A Robust Molecular Porous Material for C2 H2 /CO2 Separation.

A molecular porous material, MPM-2, comprised of cationic [Ni2 (AlF6 )(pzH)8 (H2 O)2 ] and anionic [Ni2 Al2 F11 (pzH)8 (H2 O)2 ] complexes that generate a charge-assisted hydrogen-bonded network with pcu topology is reported. The packing in MPM-2 is sustained by multiple interionic hydrogen bonding interactions that afford ultramicroporous channels between dense layers of anionic units. MPM-2 is found to exhibit excellent stability in water (>1 year). Unlike most hydrogen-bonded organic frameworks which typically show poor stability in organic solvents, MPM-2 exhibited excellent stability with respect to various organic solvents for at least two days. MPM-2 is found to be permanently porous with gas sorption isotherms at 298 K revealing a strong affinity for C2 H2 over CO2 thanks to a high (ΔQst )AC [Qst (C2 H2 ) - Qst (CO2 )] of 13.7 kJ mol-1 at low coverage. Dynamic column breakthrough experiments on MPM-2 demonstrated the separation of C2 H2 from a 1:1 C2 H2 /CO2 mixture at 298 K with effluent CO2 purity of 99.995% and C2 H2 purity of >95% after temperature-programmed desorption. C-H···F interactions between C2 H2 molecules and F atoms of AlF6 3- are found to enable high selectivity toward C2 H2 , as determined by density functional theory simulations.

Supramolecular isomerism and structural flexibility in coordination networks sustained by cadmium rod building blocks.

Bifunctional N-donor carboxylate linkers generally afford dia and sql topology coordination networks of general formula ML2 that are based upon the MN2(CO2)2 molecular building block (MBB). Herein, we report on a new N-donor carboxylate linker, ß-(3,4-pyridinedicarboximido)propionate (PyImPr), which afforded Cd(PyImPr)2via reaction of PyImPrH with Cd(acetate)2·2H2O. We observed that, depending upon whether Cd(PyImPr)2 was prepared by layering or solvothermal methods, 2D or 3D supramolecular isomers, respectively, of Cd(PyImPr)2 were isolated. Single crystal X-ray diffraction studies revealed that both supramolecular isomers are comprised of the same carboxylate bridged rod building block, RBB. We were interested to determine if the ethylene moiety of PyImPr could enable structural flexibility. Indeed, open-to-closed structural transformations occurred upon solvent removal for both phases, but they were found to be irreversible. A survey of the Cambridge Structural Database (CSD) was conducted to analyse the relative frequency of RBB topologies in related ML2 coordination networks in order to provide insight from a crystal engineering perspective.

Effects of tidal volume challenge on the reliability of plethysmography variability index in hepatobiliary and pancreatic surgeries: a prospective interventional study.

BACKGROUND: The plethysmography variability index (PVI) is a non-invasive, real-time, and automated parameter for evaluating fluid responsiveness, but it does not reliably predict fluid responsiveness during low tidal volume (VT) ventilation. We hypothesized that in a 'tidal volume challenge' with a transient increase in tidal volume from 6 to 8 ml Kg- 1, the changes in PVI could predict fluid responsiveness reliably. METHOD: We performed a prospective interventional study in adult patients undergoing hepatobiliary or pancreatic tumor resections and receiving controlled low VT ventilation. The values for PVI, perfusion index, stroke volume variation, and stroke volume index (SVI) were recorded at baseline VT of 6 ml Kg- 1, 1 min after the VT challenge (8 ml Kg- 1), 1 min after VT 6 ml Kg- 1 reduced back again, and then 5 min after crystalloid fluid bolus 6 ml kg- 1 (actual body weight) administered over 10 min. The fluid responders were identified by SVI rise ≥ 10% after the fluid bolus. RESULTS: The area under the receiver operating characteristic curve for PVI value change (ΔPVI6-8) after increasing VT from 6 to 8 ml Kg- 1 was 0.86 (95% confidence interval, 0.76-0.96), P < 0.001, 95% sensitivity, 68% specificity, and with best cut-off value of absolute change (ΔPVI6-8) = 2.5%. CONCLUSION: In hepatobiliary and pancreatic surgeries, tidal volume challenge improves the reliability of PVI for predicting fluid responsiveness and changes in PVI values obtained after tidal volume challenge are comparable to the changes in SVI.

