Flowchart for predicting achieving the target area under the concentration-time curve of vancomycin in critically ill Japanese patients: A multicenter retrospective study.

INTRODUCTION: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients. METHODS: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUCfollow-up) and target AUCfollow-up achievement was defined as an AUC of 400-600 µg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT). RESULTS: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUCfollow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUCfollow-up of 400-600 µg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m2 or higher; the accuracy was adequate (92 %, R2 0.52). CONCLUSION: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated.

Clinical outcomes of personalized blastocyst embryo transfer after endometrial receptivity analysis: A multicenter, retrospective cohort study.

Purpose: To evaluate clinical outcomes after endometrial receptivity analysis (ERA). Methods: This was a multicenter, retrospective cohort study involving 861 women who underwent ERA testing at certified fertility clinics in Japan, and who received subsequent personalized blastocyst embryo transfers (ET) between 2018 and 2020. Clinical outcomes, including pregnancies, miscarriages, and live births, were evaluated according to receptivity status for ERA. Results: Mean patient age was 37.7 years (SD = 4.0), and the median number of previous ETs was 2 (interquartile range, 2-3). 41.0% (353/861) of patients were non-receptive for ERA testing. Clinical pregnancy, miscarriage, and live birth rates for personalized blastocyst ET were 44.5% (226/508), 26.1% (59/226), and 26.8% (136/508) for receptive patients, and 43.1% (152/353), 28.3% (43/152), and 28.9% (102/353) for non-receptive patients, all statistically nonsignificant. Multiple logistic regression demonstrated similar nonsignificant associations between receptivity and clinical outcomes. Greater patient age, smoking, and longer duration of infertility were significantly and negatively associated with receptivity, whereas a history of delivery was positively associated and statistically significant. Conclusions: Clinical outcomes after ERA testing were similar between receptive and non-receptive patients. Further prospective study including an appropriate comparison group are warranted to evaluate the efficacy of ERA testing.

Do heel-unloading orthoses improve clinical outcomes in patients after surgical treatment of calcaneal fracture? A propensity-matched, multicenter analysis of the TRON database.

BACKGROUND: Postoperative protocols after surgical treatment of calcaneal fracture have not been standardized to date. There are only a few reports on the efficacy of heel-unloading orthoses (HUOs; Mars shoe, Graffin orthosis), and thier efficacy is uncertain. OBJECTIVES: The purpose of this study was to compare postoperative radiologic and clinical outcomes in patients with calcaneal fractures who used Graffin orthosis. STUDY DESIGN: Multicenter retrospective study. METHODS: We finally extracted 182 patients from a database of the Trauma Research Group of Nagoya and divided them into two groups: group C (underwent casting or splinting only) and group O (Graffin orthosis was used). A propensity score algorithm was used to match group C to group O in a 1:1 ratio. We evaluated American Orthopaedic Foot and Ankle Society (AOFAS) score at three and six months after surgery and at final follow-up. Differences in reduction of the Böhler angle between the two groups were evaluated radiographically. All data were analyzed with a t-test or Fisher's exact test. P < .05 was considered statistically significant. RESULTS: The AOFAS score 3 months after surgery in group O was significantly higher than that in group C (69.57 vs. 77.22; P = .004). However, there were no statistically significant differences between group C vs. group O in AOFAS scores at 6 months after surgery and at final follow-up (81.92 vs. 85.67 and 89.18 vs. 88.13; P = .087 and 0.597, respectively). There was no significant statistical difference in the reduction of the Böhler angle (5.07 vs. 5.89; P = .529). CONCLUSIONS: At 3 months postoperatively, the orthosis group showed predominantly better functional results. We believe that heel-unloading orthoses are useful for patients who require an early return to work and to daily life.

Successful monozygotic triplet pregnancy after a single blastocyst transfer following in vitro maturation of oocytes from a woman with polycystic ovary syndrome: a case report.

