Lactobacillus strains reduce the toxic effects of a subchronic exposure to arsenite through drinking water.

The aim of the present study was to determine the efficacy of LAB strains in reducing the intestinal toxicity of arsenite [As(III)] and its tissue accumulation. For this purpose, Balb/c mice were randomly separated in four groups. One group received no treatment (control), one group received only As(III) (30 mg/L) via drinking water and the remaining two groups received As(III) via water and a daily dose of two LAB strains (Lactobacillus intestinalis LE1 and Lacticaseibacillus paracasei BL23) by gavage during 2 months. The results show that both strains reduce the pro-inflammatory and pro-oxidant response observed at the colonic level, partially restore the expression of the intercellular junction proteins (CLDN3 and OCLN) responsible for the maintenance of epithelial integrity, and increase the synthesis of the major mucin of the colonic mucus layer (MUC2), compared to animals treated with As(III) alone. Microbial metabolism of short-chain fatty acids also undergoes a recovery and the levels of fatty acids in the lumen reach values similar to those of untreated animals. All these positive effects imply the restoration of mucosal permeability, and a reduction of the marker of endotoxemia LPS binding protein (LBP). Treatment with the bacteria also has a direct impact on intestinal absorption, reducing the accumulation of As in the internal organs. The data suggest that the protective effect may be due to a reduced internalization of As(III) in intestinal tissues and to a possible antioxidant and anti-inflammatory activity of the bacteria through activation of pathways such as Nrf2 and IL-10. In vitro tests show that the protection may be the result of the combined action of structural and metabolic components of the LAB strains.

Drilling accuracy evaluation of a mouldable surgical targeting system for minimally invasive access to anatomic targets in the temporal bone.

PURPOSE: Minimally invasive cochlear implant surgery using a micro-stereotactic surgical targeting system with on-site moulding of the template aims for a reliable, less experience-dependent access to the inner ear under maximal reduction of trauma to anatomic structures. We present an accuracy evaluation of our system in ex-vivo testing. METHODS: Eleven drilling experiments were performed on four cadaveric temporal bone specimens. The process involved preoperative imaging after affixing the reference frame to the skull, planning of a safe trajectory preserving relevant anatomical structures, customization of the surgical template, execution of the guided drilling and postoperative imaging for determination of the drilling accuracy. Deviation between the drilled and desired trajectories was measured at different depths. RESULTS: All drilling experiments were successfully performed. Other than purposely sacrificing the chorda tympani in one experiment, no other relevant anatomy, such as facial nerve, chorda tympani, ossicles or external auditory canal were harmed. Deviation between the desired and achieved path was found to be 0.25 ± 0.16 mm at skulls' surface and 0.51 ± 0.35 mm at the target level. The closest distance of the drilled trajectories' outer circumference to the facial nerve was 0.44 mm. CONCLUSIONS: We demonstrated the usability for drilling to the middle ear on human cadaveric specimen in a pre-clinical setting. Accuracy proved to be suitable for many applications such as procedures within the field of image-guided neurosurgery. Promising approaches to reach sufficient submillimetre accuracy for CI surgery have been outlined.

Hydraulic insertions of cochlear implant electrode arrays into the human cadaver cochlea: preliminary findings.

OBJECTIVES: (1) To evaluate the feasibility of a non-invasive, novel, simple insertion tool to perform automated, slow insertions of cochlear implant electrode arrays (EA) into a human cadaver cochlea; (2) to estimate the handling time required by our tool. METHODS: Basic science study conducted in an experimental OR. Two previously anonymized human cadaver heads, three commercially available EAs, and our novel insertion tool were used for the experiments. Our tool operates as a hydraulic actuator that delivers an EA at continuous velocities slower than manually feasible. INTERVENTION(S): the human cadaver heads were prepared with a round-window approach for CI surgery in a standard fashion. Twelve EA insertion trials using our tool involved: non-invasive fixation of the tool to the head; directing the tool to the round window and EA mounting onto the tool; automated EA insertion at approximately 0.1 mm/s driven by hydraulic actuation. Outcome measurement(s): handling time of the tool; post-insertion cone-beam CT scans to provide intracochlear evaluation of the EA insertions. RESULTS: Our insertion tool successfully inserted an EA into the human cadaver cochlea (n = 12) while being attached to the human cadaver head in a non-invasive fashion. Median time to set up the tool was 8.8 (7.2-9.4) min. CONCLUSION: The first insertions into the human cochlea using our novel, simple insertion tool were successful without the need for invasive fixation. The tool requires < 10 min to set up, which is clinically acceptable. Future assessment of intracochlear trauma is needed to support its safety profile for clinical translation.

