSIONS: We have evidence of an obvious retention of a specific magnetic resonance signal when a substance (lactose, copper, Gelsemium) is diluted/potentized in pure water. This means that homeopathic solutions cannot be considered to be pure water. O2 is a covariant and not an explanatory variable: this factor itself is too weak to explain the NMR signal specificities in potentized samples. Homeopathic dilutions may thus have a specific material configuration governed not only by the potentized substance but also by the chemical nature of the containers, the chemical nature of dissolved gases and even by the electromagnetic environment. This sensitivity of homeopathically prepared medicines to electromagnetic fields may be amplified by the processes routinely applied during their preparation; because it occurs only when a dynamization has been performed, we may call this phenomenon "dynamic pharmacy".

Fast track protocol for primary total hip arthroplasty in non-trauma cases reduces the length of hospital stay: Prospective French multicenter study.

BACKGROUND: Fast-track (FT) procedures continue to evolve; however, their benefits are still controversial. This led us to conduct a prospective study of FT procedures for total hip arthroplasty (THA) on a national scale in France with historical control data. The aims were to (1) evaluate the effectiveness of FT procedures after THA on the length of hospital stay (LOS) in a multicenter analysis, (2) measure the immediate return to home, rehospitalization and reoperation rates. HYPOTHESIS: FT procedures reduce the LOS after primary THA for non-traumatic indications relative to national historical data. METHODS: A prospective observational study was done at 11 hospital facilities throughout France. Patients who underwent primary THA for a non-traumatic condition and FT procedures were followed for 3 months. The average LOS, discharge to home, unexpected readmissions, and reoperation rate were compared to 2016 figures from the French national database of 104,745 procedures on the same population. RESULTS: The study included 1,110 patients, 499 men (45%) and 611 women (55%), with a mean age of 67.5±11.9 years. The average LOS was 3.3±2.9 days versus 7.5±5.3 days in the national database (p<0.001). Eight hundred eighty patients (79%) were discharged directly to home versus 72,577 (69%) in the national database (p<0.001). Forty-two patients (4%) were readmitted to the hospital within 90 days of the THA versus 11,092 (11%) in the national database (p<0.001). Eighteen patients (1.6%) were reoperated within 90 days of the THA procedure versus 2100 (2.0%) in the national database (p=0.72). DISCUSSION: FT procedures help to significantly reduce the average LOS and rehospitalization rate after primary THA for non-traumatic conditions and significantly increased the percentage of patients being discharged directly to home relative to national historical data, without altering the risk of reoperation. FT procedures should become the standard of care after THA. LEVEL OF EVIDENCE: III; prospective case-control study.

Bleeding and thromboembolism risk of standard antithrombotic prophylaxis after hip or knee replacement within an enhanced recovery program.

INTRODUCTION: Prevention of venous thromboembolism (VTE) generally consists of low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Enhanced recovery after surgery (ERAS) protocols may reduce the VTE risk after these procedures. The aim of this study was to compare the risk of VTE and the risk of bleeding complications in a non-selected population of primary THA and TKA cases done within an ERAS protocol. HYPOTHESIS: The risk of postoperative VTE after primary THA and TKA is lower than the risk of bleeding complications within an ERAS protocol. METHODS: This was a prospective observational study conducted on a national scale in France. All patients who underwent primary unilateral THA or TKA at one of 11 participating hospitals between October 2016 and October 2017 were enrolled and followed for 3 months. The occurrence of a VTE or major bleeding event was recorded. No patients were lost to follow-up at 3 months. RESULTS: Of the 1110 THA cases, there were 5 VTE (0.4%) and 19 bleeding events (1.7%). Of the 893 TKA cases, there were 9 VTE (1.0%) and 14 bleeding events (1.7%). There was no significant difference in the VTE incidence and bleeding event incidence after THA and TKA. The overall incidence of bleeding complications (1.7%) was significantly greater than the overall incidence of VTE complications (0.7%) (p=0.005). This was the case after THA (p=0.004) but not after TKA. DISCUSSION: The primary finding of this study is that bleeding complications are significantly more common than VTE complications after THA or TKA within an ERAS protocol. Based on these findings, the cost-benefit ratio of antithrombotic prophylaxis by LMWH or DOACs in this context should be reassessed. LEVEL OF EVIDENCE: IV; Prospective cohort study without control group.