BACKGROUND: Although women with polycystic ovarian syndrome (PCOS)-related sub-fertility are high responders to controlled ovarian stimulation, it is difficult to obtain mature oocytes in these women. Therefore, in vitro maturation (IVM), which is the technique of letting the contents of the ovarian follicles and the oocytes inside mature in vitro, has often been proposed in such women. We describe the first successful delivery of monozygotic triplets resulting from transfer of a single blastocyst following IVM of oocytes. CASE PRESENTATION: A 32-year-old nulligravida female with PCOS underwent IVM. She underwent vitrified-warmed single blastocyst transfer following IVM, and a dichorionic triamniotic triplet pregnancy was confirmed at 8 weeks. Healthy triplets were delivered by cesarean section at 33 weeks' gestation. This is the first case of monozygotic triplets derived from IVM oocytes that were successfully delivered. The determination of chorionicity and amnionicity is generally supposed until 3 days after fertilization, and no division or splitting of her embryo was observed on transfer. Interestingly, her embryo might have split after the transfer, resulting in a dichorionic triamniotic triplet pregnancy. CONCLUSIONS: Patients should be informed of a possible increased risk of monozygotic multiple pregnancies after single embryo transfer following IVM.

Scanning electoronmicroscopical analysis of the loose bodies of synovial chondoromatosis in temporomandibular joint.

The aim of this study is to reveal the morphological property about the loose bodies (LBs) of temporomandibular joint (TMJ) by scanning electron microscope (SEM). We obtained specimens from two female cases of released loose body by surgical operation. These specimens were fixed by soaking in a mixture of 5% glutaraldehyde or 4% formaldehyde for one week. They were cut into half pieces. These specimens were observed at an accelerating voltage of 3 kV under a SEM (JSM-5500, JEOL, Tokyo). In the electron microscopic findings, it seems to be separated into two different parts as inside part and outside part. On the inside part, collagen fibers were running very densely in the same direction in an orderly neatly manner. Whereas, we observed waved collagen fibers running irregularly with many spaces on the outside part. Outside part seems to be porous pattern compared with inside part. It might be that the surface and outside part included many active fibroblasts. As results, it seems that the LBs might develop in a multi-layer style, in which fibrous tissues were piled up loosely around the inside part. The proliferating activity of LBs grows from the inside to outside of SC in TMJ.

The clinical outcome of Dienogest treatment followed by in vitro fertilization and embryo transfer in infertile women with endometriosis.

BACKGROUND: Endometriosis is considered to be the most intractable cause of female infertility. Administering any type of treatment for endometriosis before in vitro fertilization and embryo transfer (IVF-ET) is an important strategy for improving the IVF-ET outcomes for infertile women with endometriosis. In fact, treatment with a gonadotropin-releasing hormone (GnRH) agonist just before IVF-ET has been reported to improve the clinical outcome in endometriosis patients. However, the benefit of Dienogest (DNG), a synthetic progestin, treatment just before IVF-ET remains unclear. METHODS: Sixty-eight infertile women with Stage III or IV endometriosis (ovarian endometrial cyst < 4 cm) were recruited for this study. The subjects were divided into 2 groups: a DNG group (n = 33) and a control group (n = 35). DNG was administered orally every day for 12 weeks prior to the conventional IVF-ET cycle in the DNG group. Standard controlled ovarian hyperstimulation with the GnRH agonist long protocol was performed in the control group. The numbers of mature follicles and retrieved oocytes, fertilization rates, implantation rates, and clinical pregnancy rate were compared between the two groups. In addition, the concentrations of inflammatory cytokines, oxidative stress markers, and antioxidants in follicular fluids were also measured. RESULTS: The numbers of growing follicles, retrieved oocytes, fertilized oocytes, and blastocysts were significantly lower in the DNG group than in the control group. The fertilization and blastocyst rates were also lower in the DNG group than in the control group. Although there was no significant difference in the implantation rate between the groups, the cumulative pregnancy rate and live birth rate were lower in the DNG group than in the control group. There was no significant difference in the abortion rate. Our results failed to show that DNG reduces the inflammatory cytokine levels and oxidative stress in follicular fluids. CONCLUSIONS: Administering DNG treatment just before IVF-ET did not provide any benefits to improve the clinical outcomes for infertile women with endometriosis.