First national record of Aedes melanimon (Diptera: Culicidae) in Mexico.

Aedes (Ochlerotatus) melanimon Dyar 1924 has been considered an important pest in agricultural and rural communities. Aedes melanimon is a vector of WEEV and CEV and is a competent laboratory vector of WNV. The known range of Ae. melanimon extends throughout Southwest Canada, part of Central and most of Western USA. Here we report the first record of Ae. melanimon in Mexico, at Ciudad Juárez, Chihuahua. The collect represents the southernmost distributional record for this species. Its indigenous presence in a highly urbanized and dry area was not expected. A permanent surveillance program to detect and determine the species in border-crossing cities is encouraged.

Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains.

AIM: As options to treat recalcitrant bacterial infections which are increasingly limited due to multidrug-resistant strains, searching for new, effective antibacterial compounds is necessary. One strategy is to generate treatment alternatives by drug repurposing. METHODS AND RESULTS: In this work, phenotypic microarrays were used for the screening of miscellaneous compounds against the growth and biofilm formation of Acinetobacter baumannii, an important emergent multidrug-resistant opportunistic pathogen. The results showed that the phenothiazine derivatives, such as promethazine, trifluoperazine, thioridazine, and chlorpromazine, inhibited the growth of antibiotic-sensitive and multidrug-resistant strains (showing minimal inhibitory concentrations ranging from 0·05 to 0·6 g l-1 and minimal bactericidal concentrations ranging from 0·1 to 2·5 g l-1 ). All phenothiazine derivatives were active against biofilm cells (with minimal biofilm eradication concentrations ranging from 0·5 to >3 g l-1 ). Chlorpromazine promoted reactive oxigen species (ROS) production, and cell membrane and DNA damage. Chlorpromazine showed synergy with antibiotics such as ceftazidime, meropenem, and colistin and was an effective treatment for experimentally infected Galleria mellonella when combined with ceftazidime. CONCLUSIONS: It was demonstrated that phenothiazine derivatives, especially chlorpromazine, are drugs with attractive antibacterial properties against nosocomial MDR strains of A. baumannii, by generating ROS and cell membrane and DNA damage. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicates that repurposing phenothiazine derivatives for treating recalcitrant infections by A. baumannii could be promising.

Acclimation of microorganisms for an efficient production of volatile fatty acids and biogas from mezcal vinasses in a dark fermentation process.

Mezcal is an alcoholic artisanal drink made from agave plants in Mexico. Its production causes the generation of wastewater called vinasses, which are highly polluting residues due to its concentration of organic matter as chemical oxygen demand (COD) (35,000-122,000 mg/L) and acidity (pH < 4). Due to their organic content, these residues can be used in dark fermentation to obtain biogas, which is rich in hydrogen. In this work, the acclimation of inoculum by means of a dark fermentation process, in the presence of toxic compounds from mezcal vinasses was studied. The strategy of increasing the initial concentration of vinasse in each treatment cycle in a sequencing batch reactor (SBR) reactor was applied. It was possible to obtain a maximum biogas production of 984 ± 187 mL/L, from vinasses (18,367 ± 1,200 mg COD/L), with an organic matter removal efficiency of 20 ± 1%. A maximum generation of volatile fatty acids (VFA) of 980 ± 538 mg/L equivalent to a production of 74 ± 21% of the influent concentration and removal rate of organic matter of 1,125 ± 234 mg COD/L d-1 equivalent to a removal efficiency of 20 ± 4% was obtained from vinasses with a concentration of 19,648 ± 1,702 mg COD/L.

Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis. / Relación entre psoriasis y síndrome metabólico en Latinoamérica. Revisión sistemática y metaanálisis.

INTRODUCTION: Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included. METHODOLOGY: We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies. RESULTS: Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; P=.03). In studies using the Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies. CONCLUSION: The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-III criteria are used for diagnosis.

Mesquite wood chips (Prosopis) as filter media in a biofilter system for municipal wastewater treatment.

The biofiltration system over organic bed (BFOB) uses organic filter material (OFM) to treat municipal wastewater (MWW). This study evaluated the performance of a BFOB system employing mesquite wood chips (Prosopis) as OFM. It also evaluated the effect of hydraulic loading rates (HLRs) in order to achieve the operational parameters required to remove organic matter, suspended material, and pathogens, thus meeting Mexican and US regulations for reuse in irrigation. Two biofilters (BFs) connected in series were installed; the first one aerated (0.62 m(3)air m(-2)h(-1)) and the second one unaerated. The source of MWW was a treatment plant located in Durango, Mexico. For 200 days, three HLRs (0.54, 1.07, and 1.34 m(3)m(-2)d(-1)) were tested. The maximum HLR at which the system showed a high removal efficiency of pollutants and met regulatory standards for reuse in irrigation was 1.07 m(3)m(-2)d(-1), achieving removal efficiencies of biochemical oxygen demand (BOD5) 92%, chemical oxygen demand (COD) 78%, total suspended solids (TSS) 95%, and four log units of fecal coliforms. Electrical conductivity in the effluent ensures that it would not cause soil salinity. Therefore, mesquite wood chips can be considered an innovative material suitable as OFM for BFs treating wastewaters.

Characterization of the response to low pH of Lactobacillus casei ΔRR12, a mutant strain with low D-alanylation activity and sensitivity to low pH.

AIMS: To identify the differences that account for the acid sensitivity of Lactobacillus casei ΔRR12. RR12 controls the expression of the dlt operon, and its inactivation leads to a diminished teichoic acid D-alanylation activity. To this end, a comparison of its response of ΔRR12 to low pH with the parental strain Lact. casei BL23 was carried out. METHODS AND RESULTS: The ability to induce an acid tolerance response (ATR), fatty acid (FA) composition and proteome changes induced in both strains in response to acid were investigated. Results obtained showed that both strains induce a growth-phase-dependent ATR. However, significant differences in the content of FAs and membrane-associated proteins were detected. CONCLUSIONS: The greater abundance of cytoplasmic proteins in the membrane fraction of the mutant strain ΔRR12 suggests an increased permeability of the cell membrane in this strain. SIGNIFICANCE AND IMPACT OF THE STUDY: The analysis of the response to low pH of strain ΔRR12 indicated that the inactivation of TCS12 affected the content of FAs and proteins associated to the cell envelope. Increased abundance of cytoplasmic proteins suggested that low alanylation of teichoic acids affected the permeability of the cell membrane and possibly accounts for the acid sensitivity of strain ΔRR12.

Optimizing ocular vestibular evoked myogenic potential testing for superior semicircular canal dehiscence syndrome: electrode placement.

OBJECTIVE: To compare the sensitivity and specificity of ocular vestibular evoked myogenic potentials (oVEMPs) using 2 electrode montages for the diagnosis of superior canal dehiscence syndrome (SCDS). SUBJECTS: 16 SCDS patients (17 affected-SCDS ears, 15 contralateral-SCDS ears) and 12 controls (24 ears). METHODS: oVEMPs were recorded in response to 500-Hz tone bursts using 2 electrode montages. For both montages the active electrode was placed approximately 5 mm below each eye and a ground electrode on the sternum. For montage 1 (standard), the reference electrode was centered 2 cm below each active electrode. For montage 2, the reference electrode was placed on the chin. RESULTS: For either montage, the separation between oVEMP amplitudes in affected-SCDS ears and controls was significant (p < 0.001), with excellent sensitivity and specificity (>90%). CONCLUSION: oVEMP recordings with the standard montage remain a reliable method for evaluation of SCDS.