Dipyrrolyldiketonato Titanium(IV) Complexes from Monomeric to Multinuclear Architectures: Synthesis, Stability, and Liquid-Crystal Properties.

Dipyrrolyldiketone ligands (dpkH) are used with Ti(OiPr)4 to afford monomeric titanium(IV) complexes displaying the general formula C2-[Ti(dpk)2(OiPr)2]. The dpkH ligands employed consist of two dipyrrolyldiketone compounds (2H and 3H) and three diphenyl-substituted analogues (4H-6H). The behavior of these octahedral [Ti(dpk)2(OiPr)2] species in solution was investigated by 1H NMR at variable temperatures. Dynamic phenomena were evidenced, and the activation parameters associated with these processes (ΔH⧧, ΔS⧧, and ΔG⧧) were retrieved. [Ti(dpk)2(OiPr)2] complexes are precursors for the formation of high-nuclearity aggregates whose structures depend on the substituents on the diketone backbone. The crystal structures of monomeric ([Ti(1)2(OiPr)2]; 1 is the 1,3-diphenyl-1,3-propanedionato ligand) and [Ti(2)2(OEt)2]), dimeric ([Ti2(1)4(µ2-O)2]), and tetrameric ([Ti4(4)8(µ2-O)4]) species have been established, and the origin of this structural diversity is discussed. The solid-state optical properties of several complexes were determined and interpreted with the help of DFT calculations. Finally, the dinuclear complex [Ti(6)2(µ2-O)2] was synthesized, where ligand 6 incorporates six long alkyl chains (C16H33). This complex shows rich mesomorphic properties, with an original room-temperature plastic crystal phase followed by a hexagonal columnar liquid-crystalline phase.

Bent 1,10-Phenanthroline Ligands within Octahedral Complexes Constructed around a TiO4N2 Core.

The synthesis of monomeric octahedral complexes constructed around a TiO4N2 core bearing neocuproine derivatives is detailed. These architectures follow the [Ti(1)2(N-N)] general formulas, where 1 is the 6,6'-diphenyl-2,2'-biphenolato ligand and N-N is a 1,10-phenanthroline derivative. Single-crystal analysis revealed that the neocuproine-based ligands within these architectures adopt a nonplanar geometry. The distortion of these aromatic diimine systems has been quantified through measurement of a torsion angle (α) and a dihedral angle (ß) defined by two planes within the aromatic diimine molecule (π1 and π2), permitting one to evaluate the twisting and bending of a coordinated nitrogen ligand, respectively. Next, the scope of this investigation was extended to the synthesis of a dimeric architecture, [Ti2(1)4(3)], where 3 is the 5,5'-bis(neocuproine) ligand. Again, a strong distortion of the neocuproine fragments was characterized in the crystalline state for such a complex. The UV-visible properties of these complexes were interpreted with the help of time-dependent density functional theory calculations. The solution behavior as well as good hydrolytic stability of these species has been established.

Impact of in vitro fertilization by refrigerated versus frozen buffalo semen on developmental competence of buffalo embryos.