Diagnostic usefulness of panoramic imaging of the pterygopalatine fossa: case of a schwannoma causing pterygopalatine fossa expansion.

The pterygopalatine fossa is a small area between the posterior wall of the maxillary sinus and the anterior surface of the pterygoid process of the sphenoid bone. The pterygopalatine fossa can be seen clearly on panoramic imaging. We present the case of a 57-year-old man who exhibited right pterygopalatine fossa expansion on panoramic imaging. Computed tomography (CT), magnetic resonance imaging (MRI), and panoramic imaging all showed a tumor at the right pterygopalatine fossa in this patient. CT indicated that the tumor replaced right retromaxillary fat and displaced the posterior wall of the maxillary sinus. On MRI, the tumor showed intermediate signal intensity at the paranasal area on T1-weighted images, and variable intermediate and high signal intensities on fat-suppressed T2-weighted images. It was eventually diagnosed as a schwannoma. Thus, panoramic imaging can be used for disease screening at the posterior border of the maxilla. Our conclusion is based on this report of a patient with a schwannoma at the posterior wall of the maxillary sinus, which panoramic imaging revealed to have pterygopalatine fossa expansion.

Intracranial meningeal melanocytoma diagnosed using an interdisciplinary approach: a case report and review of the literature.

BACKGROUND: Meningeal melanocytoma is a rare pigmented tumor arising from leptomeningeal melanocytes. Patients with this tumor might initially consult a dentist because a mass lesion in Meckel's cave could manifest as dental pain and malocclusion, thereby mimicking temporomandibular disorder. The diagnostic approach, especially using imaging modalities, would be challenging in such cases unless an interdisciplinary approach is used. CASE PRESENTATION: Here, we report a case of a 39-year-old Japanese man who had a history of pain and numbness on the left side of his face and malocclusion for 3 months before the initial visit. The diagnosis was primary intracranial meningeal melanocytoma arising from Meckel's cave. CONCLUSIONS: The process by which the final diagnosis of meningeal melanocytoma was reached highlights the importance of collaboration between the medical and dental disciplines. This case also demonstrates that meningeal melanocytoma has a specific signal pattern on magnetic resonance imaging, including high signal intensity on T1-weighted images and low signal intensity on T2-weighted images.

Potassium bromate disrupts mitochondrial distribution within murine oocytes during in vitro maturation.

PURPOSE: As disturbed mitochondrial distribution is thought to be a cause of the aging of oocytes, it was investigated whether oxidizing agents exert harmful effects on nuclear maturation and mitochondrial cluster formation in murine oocytes and whether antioxidants could rescue such harmful effects in vitro. METHODS: Oocytes were obtained from female Institute of Cancer Research mice 48 h after an intraperitoneal injection of 7.5 IU pregnant mare serum gonadotropin. The oocytes were cultured with potassium bromate, an oxidizing agent, in the presence or absence of the antioxidant, resveratrol. After 12 h, the nuclear phases and mitochondrial distribution were observed. RESULTS: Significantly decreased rates of metaphase II (MII) oocytes were observed with 750 µM and 1000 µM of potassium bromate, while a significant increase in abnormal mitochondrial clusters was induced at 500 µM, 750 µM, and 1,000 µM. The addition of 10 µM or 20 µM resveratrol improved both MII maturity and the cluster formation rates in the presence of potassium bromate. CONCLUSIONS: The addition of potassium bromate reduced MII maturity rates and induced abnormal mitochondrial cluster formation. This effect was alleviated by the antioxidant, resveratrol. The in vitro model used herein is useful for investigating the functions of antioxidants in the aging of oocytes.