Black Titanium-Oxo Clusters with Ultralow Band Gaps and Enhanced Nonlinear Optical Performance.

A series of catecholate-functionalized titanium-oxo clusters (TOCs), PTC-271 to PTC-277, with atomically precise structures were synthesized and characterized, including distinctive "boat" and "chair" conformations in PTC-273 and PTC-274, respectively. These cluster compounds are prominent for their ultralow optical band gaps, as is visually evident from the rather unusual black TOCs (B-TOCs), PTC-272 to PTC-277. The cluster structures were found to be ultrastable with respect to air, water, organic solvents, and even acidic or basic aqueous solutions in a wide pH range (pH 0-13), owing to the stabilizing effects of catecholate and its derivatives, as well as the carboxylate ligands. Another prominent feature is the occurrence of third-order nonlinear optical (NLO) performance, which has previously been unreported in the field of homometallic titanium-oxo clusters. Open-aperture Z-scan experiments show significant solid-state optical limiting (OL) applications of these B-TOCs, with high laser irradiation stability and low minimum normalized transmittance (Tmin) of PTC-273 as ∼0.17. Meanwhile, theoretical calculations indicate that the smaller band gaps of B-TOCs were beneficial for strengthening the NLO response. This work not only represents a significant milestone in the construction of stable low-band gap black titanium oxide materials but also contributes to the mechanism insights into their optical applications.

Scalable Room-Temperature Synthesis of Highly Robust Ethane-Selective Metal-Organic Frameworks for Efficient Ethylene Purification.

The development of new techniques and materials that can separate ethylene from ethane is highly relevant in modern applications. Although adsorption-based separation techniques using metal-organic frameworks (MOFs) have gained increasing attention, the relatively low stability (especially water resistance) and unscalable synthesis of MOFs severely limit their application in real industrial scenarios. Addressing these challenges, we rationally designed and synthesized two new C2H6-selective MOF adsorbents (NKMOF-8-Br and -Me) with ultrahigh chemical and thermal stability, including water resistance. Attributed to the nonpolar/hydrophobic pore environments and appropriate pore apertures, the MOFs can capture C2 hydrocarbon gases at ambient conditions even in high humidity. The single-crystal structures of gas@NKMOF-8 realized the direct visualization of adsorption sites of the gases. Both the single-crystal data and simulated data elucidate the mechanism of selective adsorption. Moreover, the NKMOF-8 possesses high C2H6 adsorption capacity and high selectivity, allowing for efficient C2H6/C2H4 separation, as verified by experimental breakthrough tests. Most importantly, NKMOF-8-Br and -Me can be scalably synthesized through stirring at room temperature in minutes, which confers them with great potential for industrial application. This work offers new adsorbents that can address major chemical industrial challenges and provides an in-depth understanding of the gas binding sites in a visual manner.

Tetrahedral Geometry Induction of Stable Ag-Ti Nanoclusters by Flexible Trifurcate TiL3 Metalloligand.

A series of increasingly large silver nanoclusters with a varied combination of Archimedean and/or Platonic solid arrangements was constructed using a flexible trifurcate TiL3 (L = Salicylic acid or 5-fluorosalicylic acid) metalloligand: Ag4@Ag4@Ti4 (PTC-85), Ag12@Ti4 (PTC-86), Ag4@Ag6@Ag12@Ti4 (PTC-87), Ag6@Ag24@Ag12@Ti4 (PTC-88), and Ag12@Ag24@Ti4 (PTC-89). The silver nanoclusters are each capped by four TiL3 moieties, thereby forming {Ti4} supertetrahedra with average edge lengths ranging from ∼8.12 Å to ∼17.37 Å. Such {Ti4} moieties further induce the tetrahedral geometry of the encapsulated silver nanoclusters. These atomically precise metallic clusters were found to be ultrastable with respect to air for several months, and to water for more than 3 days, due to the stabilizing effects of the TiL3 metalloligand. Moreover, the obtained clusters exhibit nonlinear optical (NLO) effects in optical limiting tests and also temperature-dependent photoluminescent properties. This work provides an interesting metalloligand method not only to induce the spatial growth of metallic clusters to achieve highly symmetric structures, but also to enhance their stability which is crucial for future application.

