Impact of gynecological cancers on health-related quality of life: historical context, measurement instruments, and current knowledge.

Gynecologic cancers, comprising 14.4% of newly diagnosed cancer cases in women globally, are substantial causes of both mortality and morbidity, with a profound impact on the quality of life (QoL) of survivors. Over the past few decades, advancements in interdisciplinary and interprofessional care have contributed to an increase in the average life expectancy of gynecological cancer patients. However, the disease and its treatments have a profound impact on patients, leading to physical changes and psychological consequences, including psychosocial and psychosexual effects, which negatively affect their QoL.The primary objective of management strategies is to minimize harm while improving survival rates and enhancing QoL during the survivorship stage. QoL measures play a crucial role in enhancing our comprehension of how cancer and its treatments affect individuals. Consequently, various measurement instruments, such as the EORTC QLQ 30, PROMIS-29, FACT-G, and QOL-CS, have been developed to assess health-related quality of life (HRQoL). Pre- and post-treatment HRQoL measurements have been shown to be predictive factors for post-operative complications and prognostic factors for overall survival and progression-free survival in gynecological oncology patients. Patient-reported outcomes related to HRQoL are essential tools for measuring patient outcomes and enabling patient-centered clinical decision-making.This article focuses on HRQoL, providing a historical context, summarizing measurement instruments, and discussing the current understanding of the impact of gynecological cancers on HRQoL.

Changes in biomarkers of redox status in serum and saliva of dogs with hypothyroidism.

BACKGROUND: Hypothyroidism is the most common endocrine disorder diagnosed in dogs, leading to deleterious effects on a dog's life quality. This study aims to evaluate changes in the redox status in canine hypothyroidism. For this purpose, a comprehensive panel of antioxidants and oxidants biomarkers were measured in serum and saliva of 23 dogs with hypothyroidism, 21 dogs with non-thyroidal illness, and 16 healthy dogs. Among the antioxidants, cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), thiol, paraoxonase type 1 (PON-1) and glutathione peroxidase (GPx) were determined in serum and CUPRAC, ferric reducing ability of saliva (FRAS) and TEAC in saliva. The oxidant biomarkers included were total oxidant status (TOS), peroxide-activity (POX-Act), reactive oxygen-derived compounds (d-ROMs), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) in serum and AOPP and TBARS in saliva. RESULTS: Results showed a significantly higher TEAC, PON-1, GPx, TOS, POX-Act, and d-ROMs, and a significantly lower AOPP in serum of dogs with hypothyroidism. Meanwhile, significantly lower FRAS and AOPP were observed in saliva of dogs with hypothyroidism. Once salivary concentrations were corrected based on their total protein concentrations, the only analyte showing significant changes was TBARS which was significantly higher in dogs with hypothyroidism. CONCLUSIONS: Our results show that dogs with hypothyroidism present alterations in the redox status in both serum and saliva. This study should be considered a preliminary study and further research addressing these changes should be made using larger populations.

Sacubitril-valsartan in heart failure and multimorbidity patients.

AIMS: The poor control of symptoms in patients with advanced heart failure with reduced ejection function (HFrEF) can limit the functionality of patients. Sacubitril-valsartan, compared with enalapril, has been shown to reduce mortality and hospitalization, and nowadays, there is still little evidence about the improvement on functionality. The aim of our study is to analyse the improvement of the functional class and the 6 min walking test (6MWT) in patients with multiple pathologies and advanced heart failure. METHODS AND RESULTS: From September 2016 to March 2018, 65 multimorbidity patients with severe symptomatic HFrEF were initiated to receive sacubitril-valsartan. Mean age was 78.6 ± 7.4 years, and 68% were male. The Charlson co-morbidity index was 8 points. Seventy-four per cent had New York Heart Association (NYHA) Functional Class IV. After the treatment, patients were able to achieve 55.68 m or more on 6MWT, and 91% presented an improvement in the NYHA functional class. CONCLUSIONS: Sacubitril-valsartan relieves symptoms and improves functional class prognostic risk of patients with advanced HFrEF and co-morbidity.

