Despite the introduction of targeted agents leading to therapeutic advances, clinical management of patients with metastatic colorectal cancer (mCRC) is still challenged by significant interindividual variability in treatment outcomes, both in terms of toxicity and therapy efficacy. The study of germline genetic variants could help to personalize and optimize therapeutic approaches in mCRC.

A systematic review of pharmacogenetic studies in mCRC patients published on PubMed between 2011 and 2021, evaluating the role of germline variants as predictive markers of toxicity and efficacy of drugs currently approved for treatment of mCRC, was perfomed.

Despite the large amount of pharmacogenetic data published to date, only a few genetic markers (i.e.
and
variants) reached the clinical practice, mainly to prevent the toxic effects of chemotherapy. The large heterogeneity of available studies represents the major limitation in comparing results and identifying potential markers for clinical use, the role of previously overlooked rare variants has been pointed out.Weakening and cleaving N-H bonds is crucial for improving molecular ammonia (NH3) oxidation catalysts. We report the synthesis and H-atom-abstraction reaction of bis(ammonia)chromium porphyrin complexes Cr(TPP)(NH3)2 and Cr(TMP)(NH3)2 (TPP = 5,10,15,20-tetraphenyl-meso-porphyrin and TMP = 5,10,15,20-tetramesityl-meso-porphyrin) using bulky aryloxyl radicals. The triple H-atom-abstraction reaction results in the formation of CrV(por)(≡N), with the nitride derived from NH3, as indicated by UV-vis and IR and single-crystal structural determination of Cr(TPP)(≡N). Subsequent oxidation of this chromium(V) nitrido complex results in the formation of CrIII(por), with scission of the Cr≡N bond. Computational analysis illustrates the progression from CrII to CrV and evaluates the energetics of abstracting H atoms from CrII-NH3 to generate CrV≡N. The formation and isolation of CrV(por)(≡N) illustrates the stability of these species and the need to chemically activate the nitride ligand for atom transfer or N-N coupling reactivity.
Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting.

We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT.

Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD 13.59) years. https://www.selleckchem.com/CDK.html Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (- 8.5, 95% CI - 14.6, - 2.5) were associated with AMT response.

This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea.
This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea.Sarcopenia has an insidious start that can induce physical malfunction, raise the risk of falls, disability, and mortality in the old, severely impair the aged persons' quality of life and health. More and more studies have demonstrated that sarcopenia is linked to neurological diseases in recent years. This review examines the advancement of sarcopenia and neurological illnesses research.
The decision of the Federal Joint Committee has resulted in the further development of in-hospital emergency medicine through the establishment of central emergency departments and staged emergency care. In addition, the additional training in clinical acute and emergency medicine was established.

The aim of this work is on the one hand to make trauma surgeons aware of these structural changes. On the other hand, we would like to evaluate an opinion and discuss the position of trauma surgery in emergency medicine.

Aweb-based online survey was conducted at the Trauma Network and Trauma Registry Congress to collect participants' opinions on the position of trauma surgery in emergency medicine.

Of 143 congress participants, 98 (67%) responded to the survey. The majority of participants were male (n = 78, 80%), over 40years of age (n = 62, 63%), and in aprofessional position with staff responsibility (n = 73, 75%). Emergency medicine (mean 84.8; SD 18.7) and intensive care medicine (mean 78.3; SD 20.4) training appears important. On the other hand, subsequent work in these areas appears less important (prehospital emergency medicine mean 65.1; SD 28.0; ICU mean 53.7, SD 30.3); however, activity in an emergency department is rated higher (MW 87.0; SD 18.7). There is high agreement that the trauma leader should be atrauma surgeon (mean 87.9; SD 19.7).

Ahigh volume of emergency trauma surgery patients and the care of severely injured patients in designated trauma centers show that trauma surgery expertise is mandatory in acentral emergency department. Senior positions should also be sought to ensure high quality standards.
A high volume of emergency trauma surgery patients and the care of severely injured patients in designated trauma centers show that trauma surgery expertise is mandatory in a central emergency department. Senior positions should also be sought to ensure high quality standards.
Our study examined renal function change in older adults with osteoporosis, treated with zoledronic acid. Risk of nephrotoxicity was low. Future studies are needed to evaluate use of zoledronic acid in patients with a CCr < 35mL/min, as patients may be inappropriately excluded from its use.