The objective of this study was to evaluate the fertility of buffalo semen for in vitro embryo production (IVEP) by comparing the effectiveness of refrigerated versus frozen semen. Three OPU sessions were held at 30-day intervals. For oocyte fertilization three buffalo bulls were used, one per session. At each OPU-IVEP session, one ejaculate was collected and divided into two equal aliquots. Each aliquot was either refrigerated at 5ºC/24 hours or frozen. A TRIS extender containing 10% low density lipoproteins, 0.5% lecithin and 10 mM acetylcysteine was used adding 7% glycerol for freezing. Sperm motility/kinetic was evaluated by CASA and sperm membrane integrity by the hypoosmotic swelling test. The evaluations were performed at 0 h (post final dilution at 37ºC), at 4 and 24 hs post-incubation at 5ºC and post-thaw. At 24 hs incubation and immediately post thaw sperm cells were used for in vitro fertilization of buffalo oocytes equally distributed between both groups. Cleavage rates and embryo development were followed. The embryo/matured and embryo/cultured rates were 25.4 x 14.0% and 29.4 x 18.5% (P<0.05), for chilled and frozen semen, respectively. It is concluded that cooled semen can be used for in vitro embryo production in buffalo and that a better efficiency may be expected for cooled compared to frozen semen.

Clinical interest of quantitative bone SPECT-CT in the preoperative assessment of knee osteoarthritis.

The aim of the study was to evaluate the interest of quantitative bone SPECT-CT in the preoperative assessment of knee osteoarthritis (OA) before unicompartmental knee arthroplasty (UKA).Patients eligible for UKA were prospectively included in 2 centers and underwent a preoperative SPECT-CT. Images were reconstructed with an OSEM, an OSCGM (allowing SUV quantification) and an enhanced OSCGM (containing uptakes to bones) algorithms. Visual analysis and quantification (SUVmax) were performed for each compartment (medial compartment [MC], lateral compartment [LC], and patellofemoral compartment [PFC]). Clinical data were preoperatively assessed. The gold standard was the per-operative OA staging (International Cartilage Repair Society [ICRS] scale). Spearman's correlation coefficient was used for correlations. Sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy of SPECT-CT were assessed.One hundred three patients (50 women, 53 men, mean age = 64.5 ±â€Š10.3 y/o, 120 preoperative knees) were analyzed. There was no correlation between SUVmax and clinical data. There was a correlation between ICRS staging and SUVmax with both OSCGM (MC [rs = 0.25], LC [rs = 0.51], and PFC [rs = 0.27]), and enhanced OSCGM, except in the PFC (MC [rs = 0.22], LC [rs = 0.62], and PFC [rs = 0.03]). The Se, Sp, PPV, NPV, and accuracy of SPECT-CT were, respectively, 0.99, 0.67, 0.98, 0.80, 0.97 for the MC; 0.50, 0.85, 0.42, 0.89, 0.79 for the LC; and 0.23, 0.86, 0.50, 0.64, 0.62 for the PFC.Bone SPECT-CT SUVmax is correlated with per-operative OA staging. Despite the low sensitivity of SPECT-CT in the LC, its high specificity in the LC should prompt the surgeon to be vigilant before UKA surgery.

From monomeric complexes to double-stranded helicates constructed around trans-TiO4N2 motifs with intramolecular inter-ligand hydrogen-bonding interactions.

A coordination chemistry involving trans-TiO4N2 motifs is described, where the oxygen ligands are 2,2'-biphenolato derivatives (L1 or L2) and the nitrogen ligands are pyridine (Pyr), 2,3-dihydro-7-azaindole (DHA) or 2-(methylamino)pyridine (MePyr). Monomeric complexes and double-stranded helicates incorporating this set of ligands are characterized. The monomeric species are obtained from the precursor [Ti(L1)2(HOiPr)2] whereas the helical dinuclear architectures are synthesized following a multicomponent self-assembly approach starting from L2H4, Ti(OiPr)4 and two equivalents of the nitrogen ligand. It is proposed that the trans isomerism in TiO4N2 observed in these structures results from the destabilisation of the cis isomer by the trans influence of the Ti-N bonds. The crystal structures and infra-red analysis demonstrate hydrogen bonding interactions occurring between the NH group of DHA or MePyr and the oxygens belonging to the titanium coordination sphere. The strength of these interactions is estimated using the PACHA (Partial Atomic Charges Analysis) software.

Label-free proteome of water buffalo (Bubalus bubalis) seminal plasma.