Fabricating Covalent Organic Framework Capsules with Commodious Microenvironment for Enzymes.

Enzyme immobilization has been demonstrated to be a favorable protocol to promote industrialization of biomacromolecules. Despite tremendous efforts to develop new strategies and materials to realize this process, maintaining enzyme activity is still a formidable challenge. Herein we created a sacrificial templating method, using metal-organic frameworks (MOFs) as sacrificial templates to construct hollow covalent organic framework (COF) capsules for enzyme encapsulation. This strategy can provide a capacious microenvironment to unleash enzyme molecules. The improved conformational freedom of enzymes, enhanced mass transfer, and protective effect against the external environment ultimately boosted the enzymatic activities. We also found that this strategy possesses high versatility that is suitable for diverse biomacromolecules, MOF templates, and COF capsules. Moreover, the dimensions, pore sizes, and shell thickness of COF capsules can be conveniently tuned, allowing for customizing bioreactors for specific functions. For example, coencapsulation of different enzymes with synergistic functions were successfully demonstrated using this bioreactor platform. This study not only opens up a new avenue to overcome the present limitations of enzymatic immobilization in porous matrixes but also provides new opportunities for construction of biomicrodevices or artificial organelles based on crystalline porous materials.

Supramolecular Cages Based on a Silver Complex as Adaptable Hosts for Poly-Aromatic Hydrocarbons.

In this work, an L-shaped silver complex, AgLClO4 (L = 2,3-bis[3-(pyridin-2-yl)-1H-pyrazol-1-yl·methyl]quinoxaline), M, is found to be adaptable enough to host a range of medium and large aromatic hydrocarbons including several polycyclic aromatic hydrocarbons (PAHs). The transformation of M from as-synthesized closed (nonporous) crystalline to at least three types of open phase structures in the presence of different aromatic hydrocarbons enables the adaptable binding of M to these aromatics. In essence, M can rearrange its cavities to fit the different sizes and shapes of the guest molecules in the manner that is infeasible with cage compounds or coordination networks. Single-crystal and powder X-ray diffraction confirm the adaptable structures of the resulting host-guest complexes, M·nG (G = guest, n = 0.5 or 0.75). Detailed 1D and 2D nuclear magnetic resonance spectra, along with the fluorescence spectroscopy, reveal that the host-guest complexes feature similar chemical compositions in the solution, but are in the states of rapid exchange in and outside the cages. Such an adaptability of M provides insights into the strength of host-guest interactions and enables a new class of adsorptive molecular materials that can bind a large number of aromatics, specifically PAHs.

Combined Intrinsic and Extrinsic Proton Conduction in Robust Covalent Organic Frameworks for Hydrogen Fuel Cell Applications.

Developing new materials for the fabrication of proton exchange membranes (PEMs) for fuel cells is of great significance. Herein, a series of highly crystalline, porous, and stable new covalent organic frameworks (COFs) have been developed by a stepwise synthesis strategy. The synthesized COFs exhibit high hydrophilicity and excellent stability in strong acid or base (e.g., 12 m NaOH or HCl) and boiling water. These features make them ideal platforms for proton conduction applications. Upon loading with H3 PO4 , the COFs (H3 PO4 @COFs) realize an ultrahigh proton conductivity of 1.13×10-1  S cm-1 , the highest among all COF materials, and maintain high proton conductivity across a wide relative humidity (40-100 %) and temperature range (20-80 °C). Furthermore, membrane electrode assemblies were fabricated using H3 PO4 @COFs as the solid electrolyte membrane for proton exchange resulting in a maximum power density of 81 mW cm-2 and a maximum current density of 456 mA cm-2 , which exceeds all previously reported COF materials.