Zoledronic acid (ZA) is used for the treatment of osteoporosis (OP). Renal impairment is a known risk factor for the rare occurrence of nephrotoxicity after ZA infusions, leading to use being contraindicated below creatinine clearance (CCr) of 35mL/min. Our aims are to examine changes in serum creatinine (SCr) after infusions, capture frequency of acute kidney injury (AKI), and describe baseline kidney function estimates in adults 75years and older being treated for OP.

This was a retrospective, cross-sectional, pre-post analysis that examined change in SCr before and after ZA infusions. The primary outcome was assessed using a paired Student t-test. Incidence of AKI within 1year following infusions was noted and e Cockcroft-Gault (CG) equation in comparison to CKD-EPI. We believe use of the CG equation in this population may be inappropriately limiting our ability to use ZA for treatment of OP in older adults but more evidence is necessary.The development of sustainable C(sp3)-H functionalization methods is of great interest to the pharmaceutical and agrochemical industries. Anodic oxidation is an efficient means of producing benzylic cations that can undergo subsequent in situ nucleophilic attack to afford functionalized benzylic products. Herein, we demonstrate the suitability of carboxylic acids as nucleophiles to yield benzylic esters. This method employs a series of secondary benzylic substrates and functionalized carboxylic acids and is demonstrated on a gram scale in flow.The corpus callosum is the largest fiber bundle in the cerebral white matter in the human brain. A multitude of disorders including congenital malformations, acute and chronic traumatic lesions, ischemia, neoplasms, secondary manifestations of metabolic, toxic or degenerative diseases as well as chronic inflammatory and demyelinating diseases can primarily or secondarily affect the corpus callosum. This article presents magnetic resonance imaging (MRI) characteristics of the most relevant diseases affecting the corpus callosum.This study aimed to analyze the association between temperature and precipitation and the incidence of hepatitis A in Seoul, Korea, as meteorological factors may have different effects on specific diseases depending on the lifestyle in each region. Weekly cases of hepatitis A, weekly mean daily precipitation, and temperature data from 2016 to 2020 were analyzed. Quasi-Poisson-generalized linear models with time variable adjusted by spline function were used considering 0-6-week lags. The association of each variable and hepatitis A incidence was assessed by the single lag and the constrained distributed lag model. Multivariable distributed lag linear and non-linear models were used to develop models with significant independent variables. Weekly mean of daily mean temperature (Tmean) and maximum temperature (Tmax) were negatively associated with hepatitis A in the 6-week lag. Precipitation was negatively associated with hepatitis A in the 5- and 6-week lags. The multivariable model showed the negative association of Tmax, precipitation and hepatitis A in the 5- and 6-week lags. In the non-linear models, the incidence rate ratio (IRR) was the highest at a Tmax of 11 °C and decreased thereafter. IRR was the highest at 12 mm of precipitation and showed decrease pattern to 25 mm and then gradually increased in the 5- and 6-week lags. Identifying the impact of climate factors on hepatitis A incidence would help in the development of strategies to prevent diseases and indirectly estimate the impact of climate change on hepatitis A epidemiology.An efficient Agrobacterium-mediated transient expression method was developed, which contributed to the functional characterization of the transcription factor CqPHR1, and demonstrates the potential application of gene editing in quinoa. Chenopodium quinoa is a crop expected to ensure global food security in future due to its high resistance to multiple abiotic stresses and nutritional value. We cloned one of the paralogous genes of the Arabidopsis homolog PHR1 (PHOSPHATE STARVATION RESPONSE 1) in quinoa-inbred lines by reverse genetic approach. Overexpression of CqPHR1 driven by the constitutive CaMV 35S promoter in Arabidopsis phr1 mutant can complement its phenotypes, including the induction of phosphate starvation-induced (PSI) genes and anthocyanin accumulation in leaves. By Agrobacterium-mediated gene transient expression, we found that CqPHR1 localized in the nucleus of quinoa cells, and overexpression of CqPHR1 in quinoa cells promoted PSI genes expression, which further revealed the function of CqPHR1 as a transcription factor. We have also shown that the transient expression system can be used to express Cas9 protein in various quinoa-inbred lines and perform effective gene editing in quinoa tissue. The method developed in this study will be useful for verifying the effectiveness of gene-editing systems in quinoa cells and has potential application in the generation of gene-edited quinoa with heritable traits.