Rectosigmoid deep infiltrating endometriosis and ureteral involvement with loss of renal function.

UNLABELLED: Endometriosis is a complex disease with unclear pathogenesis, defined as the presence of endometrial tissue (glands and stroma) outside its usual location in the uterine cavity. Ureteral involvement is rare, with an estimated frequency of 10-14% in cases of deep endometriosis with nodules of 3 cm or larger. An important complication of ureteral involvement is asymptomatic loss of renal function. In a patient with asymptomatic renal failure the relevance of extrinsic ureteral involvement by deep endometriosis has been taken to account. CASE REPORT: A 32-year-old nulliparous woman presented with chronic pelvic pain associated with severe dysmenorrhea, dyspareunia and digestive problems including diarrhea, occasional constipation and rectal bleeding. She reported no urological symptoms. Magnetic resonance imaging (MRI) identified a 4 cm nodule in the recto-vaginal septum, compressing and infiltrating the rectal wall, and chronic left hydronephrosis. Isotope renogram revealed 91% function in the right kidney and 9% in the left kidney. A multidisciplinary surgical team including consultants from the departments of digestive surgery and urology assessed the patient. The treatment recommended was a joint approach of laparoscopic surgery to perform adhesiolysis, ureterolysis, freeing of the uterus and appendages, resection of the rectovaginal septum nodule, and left nephrectomy. COMMENT: Diagnosis and treatment of deep endometriosis should be performed in specialized centers and in the context of multidisciplinary collaboration. We must be aware of the potential risk of ureteral involvement and the asymptomatic loss of renal function in any patient with endometriosis nodules of 3 cm or larger.

[Control of cardiovascular risk factors in patients with stroke attended in primary care in Spain. ICTUSCARE study]. / Control de los factores de riesgo cardiovascular en pacientes con ictus atendidos en Atención Primaria en España. Estudio ICTUSCARE.

BACKGROUND: The aim of this cross-sectional, multicenter survey was: 1) To investigate the level of control of cardiovascuar risk factors in patients with a previous stroke. 2) To know the pharmacological therapy used to attain the control. PATIENTS AND METHODS: Data obtained from a total of 955 patients were included in the analysis.. There were evaluated cardiovascular risk factors, parameters related to the degree of control, analytical parameters, antropometric and pharmacological indicated treatment. RESULTS: The majority (61%) had suffered an ischemic stroke and 97.7% presented at least one associated cardiovascular risk factor, being hypertension (84.8%) and dyslipidemia (61.8%) the most frequent. Other factors were abdominal obesity (42.9%), diabetes mellitus (35.6%) and smoking (25.1%). Only 1.2% of the patients presented an adequate control of all cardiovascular risk factors. Only 17.6% had a well controlled blood pressure and in 29.8% LDL-cholesterol was well controlled. In 50.2% of diabetic patients HbA1c was well controlled. Angiotensin receptor blockers were the most widely used antihypertensive drugs (57.6%) while thiazide diuretics were prescribed in 33.4%. Statins were prescribed in 72.8% of patients and metformin, aspirin and acenocumarol in 30.2%, 57.3%, and 15.0% respectively. CONCLUSIONS: In conclusion, in patients with a past history of stroke arterial hypertension is the most common cardiovascular risk factor and the control of these factors requires an improvement.

Acetonimine and 4-imino-2-methylpentan-2-amino platinum(II) complexes: synthesis and in vitro antitumor activity.