Creation of Superhydrophobic Poly(L-phenylalanine) Nonwovens by Electrospinning.

From the viewpoint of green chemistry and environmental chemistry, an important challenge in the field of superhydrophobic materials is to create them with only bio-based molecules. We developed superhydrophobic and chemically stable poly(L-phenylalanine) (PolyPhe) nonwovens by electrospinning. PolyPhe was selected because, due to its very rigid chemical structure, it is one of the toughest and most hydrophobic polymers among polymers composed only of amino acids. The water contact angle on the nonwovens is a maximum of 160°, and the droplets are stably adhered and remain still on the nonwoven surface even if it is turned over, thereby suggesting a petal-type superhydrophobicity. The nonwovens show a good chemical stability, and their weight remains unchanged after 5 days immersion in acidic (pH 2) and basic (pH 12) conditions. In addition, the superhydrophobic property is not lost even after the alkali treatment. Such tough superhydrophobic materials are intriguing for further biomedical and environmental applications.

Prediction of progression of damage to articular cartilage 2 years after anterior cruciate ligament reconstruction: use of aggrecan and type II collagen biomarkers in a retrospective observational study.

BACKGROUND: We aimed to determine whether synovial fluid (SF) biomarkers can predict the progression of articular cartilage damage as determined by arthroscopic evaluation during and after anterior cruciate ligament (ACL) reconstruction. METHODS: Arthroscopic assessment of articular cartilage damage was performed twice in 62 patients, first during ACL reconstruction and then approximately 2 years later during implant removal for ligament fixation. SF levels of the collagenase-generated cleavage neoepitope of type II collagen (C2C) and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate (Δdi-C4S), and chondroitin-6-sulfate (Δdi-C6S) were measured at ACL reconstruction. Associations between baseline biomarker levels and subsequent progression of cartilage damage were determined using receiver operating characteristic analysis and multivariable logistic regression analysis. RESULTS: No radiographic changes were observed in any of the patients. Progression of high-grade cartilage damage, observed arthroscopically, was negatively correlated with levels of Δdi-C6S and KS, as well as the ratio of Δdi-C6S to Δdi-C4S (C6S/C4S). Logistic regression analysis revealed significant associations of Δdi-C6S (cut-off: 55.7 nmol/ml, odds ratio (OR) 0.231, 95% confidence interval (CI) 0.061-0.879), KS (cut-off: 10.6 µg/ml, OR 0.114, 95% CI 0.024-0.529), and C6S/C4S ratio (cut-off: 4.6, OR 0.060, 95% CI 0.005-0.737) with the progression of high-grade cartilage damage after adjusting for age, the duration from injury to first surgery, sex, and the number of high-grade lesions (grades III and IV) at baseline. CONCLUSIONS: The progression of high-grade cartilage damage was significantly associated with baseline levels of proteoglycan glycosaminoglycan biomarkers; namely, Δdi-C6S, KS, and C6S/C4S ratio.

The role of computed tomography and magnetic resonance imaging in diagnosing clear cell ameloblastoma: A case report.

Ameloblastoma is the most common and clinically relevant type of odontogenic tumor. Clear cell odontogenic carcinoma is histologically characterized by solid sheets and nests of clear cells, whereas clear cell ameloblastoma (CCAM) is histologically characterized by an ameloblastomatous component intermixed with an extensive clear cell component. A total of 12 reports have been published on the histological etiology for CCAM; however, no reports have made regarding the detailed computed tomography and/or magnetic resonance imaging features of tumors of this type. The present study describes a case of a well-circumscribed 20-mm radiolucent lesion of the anterior mandible that was misdiagnosed as a clear cell odontogenic carcinoma. The study describes the detailed radiological characteristics of a case of CCAM.

Anesthetic Management of a Patient With Ehlers-Danlos Syndrome.