Protein-Structure-Directed Metal-Organic Zeolite-like Networks as Biomacromolecule Carriers.

Fabrication of zeolite-like metal-organic frameworks (ZMOFs) for advanced applications, such as enzyme immobilization, is of great interest but is a great synthetic challenge. Herein, we have developed a new strategy using proteins as structure-directed agents to direct the formation of new ZMOFs that can act as versatile platforms for the in situ encapsulation of proteins under ambient conditions. Notably, protein incorporation directs the formation of a ZMOF with a sodalite (sod) topology instead of a non-porous diamondoid (dia) topology under analogous synthetic conditions. Histidines in proteins play a crucial role in the observed templating effect. Modulating histidine content thereby influenced the resultant MOF product (from dia to dia + sod mixture and, ultimately, to sod MOF). Moreover, the resulting ZMOF-incorporated proteins preserved their activity even after exposure to high temperatures and organic solvents, demonstrating their potential for biocatalysis and biopharmaceutical applications.

Dinuclear Copper Sulfate-Based Square Lattice Topology Network with High Alkyne Selectivity.

Porous coordination networks (PCNs) sustained by inorganic anions that serve as linker ligands can offer high selectivity toward specific gases or vapors in gas mixtures. Such inorganic anions are best exemplified by electron-rich fluorinated anions, e.g., SiF62-, TiF62-, and NbOF52-, although sulfate anions have recently been highlighted as inexpensive and earth-friendly alternatives. Herein, we report the use of a rare copper sulfate dimer molecular building block to generate two square lattice, sql, coordination networks which can be prepared via solvent layering or slurrying, CuSO4(1,4-bib)1.5, 1, (1,4-bib = 1,4-bisimidazole benzene) and CuSO4(1,4-bin)1.5, 2, (1,4-bin = 1,4-bisimidazole naphthalene). Variable-temperature SCXRD and PXRD experiments revealed that both sql networks underwent reversible structural transformations due to linker rotations or internetwork displacements. Gas sorption studies conducted upon the narrow-pore phase of CuSO4(1,4-bin)1.5, 2np, found a high calculated 1:99 selectivity for C2H2 over C2H4 (33.01) and CO2 (15.18), as well as strong breakthrough performance. Across-the-board, C3H4 selectivity vs C3H6, CO2, and C3H8 was also observed. Sulfate-based PCNs, although still understudied, appear increasingly likely to offer utility in gas and vapor separations.

First Episode of Psychosis in the Context of Varenicline Treatment for Smoking Cessation.

Smoking is one of the leading causes of preventable death worldwide. Several pharmacological therapies have been established over the years to aid in smoking cessation, including Varenicline, a partial nicotine agonist. Neuropsychiatric adverse events have been reported in patients treated with Varenicline. Here, we present a case of first-episode psychosis in the context of Varenicline therapy. The patient's chart was retrospectively reviewed for relevant medical and psychiatric history, in addition to the use of current or past medications. Routine laboratory investigations and brain imaging were performed. The Naranjo Adverse Drug Reaction Probability Scale was also done independently by two physicians involved in the patient's treatment. He was admitted for psychotic symptoms elicited in the context of a probable adverse reaction to Varenicline. The current evidence linking Varenicline to psychosis remains controversial. Speculatively, there could be a link between Varenicline, which supposedly increases dopamine levels in the prefrontal cortex through the mesolimbic pathways, and psychotic symptoms. It is therefore beneficial to be cognizant, in a clinical setting, of the possibility of the emergence of these symptoms with Varenicline therapy.