The reaction of [Pt(dmba)(PPh3)Cl] [where dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl] with aqueous ammonia in acetone in the presence of AgClO4 gives the acetonimine complex [Pt(dmba)(PPh3)(NH=CMe2)]ClO4 (1). The reaction of [Pt(dmba)(DMSO)Cl] with aqueous ammonia in acetone in the presence of AgClO4 gives a mixture of [Pt(dmba)(NH=CMe2)2]ClO4 (2) and [Pt(dmba)(imam)]ClO4 (3a) (where imam = 4-imino-2-methylpentan-2-amino). [Pt(dmba)(DMSO)Cl] reacts with [Ag(NH=CMe2)2]ClO4 in a 1:1 molar ratio to give [Pt(dmba)(DMSO)(NH=CMe2)]ClO4 (4). The reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone at 70 degrees C in the presence of KOH gives [Pt(dmba)(CH2COMe)(NH=CMe2)] (5), whereas the reaction of [Pt(dmba)(DMSO)Cl] with 20% aqueous ammonia in acetone in the absence of KOH gives [Pt(dmba)(imam)]Cl (3b). The reaction of [NBu4]2[Pt2(C6F5)4(mu-Cl)2] with [Ag(NH=CMe2)2]ClO4 in a 1:2 molar ratio produces cis-[Pt(C6F5)2(NH=CMe2)2] (6). The crystal structures of 1 x 2 Me2CO, 2, 3a, 5, and 6 have been determined. Values of IC50 were calculated for the new platinum complexes against a panel of human tumor cell lines representative of ovarian (A2780 and A2780 cisR) and breast cancers (T47D). At 48 h incubation time complexes 1, 4, and 5 show very low resistance factors against an A2780 cell line which has acquired resistance to cisplatin. 1, 4, and 5 were more active than cisplatin in T47D (up to 30-fold in some cases). The DNA adduct formation of 1, 4, and 5 was followed by circular dichroism and electrophoretic mobility.

New palladium(II) and platinum(II) complexes with 9-aminoacridine: structures, luminiscence, theoretical calculations, and antitumor activity.

The new complexes [Pd(dmba)( N10-9AA)(PPh 3)]ClO 4 ( 1), [Pt(dmba)( N9-9AA)(PPh 3)]ClO 4 ( 2), [Pd(dmba)( N10-9AA)Cl] ( 3), and [Pd(C 6F 5)( N10-9AA)(PPh 3)Cl] ( 4) (9-AA = 9-aminoacridine; dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl) have been prepared. The crystal structures have been established by X-ray diffraction. In complex 2, an anagostic C-H...Pt interaction is observed. All complexes are luminescent in the solid state at room temperature, showing important differences between the palladium and platinum complexes. Complex 2 shows two structured emission bands at high and low energies in the solid state, and the lifetimes are in agreement with excited states of triplet parentage. Density functional theory and time-dependent density functional theory calculations for complex 2 have been done. Values of IC 50 were also calculated for the new complexes 1- 4 against the tumor cell line HL-60. All of the new complexes were more active than cisplatin (up to 30-fold in some cases). The DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pB R322 were also obtained.

Palladium(II) and platinum(II) organometallic complexes with 4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine. Antitumor activity of the platinum compounds.