We describe the case of a 37-year-old woman who had been diagnosed with Ehlers-Danlos syndrome (EDS) 4 years earlier and was scheduled to undergo removal of synovial chondromatosis in the temporomandibular joint. EDS is a heritable connective tissue disorder and has 6 types. In this case, the patient was classified into EDS hypermobility type. The major clinical feature of this type is joint hypermobility. The patient had sprain or subluxation of the elbows and ankles and dislocation of the knees. Anticipated problems during general anesthesia would be affected by the disease type. For this patient, extra attention was directed to positional injury-induced neuropathy and articular luxation, cutaneous injuries, injuries related to intubation and ventilation, and postoperative pain. Anesthesia was induced with propofol, remifentanil, and rocuronium and maintained with oxygen-air-desflurane, propofol, remifentanil, fentanyl, and rocuronium. In this case, the patient was safely managed without adverse events.

Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD.

1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) as a novel and effective solvent to facilely prepare cyclodextrin-assembled materials.

We found that cyclodextrins (CDs) have a high solubility in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Evaporating HFIP from CD solutions on a glass plate gave crystalline solids composed of channel-type CD assemblies, and electrospinning with an HFIP solution of CDs fabricated CD microfibers.

Analysis of MRI findings in minimum invasive treatment for habitual temporomandibular joint dislocation by autologous blood injection around the temporomandibular joint capsule.

The aim of this study was to investigate magnetic resonance imaging (MRI) findings following autologous blood injection (ABI) for habitual temporomandibular joint (TMJ) dislocation. MRI was performed one hour and four and twelve weeks after ABI, revealing three types of significant findings. The first type was similar to hematoma and/or joint effusion in the articular capsule of the TMJ (type I). The second showed sporadic and diffuse T2 emphasis around the TMJ capsule (type II). The third involved a decreased range of condyle movement compared to before ABI (type III). Furthermore, we analyzed the three types of significant MRI findings. At one hour after ABI, type I was Grade 0 in 0 of 14 patients, Grade 1 in 8, Grade 2 in 2, and Grade 3 in 4. Type II was seen in 9 of the 14 cases and type III in 8. After twelve weeks, all cases of type I were Grade 0, no type II cases were evident, and type III was seen in 11 cases. Injecting autologous blood into surrounding TMJ tissues is an important factor in ABI. Minimally invasive treatment for habitual TMJ dislocation using ABI around the TMJ capsule appears to represent a very effective and safe treatment.

The expression of cytokeratin in keratocystic odontogenic tumor, orthokeratinized odontogenic cyst, dentigerous cyst, radicular cyst and dermoid cyst.

The epithelial lining of odontogenic keratocysts exhibits either parakeratosis or orthokeratosis. In 2005, the WHO classified odontogenic keratocysts with parakeratosis as keratocystic odontogenic tumors (KCOT). Odontogenic keratocysts with orthokeratosis were not classified as odontogenic tumors, but instead referred to as orthokeratinized odontogenic cysts (OOC). To clarify the difference between these two lesions, we investigated their biological characteristics using immunohistochemical studies for cytokeratins (CK) in KCOT and OOC as well as in dentigerous cysts (DC), radicular cysts (RC) and dermoid cysts (DMC). We examined twenty-five cases of KCOT, fifteen cases each of OOC, DC and RC, and ten cases of DMC. We studied the immunohistochemical expression of CK10, 13, 17 and 19. To evaluate the immunohistochemical staining pattern, we divided the epithelial lining of the lesions into three layers (surface layer: su, spinous layer: sp, basal layer: ba). For CK10, most OOC and DMC specimens of su and sp were positive. For CK13 and 19, most KCOT, DC and RC specimens of su and sp were positive. For CK17, most KCOT specimens of su and sp were positive. The percentages of total CK expression of su and sp, and ba of CK19 differed significantly between the lesions (P < 0.001). These results support the hypothesis that OOC originate from not the odontogenic apparatus, but the oral epithelial component.