A randomized placebo-controlled, double-blind study to investigate the effect of a high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients, new insights on serum STAT-3 and hepassocin.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease affecting millions globally. This study aimed to assess the safety and efficacy of a high oral loading dose of cholecalciferol supplement on NAFLD patients and to investigate its potential role on serum inflammatory biomarkers. PATIENTS AND METHODS: One hundred patients with NAFLD and type 2 diabetes mellitus were involved in the study. Eligible patients were randomized among two equal groups. Group 1 received the standard conventional therapy in addition to a placebo. Group 2 received the conventional therapy plus cholecalciferol for 4 months. The improvement in the patients' glycaemic control parameters, liver function tests, lipid profile, and serum 25-hydroxy vitamin D at the end of the study was set as a primary outcome. The secondary outcome was the decrease in steatosis grade in the ultrasound and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), signal transducer and activator of factor-3 (STAT-3), nitric oxide (NO), malondialdehyde (MDA), and hepassocin serum levels at the end of the study. RESULTS: Group 2 revealed a significant reduction in the serum levels of lipid profile measures, hs-CRP, alanine aminotransferase (ALT), STAT-3, NO, hepassocin, and MDA compared to the baseline and group 1 results. Whereas group 1 did not show these significant changes. Both groups observed no significant changes in glycemic index, TNF-α, aspartate aminotransferase (AST), and albumin levels. CONCLUSIONS: Cholecalciferol is recommended as additional therapy to modulate lipid peroxidation and systemic inflammation alongside other NAFLD therapies.

Comparative analysis as a management tool for broiler breeder farms: simulated individual farm analysis (IFAS).

The objective of this study was to develop a management information system to evaluate the tactical management of a breeder flock using individual farm analysis with a deterministic simulation model (IFAS). Individual farm analysis is a method that evaluates the performance of individual farms by comparing them with standards. In the first step of IFAS, a farm accounting system is used to compare performance indicators of a flock with the same performance indicators of the average of a group of flocks that produced in the same time period. In the next step, a deterministic simulation model is used to determine the factors causing the traced deviations in performances. Then, relevant deviations are determined based on the economic and statistical importance of each traced deviation. Finally, the deviations are identified by relevance to give farmers an indication of their strong and weak management practices.

Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review.

Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.

Polymorphism in Ionic Cocrystals Comprising Lithium Salts and l-Proline.

The occurrence of polymorphism in ionic cocrystals formed by two lithium salts, lithium salicylate (LIS) and lithium 4-methoxybenzoate (L4M), and l-proline (PRO) has been investigated. The previously reported monoclinic form of the 1:1 cocrystal of LIS and PRO, LISPRO(α), and a new thermodynamically stable orthorhombic polymorph, LISPRO(ß), were prepared and characterized. The two polymorphs form square grid, sql, topology coordination networks and differ mainly in the conformation of the salicylate ions and positioning of the sql nets. LISPRO(α) was observed to transform to LISPRO(ß) under slurry conditions. The 1:1 ionic cocrystal of L4M and PRO (L4MPRO) was found to form three polymorphs. Apart from the previously reported orthorhombic crystal form, L4MPRO(α), two new monoclinic crystal forms, L4MPRO(ß) and L4MPRO(γ), were obtained by modifying crystallization conditions. The new polymorphs were found to be metastable, undergoing transformations to L4MPRO(α) upon exposure to humidity. Experimental conditions that induce transformations between the polymorphs of LISPRO and L4MPRO are detailed, and the structural differences between the polymorphs are discussed in the broader context of polymorphism.

Conformational Trimorphism in an Ionic Cocrystal of Hesperetin.