Palladium and platinum complexes with HmtpO (where HmtpO=4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine, an analogue of the natural occurring nucleobase hypoxanthine) of the types [M(dmba)(PPh3)(HmtpO)]ClO4[dmba=N,C-chelating 2-(dimethylaminomethyl)phenyl; M=Pd or Pt], [Pd(N-N)(C6F5)(HmtpO)]ClO4[N-N=2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), or N, N, N', N'-tetramethylethylenediamine (tmeda)] and cis-[M(C6F5)2(HmtpO)2] (M=Pd or Pt) (head-to-head atropisomer in the solid state) have been obtained. Pd(II) and Pt(II) complexes with the anion of HmtpO of the types [Pd(tmeda)(C6F5)(mtpO)], [Pd(dmba)(micro-mtpO)] 2, and [NBu4]2[M(C6F5)2(micro-mtpO)]2(M=Pd or Pt) have been prepared starting from the corresponding hydroxometal complexes. Complexes containing simultaneously both the neutral HmtpO ligand and the anionic mtpO of the type [NBu4][M(C6F5)2(HmtpO)(mtpO)] (M=Pd or Pt) have been also obtained. In these mtpO-HmtpO metal complexes, for the first time, prototropic exchange is observed between the two heterocyclic ligands. The crystal structures of [Pd(dmba)(PPh 3)(HmtpO)]+, cis-[Pt(C6F5)2(HmtpO)2].acetone, [Pd(C6F5)(tmeda)(mtpO)].2H2O, [Pd(dmba)(micro-mtpO)]2, [NBu4]2[Pd(C6F5)2(micro-mtpO)]2.CH2Cl2.toluene, [NBu4]2[Pt(C6F5)2(micro-mtpO)](2).0.5(toluene), and [NBu4][Pt(C6F5)2(mtpO)(HmtpO)] have been established by X-ray diffraction. Values of IC50 were calculated for the new platinum complexes cis-[Pt(C6F5)2(HmtpO)2] and [Pt(dmba)(PPh3)(HmtpO)]ClO4 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780 cisR), lung (NCI-H460), and breast cancers (T47D). At 48 h incubation time, both complexes were about 8-fold more active than cisplatin in T47D and show very low resistance factors against an A2780 cell line, which has acquired resistance to cisplatin. The DNA adduct formation of cis-[Pt(C6F5)2(HmtpO)2] and [Pt(dmba)(PPh3)(HmtpO)]ClO4 was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by these platinum complexes on plasmid DNA pB R322 were also obtained.

Structure and magnetic properties of carbonate-bridged five-coordinate nickel(II) complexes controlled by solvent effect.

CO2 and HCO3- react with the dinuclear hydroxo-complex [Ni(mcN3)(mu-OH)]2(PF6)2 (mcN3 = 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene) to form micro-CO3 bridged nickel(II) complexes, [{Ni(mcN3)}2(mu-CO3)](PF6)2 (1a) with a symmetric core in which both nickel atoms are five-coordinate and [Ni(mcN3)(mu-CO3)Ni(mcN3)(MeCN)](PF6)2 (1b) with an asymmetric dinuclear core containing five- and six-coordinate nickel atoms. The magnetic behaviour indicates the existence of antiferromagnetic coupling between the metallic centres. A substantial increase in the value of J occurs when the symmetric five-coordinate nickel species transforms to an asymmetric five- and six-coordinate species by axial coordination of acetonitrile.

Palladium(II) and platinum(II) organometallic complexes with the model nucleobase anions of thymine, uracil, and cytosine: antitumor activity and interactions with DNA of the platinum compounds.

Pd(II) and Pt(II) complexes with the anions of the model nucleobases 1-methylthymine (1-MethyH), 1-methyluracil (1-MeuraH), and 1-methylcytosine (1-MecytH) of the types [Pd(dmba)(mu-L)]2 [dmba = N,C-chelating 2-((dimethylamino)methyl)phenyl; L = 1-Methy, 1-Meura or 1-Mecyt] and [M(dmba)(L)(L')] [L = 1-Methy or 1-Meura; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium complexes of the types [Pd(C6F5)(N-N)(L)] [L = 1-Methy or 1-Meura; N-N = N,N,N',N'-tetramethylethylenediamine (tmeda), 2,2'-bipyridine (bpy), or 4,4'-dimethyl-2,2'-bipyridine (Me2bpy)] and [NBu4][Pd(C6F5)(1-Methy)2(H2O)] have also been prepared. The crystal structures of [Pd(dmba)(mu-1-Methy)]2, [Pd(dmba)(mu-1-Mecyt)]2.2CHCl3, [Pd(dmba)(1-Methy)(PPh3)].3CHCl3, [Pt(dmba)(1-Methy)(PPh3)], [Pd(tmeda)(C6F5)(1-Methy)], and [NBu4][Pd(C6F5)(1-Methy)2(H2O)].H2O have been established by X-ray diffraction. The DNA adduct formation of the new platinum complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the platinum complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the new platinum complexes against the tumor cell line HL-60. All the new platinum complexes were more active than cisplatin (up to 20-fold in some cases).