Prognostic factor of mandibular condylar movement exercise for patients with internal derangement of the temporomandibular joint on initial presentation: preliminary report.

PURPOSE: The aim of this study is to examine the factors, which predict the effect of mandibular condylar movement exercise (MCME). MATERIAL AND METHODS: We investigated the efficiency of MCME and the significant difference in average age and the mean duration length of closed lock symptoms prior to the initial consultation in both success cases and failure cases in initial visiting. Seventy-four women aged between 19 and 75 (mean: 41.4) years were included in this study. RESULTS: On the initial visiting day, the success cases were 50 cases (67.6%) and the failures were 24 cases (23.4%). The average age of success cases is 38.0 years, and failure cases are 48.4 years. Duration of the lock in success cases is 35.3 days, and failure cases are 87.6 days. CONCLUSION: These results suggested that lower improvement rates thus correlated with increasing age with exercise. MCME is effective mouth-opening exercise in patients with a history of short duration of locking. In conclusion, age and duration of locking, it must become the important factor predict an effect MCME.

Preliminary report of Ki-67 reactivity in synovial chondromatosis of the temporomandibular joint: an immunohistochemical study.

BACKGROUND: Synovial chondromatosis (SC) is rare benign condition characterized by the formation of metaplastic cartilaginous nodules in the synovial membrane and joint space. Cartilaginous nodules from and may become pedunculated and detached from the synovial membrane, so becoming loose bodies within the joint space. PURPOSE: The aim of this study was to determine the proliferative activity of loose body and synovial membrane of SC in temporomandibular joint by using Ki-67 antibody. MATERIAL AND METHODS: We obtained 4 specimens (4 female) of released loose body and 2 specimens of synovial membrane with attached loose bodies by surgical operation. The specimens were fixed in 10% formalin solution, and embedded in paraffin. The immunohistochemical study was carried out using an anti-human Ki-67 monoclonal antibody. The sections were visualized by 3, 3'-diaminobenzidine-tetrahydrochloride (DAB). RESULTS: The expression of Ki-67 was scarcely detected in all cases of loose bodies. In second phase cases, the mild expression of Ki-67 was detected at both cases of synovial membrane which were attached loose bodies. CONCLUSION: These results suggested that released loose bodies into the joint compartment did not have independent proliferating activity. However, the synovial membrane may play a very important role in the proliferation of the loose bodies.

Evaluation of mandibular condylar movement exercise for patients with internal derangement of the temporomandibular joint on initial presentation.

The aim of the present study was to evaluate mandibular condylar movement in a group of Japanese women who presented with closed lock of the temporomandibular joint. A total of 148 women aged between 19 and 75 years were included in the study. We examined mouth-opening, protrusion, and lateral excursive movements, and divided the patients into two groups (74 experimental cases and 74 controls). The experimental group was treated with exercises of the mandibular condyle, and the median (range) maximum mouth-opening increased from 27 (range 11-34)mm to 38 (24-47)mm. In control cases, it increased from 29 (range 20-35)mm to 30 (20-39)mm without exercise. In the experimental group, the median (range) maximum lateral movement on the opposite (unaffected) side increased from 8 (3-12)mm to 9 (5-13)mm. In the control group it remained similar at 7 (3-12)mm and 7 (3-12)mm. In the experimental group, the median (range) lateral movement on the affected side increased from 6 (2-13)mm to 8 (3-13)mm. In controls it remained similar at 6 (2-12)mm and 6 (2-12)mm. In the experimental group, the median (range) maximum protrusion increased from 6 (3-12)mm to 7 (4-12)mm, and in the control group from 6 (2-10)mm to 7 (2-10)mm. There was a significant difference between the experimental (50/74, 68%) and control groups (3/74, 4%) in the degree of increased mouth-opening. Exercise of the first mandibular condylar seems to be useful in the treatment of closed lock on initial treatment.