Modeling the impact of a supervised consumption site on HIV and HCV transmission among people who inject drugs in three counties in California, USA.

BACKGROUND: Supervised consumption sites (SCS) have been shown to reduce receptive syringe sharing among people who inject drugs (PWID) in the United States and elsewhere, which can prevent HIV and hepatitis C virus (HCV) transmission. PWID are at risk of disease transmission and may benefit from SCS, however legislation has yet to support their implementation. This study aims to determine the potential impact of SCS implementation on HIV and HCV incidence among PWID in three California counties. METHODS: A dynamic HIV and HCV joint transmission model among PWID (sexual and injecting transmission of HIV, injecting transmission of HCV) was calibrated to epidemiological data for three counties: San Francisco, Los Angeles, and San Diego. The model incorporated HIV and HCV disease stages and HIV and HCV treatment. Based on United States data, we assumed access to SCS reduced receptive syringe sharing by a relative risk of 0.17 (95 % CI: 0.04-1.03). This model examined scaling-up SCS coverage from 0 % to 20 % of the PWID population within the respective counties and assessed its impact on HIV and HCV incidence rates after 10 years. RESULTS: By increasing SCS from 0 % to 20 % coverage among PWID, 21.8 % (95 % CI: -1.2-32.9 %) of new HIV infections and 28.3 % (95 % CI: -2.0-34.5 %) of new HCV infections among PWID in San Francisco County, 17.7 % (95 % CI: -1.0-30.8 %) of new HIV infections and 29.8 % (95 % CI: -2.1-36.1 %) of new HCV infections in Los Angeles County, and 32.1 % (95 % CI: -2.8-41.5 %) of new HIV infections and 24.3 % (95 % CI: -1.6-29.0 %) of new HCV infections in San Diego County could be prevented over ten years. CONCLUSION: Our models suggest that SCS is an important intervention to enable HCV elimination and could help end the HIV epidemic among PWID in California. It could also have additional benefits such facilitating pathways into drug treatment programs and preventing fatal overdose.

[Executive functions in patients with obstructive sleep apnea: exploring the prefrontal model]. / Funciones ejecutivas en pacientes con apnea obstructiva del sueño: explorando el modelo prefrontal.

INTRODUCTION: According to the prefrontal model, individuals with obstructive sleep apnea (OSA) manifest behaviours mimicking dysexecutive syndrome as a result of blood gas abnormalities and sleep fragmentation. OBJECTIVE: To compare executive functions in OSA patients with normative values and explore their relationship with blood gas abnormalities and sleep fragmentation. PATIENTS AND METHODS: Patients were recruited from the wider community and from a tertiary care hospital. The score obtained in the neuropsychological assessment was compared with Student's t-test for a sample. A multiple linear regression analysis was subsequently estimated, using polysomnographic parameters of hypercapnia, hypoxemia and sleep fragmentation as the predictor variables, and the executive function score as the variable to be predicted. RESULTS: Although the neuropsychological assessment performance of 26% of this sample was classified as executive impairment, indicators of sleep fragmentation and gas abnormalities failed to predict the performance of executive functions. CONCLUSION: A proportion of the patients with OSA presented performance similar to a dysexecutive syndrome; however, the factors underlying and fostering this type of cognitive manifestation remain unclear. Early treatment for this public health problem could be the best tool available for improving quality of life and preventing health risks.