The study aimed to describe the Bubalus bubalis seminal plasma proteome using a label-free shotgun UDMSE approach. A total of 859 nonredundant proteins were identified across five biological replicates with stringent identification. Proteins specifically related to sperm maturation and protection, capacitation, fertilization and metabolic activity were detected in the buffalo seminal fluid. In conclusion, we provide a comprehensive proteomic profile of buffalo seminal plasma, which establishes a foundation for further studies designed to understand regulation of sperm function and discovery of novel biomarkers for fertility. MS data are available in the ProteomeXchange with identifier PXD003728.

Biological scoring system for early prediction of acute bowel ischemia after cardiac surgery: the PALM score.

BACKGROUND: Bowel ischemia is a life-threatening emergency defined as an inadequate vascular perfusion leading to bowel inflammation resulting from impaired colonic/small bowel blood supply. Main issue for physicians regarding bowel ischemia diagnosis lies in the absence of informative and specific clinical or biological signs leading to delayed management, resulting in a poorer prognosis, especially after cardiac surgery. The aim of the present series was to propose a simple scoring system based on biological data for the diagnosis of bowel ischemia. METHODS: In a retrospective monocentric study, patients admitted in cardiac ICU, after cardiovascular surgery, were screened for inclusion. According to a 1:2 ratio (case-control), matching between two groups was based on sex, type of cardiovascular surgery, and the operative period (per month). Patients were divided into two groups: "ischemic group" which corresponds to patients with confirmed bowel ischemia and "non-ischemic group" which corresponds to patients without bowel ischemia. Primary objective was the conception of a scoring system for the diagnosis of bowel ischemia. Secondary objectives were to detail the postoperative morbidity and the diagnostic features for the distinction between acute mesenteric ischemia and ischemic colitis. RESULTS: Forty-eight patients (1.3%) had confirmed bowel ischemia ("ischemic group"). According to the 2:1 matching, 96 patients were included in the "non-ischemic group." Aspartate aminotransferase > 449 UI/L, lactate > 4 mmol/L, procalcitonin > 4.7 µg/L, and myoglobin > 1882 µg/L were found to be independently associated with bowel ischemia. Based on their respective odds ratios, points were assigned to each item ranging from 4 to 8. AUROCC [95% confidence interval] of the scoring system to diagnose bowel ischemia was 0.93 [0.91-0.95], p < 0.001. The optimal threshold after bootstrapping was ≥ 14 points; this yielded a sensitivity of 85.4%, a specificity of 94.8%, a positive likelihood ratio of 16.42, a negative likelihood ratio of 0.15, a Youden's index of 0.802, and a diagnostic odds ratio of 106.62. CONCLUSIONS: A biological scoring system based on PCT, ASAT, lactate, and myoglobin measurement allows the diagnosis of bowel ischemia after cardiac surgery with high accuracy. This score could help clinician to propose an early diagnosis and an early treatment in this high mortality disease.

Fertility in male rats: Disentangling adverse effects of arsenic compounds.

Arsenic impairs male reproductive functions. However, it is not clear whether different arsenic compounds similarly affect fertility. In this study, we compared the impact of sodium arsenite and arsenate on sperm quality and fertility. After 56 d exposure, male Wistar rats were mated and pregnant females were evaluated by fertility indexes. Clearly, exposure to 10 mg/L arsenite reduced daily sperm production via H2O2 overproduction and germ cells loss. Animals from this group also showed a decrease in epididymal sperm counts and percentage of sperm with intact membranes. Moreover, they presented low fertility potential and high preimplantation loss. In contrast, 10 mg/L arsenate caused oxidative stress in testis, mineral imbalance in epididymis, and sperm membranes damage, with no effects on fertility. Both arsenic compounds at 0.01 mg/L altered reproductive parameters. We concluded that arsenite is more harmful than arsenate to sperm quality and male fertility, with negative influences in early pregnancy.

Nuclear Magnetic Resonance characterization of traditional homeopathically manufactured copper (Cuprum metallicum) and plant (Gelsemium sempervirens) medicines and controls.