New palladium(II) and platinum(II) complexes with the model nucleobase 1-methylcytosine: antitumor activity and interactions with DNA.

Palladium and platinum complexes with the model nucleobase 1-methylcytosine (1-Mecyt) of the types [Pd(N-N)(C6F5)(1-Mecyt)]ClO4 [N-N = bis(3,5-dimethylpyrazol-1-yl)methane (bpzm), bis(pyrazol-1-yl)methane (bpzm), N,N,N',N'-tetramethylethylenediamine (tmeda), or 2,2'-bipyridine (bpy)] and [M(dmba)(L')(1-Mecyt)]ClO4 [dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium and platinum complexes of the types cis-[M(C6F5)2(1-Mecyt)2] (M = Pd or Pt) and cis-[Pd(L')(C6F5)(1-Mecyt)2]ClO4 (L' = PPh(3) or t-BuNC) have also been prepared. The crystal structures of [Pd(bpzm)(C6F5)(1-Mecyt)]ClO4, [Pt(dmba)(DMSO)(1-Mecyt)]ClO4, cis-[Pd(C6F5)2(1-Mecyt)2], and cis-[Pd(t-BuNC)(C6F5)(1-Mecyt)2]ClO4 have been established by X-ray diffraction. There is extensive hydrogen bonding (N-H...O, C-H...F or C-H...O) in all the compounds. There are also intermolecular pi-pi interactions between pyrimidine rings of adjacent chains in [Pd(C6F5)2(1-Mecyt)2]. DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC(50) were also calculated for the new complexes against the tumor cell line HL-60. At a short incubation time (24 h) almost all new complexes were more active than cisplatin.

Five-coordinate nickel(II) complexes with carboxylate anions and derivatives of 1,5,9-triazacyclododec-1-ene: structural and 1H NMR spectroscopic studies.

The hydroxo complexes [Ni2(mcN3)2(mu-OH)2]2(PF6)2[mcN3 = 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene (Me3-mcN3) or 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene (Me4-mcN3)] react with the corresponding carboxylic acid [HA = benzoic (Hbz), salicylic (Hsal) or acetylsalicylic (Hacsal) acid] to give five-coordinate nickel(II) complexes of the type [Ni(mcN3)(A)](PF6). The complexes have been studied by spectroscopic methods (IR, UV-Vis and 1H NMR). In acetone solution they exhibit isotropically shifted 1H NMR resonances. The full assignment of these resonances has been made using one- and two-dimensional 1H NMR techniques. The single-crystal structures of [Ni(Me4-mcN3)(bz)](PF6), [Ni(Me4-mcN3)(sal)](PF6) and[Ni(Me4-mcN3)(acsal)](PF6) have been established by X-ray diffraction.

Pentacoordinate nickel(II) complexes double bridged by phosphate ester or phosphinate ligands: spectroscopic, structural, kinetic, and magnetic studies.