TITLE: Funciones ejecutivas en pacientes con apnea obstructiva del sueño: explorando el modelo prefrontal.Introducción. El modelo prefrontal propone que los individuos con apnea obstructiva del sueño (AOS) manifiestan conductas similares a un síndrome disejecutivo como resultado de las alteraciones de gases en la sangre y la fragmentación del sueño. Objetivo. Comparar las funciones ejecutivas en pacientes con AOS con valores normativos y explorar su relación con las alteraciones de gases en la sangre y la fragmentación del sueño. Pacientes y métodos. Se reclutó a pacientes de la comunidad general y de un hospital de tercer nivel. La puntuación obtenida en la evaluación neuropsicológica se contrastó con la t de Student para una muestra. Posteriormente, se estimó un análisis de regresión lineal múltiple mediante parámetros polisomnográficos de hipercapnia, hipoxemia y fragmentación del sueño como variables predictoras, y la puntuación de funciones ejecutivas como variable que se debe predecir. Resultados. Pese a que el desempeño en la evaluación neuropsicológica del 26% de esta muestra se clasificó como alteración ejecutiva, los indicadores de fragmentación del sueño y alteraciones de gases no predijeron el desempeño ejecutivo. Conclusión. Una fracción de los pacientes con AOS mostró un desempeño similar a un síndrome disejecutivo; no obstante, permanecen indefinidos los factores que subyacen y favorecen este tipo de manifestaciones cognitivas. La atención temprana de este problema de salud pública podría ser la mejor herramienta disponible en aras de mejorar la calidad de vida y prevenir riesgos a la salud.

Type II diabetes mellitus and menopause: a multinational study.

BACKGROUND: Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. OBJECTIVES: To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. METHODS: A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. RESULTS: The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confidence interval (CI) 3.47-5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22-1.94), hormonal therapy (OR 1.46; 95% CI 1.11-1.92), ≥ 50 years of age (OR 1.48; 95% CI 1.17-1.86), overweight or obese (OR 1.47; 95% CI 1.15-1.89), and waist circumference ≥ 88 cm (OR 1.32; 95% CI 1.06-1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35-0.87), alcohol (OR 0.73; 95% CI 0.54-0.98) and living in cities > 2500 meters above sea level (OR 0.70; 95% CI 0.53-0.91) or with high temperatures (OR 0.67; 95% CI 0.51-0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. CONCLUSION: Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.

Intestinal homeostasis disruption in mice chronically exposed to arsenite-contaminated drinking water.

Chronic exposure to inorganic arsenic [As(III) and As(V)] affects about 200 million people, and is linked to a greater incidence of certain types of cancer. Drinking water is the main route of exposure, so, in endemic areas, the intestinal mucosa is constantly exposed to the metalloid. However, studies on the intestinal toxicity of inorganic As are scarce. The objective of this study was to evaluate the toxicity of a chronic exposure to As(III) on the intestinal mucosa and its associated microbiota. For this purpose, BALB/c mice were exposed during 6 months through drinking water to As(III) (15 and 30 mg/L). Treatment with As(III) increased reactive oxygen species (43-64%) and lipid peroxidation (8-51%). A pro-inflammatory response was also observed, evidenced by an increase in fecal lactoferrin (23-29%) and mucosal neutrophil infiltration. As(III) also induced an increase in the colonic levels of pro-inflammatory cytokines (24-201%) and the activation of some pro-inflammatory signaling pathways. Reductions in the number of goblet cells and mucus production were also observed. Moreover, As(III) exposure resulted in changes in gut microbial alpha diversity but no differences in beta diversity. This suggested that the abundance of some taxa was significantly affected by As(III), although the composition of the population did not show significant alterations. Analysis of differential taxa agreed with this, 21 ASVs were affected in abundance or variability, especially ASVs from the family Muribaculaceae. Intestinal microbiota metabolism was also affected, as reductions in fecal concentration of short-chain fatty acids were observed. The effects observed on different components of the intestinal barrier may be responsible of the increased permeability in As(III) treated mice, evidenced by an increase in fecal albumin (48-66%). Moreover, serum levels of Lipopolysaccharide binding proteins and TNF-α were increased in animals treated with 30 mg/L of As(III), suggesting a low-level systemic inflammation.

Preclinical evaluation of a tool for insertion force measurements in cochlear implant surgery.