BACKGROUND: NMR proton relaxation is sensitive to the dynamics of the water molecule H2O, through the interaction of the spin of the proton (1H) with external magnetic and electromagnetic fields. METHODS: We measured dilution and potentization processes through measurements of 1H spin-lattice T1 and spin-spin T2 relaxation times. In order to interpret the recorded fluctuations in T1- or T2-values, experimental data were linearized by investigating how the area under a fluctuating time = f(dilution) curve (dilution integral or DI) changes with dilution. Two kinds of fitting procedures were considered: chi-square fitting with a goodness-of-fit probability, and least absolute deviations criterion with Pearson's linear correlation coefficient. RESULTS: We showed that fluctuations are not attributable to random noise and/or experimental errors, evidencing a memory effect quantifiable by the slope of the DI = f(dilution) straight line. For all experiments, correlation coefficients were found to lie above 0.9999, against 0.999 for random noise. The discrimination between experimental slopes and slopes associated with random noise data was very good at a five-sigma level of confidence (i.e. probability 3 × 10-7). Discrimination between experimental slopes at a five-sigma level was possible in most cases, with three exceptions: gelsemium aqua pura v gelsemium dilution (four-sigma); copper aqua pura v gelsemium aqua pura (four-sigma) and copper simple dilution v gelsemium simple dilution (three-sigma). All potentized samples show very good discrimination (at least nine-sigma level) against aqua pura, lactose or simple dilution. It was possible to transform the associated relaxation times into a molecular rotational correlation time τc and an average spin-spin distance d. Our experiments thus point to a considerable slowing down of molecular movements (τc > 1300 ps or T = 224-225 K) around water molecules up to a distance of 3.7 Å, values. It was also possible to rule out other possible mechanisms of relaxation (diffusive motion, 17O-1H relaxation or coupling with the electronic spin, S = 1, of dissolved dioxygen molecules). CONCLUSION: There is clear evidence that homeopathic solutions cannot be considered as pure water as commonly assumed. Instead, we have evidenced a clear memory effect upon dilution/potentization of a substance (water, lactose, copper, gelsemium) reflected by different rotational correlation times and average H⋯H distances. A possible explanation for such a memory effect may lie in the formation of mesoscopic water structures around nanoparticles and/or nanobubbles mediated by zero-point fluctuations of the vacuum electromagnetic field as suggested by quantum field theories. The existence of an Avogadro's 'wall' for homeopathically-prepared medicines is not supported by our data. Rather it appears that all dilutions have a specific material configuration determined by the potentized substance, also by the chemical nature of the containers, and dissolved gases and the electromagnetic environment. This sensitivity of homeopathically-prepared medicines to electromagnetic fields may be amplified by the highly non-linear processing routinely applied in the preparation of homeopathic medicines. Future work is needed in such directions. The time is now ripe for a demystification of the preparation of homeopathic remedies.

Titanium(iv)-based helicates incorporating the ortho-phenylenediamine ligand: a structural and a computational investigation.

The multicomponent coordination chemistry involving Ti(OPri)4, the ortho-phenylenediamine ligand (opda) and 2,2'-biphenol-based proligands (L2H4 and L3H6) is described. The proligands L2H4 and L3H6 incorporate two and three 2,2'-biphenol units linked with p-phenylene bridges (p-PLB) respectively. We demonstrate that this selected set of components allows the spontaneous formation of neutral double-stranded helicates. In particular, we report the X-ray crystal structure of a multicomponent helicate formed with L2, named Ti2(L2)2(opda)2. The molecular structure of the helicate shows two inequivalent L2 ligands. 1H NMR analysis at variable temperature highlights an intramolecular fluxional phenomenon for this species. An insight into this dynamic behaviour is obtained via the energy profiles of Ti2(L2)2(opda)2 resulting from the full rotation of the p-PLB rings. Additionally, the thermodynamic parameters associated with the formation of the Ti2(L2)2(opda)2 complex are modelled and discussed related to the ones linked to the formation of a related monomeric complex.