The bis(phosphatediester)-bridged complexes [[Ni([12]aneN(3))(mu-O(2)P(OR)(2))](2)](PF(6))(2) [[12]aneN(3)=Me(3)[12]aneN(3), 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene; R=Me (1), Bu (2), Ph (3), Ph-4-NO(2) (4); [12]aneN(3)=Me(4)[12]aneN(3), 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene; R=Me (5), Bu (6), Ph (7), Ph-4-NO(2) (8)] were prepared by hydrolysis of the phosphate triester with the hydroxo complex [[Ni([12]aneN(3))(mu-OH)](2)](PF(6))(2) or by acid-base reaction of the dialkyl or diaryl phosphoric acid and the above hydroxo complex. The acid-base reaction was also used to synthesise the phosphinate-bridged complexes [[Ni([12]aneN(3))(mu-O(2)PR(2))](2)](PF(6))(2) [[12]aneN(3)=Me(3)[12]aneN(3), R=Me (9), Ph (10); [12]aneN(3)=Me(4)[12]aneN(3), R=Me (11), Ph (12)]. The molecular structures of complexes 2, 3 and 12 were established by single crystal X-ray diffraction studies. The eight-membered rings defined by the nickel atoms and the bridging ligands show distorted twist-boat, chair and boat-boat conformations in 2, 3 and 12, respectively. The experimental susceptibility data for compounds 2, 3 and 12 were fitted by least-squares methods to the analytical expression given by Ginsberg. The best fit was obtained with values of J=-0.11 cm(-1), D=-9.5 cm(-1) and g=2.20 for 2; J=-0.97 cm(-1), D=-9.3 cm(-1) and g=2.21 for 3; and J=-0.14 cm(-1), D=-11.9 cm(-1) and g=2.195 for 12. The magnetic-exchange pathways must involve the phosphate/phosphinate bridges, because these favour antiferromagnetic interactions. The observation of a higher exchange parameter for compound 3 is a consequence of a favourable disposition of the O-P-O bridges. The kinetics for the hydrolysis of TNP (tris(4-nitrophenyl)phosphate) with the dinuclear nickel(II) hydroxo complex [[Ni(Me(3)[12]aneN(3))(mu-OH)](2)](PF(6))(2) was studied by UV-visible spectroscopy. The proposed mechanism for TNP-promoted hydrolysis can be described as one-substrate/two-product, and can be fitted to a Michaelis-Menten equation.

Oxamidate-bridged dinuclear five-coordinate nickel(II) complexes: a magneto-structural study.

The preparation, spectroscopic characterization, and magnetic study of three new oxamidate-bridged nickel(II) dinuclear complexes of formulas ([Ni(Me3[12]aneN3)]2(mu-oa))(PF6)2 (1), ([Ni(Me3[12]aneN3)]2(mu-dmoa))(PF6)2 (2), and ([Ni(Me3[12]aneN3)]2(mu-dpoa))(PF6)2 (3) (Me3[12]aneN3 = 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene, oa = oxamidate, dmoa = N,N'-dimethyloxamidate, and dpoa = N,N'-diphenyloxamidate) are reported. The crystal structures of two of them (1 and 3) have been determined. 1 and 3 crystallize in the monoclinic system, space group P2(1)/c, with Z = 2 and a = 7.901(4) A, b = 13.597(6) A, c = 17.565(10) A, and beta = 96.46(4) degrees for 1 and a = 13.854(3) A, b = 17.469(4) A, c = 12.543(3) A, and beta = 116.22(3) degrees for 3. The structures of 1 and 3 consist of dinuclear ([Ni(Me3[12]aneN3)]2(mu-oa))2+ and ([Ni(Me3[12]aneN3)]2(mu-dpoa))2+ cations and hexafluorophosphate anions. Each nickel in 1-3 is five-coordinate, and the substitution of the hydrogen atom of the amidate nitrogen of 1 by a methyl (2) or a phenyl (3) group causes a significant modification of the stereochemistry of the nickel(II) ions from square pyramidal toward trigonal bipyramidal (tau values of 0.12 and 0.48 for 1 and 3, respectively). The NOESY spectrum of 3 has allowed us to achieve the assignment of the phenyl protons of the N,N'-diphenyloxamidate. The value of magnetic coupling between the two nickel(II) ions across the oxamidate bridge [J = -57.0 (oa, 1), -38.0 (dmoa, 2) and -30.5 cm(-1) (dpoa, 3)] is very sensitive to this stereochemical change, and its variation is explained on the basis of orbital considerations. DFT type calculations have been performed to analyze and substantiate the trend of the magnetic coupling in 1-3.