PURPOSE: Trauma that may be inflicted to the inner ear (cochlea) during the insertion of an electrode array (EA) in cochlear implant (CI) surgery can significantly decrease the hearing outcome of patients with residual hearing. Interaction forces between the EA and the cochlea are a promising indicator for the likelihood of intracochlear trauma. However, insertion forces have only been measured in laboratory setups. We recently developed a tool to measure the insertion force during CI surgery. Here, we present the first ex vivo evaluation of our tool with a focus on usability in the standard surgical workflow. METHODS: Two CI surgeons inserted commercially available EAs into three temporal bone specimens. The insertion force and the orientation of the tool were recorded together with camera footage. The surgeons answered a questionnaire after each insertion to evaluate the surgical workflow with respect to CI surgery. RESULTS: The EA insertion using our tool was rated successful in all 18 trials. The surgical workflow was evaluated to be equivalent to standard CI surgery. Minor handling challenges can be overcome through surgeon training. The peak insertion forces were 62.4 mN ± 26.7 mN on average. Peak forces significantly correlated to the final electrode insertion depth, supporting the assumption that the measured forces mainly correspond to intracochlear events and not extracochlear friction. Gravity-induced forces of up to 28.8 mN were removed from the signal, illustrating the importance of the compensation of such forces in manual surgery. CONCLUSION: The results show that the tool is ready for intraoperative use. In vivo insertion force data will improve the interpretability of experimental results in laboratory settings. The implementation of live insertion force feedback to surgeons could further improve residual hearing preservation.

Ex Vivo Evaluation of a Minimally Invasive Approach for Cochlear Implant Surgery.

OBJECTIVES: Drilling a minimally invasive access to the inner ear is a demanding task in which a computer-assisted surgical system can support the surgeon. Herein, we describe the design of a new micro-stereotactic targeting system dedicated to cochlear implant (CI) surgery and its experimental evaluation in an ex vivo study. METHODS: The proposed system consists of a reusable, bone-anchored reference frame, and a patient-specific drilling jig on top of it. Individualization of the jig is simplified to a single counterbored hole drilled out of a blank. For accurate counterboring, the setup includes a manufacturing device for individual positioning of the blank. The system was tested in a preclinical setting using twelve human cadaver donors. Cone beam computed tomograph (CBCT) scans were obtained and a drilling trajectory was planned pointing towards the basal part of the cochlea. The surgical drill was moved forward manually and slowly while the jig constrained the drill along the predetermined path. RESULTS: Drilling could be performed with preservation of facial nerve in all specimens. The mean error caused by the system at the target point in front of the cochlea was 0.30 mm ± 0.11 mm including an inaccuracy of 0.09 mm ± 0.03 mm for counterboring the guiding aperture into the jig. CONCLUSION: Feasibility of the proposed system to perform a minimally invasive posterior tympanotomy approach was shown successfully in all specimens. SIGNIFICANCE: First evaluation of the new system in a comprehensive ex vivo study demonstrating sufficient accuracy and the feasibility of the whole concept.

A Tool to Enable Intraoperative Insertion Force Measurements for Cochlear Implant Surgery.

OBJECTIVE: Residual hearing preservation during cochlear implant (CI) surgery is closely linked to the magnitude of intracochlear forces acting during the insertion process. So far, these forces have only been measured in vitro. Therefore, the range of insertion forces and the magnitude of damage-inducing thresholds in the human cochlea in vivo remain unknown. We aimed to develop a method to intraoperatively measure insertion forces without negatively affecting the established surgical workflow. Initial experiments showed that this requires the compensation of orientation-dependent gravitational forces. METHODS: We devised design requirements for a force-sensing manual insertion tool. Experienced CI surgeons evaluated the proposed design for surgical safety and handling quality. Measured forces from automated and manual insertions into an artificial cochlea model were evaluated against data from a static external force sensor representing the gold standard. RESULTS: The finalized manual insertion tool uses an embedded force sensor and inertial measurement unit to measure insertion forces. The evaluation of the proposed design shows the feasibility of orientation-independent insertion force measurements. Recorded forces correspond well to externally recorded reference forces after reliable removal of gravitational disturbances. CI surgeons successfully used the tool to insert electrode arrays into human cadaver cochleae. CONCLUSION: The presented positive evaluation poses the first step towards intraoperative use of the proposed tool. Further in vitro experiments with human specimens will ensure reliable in vivo measurements. SIGNIFICANCE: Intraoperative insertion force measurements enabled by this tool will provide insights on the relationship between forces and hearing outcomes in cochlear implant surgery.