We report the existence of conformational polymorphism in an ionic cocrystal (ICC) of the nutraceutical compound hesperetin (HES) in which its tetraethylammonium (TEA+) salt serves as a coformer. Three polymorphs, HESTEA-α, HESTEA-ß and HESTEA-γ, were characterized by single-crystal X-ray diffraction (SCXRD). Each polymorph was found to be sustained by phenol···phenolate supramolecular heterosynthons that self-assemble with phenol···phenol supramolecular homosynthons into C 3 2(7) H-bonded motifs. Conformational variability in HES moieties and different relative orientations of the H-bonded motifs resulted in distinct crystal packing patterns: HESTEA-α and HESTEA-ß exhibit H-bonded sheets; HESTEA-γ is sustained by bilayers of H-bonded tapes. All three polymorphs were found to be stable upon exposure to humidity under accelerated stability conditions for 2 weeks. Under competitive slurry conditions, HESTEA-α was observed to transform to the ß or γ forms. Solvent selection impacted the relationship between HESTEA-ß (favored in EtOH) and HESTEA-γ (favored in MeOH). A mixture of the ß and γ forms was found to be present following H2O slurry.

Standardized data in the broiler value chain.

In the Dutch broiler chain, data are collected as a routine practice. However, there is wide variation in the content of data collected and in data collection systems. This variability hampers the use of field data in management information systems to support decisions. The objective of this study was to analyze the quality of data and to standardize the content of data sets in the broiler production chain. To evaluate the quality of data, data sets from 3 Dutch hatcheries, from 23,637 batches of eggs, were assessed. The quality of data was assessed intuitively based on 7 quality attributes. To standardize the content of the data set, a protocol was proposed and validated. The protocol was validated at 30 breeder farms, 3 hatcheries, and 104 broiler farms by using 3 quality attributes: consistency, uniformity, and completeness. Results of the data quality analysis of the 3 Dutch hatcheries showed that the data sets had some fields with inaccurate, incorrect, inconsistent, nonuniform, incomprehensible, missing relevant, or incomplete data. Results of the validation protocol were as follows: feedback was obtained from 23 (77%) breeder farms, 3 (100%) hatcheries, and 7 (7%) broiler farms. Of all the questions, on average 88% were answered on breeder farms; 57, 65, and 82% were answered at each of the 3 hatcheries, respectively; and 79% were answered on the broiler farms. Data collected at 2 hatcheries were more consistent than those collected at the third hatchery. Hatchery data were less consistent than breeder farm data, but the number of data entries at hatcheries far exceeded the number at the farm level. Data from the hatcheries, breeder farms, and broiler farms were not always uniform, possibly because of differences in management strategies. This protocol enables the listing of relevant and standard contents of a data set whereby information exchange along the chain can be simplified. However, it is recommended that the protocol be supplemented with some rules for data collection and management, for example, that variables must be recorded in the provided fields, and that a variable must have one and only one name or code, the same unit of measurement, and the same definition.

Field study on broilers' first-week mortality.

In the Dutch poultry meat production chain, first week mortality (FWM) of the chicks is an important measure to quality and is therefore highly related to the price of the chicks that the broiler farm has to pay to the hatchery. Therefore, next to the total number of broiler eggs produced per hen and hatchability, this figure is often used as a measure of efficiency in the breeder-hatchery-broiler production chain. In this study, factors that are related to chick mortality in the first week at broiler farms were investigated. Field data obtained from 2 commercial Dutch hatcheries, for which 482 broiler farms voluntarily recorded FWM of 16,365 flocks of broiler chicks over the years 2004, 2005, and 2006, were analyzed. These represented 79% of the total number of day-old chicks delivered to separate broiler farms. First week mortality was significantly related to breeder age, egg storage length at the hatchery, season, strain, feed company of the breeder farm, year, and hatchery. Furthermore, FWM differed significantly between chicks originating from eggs of different breeder flocks and which were kept for grow-out at different broiler farms.

A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3 supplementation in adult patients with migraine.

BACKGROUND: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460). METHODS: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18-65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n = 24, 18 women and 6 men, 100 µg/day D3-Vitamin) or placebo (n = 24, 18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)2D were assessed from baseline to week 24. RESULTS: The number of headache days changed from 6.14 ± 3.60 in the treatment group and 5.72 ± 4.52 in the placebo group at baseline to 3.28 ± 3.24 and 4.93 ± 3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p < .001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)2D. No side-effects were reported or noted. CONCLUSIONS: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D3 might be one of the prophylactic options for adult patients with migraine.